Input: Task: corroborate the claim using the given text. Claim: Sustainable economic growth focuses on balancing development with environmental protection. [SEP] Text: The main concern is with the co-production of “demonstrably usable” knowledge for policymaking (Dilling & Lemos, and Lemos2011), such as commonalities with transdisciplinary approaches (et al. , Hadorn, Hoffmann-Riem, Biber-Klemm, Grossenbacher-Mansuy, Joye, Pohl and Zemp2008). Such deliberate processes for producing actionable knowledge about the combined effects of climatic and societal change therefore include collaboration between different kinds of knowledge systems. By bringing together natural and social scientists and expert practitioners from tourism organisations, all with different knowledge systems and approaches, we can address change, understand policy, and find innovative solutions to sustainability challenges. Co-production of knowledge is ideally a continuous collaborative and iterative process throughout various stages of a project, from design, data collection, and analysis (Dilling & Lemos, and Lemos2011). This approach permeates our study from the initial and subsequent discussions with and AECO during which the focus and research questions were developed for the project proposal. This means that the focal points of the project were co-produced at the onset and will in a similar manner be refined as the research develops. Through multiple methods including document analysis, semi-structured interviews, participant observation and scenario development, as well as ongoing conversations among collaborators, research questions, methods, and findings are discussed, reconsidered, and proposed: knowledge exchange between the different scientific disciplines and expert practitioners identifies the scope and content of the document analysis; the interview guide for the semi-structured interviews is a collaborative effort as are decisions on who to interview. Scenario workshops are a particularly important arena for co-producing knowledge are is based on a participatory scenario approach aimed at facilitating learning across different fields of expertise (Nilsson et al. , and Pelyasov2019; Dannevig et al. , and Labriola2019). Participatory scenario methods identify the main drivers of change, impacts, responses, and solutions. By linking identification of local drivers of change relevant for tourism with an assessment of how these may play out under different conditions at larger scales (Nilsson et al. , 2017), narrative scenarios of different sustainable solutions for tourism are co-produced. Attention to surprises and tipping points in the dynamics of the coupled social-ecological systems ensures relevance for tourism activities (Nilsson et al. , and Pelyasov2019). [SEP] Justify:

Output: The text corroborates the claim by discussing the importance of co-production of knowledge in addressing sustainability challenges, which inherently involves balancing development with environmental considerations. It emphasizes collaboration between various knowledge systems, including those from natural and social sciences, to find innovative solutions to sustainability issues. This indicates a focus on integrating developmental goals with environmental protection strategies, aligning with the claim's assertion about sustainable economic growth.


Input: Task: contrast the claim using the given text. Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: Because maximal lifespan, together with brain size, correlates positively with the length of the gestation period (Sacher & Staffeld, 1974; Jones & MacLarnon, 2004), this result does not independently confirm the Dsshr->Dssht convergence hypothesis, despite that the mechanisms assumed to cause the correlations with lifespan and those with gestation length differ: lifespan is presumed to increase because convergence increases mutational robustness (only extreme convergence decreases mutational robustness and lifespan); at the same time, convergence decreases the rates of replication and transcription,, and presumably also developmental rates. Figure 7. Developmental stability in subdigital lamellae counts as a function of a measure of convergence between replication and transcription in lizard mitochondrial genomes possessing only one Dloop region. X axis is as in Figure 4. Species names are followed by NCBI (genbank) entries: Abronia graminea (NC_005958), Calotes versicolor (NC_009683), Coleonyx variegatus (NC_008774), Eumeces egregius (NC_000888), Gekko gecko (NC_007627), Gekko vittatus (NC_008772), Heloderma suspectum (NC_008776), Iguana iguana (NC_002793), Lacerta viridis (NC_008328), Lepidophyma flavimaculatum (NC_008775), Sceloporus occidentalis (NC_005960), Takydromus tachydromoides (NC_008773). However, the rationale that Dsshr->Dssht convergence affects both lifespan and gestation yields a prediction that is not trivial, despite the strong positive correlation that exists between lifespan and the length of the gestation period: in groups of species with high fertility and rates of development (short gestation), considered as r-strategists, one expects that Dsshr->Dssht convergence adaptively coevolved with the length of gestation, while in groups of species with low fertility and rates of development (long gestation and lifespan), considered as K-strategists, it makes sense to expect adaptive coevolution between Dsshr->Dssht convergence and lifespan. [SEP] Justify:

Output: The text contrasts the claim by explaining complex biological relationships between lifespan, gestation period, and the Dsshr->Dssht convergence hypothesis. It states that while there is a positive correlation between lifespan and gestation length, this correlation does not provide independent confirmation that biohacking can guarantee increased longevity or double the average human lifespan.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: zip Figure 2 with 1 supplement Download asset Open asset NLRP12-deficiency leads to increased inflammation in the liver. WT and Nlrp12-/- mice were injected with DEN (25 mg/kg i. p. ) at the age of 14 days and euthanized 10 months later. (A–B) H and E-stained liver sections were examined histopathologically and scored for inflammation, steatosis, and fibrosis. Representative images of inflammation, steatosis, and fibrosis are shown. Data represent means ± SEM (n = 15). Statistical difference was determined by two-tailed unpaired t-test. (C) Real-time qPCR analysis of cytokines and chemokines in the HCC tissues. Data represent means ± SEM (n = 15). Statistical difference was determined by two-tailed unpaired t-test. (D) Tumor tissues were analyzed for the quantification of T cells (CD45+, TCRb+, CD11b-), dendritic cells (CD45+, CD11b+, CD11c+high, Gr1-), Kupffer cells (CD45+, CD11b+, F4/80+, Gr1-), and neutrophils (CD45+, CD11b+, Gr1+, CD11c-) by flow cytometry. (E) Relative abundance of different immune cell types was analyzed by FlowJo software. Data represent means ± SEM (n = 5). Statistical difference was determined by two-tailed unpaired t-test. (F) Formalin-fixed and paraffin-embedded HCC sections were stained with F4/80 antibody and the number of F4/80+ cells (brown) per high power field (20X) was counted. The picture shows representative immunostaining of F4/80 (brown). Data represent means ± SEM (n = 25). Statistical difference was determined by two-tailed unpaired t-test. (G) The expression of Emr1 (F4/80) in the HCC tissues was measured by real-time PCR. Data represent means ± SEM (n = 13–14). Statistical difference was determined by two-tailed unpaired t-test. Figure 2—source data 1 NLRP12-deficiency leads to increased inflammation in the liver. Download elife-40396-fig2-data1-v2. [SEP] Justify:

Output: The text does not address the claim regarding urban living and stress levels. Instead, it discusses the effects of NLRP12 deficiency on liver inflammation and provides detailed experimental data on various immune cell types, indicating that it is irrelevant to the claim about stress and urban living.


Input: Task: corroborate the claim using the given text. Claim: Sustainable economic growth focuses on balancing development with environmental protection. [SEP] Text: Co-production of knowledge in this way provides a deeper understanding of how to prepare for the future and to discern whether and how the action space emerging in balancing different demands and pressures can be utilised by the tourism operators. Local perspectives on global challenges: meeting the demands for sustainable tourism The need to balance the impacts of climate change and habitat degradation with maintaining a viable community on Longyearbyen, while meeting the emission targets and adhering to the is embedded in Svalbard policy, and is shaped by national policy and international agreements such as the SDGs. Meanwhile, decision-makers tasked with implementing these competing priorities have not been given the tools to solve internal inconsistencies among targets. Indeed, this is not a challenge unique to Svalbard, but is common to global communities faced with solving the core challenge of sustainability. As such, this “balancing act” is a tall order for Svalbard tourism operators. Nevertheless, conversation investigating how competing national and local priorities shape the action space available to tourism operators and organisations is a useful starting point for innovation. The action space might be constrained where meeting economic targets through tourism growth negates reaching environmental targets due to trampling or habitat encroachment and vice versa. Co-producing strategies for developing a sustainable tourism sector in Svalbard, as outlined earlier, ensures greater salience, relevance and legitimacy of the findings (Cash et al. , and Mitchell2003; Dannevig & Hovelsrud, and Hovelsrud2016; Dannevig et al. , Reference Dannevig, Hovelsrud, Hermansen and Karlsson2020), and insights are more likely to be embraced by local actors in future economic development as well as conservation measures. Given the increasing attention to sustainability and ways to reduce the carbon footprint, BalancingAct creates a platform to think creatively about tourism products that may sensitise visitors to Earth system sustainability and how such products may dissuade carbon-intensive travel in the vulnerable Arctic environments. This is a challenge for tourism organisations and operators who wish to maintain a viable business and at the same time respond to increasing demands of reduced GHGs and ecosystem conservation. International policy instruments such as the SDGs provide relevant context for Svalbard as the internal inconsistencies among Svalbard policy targets are replicated in these global efforts to balance needs to achieve human well-being. [SEP] Justify:

Output: The text corroborates the claim by discussing the need to balance economic activities, such as tourism, with environmental concerns in Svalbard. It emphasizes that decision-makers face the challenge of addressing 'competing priorities' which include 'balancing the impacts of climate change and habitat degradation with maintaining a viable community'. This highlights that sustainable growth not only looks at economic development but also places significant importance on environmental protection, aligning directly with the claim made.


