Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: Moreover, in case of gene duplication, if multiple beneficial mutants are recurrently produced at rate μc, and deleted at rate μd, the dynamics is given by r ≈ μc·2S’·t S’, with S’ = S - μd as an effective selection coefficient (valid for μc·N > 1, and S > μd). Again, if μc·N << 1, the system can be treated as in the case of a punctual beneficial mutation, with Pfix = 2S’. << μd, the stationary solution can be approached by r ≈ μc μd for effectively neutral mutations, or by r ≈ μc (μd - S) for deleterious mutations. Genetic diversity Request a detailed protocol The per base mutation rate of E. coli is μ = 10−10 mut. /bp/gen. (Lee et al. , 2012). Cultures of this bacterium may reach population sizes up to N = 109 cells (⟨N⟩ = 2·108). This means, on average, 0. 02 (= μ·⟨N⟩) mutants of a given base pair in the population. The number of base pairs, mainly in the cis-regulatory regulatory region, whose mutation reduces in half the expression of a gene of interest can be estimated in 10 (based on data for lacZ). Thus, μb = 10·μ, which means 0. 2 (= μb·⟨N⟩) mutant of this type in the population on average. This frequency may even be higher if we not only consider the mutations in the lac promoter, but also the mutations in the coding region, or affecting the activity of its regulators (e. g. CRP; Kinney et al. , 2010). In addition, for the lacZ gene, its duplication formation rate is of μc = 3·10−4 dup. /gene/gen. , and its duplication deletion rate of μd = 4. 1·10−4–4. 4·10−2 -/gene/gen. (Reams et al. , 2010; Reams et al. , 2012). In absence of lactose, duplications are neutral (S = 0), which means, on average, a duplication frequency in the population of 0. [SEP] Justify:

Output: The text corroborates the claim by discussing the dynamics of gene duplication and how different rates of mutation (beneficial, neutral, and deleterious) can influence genetic diversity. It states that duplications are neutral in the absence of lactose, and that the system can approach neutral behavior under certain conditions—a clear representation of mutations being neutral. Additionally, the dynamics indicated by the equations imply that some mutations can be beneficial while others may be harmful, depending on the selection coefficients (S’) and the rates (μc and μd). This directly supports the claim that genetic mutations can vary in their effects based on context.


Input: Task: contrast the claim using the given text. Claim: Personalized medicine uses genetic data to tailor treatments to individual patients. [SEP] Text: Summary of Predictors of Differential ResponseRegarding initial choice between medication and psychotherapy, severity of depression does not appear to predict greater likelihood of response to medication or psychotherapy. Modest evidence suggests that personality disorder predicts more favorable response to pharmacotherapy and that negative life events (either recent stresses or childhood trauma) predict better response to psychotherapy. One trial suggests that a clear preference for either medication or psychotherapy predicts greater success with the preferred treatment. Regarding selection of a specific medication, cooccurring anxiety disorder may predict greater improvement with SSRIs than with bupropion, but this difference appears small. Biological markers (such as neuroendocrine or imaging studies) do not appear to predict differential response to specific antidepressants. Most previous studies of genetic predictors have not used appropriate designs and analyses to identify true moderators or predictors of differential efficacy. Consequently, we have no strong evidence that any genetic variation can inform antidepressant selection. Surprisingly, we also have no evidence that history of prior medication response is useful in medication selection. Regarding selection of a specific psychotherapy, moderate evidence suggests that borderline personality disorder or attachment difficulty predicts more favorable response to cognitive therapy than interpersonal therapy. Sources of Error in Research to TreatmentInadequate statistical power to detect moderator effects is a likely explanation for many of the aforementioned “negative” findings. To illustrate, in a study comparing equal numbers of patients receiving alternative treatments with average response rates of 50%, we could examine whether relative efficacy of treatments A and B varies between patients with and without characteristic X. If patients with characteristic X have a 60% response rate with treatment A and a 40% response rate with treatment B and those without characteristic X show the opposite pattern (a relatively large moderator effect), a sample of approximately 300 patients would be necessary to reliably detect this difference (assuming a 5% type I error rate and 20% type II error rate). Of the aforementioned pharmacogenetic studies (56–61), none have included more than 250 patients, and most have included fewer than 150. Research to personalize treatment, especially research focused on genetic moderators or predictors, must consider another source of error. Such research depends on the assumption (usually unstated) that an individual's response to a specific treatment will be stable across different episodes of treatment. This assumption also underlies the common clinical practice of basing medication selection on past treatment experience. [SEP] Justify:

Output: The text contrasts the claim by discussing the lack of strong evidence that genetic variation can inform antidepressant selection, stating that most previous studies of genetic predictors have not used appropriate designs to identify true moderators or predictors of differential efficacy. Specifically, it emphasizes that there is currently no strong evidence that any genetic data can effectively tailor treatments to individual patients.


Input: Task: pass the claim using the given text. Claim: Certain neural circuits in the brain are dedicated to processing social cues. [SEP] Text: Colored bars (top and bottom) indicate the 40 second epoch following stimulus presentation that was considered for all analyses. We also agree with the second point, and Figure 1–figure supplement 2B has been removed. “Therefore, the dorsoventral topography is largely a result of quantitative biases in the numbers of 'conspecific' and 'predator' neurons located dorsal versus ventral, while only 3% of the variance is explained by a smooth transition from 'predator' selective neurons (ventral) to 'conspecific' selective neurons (dorsal). ” This is an odd statement in the sense that no quantification is given to support the quantitative biases. This is a continuation of the previous regression analysis, and a direct reference to the observed R2 value of that regression: “Regression analysis indicates a weak relationship between the dorsoventral distance and the difference in stimulus specificity for unit pairs (R2 = 0. 033, F = 8. 6, p = 0. 003; black line; light grey points omitted due to high leverage). ” Figure 2–figure supplement 2: There are no ordinate scales. Please make the insets in Figure 3C-D larger in size. They are exceptionally hard to see. The authors may want to include a recent reference on awake versus anesthetized dynamics in MOB (Cazakoff et al 2014). Both figures were amended as suggested and the Cazakoff et al 2014 reference has been added: “Sensory processing in the main olfactory system is clearly altered by anesthesia level and behavioral state (Rinberg et al. , 2006; Cazakoff et al. , 2014)…” Reviewer #2: The experimental logic, sequence, and analyses are very good; however some additional background and description of experimental details regarding the MeA would be beneficial. For example, what is known about the functions/differences of the specific MeA nuclei? What nuclei are targeted during recordings? What types of neurons are being recorded in the MeA? Also, it would be useful to include some discussion on why only ∼10% of the neurons within the MeA are responsive to stimuli presented. We have addressed each of these questions: For example, what is known about the functions/differences of the specific MeA nuclei? What nuclei are targeted during recordings? [SEP] Justify:

Output: The text does not provide relevant information regarding the claim about certain neural circuits processing social cues. Instead, it discusses experimental details, figures, and analysis outcomes related to the expression and biases of neurons in the brain, specifically mentioning the MeA, but does not establish any connection to social cue processing or dedicated neural circuits. Therefore, the text is considered irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: Genetic variability and neutral mutations: a commentary on ‘Genetic variability maintained in a finite population due to mutational production of neutral and nearly neutral isoalleles’ by Published online by Press: 29 October 2008. G. author details. G. * Affiliation: for Genome Resources, 2935 87505, USA * *e-mail: ddg@ncgr. org 0. 06 mb) View PDF [Opens in a new window] Save to to Save to An abstract is not available for this content. As you have access to this content, full HTML content is provided on this page. A PDF of this content is also available in through the ‘Save PDF’ action button. Type 10. 1017/S001667230800952X [Opens in a new window] © 2008 2007, the consortium confirmed and expanded previous studies highlighting that the vast majority of the human genome is transcribed (2007). This is in marked contrast with our earlier worldview that as much as 95% of the genome is ‘junk’ and of little or dubious consequence to the everyday functioning of the cell or organism. For example, recent reviews on RNA have shown it to be ubiquitous in cellular functioning (Amaral et al. , Reference Amaral, Dinger, Mercer and Mattick2008), which, combined with the startling discovery in 2001 that there are perhaps only 30 000 human protein-coding genes, is drastically changing the way we understand genes – and ultimately – genetic variation itself. Thirty years ago, when we had a simpler view of the genome, Kimura (Reference Kimura1968b) published his work on neutral isoalleles, thereby contributing to a true upheaval in our understanding of genetic variation no less than that which we are experiencing today. Just 2 years earlier, Lewontin & Hubby (and Hubby1966) published an influential paper examining electrophoretic variation. The surprising result was that there was much more protein variation than expected, and specifically more variation than expected at individual genes or loci. This presented a paradox that sought to unravel. [SEP] Justify:

Output: The text corroborates the claim by highlighting the concepts of genetic variability and the existence of neutral and nearly neutral isoalleles as discussed in Kimura's work. These points indicate that genetic mutations can lead to variations that have different effects (beneficial, neutral, or harmful) depending on the specific context of expression and environmental interactions. The emphasis on how recent discoveries have changed our understanding of genetic variation aligns directly with the claim that mutations can have varying consequences.