Input: Task: contrast the claim using the given text. Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: Too extreme convergence between replication and transcription The examination of Figures 3 and 4 shows that the trend between maximal lifespan and Dsshr->Dssht convergence has outliers, and that these outliers are usually placed in the same relative area of the graph: these are species with relatively high convergence but lower than expected lifespan. It is possible that this situation results from asymmetry in inaccuracies in maximal lifespan estimations, as sampling error can only cause lower values than the real maximal lifespan. However it makes little sense that the well studied Macaca species, for example, have a lifespan that is much greater than in Figure 3, although these species are clearly outliers in respect to the general trend in Figure 3. This situation was also observed in other taxonomic groups (results not presented graphically here but used in Figure 10), and it is remarkable that there were never cases of outliers with low convergence but high lifespan. Hence the hypothesis of statistical artifact is unlikely here, and this situation is most probably biologically meaningful. It indicates that low convergence between replication and transcription does not enable to reach a long lifespan, but that high convergence is not necessarily a sufficient condition to enable a long lifespan, and that other factors affect this. The results for Cetacea (Figure 5) indeed show that high convergence might in fact limit lifespan. Presumably, this is because at high convergence levels, the decrease in mutations due to collinearity between replication and transcription might be smaller than the increase due to longer Dssh because of increasing delays due to collisions between replication and transcription. This could explain the relatively sharp boundary between the region where convergence increases lifespan, and the one where a negative correlation is observed in Cetacea, and would account for outliers in figures presenting results for other taxa. 4. 6. Rates of development and convergence between replication and transcription The hypothesis that collisions decrease rates of replication and transcription when both processes are collinear predicts that rates of development decrease with Dsshr->Dssht convergence. The cause for this would differ from the correlation between Dsshr->Dssht convergence and lifespan. For lifespan, convergence decreases cumulation of mutations and in general, increases mutational robustness; for developmental rates, they are the direct result of decreased replication and transcription rates because of increased collision frequencies between replication and transcription forks. [SEP] Justify:

Output: The text contrasts with the claim by discussing the complexities of lifespan in relation to biological factors. It indicates that while there may be a relationship between replication and transcription convergence and lifespan, having high convergence does not guarantee a long lifespan; it states that 'high convergence is not necessarily a sufficient condition to enable a long lifespan, and that other factors affect this.' As such, the notion that biohacking can guarantee longevity or double average lifespan is countered by the findings presented.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: zip Figure 2—figure supplement 1 Download asset Open asset NLRP12 suppresses inflammatory responses in HCC tissue. (A–D) WT and Nlrp12-/- mice were injected with DEN (25 mg/kg i. p. ) at the age of 14 days followed by eight weekly injections of CCl4 (0. 5 ml/kg i. p. , dissolved in corn oil) starting at 10 weeks of age and sacrificed at the age of 6 months. (A) Formalin-fixed liver sections were stained with H and E. Representative images showing adenoma, inflammation, steatosis, and fibrosis. (B) Percentage of area covered by adenoma. Data represent means ± SEM (n = 5). *p<0. 05. **p<0. 01. Statistical difference was determined by two-tailed unpaired t-test. (C) Histopathological scorings for inflammation, steatosis and fibrosis. Data represent means ± SEM (n = 5). *p<0. 05. **p<0. 01. Statistical difference was determined by two-tailed unpaired t-test. (D) The expression of indicated genes in HCC tissues was measured by real-time qPCR. Data represent means ± SEM (n = 6). *p<0. 05. **p<0. 01. Statistical difference was determined by two-tailed unpaired t-test. (E–F) WT and Nlrp12-/- mice were injected with DEN (25 mg/kg i. p. ) at the age of 14 days and euthanized at 10 months. (E) The levels of IL-6, TNFα, and KC (CXCL1) in HCC lysates were measured by ELISA. Data represent means ± SEM (n = 9). Statistical difference was determined by two-tailed unpaired t-test. (F) Real-time qPCR analysis of IL-17, IFNγ, and IL-4 in HCC tissues. Data represent means ± SEM (n = 15). (G) Livers from untreated WT and Nlrp12-/- mice at 10 months after birth were collected and the expression of F4/80 gene was measured by real-time qPCR. Data represent means ± SEM (n = 5). [SEP] Justify:

Output: The text provided does not address the claim regarding urban living and stress levels at all. It discusses experimental procedures and results related to NLRP12 and inflammatory responses in mice, which is unrelated to the effects of urban environments on stress.


Input: Task: corroborate the claim using the given text. Claim: Sustainable economic growth focuses on balancing development with environmental protection. [SEP] Text: The SDGs are a comprehensive overview of human needs and contain both synergistic interactions, as well as cascading negative trade-offs vertically through a policy chain (national, regional, local) to the existing environmental governance regime. It is both challenging and urgent to develop policy-relevant insights that address trade-offs among the SDGs, Targets and Indicators early and constructively (Goal 17, Veland, et al. in press). When implemented in this way, the 17 SDGs are transformative in scope. The ongoing COVID-19 pandemic has created a crisis for the tourism industry, in Svalbard and elsewhere. Yet, this crisis may also be an opportunity for the transformative change needed to solve the sustainability issues that riddle tourism (e. g. significant carbon footprint and wear and tear on habitats), as suggested by Gössling and colleagues (Reference Gössling, Scott and Hall2021). Already, the decision to phase out coal from the Svalbard economy has generated a transformation in the Longyearbyen demographics, generating new influences and potential avenues for innovation. Insights produced at the local level with local actors (et al. , and Mulugetta2018; Lynch & Veland, and Veland2018) will help discover ways to innovate within the complex constraints placed on tourism by competing policy, governance, economic, and environmental processes. The way forward By combining and co-producing knowledge and data from diverse tourism industry experts and academic disciplines, we are positioned to contribute insights into how Longyearbyen residents view the tourism sector and its broader role in the Svalbard economy, society, and environment. The attitudes of the local community towards current tourism and likely future options are also relevant for developing sustainable tourism products. This includes local perceptions of environmental hazards, human safety and emergency responses, attitudes toward specific tourism development options, relationships with visitors, and environmental orientations. We are approaching the nexus of sustainable tourism and policy demands from an experimental point of view, with the full knowledge that the notion of sustainable tourism is contested in the literature. BalancingAct will test whether it is possible to co-produce knowledge for sustainability, and we expect to move the issue forward, scientifically, and practically. BalancingAct brings together tourism operators, researchers, and educators that together are responsible for setting up the Svalbard economy’s “three new legs” following the cessation of coal. [SEP] Justify:

Output: The text supports the claim by discussing the importance of addressing the trade-offs between economic developments, such as tourism, and environmental sustainability. It highlights that the Sustainable Development Goals (SDGs) focus on synergistic interactions and potential negative trade-offs, which indicates a need to balance human needs with environmental protection. The mention of the ongoing COVID-19 pandemic creating an opportunity for transformative change in the tourism sector further reinforces the concept of balancing development with sustainability.