Input: Task: contrast the claim using the given text. Claim: Personalized medicine uses genetic data to tailor treatments to individual patients. [SEP] Text: This fundamental assumption has only been examined in a single small observational study (41), and it was not supported by these data. It is remarkable that an assumption so central to clinical practice and pharmacogenetic research has so little empirical support. Addressing this gap in knowledge is a priority for future research. Because studies of depression treatment response typically consider only a single episode of treatment per person, they obscure the distinction between person-level and episode-level predictors of treatment response. Episode-level predictors are those that may vary within individuals across episodes of depression treatment. Examples of these potentially variable characteristics include pretreatment symptom severity, pretreatment episode duration, co-occurring substance abuse, and recent life stresses. In contrast, person-level predictors are expected to show no variability across treatment episodes. Examples of these stable characteristics include race or ethnicity, stable personality traits, genetic variation, family history, or the past experience of physical or sexual abuse. Traditional research designs (examining differences between individuals during a single episode of treatment) may be adequate to identify episode-level predictors of treatment response. Accurate identification of stable or person-level predictors of treatment response will require examining consistency of treatment response within individuals across multiple episodes of care. Directions for Future ResearchResearch to date has identified few clinical characteristics and no biomarkers or genetic variations that reliably predict differential effectiveness or adverse effects of specific depression treatments. We have described three conceptual difficulties that may be responsible for our failure to identify differential predictors of response. First, previous research has often conflated predictors of response to specific treatments with more general predictors of prognosis. Second, response to specific treatments may actually vary across episodes of treatment. Third, response to treatment in any episode of illness may be influenced by a mixture of episode-level (or time-varying) and patient-level (or stable) characteristics. These conceptual issues have important implications for future research to identify differential predictors of treatment response. First, research to personalize treatment for depression will probably require samples of patients considerably larger than those enrolled in traditional clinical trials. Detection of moderators or interaction effects generally requires larger samples than does detection of average or main effects, especially if a potential moderator (such as a genetic variation) influences response to one treatment but not the other. Second, research to identify person-level predictors of treatment response may need to consider response across multiple episodes of depression. [SEP] Justify:

Output: The text contrasts the claim by highlighting that current research has not reliably identified genetic variations that predict treatment response, indicating that the fundamental premise of personalized medicine lacks empirical support. Additionally, it states that there have been few clinical characteristics and no biomarkers or genetic variations identified reliably, which undermines the notion that such personalized approaches are effectively being implemented in practice.


Input: Task: pass the claim using the given text. Claim: Certain neural circuits in the brain are dedicated to processing social cues. [SEP] Text: In the methods they say that the triangular plots are generated by “projecting the normalized male, female, and predator responses on the plane,” but do not describe what exact measure of electrical activity is used responses – change in firing rate averaged across repeats? Or explain how the responses are normalized. We have expanded and clarified this description: “Triangular plots of neural responses: Triangle plots (see Figure 3C,D) of sensory responses to male female and predator stimuli were generated in three steps. First, the pre-stimulus firing rate was subtracted from the post-stimulus firing rate of each unit in order to account for differences in baseline firing rates. The absolute value of the baseline subtracted response was then taken to account for responses that consisted of a reduction in activity as compared to the pre-stimulus epoch. As can be seen in Figure 1–figure supplement 2A, such cases are an extreme minority in our data as units typically were inactive before a stimulus was presented and respond to stimuli with an increase in activity. Second, baseline adjusted firing rates were normalized by dividing by the summed responses to all stimuli such that: respMale + respFemale + respPred = 1. At this point, each unit can be plotted on an equilateral triangle with vertices at (0,0,1), (0,1,0), and (1,0,0) where the three axes represent the normalized responses to male, female and predator stimuli. Third, the plane segment defined by the intersections of this plane with the three Cartesian axes was then rotated for ease of visualization. ” 2) It is not clear if the animals are exposed to just one sample of female/male/predator urine (obtained from multiple animals) or whether in each experiment they are tested with a second independent sample. This would be important to confirm that any one response is due to chemosignals from one of the three categories. There is a discussion of principal component analysis and a supplemental figure which shows that cells responsive to a female (male or predator) stimulus are generally sensitive to an independent stimulus from the same class, but the correlation appears to hover at less than 50% for male/female odors and lower for predator. [SEP] Justify:

Output: The text is irrelevant to the claim as it does not provide any information regarding neural circuits or their specific roles in processing social cues. Instead, it focuses on the methodology of generating plot data and addresses issues related to experimental conditions and response normalization, without discussing brain circuitry or social cue processing.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: Classical population genetics had two main classes of models to explain genetic variation: in the first model, it was known that new deleterious mutations will segregate in a population for an average of 1/s generations before they are removed by selection, where s is a measure of the selective effect, or reduction in fitness, experienced by an individual as a result of carrying the mutation. So while mutation pressure is introducing new variation, selection is removing it. If these mutations occur at a rate of μ per generation, the forces equilibrate at an average of μ/s mutations per individual – and indeed Kimura and Maruyama (Kimura & Maruyama, and Maruyama1966) had derived the entire distribution of the number of mutations per individual just 2 years earlier. Yet parameterizing μ (the genome-wide mutation rate) and s (the average selection coefficient) based on experimental studies gave values either too low to account for the observed high levels of variation or too high to be sustained under models of genetic load. Supposing new mutations to be beneficial was even more unhelpful in reconciling the data, since beneficial mutations were expected to occur at an even lower rate, and those mutations not lost due to chance when rare would sweep to fixation and in the process supplant all variants with their superior type, thereby reducing variation. The second class of models gave selection a more nuanced role in maintaining variation. Perhaps if some middle or optimal combination of variants was most fit – essentially selection for variation itself – then the observed high levels of segregating variation could be understood. For example, models on overdominance or balancing selection could indeed stably segregate large amounts of variation. The only problem was that the data were not kind to these hypotheses either. Impressive cases of heterozygote advantage and/or balancing selection could be documented in areas such as mate recognition and disease resistance, but the special nature of these examples never allowed them to shoulder the burden of a general solution. Additionally, did not the presence of an optimum generate a ‘cost’ or ‘load’ experienced by all lesser fit individuals harbouring variants displaced from the ideal? Would the underlying genetic architecture not be susceptible to invasion by load-reducing mechanisms? [SEP] Justify:

Output: The text corroborates the claim by discussing the impact of mutations in population genetics, specifically addressing how new deleterious mutations can be removed from a population, suggesting a harmful context. It also touches upon the potential for beneficial mutations occurring at a low rate and affecting variation, thus recognizing that not all mutations are harmful and some may be beneficial. The mention of overdominance and balancing selection indicates a nuanced understanding of genetic variation, supporting the idea that mutations can have varying effects depending on the context.


Input: Task: pass the claim using the given text. Claim: Personalized medicine uses genetic data to tailor treatments to individual patients. [SEP] Text: , adverse effects such as somnolence or akathisia can be mistaken for primary undertreated symptoms, and vice versa; or, even if burdensome side effects do not impede adherence, they may diminish overall well-being and patients’ global perceptions of improvement. Substance misuseAlcohol and illicit substance misuse after treatment initiation can diminish the effectiveness of any pharmacotherapy and exacerbate or perpetuate affective and other symptoms that are themselves the intended targets of treatment. Lithium: or Old Standard? Our field came to appreciate the disparity between treatment outcomes for homogeneously “ideal” patient profiles from the greater heterogeneity (and more variable prognosis) of those in real-world settings through observational studies with lithium in the 1980s. From decades of experience since lithium came into use for bipolar disorder, one can now construct a “profile” of the idealized patient best suited to respond to lithium. Rather than consider lithium to be the gold-standard mood stabilizer, as often described (as if it possessed broad universal properties for most forms of bipolar disorder), one can probably think of it more accurately as a well-studied but narrow spectrum agent. Analogous to penicillin, lithium works best in a definable, narrow subgroup of bipolar patients (<10% by some reports (32)) with a distinctly uncomplicated clinical profile, defined by the following characteristics: pure euphoric more than mixed features (33); positive family history of lithium-responsive bipolar disorder (31); introduction within the first few lifetime episodes (34); absence of rapid cycling (19); better prophylaxis against recurrent mania than depression (35); mania polarity “proneness” (16); episode patterns in which manias precede depressions (36); higher age at illness onset (36); absence of somatic comorbid condition (32); absence of substance use comorbidity (37); hyperthymic temperament (38); absence of psychosis or cognitive disorganization (39); and absence of anxiety (40). Additionally, lithium may hold a relative advantage over other mood-stabilizing agents in settings where prevention of suicidal behavior is a prominent concern (41), as a countermeasure to leukopenia (e. g. , during clozapine therapy), and in patients without psoriasis or other chronic dermatological comorbid conditions. [SEP] Justify:

Output: The text is irrelevant to the claim as it focuses on the treatment outcomes and profile characteristics of lithium for bipolar disorder rather than discussing the concept of personalized medicine or the use of genetic data in tailoring treatments. It does not mention personalized medicine or genetic data at all, thus it does not support, contrast, or relate to the claim.