Input: Task: contrast the claim using the given text. Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: It is notable that this rationale yields a molecular mechanism for the well known negative association between metabolic rates and longevities, as described in Insects (Antler flies, Bonduriansky & Brassil, 2005; Drosophila, Marden et al. , 2003; Novoseltsev et al. , 2005; Mockett & Sohal, 2006), nematodes (Jenkins et al. , 2004; Chen et al. , 2007; Lee et al. , 2006; Hughes et al. , 2007) and mice (Cargill et al. , 2003; and others, Bonsall, 2006). Some ecological data explaining the tradeoffs exist (Bonduriansky & Brassil, 2005), and results suggest the tradeoff is due to dietary metabolism (Partridge et al. , 2005a,b; Speakman, 2005a,b; Kaeberlein et al. 2006; Ruggiero & Ferrucci, 2006; Szewczyk et al. , 2006; Wolkow & Iser, 2006). Other evidence shows that this rule might not be universal (et al. , 2004; Khazaeli et al. , 2005; Johnston et al. , 2006), stressing the need for unifying hypotheses. Several molecular or biochemical mechanisms have been proposed (Balaban et al. , 2005; Bartke,2005; Knauf et al. , 2006; Powers et al. , 2006 ) but no general molecular model exists, stressing the importance to link the Dsshr->Dssht convergence hypothesis with the lifespan-growth rate tradeoff. Making a meaningful test for this prediction that Dsshr->Dssht convergence decreases developmental rates (hence increases the length of gestation) is not straightforward because of the strong positive association that exists between maximal lifespan and gestation length. However, using evolutionary ecology theory on r and K strategists, the simple molecular mechanism makes complex predictions on the relative strengths of association of Dsshr->Dssht convergence with lifespan and gestation length, respectively. The fact that these predictions are overall verified by the analysis of a large number of species and groups of species in Figure 10 is strong support for the Dsshr->Dssht convergence hypothesis and its coevolution with major life history traits. 4. 7. [SEP] Justify:

Output: The text contrasts the claim by discussing various influences on longevity, including metabolic rates and dietary metabolism, and highlights that no universal model exists for predicting lifespan increases. It mentions the need for unifying hypotheses and complex predictions related to lifespan, suggesting that while there may be mechanisms affecting longevity, the assertion that biohacking guarantees a doubling of lifespan is unsupported and overly simplistic.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Figure 2—figure supplement 1—source data 1 NLRP12 suppresses inflammatory responses during HCC. Download elife-40396-fig2-figsupp1-data1-v2. zip Figure 3 with 1 supplement Download asset Open asset Increased HCC in Nlrp12-/- mice is associated with increased cell death and proliferation in the livers. WT and Nlrp12-/- were injected with DEN (25 mg/kg i. p. ) or PBS (healthy control) at the age of 14 days and sacrificed at 10 months after DEN administration. (A) Liver tissue sections from healthy controls and DEN-treated mice were immunostained with Ki67 antibody and the number of Ki67-positive cells was counted under 20X objective. Data were collected from at least 10 fields per liver section and three mice/group. Data represent means ± SEM (n = 50). Statistical difference was determined by two-tailed unpaired t-test. (B) The expression of Ki67 in tumor tissues was measured by real-time qPCR. Data represent means ± SEM (n = 15; each sample represents individual mouse). Statistical difference was determined by two-tailed unpaired t-test. (C) Apoptosis in the healthy and HCC livers were measured by TUNEL assay. The number of TUNEL-positive cells (green) under 20X objective was counted and plotted as individual values. Data were collected from at least 10 fields per liver section and three mice/group. Data represent means ± SEM. Statistical difference was determined by two-tailed unpaired t-test. (D) Liver sections from DEN-treated mice (n = 3) were immunostained for cleaved caspase-3 (brown). Cleaved caspase-3 positive cells were counted under 20X objective. Data represent means ± SEM (n = 40). Statistical difference was determined by two-tailed unpaired t-test. (E) Liver tumor lysates were immunoblotted with anti-cleaved caspase-3, cytochrome c, and β-actin. The band intensities of caspase-3 and cytochrome c were measured. Data represent means ± SEM (n = 5; each sample represents individual mouse). Statistical difference was determined by two-tailed unpaired t-test. [SEP] Justify:

Output: The text provides detailed information on a scientific study involving mice and liver cancer (HCC) but does not address urban living or stress levels in any way. Therefore, it is irrelevant to the claim regarding urban living and stress.


Input: Task: corroborate the claim using the given text. Claim: Sustainable economic growth focuses on balancing development with environmental protection. [SEP] Text: In this collaboration, the development of new tourism products is an explicit goal and the team will organise workshops and pilot potential solutions. For instance, researchers at the in Svalbard – UNIS have suggested piloting products that expose tourists to aesthetic microscopic organisms common in the oceans surrounding Svalbard in “microscopic safaris. ” These tourism products offer a centrepiece to teach visitors about ecosystem form and function as well as influences from climate change and pollutants such as plastic. As another example, tourism operators have suggested visitors can become engaged in community-based activities during their visit. They might gather plastic waste along beaches, contribute to organising and hosting community events, participate in data collection for researchers, and so on. Then came COVID-19 The first set of empirical data emerged in the kick-off meeting for the project, held in Longyearbyen in September 2020. The team members from outside Norway could not travel because of the COVID-19 pandemic. The rest of the team found the town of Longyearbyen on a slow burner. The few restaurants that were open were supported by locals. There were no tourists, save for a group of pensioners from Norway, most hotels were closed, no cruise ships in the harbour and an industry marked by serious concerns for the future. The seriousness of the pandemic for the industry aside, the obvious question of how we study sustainable tourism when there are no tourists has come to the forefront. A major question is what the “new normal” will look like, and whether the COVID-19 pandemic has ushered a tipping point toward a transformed tourism sector. Will a “new normal” affect peoples’ attitudes towards tourism? A survey of the attitudes of tourists and residents will produce different findings post-COVID-19, and we wonder what the pandemic will teach us about transformation, resilience, vulnerability, and drivers of change. Conflict of interest The authors declare none. authors are grateful to the rest of the BalancingAct team, and ørgensen, Association of øreide and – UNIS, and Amanda Lynch, for their participation and critical inputs to the study. Financial support This work is supported by Council of Norway (grant number 302914). 354. doi: 10. 1007/s10584-008-9520-z CrossRef267. 4337. doi: 10. 1177/2514848620934337 1223. [SEP] Justify:

Output: The text discusses the development of new tourism products that aim to educate visitors about ecological functions and issues related to climate change and pollution. It highlights activities like community engagement in waste collection and offers insights into the relationship between tourism and environmental protection, suggesting a focus on balancing development with ecological awareness, aligning well with the claim of sustainable economic growth.


Input: Task: contrast the claim using the given text. Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: Causal interpretations of correlations between lifespan and convergence between replication and transcription The hypothesis that collisions decrease rates of replication and transcription when both processes are collinear enables to predict the occurrence of species that seem outliers in graphical analyses. However, the longevity-growth rate tradeoff hypothesis suggests the possibility that the causal interpretation of the association of Dsshr->Dssht convergence with maximal lifespan is opposite to the direction assumed. This is because offspring fitness decreases with parental age (Kern, 2001; Priest et al. , 2002; Moore & Harris, 2003; Moore & Sharma, 2005), putatively due to ontogenetic cumulation of mutations, especially in mothers (McIntyre & Gooding, 1998; Hercus & Hoffmann, 2000), which are inherited by offspring. This issue is particularly relevant to mitochondria. Indeed, species with long lifespan probably have relatively high transcription/replication ratios. Hence what appears to be convergence of replication gradients towards transcription gradients could be the result of increased lifespan, rather than its cause. This interpretation assumes that the gradients observed are transcription-, rather than replication ones, which remains possible despite the arguments against this in previous sections. Notwithstanding these arguments, this interpretation is not compatible with other predictions presented here about developmental rates, the relatively frequent outlying species characterized by high convergence and lower than expected lifespan, and the threshold phenomenon observed in Figure 5. In addition, this individual-based observation is a stabilizing feedback mechanism where increased longevity causes inheritance of mutations that decrease offspring longevity. This would rather predict negative correlations, or no correlation at time scales larger than that of single generations, such as in the inter-species comparisons described in the Results. The specific situation in Homo, where recent evolution caused a rapid increase in lifespan that is not paralleled by a proportionately high Dsshr->Dssht convergence, could be interpreted both ways: lifespan, which is known to have increased recently by man-made environmental changes and not cell metabolism (Larkin, 2000), does not fit what would be expected according to cell metabolism (as measured by Dsshr->Dssht convergence), suggesting that in other species where no such fast changes occurred, Dsshr->Dssht convergence explains lifespan. [SEP] Justify:

Output: The text contrasts the claim by discussing complex biological mechanisms related to lifespan and replication processes rather than supporting the idea that biohacking simplifies and guarantees an increase in lifespan. It explores the longevity-growth rate tradeoff hypothesis and indicates that increased longevity may not necessarily lead to a straightforward increase in lifespan, but rather could involve negative correlations, mutations, and the influence of evolutionary factors. This suggests that biohacking does not inherently guarantee a doubling of lifespan as proposed in the claim.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Figure 3—source data 1 Measurement of cell death and proliferation in WT and Nlrp12-deficient HCC. Download elife-40396-fig3-data1-v2. zip Figure 3—figure supplement 1 Download asset Open asset NLRP12 regulates hepatocyte death and proliferation during HCC. (A) DEN-treated mice at 10 months were injected with BrdU at 2 hr before sacrifice (n = 5/group) via i. p. Formalin-fixed liver sections were immunostained with BrdU antibody. The number of BrdU-positive cells (brown) per HPF was counted. The analysis includes counting from 10 to 15 fields/section (under 20X objective) and three mice/group. Data represent means ± SEM. *p<0. 05. **p<0. 01. Statistical difference was determined by two-tailed unpaired t-test. (B and C) Primary hepatocytes were grown on cover slip, treated with or without LPS for 24 hr, and stained for TUNEL (green). The number of TUNEL-positive cells were counted from 30 fields. Data are representative of three independent experiments. Data represent means ± SEM. *p<0. 05. **p<0. 01. Statistical difference was determined by two-tailed unpaired t-test. Figure 3—figure supplement 1—source data 1 NLRP12 regulates hepatocyte death and proliferation. Download elife-40396-fig3-figsupp1-data1-v2. zip Figure 4 with 1 supplement Download asset Open asset NLRP12-deficiency leads to increased expression of proliferative genes and activation of the JNK pathway. WT (n = 15) and Nlrp12-/- (n = 15) mice were injected with DEN (25 mg/kg i. p. ) at the age of 14 days and euthanized at 10 months later. (A) Liver tumor tissues were analyzed for the expression of the indicated genes by real-time qPCR. Data represent means ± SEM (n = 15; each sample represents individual mouse). Statistical difference was determined by two-tailed unpaired t-test. (B) Liver tumor lysates were immunoblotted for Cyclin d1, cMyc, and P-cJun. β-actin was used as a loading control. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses experimental procedures and results related to NLRP12 regulation in hepatocyte death and proliferation, which have no connection to urban living or stress levels.


Input: Task: corroborate the claim using the given text. Claim: Some studies suggest that quantum coherence may play a role in how birds navigate using Earth's magnetic field. [SEP] Text: the of Jobs at optics. org. org and + +. Calls for Top 5 + + + for an & a at : how birds navigate A proposed model for migrating birds' magnetic sense can withstand moderate orientational disorder of a key protein in the eye. 23 September 2009 Ilia A. Solov'yov and Creatures as varied as salmon, honeybees, and migratory birds such as European robins have an intriguing ‘sixth’ sense that allows them to distinguish north from south. 1–4 Yet despite decades of study, the physical basis of this magnetic sense remains elusive. Detailed understanding of magnetoreception in animals has tremendous applications. For example, it is well known that windmills constructed in the wrong places, especially older ones, cause many bird deaths. Shielding these structures with magnetic fields may reduce the death toll by keeping the animals away from the dangerous area. Similar shields could be used to protect airports from birds, as they regularly collide with airborne airplanes, causing severe problems. Damage by birds and other wildlife striking aircraft annually amounts to well over $600 million for US civil and military aviation and over 219 people have been killed worldwide as a result of wildlife strikes since 1988. 5Migratory birds' magnetic sense may be based on the protein cryptochrome, found in the retina, the light-sensitive part of the eyes. Cryptochrome's functional capabilities depend on its orientation in an external magnetic field. 6,7 But it is present in both bird and human eyes, so why do humans lack birds' navigational ability? Our recent reports6–8 offer an intriguing answer. In sensing the earth's magnetic field, cryptochrome relies on redox reactions, which exchange electrons between molecules. Such reactions are crucial for life, but can also be damaging. Antioxidants to keep them in check are produced and used naturally in the body and marketed commercially in pharmacology and as dietary supplements. For magnetoreception, cryptochrome requires small quantities of negatively charged molecular oxygen, superoxide (O2−). It is fortunate that only low doses are needed, because superoxide is toxic, despite being used elsewhere in the body for signaling. Humans have an extremely efficient antioxidant enzyme, superoxide dismutase, that keeps superoxide at a very low concentration level, apparently too low for human cryptochromes to use. It seems that somewhere in our evolutionary history we might have traded our magnetic sense for longevity. Figure 1. [SEP] Justify:

Output: The text corroborates the claim by discussing the navigational abilities of migratory birds, specifically mentioning the role of the protein cryptochrome found in their eyes. It describes how cryptochrome's function varies with its orientation in an external magnetic field, which aligns with the idea that quantum coherence may influence magnetoreception in birds. The mention of redox reactions and the properties of cryptochrome supports the notion that these biological mechanisms could be involved in how birds utilize the Earth's magnetic field for navigation.


Input: Task: contrast the claim using the given text. Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: Alternatively, one could speculate that in Homo, the recent man-made increase in lifespan did not yet alter the relative strengths of transcription versus replication gradients, following the hypothesis that a long lifespan increases more the number of transcriptions than of replication. According to that scenario, the relatively recently increased transcription/replication ratio did not yet result in stronger transcription gradients in Homo, explaining the position of that species in Figure 3. Besides that the latter interpretation is based on a more complex rationale than the former, it also seems less likely because if the causal mechanism underlying the Dsshr->Dssht convergence-lifespan association is that increased lifespan causes more transcription-related deaminations, this is due to mutations cumulating ontogenetically (see the effects of parental age on offspring quality referred to above). However, following this rationale, gradients should almost immediately react to the increase in lifespan, which is not the case in Homo. 4. 8. Developmental stability and convergence between transcription and replication It is interesting to note that the principles observed for the association between Dsshr->Dssht convergence and lifespan are also valid for that between Dsshr->Dssht convergence and developmental stability. This observation fits the general trend that developmental instability associates with low fitness and pathologies. It would be interesting to explore whether this hypothesis of convergence of replication with transcription fits with the “double-agent” unifying hypothesis of ageing and diseases based on the tradeoff between oxidative stress inducing genetic reaction mechanisms against stress and its effect on ageing and age-related disease (Lane, 2003). The molecular processes presented provide mechanistic explanations for these similarities. Advertisement 5. present the original hypothesis that heavy strand sequences of tRNA-coding genes functioning as additional light strand replication origins tend to increase the similarity of mutational patterns resulting from replication with those due to transcription, putatively decreasing cumulation of mutations during the two processes. Variation exists among mitochondrial genomes in the extent that replication mutation gradients resemble transcription gradients; in most species (mainly short lived with high metabolism), replication gradients do not resemble transcription gradients. The similarity of replication mutation gradients to transcription ones correlates positively with maximal lifespan in Primates and other taxa. Systematically, outliers to these trends have replication mutation gradients relatively resembling transcription gradients but are for short lived species, the opposite (long lived outliers with replication gradients not resembling transcription gradients) does not occur. [SEP] Justify:

Output: The text contrasts the claim by discussing complex molecular processes and their implications for lifespan and transcription/replication ratios, suggesting that a direct and guaranteed link between biohacking and doubling lifespan is unfounded. The text emphasizes that simply increasing lifespan does not ensure enhanced transcription gradients, thereby challenging the notion that biohacking guarantees longevity in such a definitive manner.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: (C) Band intensities of Cyclind1, cMyc, and P-cJun were measured. Data represent means ± SEM (n = 5, each sample represents individual mouse). Statistical difference was determined by two-tailed unpaired t-test. (D) Liver tumor lysates were analyzed for the activation of p38, p65, and STAT3 by Western blotting. β-actin was used as a loading control. Each lane represents individual mouse. (E) Band intensities of P-JNK, P-ERK, P-p65, and P-STAT3 shown in D were measured. Data represent means ± SEM (n = 5). Statistical difference was determined by two-tailed unpaired t-test. (F) The levels in p65, P-p65, P-ERK, P-JNK, P-p38, and P-STAT3 in tumor lysates (0. 5 mg/ml) from different mice were measured by ELISA. Data represent means ± SEM (n = 6). Statistical difference was determined by two-tailed unpaired t-test. (G) Hepatocytes were isolated from liver tumors and analyzed for the activation of p38, p65, and STAT3 by Western blotting. Each lane represents individual mouse sample. (H) Densitometric analysis of P-JNK, and P-p65 immunoreactive bands are shown. Data represent means ± SEM (n = 6). Statistical difference was determined by two-tailed unpaired t-test. (I) RNA isolated from the tumor hepatocytes was analyzed for the expression of chemokines and proliferative genes. Data represent means ± SEM (n = 6, each sample represents individual mouse). Statistical difference was determined by two-tailed unpaired t-test. (J) Hepatocytes, Kupffer cells, and hepatic stellate cells were isolated from liver tumors and stimulated with LPS (1 ug/ml). Activation of JNK was measured by Western blotting. Figure 4—source data 1 NLRP12 suppresses activation of JNK and expression of tumor-promoting molecules during HCC. Download elife-40396-fig4-data1-v2. zip Figure 4—figure supplement 1 Download asset Open asset NLRP12 downregulates induction of inflammatory molecules in tumor hepatocytes. [SEP] Justify:

Output: The text provides detailed experimental data regarding tumor studies and does not discuss any topics related to urban living or stress levels. Therefore, it is irrelevant to the claim about urban living and stress.


Input: Task: corroborate the claim using the given text. Claim: Some studies suggest that quantum coherence may play a role in how birds navigate using Earth's magnetic field. [SEP] Text: Structure of cryptochrome, likely involved in avian magnetoreception. The protein internally binds the FADH (the semi-reduced form of flavin adenine dinucleotide) cofactor, which governs its functioning capabilities. The signaling state is achieved through a light-induced electron-transfer reaction involving a chain of three tryptophan amino acids, Trp400, Trp377, and Trp324. Signaling is terminated by the superoxide radical O2-. Researchers have speculated that the products of such reactions in a bird's retina might somehow affect the sensitivity of light receptors. 9 If so, then modulation of the reaction products would alter the bird's visual sense, producing marks in the its field of view. The bird could find its direction by changing the orientation of its head in the magnetic field and observing how the marks moved across its vision. 9 Interestingly, studies have shown that, when using the magnetic field to orient themselves, migratory birds indeed exhibit such head-scanning behavior. 10 Cryptochrome-signaling intensity is expected to change by about 15% upon a 90° turn of the protein in the field. 7 Visual signals can also be enhanced and it is likely that cryptochrome is distributed similarly to photoreceptor cells,9,11 perpendicularly to the retina. The cryptochromes are unlikely perfectly aligned, even if bound to the ordered membrane structures found in the outer segments of rod-shaped photoreceptors. We calculated how much disorder is permitted in the cryptochrome alignment for a functional magnetic compass. Cryptochrome activation and signalingCryptochrome internally binds a flavin adenine dinucleotide (FAD) molecule. On activation by light-induced electron transfer6 involving a chain of three tryptophan amino acids, FAD gains hydrogen to form the active (signaling) state FADH. The magnetic field can influence this photoactivation process by acting on unpaired-electron spins. 6,7 The back reaction, in which FADH reverts to FAD, likely involves O2− (see Figure 1) and can also be modulated by the earth's magnetic field. 7 Cryptochrome's signaling state has a lifetime of about 1ms, controlled by the balance of the forward- and back-reaction rates. A low concentration of O2− is crucial for a sufficiently long signaling-state lifetime, in the 1–10ms range. [SEP] Justify:

Output: The text corroborates the claim by discussing cryptochrome and its involvement in avian magnetoreception, which implies a potential link to how birds navigate using Earth's magnetic field. It mentions that the magnetic field can influence the photoactivation process of cryptochrome by acting on unpaired-electron spins, suggesting a role for quantum mechanisms in bird navigation.


Input: Task: contrast the claim using the given text. Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: In some taxa such as Cetacea, this phenomenon is enhanced with two clearcut ranges in similarity between replication and transcription, one with relatively low similarities, where maximal lifespan increases with the similarity of replication gradients to transcription gradients, and another region where similarities are highest and maximal lifespan decreases with similarity. These patterns suggest that low convergence does not enable high maximal lifespans, but too high convergence limits lifespan, probably because too many collisions between replication and transcription forks decrease both replication and transcription rates, increasing durations spent single stranded, and mutation frequencies. The length of gestation periods increases also with convergence, notably, in r strategists; in K strategists, the convergence levels coevolve more with maximal lifespan, fitting the rationale that the molecular machinery is adapted for high metabolism and fertility in r strategists, and high survival in K strategists. Results are interpreted assuming that the observed phenomena are due to replication that sometimes resembles transcription, but are not due to transcription. Evidence supporting this is presented: in species possessing two gradients, one according to the classical replication origin, and one resembling transcription, both mutation gradients have very similar slopes, which is more compatible with a single enzymatic machinery (the mitochondrial gamma DNA polymerase) causing both gradients, rather than each due to a different polymerase. A method based on differences in the respective rates of replication and transcription for distinguishing between replication and transcription gradients is suggested, where the ratios between slopes of mutation gradients of purines versus pyrimidines should vary when mutation gradients are due to replication resembling transcription rather than transcription itself. The hypothesis that results are due to a causal relationship opposite to the one proposed (high longevity causes high transcription/replication ratios and hence transcription gradients dominate replication ones) is examined and discussed. This interpretation is unlikely, not only because gradients seem to be due to a single enzymatic process, but also because this hypothesis is less compatible with patterns in the data: among others it does not predict the patterns observed for outliers and the differences between r- and K-strategists. Advertisement 1. Albrecht-Buehler G. 2006 Asymptotically increasing compliance of genomes with Chargaff’s second parity rules through inversions and inverted transpositions. Proc. Nat. Acad. Sci. USA, 103 17828 17833. 2. Aldana M. Balleza E. Kauffman S. [SEP] Justify:

Output: The text contrasts the claim by providing detailed insights into genetic replication and transcription processes in different taxa. It highlights that the relationship between longevity and biological mechanisms is complex and does not support the notion that biohacking can simply double human lifespan. The discussion of how similarities between replication and transcription can impact lifespan suggests that high longevity is a product of various biological factors rather than a guarantee by biohacking.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: WT and Nlrp12-/- mice were injected with DEN (25 mg/kg i. p. ) at the age of 14 days and euthanized at 10 months later. (A) Hepatocytes, Kupffer cells, and hepatic stellate cells were isolated from liver tumor tissues. The expression of albumin (Alb), Emr1, and Pdgfr-b in the isolated cell population was measured real-time qPCR. Data represent means ± SD (n = 3). (B) The expression of Nlrp12 in hepatocytes, Kupffer cells, and hepatic stellate cells was measured by real-time qPCR. Data represent means ± SD (n = 3). (C) Hepatocytes isolated from liver tumors at 10 months following DEN administration were cultured and stimulated with LPS for 4 hr. The expression of indicated genes was measured by real-time qPCR. Data represent means ± SD (n = 3). *p<0. 05. **p<0. 01, ***p<0. 001. Statistical difference was determined by two-tailed unpaired t-test. Figure 4—figure supplement 1—source data 1 NLRP12 regulates inflammatory responses in tumor hepatocytes. Download elife-40396-fig4-figsupp1-data1-v2. zip Figure 5 with 1 supplement Download asset Open asset NLRP12 suppresses gut microbiota-dependent inflammatory responses and HCC pathogenesis. (A) Nlrp12-/- mice were treated with antibiotics in their drinking water starting at 4 weeks after birth and continued until the end of the experiment. Control groups were left untreated. At 4 weeks following antibiotics treatment, all mice (n = 10/group) were injected with DEN (100 mg/kg body weight). (B) At 38 weeks, mice were sacrificed and liver tumor development was monitored. Representative images of DEN-treated mouse livers are shown here. Number of tumors were counted. Data represent means ± SEM (n = 10). Statistical difference was determined by two-tailed unpaired t-test. (C) The expression of HCC marker AFP in the liver was measured by real-time qPCR. Data represent means ± SEM (n = 10). Statistical difference was determined by two-tailed unpaired t-test. [SEP] Justify:

Output: The text does not address the claim regarding urban living and stress levels at all. It focuses on experimental procedures involving mice and their liver responses post-treatment with DEN and antibiotics, which is irrelevant to the assertion about the impact of urban living on stress.