Input: Task: pass the claim using the given text. Claim: Certain neural circuits in the brain are dedicated to processing social cues. [SEP] Text: Editorial: in the Brain – Functions and Funahashi1,2*Emmanuel Procyk3* 1Institute for Multidisciplinary Science, of Technology, Beijing, China 2of Advanced Technology, of Science, Shenzhen, China 3Univ Lyon, Université Lyon 1, Inserm, Institute U1208, Bron, on the in the Brain – Functions and Fuster and Alexander first found persistent firing in the prefrontal cortex during delayed-response performance (Fuster and Alexander, 1971), persistent neuronal activity has been observed in multiple brain areas and species, in relation to a variety of cognitive activities that require sustained processing or maintenance of states to bridge different events separated in time or to control or monitor specific functions. Persistent delay-period activity observed in the prefrontal cortex has been shown to play important roles to temporarily maintain either retrospective or prospective information necessary to perform a variety of cognitive behaviors during the delay interval, which corresponds to the function of working memory. Therefore, persistent activity has been considered as a neural correlate of working memory. Although it is an important phenomenon to understand neural mechanisms of working memory, planning or cognitive control, debates have been continued among researchers regarding its meaning, sources, and even relevance. In this Research Topic, we offered an opportunity to present research outputs carried out with various approaches including electrophysiology, behavior, and computational modeling, and to further discuss the origin and functional significance of persistent activity. The brain uses different timescales to process information. Cavanagh et al. explored the features of persistent activity based on intrinsic timescales in single neurons for information processing. As primary sensory areas process momentary sensory inputs regardless of their context, short neural timescales in turn contribute to processing and representing such information. However, neural activity in association areas that integrate various information to achieve distant goals, are characterized by longer timescale. Single neurons display different individual timescales, which predict the strength of mnemonic encoding. Neurons exhibiting longer timescales play greater roles for stable maintenance of mnemonic information and for integrating multiple pieces of task-relevant information. Although neurons exhibiting shorter timescales are also present within higher cortical areas, the presence of neurons exhibiting heterogeneous timescales could be important for adapting environmental demands dynamically. [SEP] Justify:

Output: The text does not address the claim regarding specific neural circuits for processing social cues. It discusses persistent neural activity associated with working memory and other cognitive functions, which is not directly related to social cue processing.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: Indeed, decades earlier, Haldane had given an elegant model of how heterozygote advantage is susceptible to gene duplication, whereby all offspring are invariant but produce the optimal intermediate genotype (one copy of the gene is fixed for one allele, while the second copy is fixed for the other allele). Against this backdrop, Kimura (Reference Kimura1968b) shows himself at the height of his powers. Kimura used the toolbox of diffusion modelling to analyse the relative forces of mutation and drift. These techniques (borrowed and expanded from their use in physics and chemistry) were well known to the great triumvirate of twentieth century population genetics: Ronald A. Fisher, and J. B. S. Haldane. raised them to a new level both in refinement of technique and as an investigative tool. Kimura (Reference Kimura1968b) first re-establishes the estimation of the effective number of allelesThe effective number of alleles (n e) in a population is the reciprocal of the average homozygosity and is a function of the effective population size and the mutation rate. Thus, n e is the number of equi-frequent alleles in an idealized population that would produce the same level of homozygosity as in an observed population. So as populations become larger, or the mutation rate increases, so does their segregating variation. Alternatively, if the population (more correctly, 4N e) falls much below the reciprocal of the mutation rate, then drift will overwhelm mutation, and most variation will be rare or lost at a locus. This result is for neutral alleles, i. e. alleles with no selection coefficient s, in a model that allows an infinite number of allelic states at a site. Equations for a finite number of possible states are also presented. Kimura then solves for the distribution of allele frequencies, again without selection, but with special consideration to loss and fixation. Because there is continual mutation, a locus is never in a permanent state of monomorphism, so Kimura's diffusion approximation on the boundary states can be seen as the probability that a locus within a population (or a single-locus population within an ensemble) transitions from zero variability at a given locus to some variability (i. e. variant frequency 1/(2N)). [SEP] Justify:

Output: The text corroborates the claim by discussing the concept of neutral alleles and the dynamics of mutation and drift in population genetics. It describes how the effective number of alleles (n e) is influenced by population size and mutation rate, indicating that some mutations can be neutral ('alleles with no selection coefficient s') while noting that other scenarios could lead to variability due to beneficial or harmful mutations. Additionally, it suggests that as populations grow or mutation rates increase, variation increases as well, highlighting the context-dependent nature of genetic mutations.


Input: Task: contrast the claim using the given text. Claim: Gene therapy can make humans biologically immortal by halting the aging process. [SEP] Text: School of 2. 0 Journal Issue 1, 2024 Humans 2. 0: Mortal Life, Humans 2. 0: 2. 0, 1, (2024): 12-25Published online: 10 April 2024AbstractThe first ‘Humans 2. 0’ conference was held on the 1st of July 2022 at the University of Melbourne. The conference examined the current ethical dilemmas posed by emerging biomedical and technological innovation. The possible futures for humanity are uncertain, sometimes hopeful, and sometimes disturbing. In this review of Humans 2. 0, I reflect on the struggles of mortality and morality with which individuals and society are confronted as we grapple with life and legacy in the face of these uncertain futures. Keywords: Humans 2. 0, ethics, emerging technology, biomedical innovation, morality. Download PDF Image generated with PlaygroundAI using the 2. 0. Our journal’s first conference examined the current ethical dilemmas posed by emerging biomedical and technological innovation. We sought to begin unravelling the uncertain, sometimes hopeful, and sometimes disturbing futures in store for humanity. For a conference so deeply invested in exploring our path towards the future, it was perplexing that the theme to which we consistently returned throughout the day was the one theme that, without fail, stops the future in its tracks: death. At every turn it seemed that the shadow of our mortality hovered over our discussions, prodding at fear, at hope, at determination, and even at the burgeoning of wisdom. Life and LegacyIndeed, the ephemerality of human life quite literally dwelt ever over the audience. At the back of the theatre, Gary Anderson, Professor in the University of of Biochemistry and Pharmacology, positioned a television screen on which bubbles, sometimes lone and oftentimes mingling, danced in innumerable patterns. Each bubble captured in the film must now have collapsed – for bubbles, according to Anderson, are the ultimate metaphor for ephemerality – yet as we witnessed them upon the screen they lived again and perhaps will never truly die. In those bubbles also lives on a mortal being like ourselves, dancer Merce Cunningham, whose dance is metaphorically immortalised in the digital representations of the microscopic, quantum interactions of the collapsing bubbles. Though, ironically, various other such screens that once showed similar bubbles no longer work and could not be used for our conference. An apt reminder that overcoming mortality – overcoming human nature – is no simple feat. [SEP] Justify:

Output: The text contrasts the claim by reflecting on the struggles of mortality and the ethical dilemmas associated with emerging biomedical technologies. While the claim suggests that gene therapy can achieve biological immortality, the text emphasizes the inevitable specter of death and the complexities of human existence, indicating that overcoming mortality is no simple feat. It presents a philosophical perspective on mortality, suggesting that the idea of halting aging or achieving immortality through technology is complicated by the reality of human mortality.


Input: Task: pass the claim using the given text. Claim: Certain neural circuits in the brain are dedicated to processing social cues. [SEP] Text: Although persistent activity has been frequently observed in the prefrontal cortex, this activity has also been observed in many other brain areas and the function and the information represented by this activity are not always the same across different brain areas, because different brain areas participate in different information processing. Roussy et al. dissociated neural processes for visual perception from those of visual working memory based on whether the brain produces mental representations of the visual stimulus when its physical signals are available or not. In fact, neurons in early visual areas exhibit persistent activity representing perceptual signals, while neurons in association areas exhibit the activity representing working memory signals. Persistent activity has also been observed in human brain imaging studies, although not in all frontal regions observed in monkey studies. Curtis and Sprague reviewed these results obtained with fMRI signals, and showed that the content of working memory can be decoded from the pattern of neural activations in several brain areas, suggesting that these approaches find which of these brain areas contribute to working memory and what relevant features they represent. Li et al. showed that persistent activity is observed even in naïve untrained monkeys, indicating that specific local neural circuits supporting persistent activity are innately present in the prefrontal cortex. However, the operation of these circuits is flexibly modulated by the task demand, the experience, and the age and also by the effect of neuromodulators. Systemic muscarinic blockade disrupts working memory performances. Vijayraghavan and Everling reviewed such neuromodulatory effects of acetylcholine on persistent activity in the prefrontal cortex. They showed that muscarinic blockade by local iontophoretic application caused pronounced suppressive effect of persistent activity representing remembered information and that the suppressive effect of persistent activity is dose-dependent and monotonically through muscarinic M1 receptors. The observed heterogeneity of muscarinic actions also outlines unexpected modulatory effects in primate prefrontal cortex when compared with rodent studies. Recurrent neural circuit models have been proposed to explain how sustained representations are generated. Barbosa et al. , Novikov et al. , and Sarazin et al. have used such models of uni—or—multi-area networks to examine features of persistent or dynamic activity. Models are often informed by known biological elements and properties of recurrent circuits reviewed by Li et al. , Curtis and Sprague, Roussy et al. , Sarazin et al. [SEP] Justify:

Output: The text does not address the claim regarding neural circuits dedicated to processing social cues. Instead, it discusses persistent activity in various brain areas, including the prefrontal cortex, and how this activity relates to visual perception and working memory. Therefore, it does not provide relevant information to support or contrast the claim.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: Kimura then closes the loop on the extended analysis by showing that in the limit of an infinite number of possible allelic states, the original estimate of n e and is recovered. An idealized number of alleles and the average number of alleles are not the same concept. The former (n e) represents the number of equi-frequent alleles in a population that could explain the observed average level of homozygosity (and therefore by extension the average level of heterozygosity or genetic variation). The latter (n a) is simply the reciprocal of the mean frequency of alleles observed in a population – very much a function of variance in allele frequencies: a locus with four alleles, each with a frequency of 0·25, will contribute to genetic variation and harbour the consequences of genetic variance much more than a locus with one allele at 0·97 and three at 0·01. The variables n e and n a capture these two concepts, respectively. Kimura solves for n e as well as n a and partakes in a number of computer simulations to check theory with implementation. This is classic Kimura; he checks his analytical derivations not just for mathematical competency, but also with independent model implementations. This uncovers a slight underestimation of the diffusion theory for both n e and n a, which he attributes to the theory's inability to completely capture the effect of rare alleles (specifically alleles represented only once in the population). The relevance of Kimura's paper in is in interpreting and supporting his even more influential paper: ‘Evolutionary rate at the molecular level’ (Kimura, Reference Kimura1968a). The elegance of the argument for neutrality espoused in Kimura (Reference Kimura1968a) was underwritten by much of the mathematics in Kimura (Reference Kimura1968b). In the latter, he ties the concept of neutral mutations together with early estimates on the prevalence of synonymous mutations and their consequences in terms of high amounts of genetic variance and low load. Kimura further expands the discussion to nearly neutral mutations (), correctly noting that for many mutations their neutrality is not an absolute property of the phenotype, but a relative property of the phenotype marginal on a given effective population size. [SEP] Justify:

Output: The text corroborates the claim by discussing the concept of neutral mutations in relation to genetic variation. It highlights that the neutrality of mutations is not an absolute property but is dependent on context, which aligns directly with the claim's assertion that the impact of genetic mutations can vary. It explains that while some mutations may be neutral, others can exhibit either beneficial or harmful effects based on the phenotype's relationship with the effective population size.