Input: Task: corroborate the claim using the given text. Claim: Some studies suggest that quantum coherence may play a role in how birds navigate using Earth's magnetic field. [SEP] Text: 12 At a concentration still tolerable to an animal, encounters of FADH and O2− radicals happen every millisecond, which is optimal for compass function. Figure 2. Visual patterns in the retina modulated through the geomagnetic field for a bird flying at night and during daytime parallel to the horizon toward north and south. Acuity of vision-based compassThe acuity of this proposed vision-based magnetoreception system in birds is affected by the degree of order in the orientation of the cryptochrome proteins. Cryptochrome possesses a magnetic-field-sensing anisotropy axis6,7,13 that is roughly perpendicular to the FAD plane (see Figure 1). The protein's orientation with respect to the magnetic field can be characterized by the three Euler angles α, β, and γ. Euler angles represent the spatial orientation of any frame of reference as a composition of rotations from a frame of reference. We use a generic definition. 14 Our calculations showed that α and γ do not need to be held fixed for cryptochrome to act as a magnetic compass. The angle βis not required to be fixed precisely either. We investigated how sensitive compass acuity is to a range of β values. Figure 2 shows the visual patterns in the retina modulated in some hypothetical manner through the geomagnetic field for a bird flying parallel to the horizon and facing either north or south. The modulated patterns are calculated for cryptochrome fluctuation over a range in β of 0–10°. The size and intensity of this pattern defines the acuity of the magnetic compass. In both examples (day and night vision), one distinguishes a round spot in the lower part of the retina, which points in the direction of the magnetic field. This spot is clearly visible despite a Δβ≃10° fluctuation. The uniform background of the night-vision magnetic-field-induced pattern makes it easier to distinguish the pattern of more intense color at the top and bottom of the field of vision for the north- and south-facing flights, respectively. A biochemical magnetic compass in birds may consist of orientationally ordered proteins in the retina. Previous work has shown how such a compass could be realized through light-induced electron-transfer reactions in cryptochrome. We have now modeled the effect of orientational disorder of the protein in retinal cells on compass acuity. [SEP] Justify:

Output: The text corroborates the claim by discussing how cryptochrome proteins in birds may serve as a magnetic compass and mentions the role of biochemical processes, which aligns with the idea that quantum coherence could influence navigation. It details how the orientation and behavior of cryptochrome affect the magnetic field perception and navigation mechanisms, supporting the suggestion that quantum effects may be involved.


Input: Task: pass the claim using the given text. Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: Impact of the work: This work represents the first study addressing the turnover and retention of long-lived protein in the ovary and will be an invaluable resource for the research community, particularly for those studying ovarian aging. This work also raises important unanswered questions worthy of follow-up including interesting findings regarding the timing of turnover of cell types such as the OSE, organelles such as mitochondria, and ECM proteins such as ZP3 and Tubb family proteins. Most striking are the differences between the two timepoints used (6 and 10 months) which lead the authors to infer trajectories and kinetics of replacement of proteins potentially contributing to ovarian longevity or decline. As such I expect the work will contribute to hypothesis generation and stand to have an important impact on the field. #2 (Public Review): Summary: The manuscript by Bomba-Warczak et al. applied multi-isotope imaging mass spectrometry (MIMS) analysis to identify the long-lived proteins in mouse ovaries during reproductive aging, and found some proteins related to cytoskeletal and mitochondrial dynamics persisting for 10 months. Strengths: The manuscript provides a useful dataset about protein turnover during ovarian aging in mice. Weaknesses: The study is pretty descriptive and short of further new findings based on the dataset. In addition, some results such as the numbers of follicles and ovulated oocytes in aged mice are not consistent with the published literature. Comments on revised version: The authors did not fully address my previous concerns, especially regarding the verification of the identified proteins, and follow-up functional experiments. In addition, it is still unacceptable for me that the number of ovulated oocytes in mice at 6 months of age is only one third of young mice (10 vs 30; Fig. S1E). The most of published literature show that mice at 12 months of age still have ~10 ovulated oocytes. Moreover, based on the follicle counting method used in the present study (Fig. S1D), there are no antral follicles observed in mice at 6 months and 10 months of age, which is not reasonable. #3 (Public Review): Summary: In this study Bomba-Warczak et al focused on the reproductive aging, and they presented a map for long-lived proteins which were stable during the reproductive lifespan. [SEP] Justify:

Output: The text does not address the claim about biohacking or the guarantee of longevity through doubling the average human lifespan. It primarily discusses a study about long-lived proteins in the context of ovarian aging and does not provide any evidence or argument supporting or contrasting the claim regarding biohacking's effects on lifespan.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: (D–E) Liver tissues were analyzed for the expression of cytokines and chemokines (D) and pro-proliferative genes (E) by real-time qPCR. (D–F) Data represent means ± SEM (n = 10). Statistical difference was determined by two-tailed unpaired t-test. Figure 5—source data 1 Measurement of liver tumorigenesis and inflammatory responses following antibiotic treatment. Download elife-40396-fig5-data1-v2. zip Figure 5—figure supplement 1 Download asset Open asset Altered gut microbiota of Nlrp12-/- mice doesn’t influence immune responses in healthy livers. (A and B) Fecal DNA isolated from 10 months old untreated WT (n = 6) and Nlrp12-/- (n = 7) mice were analyzed for 16S rRNA gene sequence. Relative distribution of bacterial composition at phylum (A) and family (B) levels are shown. Data represent means ± SEM. *p<0. 05. **p<0. 01, ***p<0. 001. Statistical difference was determined by two-tailed unpaired t-test. (C) The expression of cytokines and chemokines as indicated in the liver of healthy mice (10 months old) were analyzed by real time qPCR. Data represent means ± SEM (n = 5). Statistical analysis was performed by two-tailed unpaired t-test. (D) Single cell suspension of healthy WT and Nlrp12-/- mouse livers collected at 10 months after birth were stained with antibodies for CD3, CD11b, CD11c, F4/80, and Gr-1 and analyzed by flow cytometry for the quantification of T cells (CD45+, TCRb+, CD11b-), dendritic cells (CD45+, CD11b+, CD11c+high, Gr1-), kupffer cells (CD45+, CD11b+, F4/80+, Gr1-), and neutrophils (CD45+, CD11b+, Gr1+, CD11c-) by flow cytometry. Data represent means ± SEM (n = 4). Statistical analysis was performed by two-tailed unpaired t-test. [SEP] Justify:

Output: The text is irrelevant to the claim as it provides detailed information regarding liver tissue analysis and cytokine expression in mice, without mentioning urban living, stress levels, or any related factors. Therefore, it does not support or refute the claim.