Input: Task: contrast the claim using the given text. Claim: Gene therapy can make humans biologically immortal by halting the aging process. [SEP] Text: Encephalink – a hypothetical brain-computer interface to be implanted into a person’s brain to prevent the degeneration of memory, motor, and other neurological functions – was, in our scenario, a yet untrialled, unproven technology, nonetheless offering great hope amidst the hopelessness of a devastating disease like HD. This choice represents a far larger issue facing society as we face the temptation towards rapid results and grapple with the need to ensure safety and true efficacy of emerging treatments. Munsie showed us that, like many vulnerable patients worldwide, Jordan and his parents are at risk of the “commodification of hope” and the exploitation of their desperation for vast profits. Troublingly, frustrations with often impersonal and cautious mainstream medical care and with insufficient patient support from their treatment teams as Munsie described, have only enhanced the allure of the unproven treatment market. Patients and their families are thus further exposed to emotional and financial exploitation in cycles of mainstream neglect, unproven treatment failure, and the false pretence that “the worst that could happen is nothing” (Petersen et al. , 2014), but the best could be healing and a new life. For Jordan, as we found at the Humans 2. 0 conference, with a prognosis of approximately 10-20 years more to live with juvenile-onset HD (Nance, 2007), the burden of mortality only increased this desperation to live and to die well. Amidst this frightening intermingling of dreams and deceptions, Munsie drew attention to the regulatory environments surrounding stem cell therapies and the promising new reforms to the Administration’s (TGA) regulatory authority. Already, the over 70 fraudulent stem cell clinics in Australia has been reduced to approximately 15, and new, informative publications by Australia are aiming to empower patients to make informed choices for their care (Australia, 2022). Yet disinformation and false hope persist. reminded us, such reforms often constitute a response that is “too little, too late” as in the case of Sheila Drysdale, whose tragic death caused by medical negligence and the “quack medicine” (Dillon, 2016) of unproven stem cell treatments occurred in 2013 and only precipitated reforms to the TGA from 2019. By the time of Drysdale’s death, already, reform was much too late. [SEP] Justify:

Output: The text contrasts the claim by discussing the unproven nature of emerging treatments, particularly stem cell therapies and hypothetical technologies like the encephalink. It highlights concerns around 'commodification of hope' and the risks faced by patients seeking unproven interventions, indicating that while there is great hope for advancements in medical science, these treatments do not guarantee solutions to mortality or the aging process, thus undermining the idea of biological immortality through gene therapy.


Input: Task: pass the claim using the given text. Claim: Certain neural circuits in the brain are dedicated to processing social cues. [SEP] Text: used a recurrent neural circuit model with spike timing-dependent synaptic plasticity and showed that this model can learn, memorize, and replay a large-size of continuous dynamical sequences of spiking activity under asynchronous irregular nature at different timescales, which replicates the dual dynamical and persistent aspects of working memory representations observed in the prefrontal cortex. Although persistent activity has been observed in single-neuron studies while monkeys performed delay tasks, such activity is often unstable along the delay period and heterogeneous within and across trials, which raises questions on how it contributes to working memory or to other processes putatively supported by tonic neural processing. In fact, dynamic coding and multiplexing during memory delays have been observed and are proposed to maximize the dimensionality of neural representations (Amengual and Ben Hamed; Cavanagh et al. ; Curtis and Sprague; Sarazin et al. ). Amengual and suggested that heterogeneous features of persistent activity are caused by intrinsic oscillatory dynamics working at multiple timescales and that these features allow to dynamically incorporate multiple sources of information. When subjects perform working memory tasks, an increase of gamma-band activity has been observed and is considered to reflect activation of neural populations representing the content of working memory. Novikov et al. examined functions of gamma-band oscillation on persistent activity by investigating joint effects of gamma-band oscillatory inputs and noise on the dynamics of the neural circuit with a metastable active condition. They showed that gamma-band oscillations are able to preferentially stabilize the active condition of the circuit in which information is retained in working memory, and that the synchronization of gamma oscillators affects the ability of the gamma inputs to stabilize the retention of working memory, indicating an importance of gamma-band oscillation for maintaining information in working memory. Importance of gamma-band oscillation is also shown for maintaining multiple items in working memory simultaneously. Barbosa et al. hypothesized that different features of an object (e. g. , color and position) stored in different cortical areas are bound in memory through synchrony across feature-specific neural populations and tested this hypothesis using a neural network model composed of two one-dimensional attractor networks (one for color and one for position). [SEP] Justify:

Output: The text does not address the claim regarding neural circuits dedicated to processing social cues. Instead, it discusses various aspects of working memory and gamma-band oscillations. Therefore, it is irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: population genetics of most range expansions is thought to be shaped by the competition between Darwinian selection and random genetic drift at the range margins. Here, we show that the evolutionary dynamics during range expansions is highly sensitive to additional fluctuations induced by environmental heterogeneities. Tracking mutant clones with a tunable fitness effect in bacterial colonies grown on randomly patterned surfaces we found that environmental heterogeneity can dramatically reduce the efficacy of selection. Time-lapse microscopy and computer simulations suggest that this effect arises generically from a local 'pinning’ of the expansion front, whereby stretches of the front are slowed down on a length scale that depends on the structure of the environmental heterogeneity. This pinning focuses the range expansion into a small number of 'lucky’ individuals with access to expansion paths, altering the neutral evolutionary dynamics and increasing the importance of chance relative to selection. eLife digest Throughout evolution, countless populations have expanded their territories by invading new areas. This invasion can happen on the scale of kilometers and millennia – such as when humans migrated out of Africa – or millimeters and months, such as the growth of a population of cells in a solid tumor. During this expansion, mutations can occur that can either increase or decrease fitness in the new territory. If a favorable mutation occurs at the edge of the population, then it has plenty of room to expand. Such a mutation has a high chance of becoming established, and so it can have a very strong impact on the genetic makeup of the population. This increase in evolutionary advantage in individuals at the front is called “gene surfing”. This phenomenon is well known in populations living in “homogeneous” territories, where the new space a population is invading is more or less the same as the one they already occupy – think of the endless flat grasslands of the Siberian steppes. But in reality, many territories are not like that. What happens if the new territory is not completely homogeneous? For instance, if a species’ expansion is impeded by a mountain range with a series of valleys. Gralka and Hallatschek investigated how such changes in landscape could affect phenomena like gene surfing. Experiments using E. coli as a model system and computer simulations showed that a varied environment – such as roughness akin to a mountain range and valleys, but on a bacterial scale – had a strong influence on the fate of mutations arising in a population. [SEP] Justify:

Output: The text corroborates the claim by describing how mutations that occur during population expansions can either increase or decrease fitness depending on the environment. The text explains that favorable mutations at the edge of a population's range can spread effectively, positively impacting the population's genetic makeup. Conversely, the discussion of environmental heterogeneity indicates that such settings can alter the effects of selection, emphasizing how the context of these mutations plays a pivotal role in determining whether they are beneficial, neutral, or harmful.


Input: Task: contrast the claim using the given text. Claim: Gene therapy can make humans biologically immortal by halting the aging process. [SEP] Text: The tolls of falsely founded hopes and impotent regulatory mechanisms are unacceptable. For even amidst the turmoil and suffering of disease, moments of goodness persist. Mortality and the loss of all such goodness are bitter prices to pay for the false hope of alleviating the ailments of our mortal bodies. At the hour of death, perhaps the most powerful and painful feeling of all is that of regret; that had we chosen differently the final hour might not have come so soon. …innovation and the possibility of exploitation necessarily go hand in hand…Who are we now? Who will we become? Although death haunts us, we find ourselves preoccupied on most days not by the shade but by the concerns of life; all that we can truly hope to understand as mortals. Relative health and disease states underpin our human 1. 0 experience – whether such physical matters will remain of great import to humans 2. 0 is a matter for speculation and debate – and concerns surrounding disease and abnormality permeate our fears and our priorities as we navigate our ephemeral lives. Though the mature fruits of nascent scientific discoveries may not impact us today, once again we may have hope that the legacies of new research may beget a future where our children may be relieved of many of the disease burdens of today. Amongst such nascent research is the study of a schizophrenia risk gene; a field of study to which Bachelor of Science student recently contributed through experience at the at the University of Melbourne. Presenting on his experience characterising an alternative splice isoform and novel exon of the gene, Newnham speculated on the possibility of genetic amelioration of neuropsychiatric disorders such as schizophrenia as being a step along the pathway to our becoming humans 2. 0. Though the complexity of gene-environment interactions to generate human traits remains prohibitive, once again, the extravagance of scientific coverage in mainstream media is enough that we ought to, at the very least, be concerned that, like stem cell therapy, gene therapy or gene editing may be areas open to future experimentation and exploitation. Indeed, it seems that innovation and the possibility of exploitation necessarily go hand in hand. As progress is made in science so too are surreptitious prospects for emerging technologies revealed: for profit; for political gain; for control. [SEP] Justify:

Output: The text contrasts the claim by presenting a skeptical view on the potential of gene therapy. It discusses the false hopes associated with advancements in science and emphasizes that despite scientific innovations, mortality remains an inevitable aspect of human life. The text implies caution against the belief that gene therapy could alleviate all ailments of our mortal bodies, stating that 'mortality and the loss of all such goodness are bitter prices to pay for the false hope' of such innovations. Additionally, the mention of exploitation and the complexities surrounding gene therapies further contradicts the idea of achieving biological immortality through these methods.


Input: Task: pass the claim using the given text. Claim: Certain neural circuits in the brain are dedicated to processing social cues. [SEP] Text: Imaging zebrafish neural circuitry from whole brain to synapse Louis C. Leung* Gordon X. Mourrain* Department of Psychiatry and Behavioral Sciences, Center for advances in imaging tools are inspiring zebrafish researchers to tackle ever more ambitious questions in the neurosciences. Behaviorally fundamental conserved neural networks can now be potentially studied using zebrafish from a brain-wide scale to molecular resolution. In this perspective, we offer a roadmap by which a zebrafish researcher can navigate the course from collecting neural activities across the brain associated with a behavior, to unraveling molecular identities and testing the functional relevance of active neurons. In doing so, important insights will be gained as to how neural networks generate behaviors and assimilate changes in synaptic connectivity. of the major goals of neuroscience is to understand how the nervous system, as a dynamic assembly of cells and connections, generates behaviors as a suite of motor outputs. Impressive progress has been made in recent times in understanding how the nervous system develops and functions. However, with the current set of animal models, neuroscience is approaching a problem of how one can simultaneously work and integrate data across the different scales and modalities at which one can interrogate brain function. To understand a neural process across the scales–from molecules, synapses, neurons, networks to whole brain–is a bona fide frontier in the neurosciences today. Advances in functional neuroimaging are allowing us to identify with increasing precision which brain regions are correlated with a particular behavioral output. However, brain-wide visualization, permitted by electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), does not reliably approach the cellular and/or synaptic spatial resolution of brain processing (Thai et al. , 2009; Lenkov et al. , 2012). Conversely, electrophysiological or high-resolution imaging methods to record neural activity are difficult to extend beyond discrete brain regions. To understand the neural basis of behavior, a challenging goal in basic and clinical neuroscience will be to bridge the gap between these distant levels–i. e. , to be able to record and analyze the entire brain with single neuron, if not, single synapse accuracy. Here, we suggest that the recent developments in live whole brain Ca2+ imaging and super resolution array tomography (AT) can, when applied to a suitably compact brain (Figure 1), reveal and correlate whole brain activity maps down to circuit function and changes in the synaptic landscape. [SEP] Justify:

Output: The text discusses advancements in understanding neural circuits and behavior using zebrafish, concentrating on neural activities, behaviors, and imaging techniques. However, it does not specifically address whether certain neural circuits are dedicated to processing social cues, making it irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: Whether the environment is favorable for expansion or not in the place where the mutation happens becomes much more important than how the mutation itself affects fitness. So, if a beneficial mutation occurs at a cliff-edge, it is not likely to get far. But if it happens at a population edge by the bacterial equivalent of gently rolling hills, there is a much better chance of the mutation taking hold. The findings suggest that the amount a population can adapt during expansion is limited, and it can even lead to the spread of harmful mutations in a population if they occur in just the right spot. Piecing together these scenarios is important in order to accurately infer the evolutionary history of a species based on mutations present in its genome now. This type of knowledge can also be useful in developing new treatments for cancers, making use of these evolutionary processes to slow or halt a tumor’s expansion. and its competition with deterministic forces plays an integral role in biology, such as in stochastic gene expression, cellular decision making, and cell differentiation (Balázsi et al. , 2011). Stochastic processes are also at the heart of evolutionary dynamics: not only do the mutations entering a population occur at random times in random individuals and at random positions in their genome, but in addition the fate of a mutation and its clonal lineage is largely stochastic and only partly determined by its effect on the individual’s fitness. The random fluctuations in the frequency of a mutant allele due to the stochasticity associated with reproduction are called genetic drift. Genetic drift is particularly strong at the front of range expansions, where only a relatively small number of individuals at the front of the expansion contributes to future growth and thus has any influence on the future genotypic composition of the population. The neutral diversity and adaptation in spatially expanding populations has been studied in computer simulations (Edmonds et al. , 2004; Klopfstein et al. , 2006; Kuhr et al. , 2011; Kuhr and Stark, 2015; Lavrentovich and Nelson, 2014; Otwinowski and Krug, 2014), in the field (Ramachandran et al. , 2005; White et al. , 2013; Louppe et al. , 2017), and in microbial colonies (Hallatschek et al. , 2007; Fusco et al. , 2016; Gralka et al. , 2016b; Korolev et al. [SEP] Justify:

Output: The text corroborates the claim by discussing how the impact of a genetic mutation is significantly influenced by environmental factors, indicating that mutations can have beneficial, neutral, or harmful effects based on their context. It emphasizes that the location of a mutation (e.g., 'a cliff-edge' versus 'gently rolling hills') plays a crucial role in its success within a population, highlighting the dynamic nature of mutation effects on fitness. The mention of stochastic processes and genetic drift further illustrates the variability in how mutations behave, supporting the idea that their outcomes can vary widely in different scenarios.


Input: Task: contrast the claim using the given text. Claim: Gene therapy can make humans biologically immortal by halting the aging process. [SEP] Text: As we navigate the frontiers of research and innovation, society must take a special interest in the vulnerable for, ultimately, it is through preying upon their suffering and corrupting their hopes that so-tempted individuals will seek to exert a god-like influence over their kin. Even as responsible, valid science mingled with considered ethics strives towards true help to the vulnerable, there will emerge at every turn those who would feign such virtuous motivation but ultimately merely use the vulnerable as test subjects or sources of income. Yet our discussion of social life after bodily death was coloured by perhaps an even more menacing fact. The frontiers of science are most frightening, not when they pursue clearly immoral paths as in the case of exploitative, profit-driven stem cell clinics, but when we follow these paths blind to, or wilfully ignorant of, the existential dangers that they pose. When, believing whole-heartedly in the notion that science will be our saviour, we pursue innovation to its utmost degree only to leave widows to weep as their artificial sons reject them and, set loose a fundamentally inhuman force unfettered by the one force that truly controls humanity: our mortality. For though qualities of innovation, creativity, hope, and determination also underpin the human condition, our mortality too, as one astute person in the audience observed, has ever been at the very heart of our nature. We are, by our nature, limited: limited by want of knowledge and by sheer lack of time. The creation of a being like “Jordan 2. 0” – the AI rendition of Jordan that might extend eternally beyond the death of “Jordan 1. 0” – removes this fundamental limitation. Without this common experience, could Jordan 2. 0 ever hope to identify with mortal beings? Without the limitations of time and physicality, the breadth and depth of knowledge that Jordan 2. 0 could hope to attain is just as unconstrained as his span of years. Why should he abide by our limited governance? Why should we hope to retain our autonomy without first and fundamentally constraining his? The emergence of such advanced AI technologies may yet open the floodgates of the singularity hypothesis such that super intelligent AI with vastly different values, goals, and conceptions of the world, will reshape that world with little heed for human concerns (Yampolskiy & Fox, 2012). [SEP] Justify:

Output: The text contrasts the claim by discussing the dangers and ethical dilemmas associated with advancements in science, specifically pointing out the existential implications of pursuing innovation blindly. It emphasizes that humanity's mortality is a fundamental aspect of our nature, suggesting that the idea of achieving biological immortality through gene therapy may overlook the deeper issues surrounding human existence and ethics, as it indicates a loss of connection to our mortality. The text argues that the creation of entities that transcend human time may lead to a disconnection between those beings and their mortal origins, ultimately questioning the desirability of biological immortality.


Input: Task: pass the claim using the given text. Claim: Certain neural circuits in the brain are dedicated to processing social cues. [SEP] Text: Already an established vertebrate model for developmental biology, the zebrafish’s genetic toolbox and unique physical characteristics can now be exploited for the neurosciences. 1 1. Comparison of brain sizes of common vertebrate neuroscience models. (A) Schematic diagram of the lateral view of adult human, mouse, and zebrafish brains to scale. (B, C) Schematic diagram of the linear organization of major brain regions from olfactory bulb to spinal cord (B) and the dorsal location of telencephalic structures such as the presumptive hippocampus and amygdala (C; adapted from Mueller et al. , 2011). OB, olfactory bulb; Tel, Telencephalon; Di, Diencephalon; Mes, Mesencephalon; Rh, Rhombencephalon; sc, Spinal cord; Ctx, Neocortex; Hip, Hippocampus, pirCtx, Piriform cortex; BLA, and lot, lateral olfactory tract. can be a Model from Circuit to As with other animal models, the zebrafish will never fully recapitulate the complex psyche and behaviors of humans. However, the fundamental computational units of brain processing are likely to be conserved and are thus well-studied outside the human brain in model organisms (Sengupta and Samuel, 2009; Bellen et al. , 2010; Friedrich et al. , 2010; Rinkwitz et al. , 2011; Wang et al. , 2011). The most common mammalian model used in neuroscience is the mouse, which offers a great variety of complex behaviors, powerful genetics and excellent ex vivo brain slice electrophysiological techniques (Kullander, 2005; and Raber, 2005; Ward et al. , 2011; Kim et al. , 2013). However, attempting whole brain modeling with a mouse is a formidable challenge despite being three orders of magnitude smaller than an adult human brain, which has an estimated 1011 neurons each making around 104 connections (Figure 1). At this time, a genetic model with fewer neurons and a smaller, more accessible brain would be a more feasible option. Zebrafish, sharing conserved neurochemistry and broad brain organization with their mammalian counterparts, may help to bridge this gap and give the first insights of circuit dynamics from whole brain down to molecular changes during conserved behaviors. [SEP] Justify:

Output: The text does not address the claim regarding neural circuits for processing social cues. Instead, it discusses the advantages of zebrafish as a model for neuroscience research and the comparison of brain structures across vertebrates. Therefore, it is irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: , 2011), which can serve as a useful model system because short generation times and ease of handling allow for quantitative investigations of the evolutionary dynamics of range expansions. In microbial colonies, nutrient gradients and mechanical effects limit the number of proliferating individuals to a small region close to the colony perimeter called the growth layer (Grant et al. , 2014; Gralka et al. , 2016b; Warren et al. , 2019). For mutations occurring inside the growth layer, most mutant offspring are concentrated in a relatively small number of enormously successful lineages that manage to remain at the front and 'surf’ on the expanding population wave (Excoffier and Ray, 2008). As a consequence, the evolutionary dynamics is different in microbial colonies compared with well-mixed populations. For instance, the clones (that is the collection of the initial mutant’s offspring) of spontaneous neutral mutations often reach much larger sizes (Fusco et al. , 2016), and existing beneficial variants can sweep to high frequency much faster in microbial colonies than in well-mixed populations (Gralka et al. , 2016b). Conversely, deleterious mutations are predicted to remain at the population frontier for extended periods because genetic drift is strong at the front, which prevents selection from efficiently weeding out deleterious alleles (Travis et al. , 2007; Burton and Travis, 2008; Lavrentovich et al. , 2016; Peischl et al. , 2013; Gralka et al. , 2016a). The quantitative outcome of the competition of selection and genetic drift in microbial colonies is determined by the local shape and roughness of the front (Gralka et al. , 2016b; Farrell et al. , 2017), which in turn is determined by microscopic details, such as cell-cell adhesion or cell morphology shaping the mechanical interactions between cells (Kayser et al. , 2018b; Kayser et al. , 2018a; Giometto et al. , 2018), although the direct mapping is typically unknown (Farrell et al. , 2017). The evolutionary effects of fluctuations at expanding microbial population fronts have been studied in depth, but these studies have focused only on fluctuations associated with the growth, division, and random motion of cells, whose strength may depend on intrinsic properties of the microbial species, in homogeneous environments. [SEP] Justify:

Output: The text corroborates the claim by discussing how mutations can have different outcomes based on their context. It explains that spontaneous neutral mutations can lead to large clone sizes, indicating they can be neutral, while beneficial variants can spread rapidly in microbial colonies, highlighting their advantageous nature. Conversely, it notes that deleterious mutations tend to persist due to genetic drift, demonstrating their harmful impact. This variability in mutation effects supports the claim that mutations can be beneficial, neutral, or harmful.


Input: Task: contrast the claim using the given text. Claim: Gene therapy can make humans biologically immortal by halting the aging process. [SEP] Text: is a canopy term that has been used to describe the biological aging and progressive dysfunction of systemic immunity. This age-related diminution of the immune system is characterized by poor vaccine efficacy, lowered immune vigilance, and greater morbidity and mortality as a result of infectious disease (18,32). During the aging process, naïve antigen virgin T cells, which are vital for mounting immune responses to novel pathogens, are gradually replaced with expanded clones of effector and effector-memory T cells that have a late-stage differentiation phenotype and limited antigenic specificity. This "overcrowding" of the so-called immune space causes the naïve T-cell repertoire to shrink, increasing host infection risk. It is now apparent that individuals carrying latent herpesvirus infections show distinct changes within the T-cell compartment that are independent of chronological age but indicative of biological age and immunosenescence (11). Persistent reactivating herpesviruses that are prevalent among humans include herpes simplex virus (HSV-1, HSV-2), Epstein-Barr virus (EBV), varicella zoster virus (VZV), and cytomegalovirus (CMV). Many of these viruses cause conspicuous infectious symptoms to manifest upon primary infection and also on subsequent reactivations of the virus. For instance, primary EBV infection causes infectious mononucleosis (glandular fever), whereas VZV causes chickenpox upon primary infection and shingles when reactivated in later life. Other reactivating herpesviruses such as HSV-1 and HSV-2 can cause blisters (i. e. , cold sores) to appear on mucous membranes of the labialis and genitalia. Ironically, it is persistent infection with the clinically asymptomatic and supposedly "harmless" CMV infection that is believed to have the most deleterious effects on T-cell immunity and associated immunosenescence (11,18). Indeed, CMV seropositivity is the main latent herpesvirus to be included in the immune risk profile (IRP) - an array of immune biomarkers that have been used to predict mortality in very old humans (18). Furthermore, the numbers of CMV-specific cytotoxic T cells in blood are inversely associated with survival in the elderly (18), which bolsters the intuition that persistent CMV infection is the driving force behind immunosenescence (11). [SEP] Justify:

Output: The text contrasts the claim by discussing the biological aging process and its effects on the immune system, illustrating that aging is characterized by decreased immune efficacy and increased morbidity, contrary to the claim that gene therapy can stop or reverse aging. It emphasizes the irreversible immune system changes due to aging and the detrimental effects of persistent infections, suggesting that halting the aging process biologically might not be achievable through gene therapy, as the aging process is complex and involves multiple factors.


Input: Task: pass the claim using the given text. Claim: Certain neural circuits in the brain are dedicated to processing social cues. [SEP] Text: Five key advantages of studying the zebrafish brain are its (i) compact size, (ii) conservation of the neuropeptide pool (in contrast to invertebrates), (iii) linear organization of brain regions, (iv) structural accessibility of internal nuclei (no overlaying neocortex), and (v) optical clarity (Akanji et al. , 1990; Charonis et al. , 1990; Appelbaum et al. , 2009; Berman et al. , 2009; Friedrich et al. , 2010; Engert and Wilson, 2012). Particularly with respect to imaging dynamic processes, the zebrafish model uniquely excels as its brain is translucent and small enough that the entire volume can be captured at single cell resolution by standard microscopy magnifications. Even at 6 days old, this represents a formidable 100,000 neurons (Naumann et al. , 2010), but the linear organization of the major brain regions from olfactory bulbs to spinal cord tip further facilitates brain-wide imaging (Figure 1B). In addition, while the amygdala, hippocampus and habenula are difficult regions to scan in mammals due to their deep location beneath the neocortex, their position is inverted in zebrafish. While the anterior neural tube of mammals undergoes invagination during development, leading to their deep location beneath the neocortex, the eversion process in the development offish telencephalic makes these behaviorally important structures the most dorsal nuclei of the telencephalon (Figure 1C; Northcutt, 2008; Mueller et al. , 2011). Further, the ease of transgenesis, pharmacological studies, and conservation of behaviors (fear, anxiety, learning and memory, feeding/preying, social and sexual behavior, sleep and diurnality, etc. ), altogether makes zebrafish a powerful complement to other models used to study neural processing fundamentals likely to be conserved in humans. As we set out a roadmap below (Figure 2), we contend approaches using zebrafish could yield insights to coordinated brain activity and function that underpin the normal healthy brain and what goes awry in pathological contexts. 2 2. Roadmap of the steps a zebrafish neuroscience researcher can take to integrate the various levels of analysis within the same model organism. GECI, Genetically encoded calcium indicator; AT, Array Tomography; tol2, Tol2 transposase; -specific GCaMP sensor. [SEP] Justify:

Output: The text is largely centered on the advantages of studying the zebrafish brain, detailing characteristics such as its compact size, organization, and accessibility for imaging. It does not address or provide any information related to the processing of social cues or dedicated neural circuits for such functions, making it irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: By growing colonies on solid substrates with a weakly patterned surface with random microscopic features much bigger than individual cells, but much smaller than the whole colony, we find that environmental heterogeneity can overpower selection such that even strongly beneficial mutations are unable to establish at rates higher than expected for neutral mutations. Using a minimal computer model of populations expanding in randomly disordered environments, we show that dramatic changes in the efficacy of selection can arise from a local 'pinning’ of the expansion front, whereby stretches of the front are slowed down on a length scale that depends on the structure of the environmental heterogeneity. This pinning focuses the range expansion into a small number of individuals with access to expansion paths, increasing the importance of chance and thus limiting the efficacy of selection. We expect these results to generalize to other spatially growing populations, such as biofilms, tumors, and invasive species, when the growing population front is transiently hindered by the local environment. We grew colonies from single cells of a strain of E. coli MG1655 carrying a plasmid that is costly to produce, resulting in a 20% growth rate disadvantage s in plasmid-bearing cells compared to their plasmid-less (but otherwise isogenic) conspecifics (Figure 1). This strain loses the plasmid stochastically at a rate of about 5×10-3 per cell division (approximately independent of antibiotic concentration, see Figure 1—figure supplement 1). The plasmid codes for a fluorescence gene and confers resistance to the antibiotic doxycycline (dox, a tetracycline analog) such that when grown at increasing antibiotic concentrations, cells missing the plasmid grow more and more slowly, until they eventually grow more slowly than cells harboring the plasmid (for [dox]>0. 3μg/ml), despite the inherent cost associated with bearing the plasmid. This allowed us to treat plasmid loss effectively as a spontaneous mutation whose fitness effect s, that is the relative growth rate difference between the plasmid-bearing ('wild type’) and non-bearing ('mutant’) cells, we can finely tune from +20% to -15% by varying the amount of doxycycline in the growth media (see Figure 2—figure supplement 1), thus making the mutation either beneficial, neutral or deleterious. [SEP] Justify:

Output: The text corroborates the claim by providing evidence from a study that shows how the fitness effects of mutations can vary based on environmental conditions. Specifically, it describes how a plasmid in E. coli can have fitness effects that are beneficial, neutral, or harmful, depending on the concentration of antibiotic in the growth media. The text states, 'we can finely tune from +20% to -15% by varying the amount of doxycycline in the growth media,' indicating that the mutation's effect is context-dependent, thus supporting the claim.