Input: Task: corroborate the claim using the given text. Claim: Some studies suggest that quantum coherence may play a role in how birds navigate using Earth's magnetic field. [SEP] Text: We found that moderate alignment of cryptochromes is sufficient for a reliable vision-based magnetoreception system. Our next step is to connect the angular sensitivity of the vision-based magnetic compass quantitatively to the pattern in a bird's field of vision. We want to understand in precisely which part of the photoreceptor cell cryptochrome is expressed and how it is connected to the cell membrane. Coupling of cryptochrome to visual transduction is also still hypothetical and subject to further investigation. This work has been supported by the am Main as well as by Foundation grants MCB-0744057 and PHY0822613. Ilia A. Solov'yov for Advanced StudiesFrankfurt am Main, Germany Solov'yov received his PhD from Frankfurt am in 2006. He is a postdoctoral research associate. His current research focuses on magnetoreception mechanisms in living organisms and development of theoretical and computational methods for application to biomolecular and nanostructured systems. for and Technology and Department of PhysicsUniversity of Illinois at Urbana-Champaign Urbana, IL Schulten received his PhD from in 1974. He is of physics. His professional interests are theoretical physics and theoretical biology. 1. Henrik Mouritsen, Thorsten Ritz, Magnetoreception and its use in bird navigation, Curr. Opin. Neurobiol. 15, 2005. 2. 28, 2006. 3. Wolfgang Wiltschko, Roswitha Wiltschko, Magnetic orientation and magnetoreception in birds and other animals, J. Comp. Physiol. 191, 2005. 4. S. Johnsen, K. J. Lohmann, Magnetoreception in animals, Phys. Today 61, 2008. 5. Telegraph 2009. 6. Solov'yov, Danielle E. Chandler, Klaus Schulten, Magnetic field effects in Arabidopsis thaliana cryptochrome-1, Biophys. J. 92, 2007. 7. Ilia A. Solov'yov, Klaus Schulten, Magnetoreception through cryptochrome may involve superoxide, Biophys. J. 96, 2009. 8. Ilia A. Solov'yov, Danielle E. Chandler, Klaus Schulten, Exploring the possibilities for radical pair effects in cryptochrome, Plant Signal. Behav. 3, 2008. 9. [SEP] Justify:

Output: The text corroborates the claim by discussing the role of cryptochromes in vision-based magnetoreception, which relates to how birds navigate using Earth's magnetic field. It indicates a scientific focus on understanding the mechanisms behind magnetoreception in living organisms, hence supporting the idea that there is ongoing research exploring how cryptochromes (potentially involved in quantum coherence) relate to navigation.


Input: Task: contrast the claim using the given text. Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: The claims that nucleosomes, myosin complex, and mitochondrial proteins are enriched for LLPs are well supported by GO enrichment analysis and well described within the known body of evidence that these proteins are generally long-lived in other tissues. Weaknesses: Comment 1: One small potential weakness is the lack of a mechanistic explanation of if/why turnover may be accelerating at the 6-10 month interval compared to 1-6. Response 1: At the 6-month time point, we detected more long lived proteins than the 10 month time point in both the ovary and the oocyte. We anticipated this because proteins are degraded over time, and substantially more time has elapsed at the later time point. Moreover, at the 6–10-month time point, age-related tissue dysfunction is already evident in the ovary. For example, in 6-9 month old mice, there is already a deterioration of chromosome cohesion in the egg which results in increased interkinetochore distances (Chiang et al. , 2010), and by 10 months, there are multinucleated giant cells present in the ovarian stroma which is consistent with chronic inflammation (Briley et al. , 2016). Thus, the observed changes in protein dynamics may be another early feature of aging progression in the ovary. Comment 2: A mild weakness is the open-ended explanation of OSE label retention. This is a very interesting finding, and the claims in the paper are nuanced and perfectly reflect the current understanding of OSE repair. However, if the sections are available and one could look at the spatial distribution of OSE signal across the ovarian surface it would interesting to note if label retention varied by regions such as the CLs or hilum where more/less OSE division may be expected. Response 2: We agree that the enrichment of long-lived molecules in the OSE is interesting. To make interpretable conclusions about the dynamics of long-lived molecules in the OSE, we would need to generate a series of samples at precise stages of the estrous cycle or ideally across a timecourse of ovulation to capture follicular rupture and repair. These samples do not currently exist and are beyond the scope of this study. However, this idea is an important future direction and it has been added to the discussion (lines 221-223). Furthermore, from a practical standpoint, MIMS imaging is resource and time intensive. [SEP] Justify:

Output: The text contrasts the claim by discussing the dynamics of protein longevity and aging without providing any evidence that biohacking or the specific mechanisms mentioned can guarantee increased lifespan. It highlights findings about long-lived proteins but also mentions potential weaknesses, such as the lack of mechanistic explanations and the observed age-related dysfunction in the ovary, suggesting that aging processes complicate the relationship between biomolecules and lifespan. Therefore, it does not support the claim that biohacking can double the average human lifespan.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: (E) Liver lysates from healthy mice were analyzed for P-JNK, P-p65, P-ERK, P-STAT3, and β-actin by Western blotting. Figure 5—figure supplement 1—source data 1 Analyses of gut microbiota composition and inflammatory responses in healthy WT andNlrp12-/-mouse livers. Download elife-40396-fig5-figsupp1-data1-v2. zip Figure 6 with 1 supplement Download asset Open asset NLRP12 downregulates JNK activation in hepatocytes. (A) Primary hepatocytes from healthy WT and Nlrp12-/- mouse livers were isolated and cultured. Hepatocytes were stimulated with LPS for the indicated time and analyzed for the activation of JNK, p38, ERK, and p65 by Western blotting. (B) Primary hepatocytes from healthy WT and Nlrp12-/- mouse livers were stimulated with LPS in the presence of absence of JNK inhibitor. The expression of inflammatory and proliferative molecules was measured by real-time qPCR. Data represent means ± SD (n = 3 replicates). Statistical difference was determined by two-tailed unpaired t-test. (C) HepG2 cells stably expressing either GFP or NLRP12 were stimulated with LPS and analyzed for the activation of JNK, p38, ERK, and p65 by Western blotting. (D) Primary hepatocytes isolated from untreated WT and Nlrp12-/- mouse livers were stimulated with LPS for the indicated time periods and analyzed for cMyc, P-cJun, Cyclin d1, and P-JNK by Western blotting. (E–F) Primary hepatocytes grown on coverslip were treated with or without LPS for 1 hr and immunostained for P-cJun (green) and cMyc (green). Cellular morphology was visible with filamentous actin (F-actin) staining (red). DAPI (blue) was used for nuclear staining. (F) P-cJun and cMyc fluorescence intensities were measured by software. Data represent means ± SD (n = 20) and is representative of three independent experiments. Statistical difference was determined by two-tailed unpaired t-test. [SEP] Justify:

Output: The text is irrelevant to the claim about urban living and stress levels, as it discusses laboratory experiments related to liver cell analysis, inflammation, and JNK activation in mice, without mentioning urban living or stress.


Input: Task: corroborate the claim using the given text. Claim: Some studies suggest that quantum coherence may play a role in how birds navigate using Earth's magnetic field. [SEP] Text: model for photoreceptor-based magnetoreception in birds, Biophys. J. 78, 2000. 10. birds use head scans to detect the direction of the earth's magnetic field, Curr. Biol. 14, 2004. 11. Henrik Mouritsen, Ulrike Janssen-and neuronal-activity markers colocalize in the retina of migratory birds during magnetic orientation, Proc. Nat'l Acad. Sci. USA 101, no. 39, 2004. 12. . Timmel, P. J. Hore, Henrik Mouritsen, Chemical magnetoreception: bird cryptochrome 1a is excited by blue light and forms long-lived radical-pairs, 2, pp. e1106, 2007. 13. F. Cintolesi, T. Ritz, C. recombination of an immobilized photoinduced radical pair in a 50μT magnetic field: a model avian photomagnetoreceptor, Chem. Phys. 294, 2003. 14. D. Varshalovich, A. Moskalev, V. Hersonskij, of Angular Momentum, World Scientific, Singapore, 1988. [SEP] Justify:

Output: The text corroborates the claim by mentioning various studies and models related to bird magnetoreception and the role of biological structures like cryptochrome in responding to magnetic fields. It indicates that there is scientific exploration into how birds detect the Earth's magnetic field, hinting at mechanisms where quantum coherence may be relevant.