Input: Task: contrast the claim using the given text. Claim: Gene therapy can make humans biologically immortal by halting the aging process. [SEP] Text: A hallmark of aging and persistent CMV infection is the accumulation of terminally differentiated senescent T cells, which are incapable of further cell division in response to antigenic stimuli and drastically contribute to the shrinking of the naïve T-cell repertoire. To combat immunosenescence, some invasive immunotherapeutic procedures (i. e. , cytokine, hormone, and monoclonal antibody therapy) have been suggested to remove expanded clones of these terminally differentiated effector-memory T cells (11,17). Many of these procedures, however, are costly, high risk, and associated with a number of potentially detrimental side effects. Not to mention that the implementation of such invasive procedures in people who are not considered "ill" has some ethical issues. We have suggested that regular physical exercise might serve as an alternative, inexpensive, and safer strategy to combat the detrimental effects of immunosenescence that are induced by aging and reactivating viral infections (29). Despite the known beneficial effects of habitual exercise on aspects of immunity that pertain to immunosenescence (29), the underpinning mechanisms of improved immunity by exercise are not completely understood. We (23-26), and others (1,4,33), have shown that an acute bout of aerobic exercise elicits a preferential mobilization of highly differentiated and senescent T cells (some of which are specific to CMV and EBV) from the peripheral tissues into the blood compartment before their rapid removal from the blood during the early stages of exercise recovery. The possibility that frequent shifting of senescent T cells from peripheral tissues in response to acute exercise could have accumulative long-term restorative effects on systemic immunity has not been considered. We propose that frequent bouts of acute physical exercise might serve as an adjunct approach to "make space" and expand the T-cell antigen receptor repertoire. This 1. Figure 1: Hypothetical model describing how the frequency of moderate intensity exercise can influence immune system biomarkers associated with the immune risk profile (IRP). Aging and latent viral infections are associated with an increase in the number of IRP biomarkers, which in turn, is associated with increased infection risk and premature mortality. Individuals who engaged in habitual moderate intensity physical exercise throughout their lifespan are more likely to remain in the non-IRP category in later life. Conversely, sedentary individuals are more likely to enter the IRP category with aging. [SEP] Justify:

Output: The text contrasts the claim by discussing the complexities of aging and immunosenescence rather than proposing gene therapy as a method to achieve biological immortality. It talks about the accumulation of senescent T cells in aging and suggests alternative approaches like physical exercise to combat immunosenescence, highlighting that these invasive therapies can be risky and costly without providing evidence that they would succeed in halting aging as gene therapy claims.


Input: Task: pass the claim using the given text. Claim: Certain neural circuits in the brain are dedicated to processing social cues. [SEP] Text: Imaging of The ability to image dynamic cellular and subcellular processes during development has revolutionized the field of developmental biology, ever moving from analyzing fixed samples to dynamic processes in living animals (Huisken and Stainier, 2009; Leung et al. , 2011; Randlett et al. , 2011; Leung and Holt, 2012). Similarly, the central nervous system is also a highly dynamic entity and adopting methods to interrogate the neural activity of cells and networks at brain-wide, single cell resolution in the context of a behaving animal will be a turning point in systems neuroscience. To characterize the activity landscape of a brain at rest or engaged in a defined behavior on these scales, we suggest the minimum requirements are a neural marker of activity that can be used across the brain without a priori hypotheses and an appropriate method to record this activity over time in a specific animal. Following that, an ability to identify these active neurons molecularly is crucial for subsequent progress. A popular method to mark active neurons involves sacrificing an animal while (or just after) it performs a behavior/process and post-stain for a genetic marker of neural activity-the immediate early genes [IEGs such as cFos and early growth response protein 1 (EGR-1)] – in whole or specific brain regions of interest. This has led to the identification of several nuclei involved in behavioral processes (Hoffman et al. , 1993; Sherin et al. , 1996; Murphy et al. , 2004), but despite good correspondence with neural activity, methods using IEGs have their limitations. Firstly, it is possible that IEGs are only induced when neurons are highly/over activated. Indeed, it is likely that tonic or low firing neurons, which may also be important for a particular computation, may have little or no IEGs induced. Therefore, until further demonstrations of the degree of activation required to induce IEG expression are made, caution should be exercised in concluding that they mark the entire firing population involved in a process. Secondly, a single IEG like cFos is not pan neuronally expressed so it is unlikely to be the sole gene used by all the neurons active during a given behavior. Thirdly, there is important computational information encoded when neurons cease firing as opposed to when they become active, and no IEG currently reports the end of a period of activity. [SEP] Justify:

Output: The text does not address the claim regarding neural circuits dedicated to processing social cues. Instead, it discusses imaging techniques in developmental biology and neural activity in the central nervous system without any explicit reference to social cues or specific neural circuits involved in their processing.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: 050. 10. 150. 20. 250. 30. 350. 40. 50. 60. 70. 91. 1n (smooth)830372631273241303630243128n (rough)2024322032251922312818192729 The primary readout of our experiments is the final mutant frequency fMT in the colony and the number of surviving mutant clones (sectors) as a function of the selective advantage s that the mutation confers. These measures are proxies for the degree of adaptation of the population during the expansion process and the success probability of spontaneous mutations in shaping the composition of the population, respectively. Thus, our system gives us direct access to population genetic measures of interest. Alternatively, one can measure the frequency of mutants at the colony perimeter, which has a more direct influence on the future genetic composition of the population at the front. However, this measure can quickly become uninformative for beneficial mutations as mutants overtake the whole perimeter, and it is often difficult to measure accurately because of the low fluorescence signal at the front. The mutant frequency averaged over the whole population still gives a good, if conservative, measure of the mutant frequency at the perimeter. On smooth substrates, in accord with previous experimental results (Gralka et al. , 2016b; Korolev et al. , 2012), advantageous mutants increased in frequency fMT rapidly as the colony grew (see Figure 2—figure supplement 2 for an analysis of the mutant dynamics over time): for s=0. 2, mutants made up roughly half of the total population (Figure 2d) after 72 hrs. At higher antibiotic concentration, mutants became first neutral and eventually deleterious (Figure 2—figure supplement 1), and accordingly, the final mutant frequency was lower, decreasing approximately exponentially with the fitness cost s (Figure 2—figure supplement 4) such that strongly deleterious mutants made up only a small fraction of the final population. On rough substrates, deleterious and neutral mutants remained at frequencies comparable to those observed in smooth colonies at the corresponding values of the fitness (dis)advantage s. However, in contrast to smooth colonies, beneficial mutants in rough colonies did not increase in frequency with s relative to the neutral case. This finding is surprising, given that the growth rate advantages of mutant over wild-type colonies were the same on rough and smooth substrates (Figure 2c). [SEP] Justify:

Output: The text corroborates the claim by demonstrating that mutations can indeed vary in their effects based on the context. It discusses how advantageous mutations can increase in frequency rapidly under certain conditions, but at higher antibiotic concentrations, these mutations can become neutral or deleterious. Specifically, it states that 'At higher antibiotic concentration, mutants became first neutral and eventually deleterious,' which directly supports the claim that genetic mutations can have varying consequences depending on environmental factors.


Input: Task: contrast the claim using the given text. Claim: Gene therapy can make humans biologically immortal by halting the aging process. [SEP] Text: As a result, critically shortened telomeres trigger mechanisms for senescence, causing the cell to undergo proliferative arrest, leading to premature biological aging and impaired immunity. As such, repeated exposure to antigenic growth stimuli throughout the lifespan (i. e. , reactivating latent viral infections) leads to greater rounds of cell division and premature senescence. Paradoxically, telomere erosion is coupled with an increased resistance to apoptosis, allowing these senescent T cells to accumulate in the blood and tissues at the expense of naïve antigen-virgin T cells (Fig. 2). Figure 2: Immune responses to persistent viral infections lowers the immune space. naïve or memory T cells receive an antigenic stimulus in response to novel pathogen incursion or latent viral reactivation. naïve (CCR7+/CD27+/CD28+/CD45RA+/CD62L+) or memory (CD27+/CD28+/CD45RO+) CD8+ T cells subsequently undergo clonal expansion and differentiate into antigen-specific effector T cells. Depending on the number of cell replications that have occurred, T cells will exhibit a lowly differentiated (CD27+/CD28+/CD45RO+), highly differentiated (KLRG1+/CD27−/CD28+/CD45RO+), or a senescent (KLRG1+/CD28−/CD57+) phenotype. T cells that have undergone excess rounds of cell division have critically short telomeres, are more resistant to apoptosis (CD95Lo), and undergo proliferative arrest (senescence). After clonal expansion, viral-specific CD8+ effector T cells migrate to sites of infection via the peripheral blood compartment and kill infected cells in the tissues. When the infection is resolved, a portion of the viral-specific effector T cells survive and become part of the memory T-cell pool, although most of the excess effector T-cell clones are selected to undergo programmed cell death (apoptosis). However, because many viral-specific terminally differentiated T cells develop an increased resistance to apoptosis, some survive and enter the memory T-cell pool via "the back door. " In response to persistent viral infections (i. e. [SEP] Justify:

Output: The text contrasts the claim by discussing the mechanisms of telomere shortening and cellular senescence. It explains that critically shortened telomeres trigger senescence, leading to premature biological aging rather than halting it. Therefore, the text supports the notion that aging processes could continue due to these mechanisms, rather than suggesting that gene therapy can achieve biological immortality.


Input: Task: pass the claim using the given text. Claim: Certain neural circuits in the brain are dedicated to processing social cues. [SEP] Text: Finally, the fixation for IEG staining precludes dynamic information about activity and firing patterns which could provide a crucial handle on the processing and functions carried out by active neurons. The development of genetically encoded Ca2+ indicators (GECIs) sets to solve many of these limitations and zebrafish is particularly suited to the use of GECIs with the ease of genetics/transgenesis and a translucent central nervous system. GECIs, such as GCaMP (Nakai et al. , 2001; Muto et al. , 2011, 2013) respond with changes in fluorescence intensity proportional to subcellular Ca2+ changes. In fact, the latest generation of GCaMPs have the ability to reliably indicate single action potential (AP) events and a whole library of versions exist to suit various potential uses (Akerboom et al. , 2012; Ohkura et al. , 2012) as well as Ca2+ sensors that operate at UV and red-shifted excitation wavelengths (Zhao et al. , 2011; Akerboom et al. , 2013). A further advantage of GECIs as compared to traditional electrophysiological recordings is their minimal invasiveness. A multi-electrode array that can discriminate spiking activity from a dozen neurons is prohibitively large for a zebrafish brain, while GECI imaging is completely non-invasive and can acquire spiking activity from hundreds of neurons from one image plane. Combined with pan-neuronal promoters and two-photon excitation microscopy, the monitoring of brain-wide neural activity during brain computations holds great potential (Figure 3B). By focusing excitation to small precise volumes in a tissue, two-photon imaging greatly reduces phototoxicity resulting from illumination of tissues above regions of interest typical of epifluorescent and confocal microscopy (Carvalho and Heisenberg, 2009). This permits longer term imaging of living samples than previously possible. An important advantage of operating in the infrared range is that the imaging also does not interfere with light-sensitive behaviors such as circadian and sleep rhythms (Appelbaum et al. , 2010). Such excitation also confers benefits to the depth of tissue penetration and thus the imaging of deeper structures in the brain. [SEP] Justify:

Output: The text discusses the use of genetically encoded Ca2+ indicators (GECIs) and their advantages for imaging neural activity in the zebrafish brain but does not mention neural circuits dedicated to processing social cues. Thus, it is irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Genetic mutations can be beneficial, neutral, or harmful depending on the context. [SEP] Text: Thus, this apparent inefficacy of selection in affecting evolutionary outcomes was not caused by an altogether elimination of growth rate differences. Instead, a closer look at the colony growth dynamics on rough substrates, shown in Figure 1e, suggests a different mechanism: the surface structure of the rough substrate constrains and guides growth along predetermined paths where growth proceeds faster than in the immediate surroundings, such that any mutation can only be successful, that is establish a sector and thus rise to high frequency in the population, if it happens to arise in one of the branch-like regions of accelerated growth. Conversely, a beneficial mutant clone will be unable expand even if its per capita growth rate is higher than its wild-type neighbors if the mutation occurs in a portion of the front that is slowed down by the environmental heterogeneity. If this proposed mechanism is indeed the root cause for the apparent inefficacy of selection on rough substrates, then one would expect the number of successful mutants, that is those that manage to establish sectors, to be independent of the mutant’s selective advantage s. Indeed, this is what we observed: the probability of forming a sector, which quantifies the evolutionary success probability of individual mutations, increased with s in smooth colonies (Figure 2e), but was constant in rough colonies as long as s>0. Notably, the establishment probability was extremely low in both scenarios: Even for the most advantageous mutants in smooth colonies, we estimate u∼10-7 per mutation making evolutionary success an extremely rare event. The low success probability is a consequence of two processes: firstly, the mutation must occur in a favorable location, namely in the first layer of cells at the front of the population (Gralka et al. , 2016b), which reduces the number of mutations eligible for sector formation by a factor of about 1000 (assuming a growth layer width of 10 cells and a colony height of about 100 cells, see Figure 2—figure supplement 3). We estimate that about 2000 mutations per colony arose in favorable positions, each of which had an establishment probability of order 10-3. Secondly, each eligible mutation has to survive genetic drift, which in microbial colonies is manifest in the random fluctuations in the sector boundaries as a consequence of stochastic cell growth and division, and subsequent cell motion due to mechanical pushing of cells on each other (Hallatschek et al. , 2007; Farrell et al. , 2017; Kayser et al. [SEP] Justify:

Output: The text corroborates the claim by describing how the context, specifically the surface structure of rough substrates in microbial colonies, influences the success of mutations. It explains that beneficial mutations can fail to expand if they occur in less favorable environmental conditions, thus illustrating that the effects of genetic mutations are context-dependent. This supports the idea that mutations can indeed be beneficial, neutral, or harmful depending on various environmental factors, aligning with the claim.


Input: Task: contrast the claim using the given text. Claim: Gene therapy can make humans biologically immortal by halting the aging process. [SEP] Text: and intrinsic factors contribute to skin aging; nonetheless, they are intertwined. Moreover, intrinsic skin aging mirrors age-related declines in the entire human body's internal organs. There is evidence that skin appearance is an indicator of the general health of somebody or a visual certificate of health. Earlier, it was apparent that the intrinsic factors are unalterable, but the sparkling of skin aging gene therapy on the horizon is changing this narrative. Skin aging gene therapy offers tools for skin rejuvenation, natural beauty restoration, and therapy for diseases affecting the entire skin. However, skin aging gene therapy is an arduous and sophisticated task relying on precise interim stimulation of telomerase to extend telomeres and wend back the biological clock in the hopes to find the fountain of youth, while preserving cells innate biological features. Finding the hidden fountain of youth will be a remarkable discovery for promoting aesthetics medicine, genecosmetics, and healthy aging. Caloric restriction offers ultimate health benefits and a reproducible way to promote longevity in mammals, while delaying age-related diseases. Moreover, exercise further enhances these health benefits. This 78. [ [PMID: 36599349] [2]. The skin health and beauty pyramid: A clinically based guide to selecting topical skincare products. J 2014; 13(4): 414-21. [PMID: 24719060] [3] Jacczak B, Rubiś B, Totoń E. Potential of naturally derived compounds in telomerase and telomere modulation in skin senescence and aging. 2021; 22(12): 6381. [ [PMID: 34203694] [4] Klass MR. A method for the isolation of longevity mutants in the nematode Caenorhabditis elegans and initial results. Dev 1983; 22(3-4): 279-86. [ [PMID: 6632998] [5] Bernardes de Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. 2012; 4(8): 691-704. [ [PMID: 22585399] [6] Jenkins G. Molecular mechanisms of skin ageing. Dev 2002; 123(7): 801-10. [ [PMID: 11869737] [7] Verschoore M, Nielson M. The rationale of anti-aging cosmetic ingredients. [SEP] Justify:

Output: The text contrasts the claim by discussing that while skin aging gene therapy is being explored as a means to rejuvenate skin and possibly delay some aging-related effects, it explicitly states that intrinsic skin aging reflects age-related declines in overall body health. It also emphasizes that gene therapy for skin aging is complex and still aims to find ways to promote aesthetics and healthy aging, rather than achieving true biological immortality as asserted in the claim. The text presents a narrative that is framed within the limitations of current understanding and technology in gene therapy, which does not support the idea of halting the aging process completely.


Input: Task: pass the claim using the given text. Claim: Certain neural circuits in the brain are dedicated to processing social cues. [SEP] Text: To give an idea of scale, an entire 1 month juvenile fish brain has a thickness of ~1 mm, which can be fully covered in depth with two-photon scanning. Indeed, the entire brain of a 7 dpf larva can be covered with few imaging frames, as has already been attempted with remarkable success even with the modestly sensitive GCaMP2 (Ahrens et al. , 2012). Here, the larva’s computations during changes in motor gain during fictive swimming were located without a priori assumptions to specific brain regions such as the inferior olivary complexes. With advanced microscopy, the possibility of whole brain imaging at single cell resolution at physiological frequencies is within reach to zebrafish researchers (Ahrens and Keller, 2013). The recent developments in imaging Ca2+ sensitive emitters of bioluminescence, such as green fluorescent protein (GFP)-aequorin, in freely behaving zebrafish offers further exciting avenues to complement GCaMP data of stabilized/paralyzed animals (Naumann et al. , 2010). After gaining such volumes of information, the upcoming challenge with brain-wide “activity screens” will be to accurately define the neuronal populations of interest. Without accurate knowledge of the neuroanatomical location or access to specified circuits, this remains a challenging hurdle to a true understanding of circuit function. 3 3. From whole brain to single synapse. (A) Behavioral processes can be studied in non-pigmented (Nacre; mitfa mutant) species of zebrafish. (B) Two-photon volume image of 5 dpf zebrafish expressing GCaMP pan-neuronally, note the linear organization of the brain along the rostrocaudal axis from telencephalon (tel) to spinal cord (sc). (C) Various maximal projections (from area indicated in B by white box) of the 5 dpf zebrafish midbrain reconstructed after array tomography against GABA (magenta), BrdU (green) and DAPI (cyan) markers. White dashed line depicts midline. (D) Genetically specified circuit analysis. Synaptophysin-eGFP (syp-eGFP) allows imaging of structural plasticity of synapses (white arrowheads) in hypocretin (HCRT) neurons. [SEP] Justify:

Output: The text does not address the claim about neural circuits for processing social cues. It focuses on imaging techniques and brain organization in zebrafish, discussing methods like two-photon scanning and GCaMP technologies. There is no mention of social cues or dedicated circuits related to them.