Input: Task: contrast the claim using the given text. Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: In humans, oocytes initiate meiosis during fetal development, and by birth, all oocytes are arrested at prophase of meiosis I (17, 18). This cell cycle arrest is maintained until ovulation, which occurs any time between puberty and menopause, and thus can span decades. The oocytes are particularly sensitive to protein metabolism alterations because they contribute the bulk cytoplasm to the embryo following fertilization. Thus, maternal proteins produced during oogenesis are essential to generate high-quality gametes (9). The ovarian microenvironment is a critical determinant of gamete quality and has been shown to become fibro-inflamed and stiff with age (19-21). Although a small number of oocyte-specific proteins have been identified as long-lived, including cohesins and several centromere-specific histones, there has not been a discovery-based approach to define the long-lived proteome of the ovary and oocyte. Thus, the potential contribution of LLPs to the age-related deterioration of the reproductive system in mammals remains to be elucidated. In this study we used multi-generational whole animal metabolic stable isotope labeling and leading mass spectrometry (MS)-based quantitative proteomic approaches to visualize and identify ovarian and oocyte long lived macromolecules in vivo during milestones relevant to the reproductive system. Exceptional longevity of ovarian structures and molecules in mammalsThe mammalian ovary is a structurally complex, heterogenous, and dynamic organ with follicles at different stages of development, remnants of ovulation (corpora lutea), and a heterogeneous stroma (22) (Fig. 1A). Very little is known about the long-term homeostasis and relative turnover of the ovarian tissue components during aging. To address this, we visualized the lifespan of ovarian macromolecules in mammals using a combination of stable isotope labelling and multi-isotope imaging mass spectrometry (MIMS) (fig. S1A). First, using a two-generational metabolic labelling of animals with 15N, we generated a cohort of fully 15N-labelled female pups, which were kept on 15N-chow until one month of age. This was then followed by an 14N-chow chase for 6 months. Since at this age mice begin to manifest reproductive aging phenotypes, including follicle loss (fig. [SEP] Justify:

Output: The text contrasts the claim by discussing biological and reproductive aging in mammals, specifically focusing on the ovarian structures and their changes over time. It highlights that the understanding of longevity and reproductive aging is still limited, noting that few proteins have been identified as long-lived and that significant contributions of long-lived proteins to reproductive aging remain unexplored. This implies that biohacking cannot be conclusively claimed to guarantee longevity or significantly increase human lifespan based on the current scientific understanding presented in the text.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: (G–H) Nlrp12-/- primary hepatocytes were transiently transfected with either GFP or Nlrp12 constructs followed by stimulation with LPS. The levels of P-JNK, cMyc, P-cJun, and P-p65 were measured by Western blotting (G) and the expression KC (Cxcl1), MIP2 (Cxcl2), and MCP1 (Ccl2) was analyzed by real-time qPCR (H). Data represent means ± SD (n = 3 replicates) and is representative of three independent experiment. Statistical difference was determined by two-tailed unpaired t-test. Figure 6—source data 1 NLRP12 negatively regulates JNK activation and production of inflammatory molecules in hepatocytes. Download elife-40396-fig6-data1-v2. zip Figure 6—figure supplement 1 Download asset Open asset NLRP12 downregulates multiple JNK activating pathways in hepatocytes. (A) For checking the purity of primary hepatocytes, hepatocytes isolated from healthy WT and Nlrp12-/- mouse livers were immunostained with antibody for hepatocyte-specific marker Albumin and counterstained with DAPI. (B) Primary hepatocytes from WT and Nlrp12-/- healthy mouse livers were cultured and stimulated with LPS (1 μg/mL), PGN (10 μg/mL), TNFα (20 ng/mL), and IL-6 (20 ng/mL) for 4 hr. The expression of indicated genes was analyzed by real-time qPCR. Data represent means ± SD (n = 3) and representative of three independent experiments. *p<0. 05. **p<0. 01, ***p<0. 001. Statistical difference was determined by two-tailed unpaired t-test. (C) HepG2 cells stably expressing either GFP or NLRP12 were stimulated with LPS (1 μg/mL), PGN (10 μg/mL), TNFα (20 ng/mL), and IL-6 (20 ng/mL) for 4 hr, and the expression of indicated genes was analyzed by real-time qPCR. Data represent means ± SD (n = 3) and representative of three independent experiments. *p<0. 05. **p<0. 01, ***p<0. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses experimental procedures involving Nlrp12-/- primary hepatocytes and their response to various stimuli, without addressing urban living or stress levels.


Input: Task: corroborate the claim using the given text. Claim: Quantum biology is a relatively new field that merges principles of quantum mechanics and biology. [SEP] Text: of this paper, YinYang bipolar quantum agent (BQA), bipolar quantum geometry (BQG) and 2-dimensional generic bipolar quantum superposition are introduced with a geometrical and logical exposition of Dirac 3-polarizer experiment. While the exposition qualifies BQG as a geometry of light, it is shown in this paper that the logical exposition can be extended to an analytical paradigm of quantum mechanics and quantum biology. It is shown that BQG as the geometry of light is also the geometry of Nature with a logical unification of matter and antimatter atoms into a bipolar quantum cellular automaton (BQCA) through multidimensional YinYang bipolar quantum superposition using bipolar quantum linear algebra (BQLA). With the BQCA interpretation of quantum mechanics, it is shown matter and antimatter self-organization and spacetime emergence is logically possible within BQG. A scalable BQCA model for biological repression-activation and/or degeneration-regeneration is introduced. Bipolar cellular division and bipolar fractality are proposed. Background independent normal and abnormal bipolar fractal branching is proposed. A discussion on quantum gravity and mathematical abstraction is presented. A few challenges and predictions are posted. It is contended that and BQCA constitute an analytical paradigm of quantum mechanics and quantum biology that may contribute to equilibrium-based analysis of quantum decoherence and collapse as associated with quantum measurement. Key words bipolar quantum linear algebra, multidimensional bipolar quantum superposition, bipolar quantum cellular automaton, background independence, equilibrium-based bipolar fractality, analytical quantum biology, quantum gravity, five challenges for a theory of everything, falsifiability [1] bipolar quantum agent (BQA), bipolar quantum geometry (BQG) and bipolar quantum superposition (BQS) are introduced based on bipolar dynamic logic (BDL) and bipolar quantum linear algebra (BQLA) [2-5]. and BQS have led to a logical exposition of Dirac 3-polarizer experiment [6]. The logical exposition suggests that BQG can serve as a geometry of light. The exposition, however, could be deemed isolated and accidental unless the result can be mathematically and physically generalized. This paper presents such a generalization. We show that BQG can be further extended to an analytical paradigm of quantum mechanics and quantum biology. [SEP] Justify:

Output: The text corroborates the claim by discussing how the paper introduces key concepts related to 'quantum biology' and positions it as an analytical paradigm that links quantum mechanics with biological phenomena. It explicitly states that the logical exposition can be extended to an 'analytical paradigm of quantum mechanics and quantum biology,' thereby reinforcing the assertion that quantum biology is a merging of these two fields.


Input: Task: contrast the claim using the given text. Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: Myosin and actin were also identified as LLPs with relatively high fractional abundance indicating exceptional longevity beyond 6-months. These proteins play numerous roles in oocyte maturation, fertilization, and egg activation, including nuclear positioning, spindle rotation and anchoring, chromosome segregation, cytokinesis, cortical granule exocytosis, and cytoplasmic flow (19, 38-42). Defects in many of these processes have been reported with advanced reproductive age, but whether long-lived pools of actin and myosins contribute to this etiology remains to be elucidated (43). Interestingly, F-actin stabilization restricts chromosome segregation errors due to cohesion loss which increase with age, so long lived pools of actin may confer a beneficial effect and protect against aneuploidy (42). Mitochondrial proteins were the predominant LLPs in isolated oocytes across the reproductive lifespan, and it is plausible that 15N cytoplasmic hotspots in oocytes that were observed in MIMS may correspond to mitochondria. Various aspects of mitochondrial dysfunction have been long-implicated in the age-dependent decline in gamete quality, with an age-dependent decrease in the number of mitochondria, an increase in abnormal morphology, and altered subcellular distribution (44). Moreover, mtDNA copy number decreases with age, whereas mtDNA mutations increase (45, 46). Finally, the functional capacity of mitochondria decreases with age with decreased membrane potential, increased reactive oxygen species, increased oxidative stress, and decrease energy output (47). Although it is possible that oocyte long lived mitochondrial proteins deteriorate with age and contribute to mitochondrial dysfunction, a different model is emerging for these proteins. Mitochondrial proteins are exceptionally long lived in tissues containing long-lived terminally differentiated cells and have now been documented in the brain (neurons), heart (cardiac myocytes), and the ovary (oocytes) (13). These mitochondrial LLPs are primarily localized to the cristae invaginations, which are throughout to serve as long-term stable ultrastructure within mitochondria. This strategic enrichment is hypothesized to serve as a lifelong structural pillar of mitochondria to support and maintain these organelles over long time frames (16). Although mitochondrial LLPs persist for at least 6 months in oocyte, the majority were undetectable by 10 months. [SEP] Justify:

Output: The text contrasts the claim by providing a detailed examination of the longevity-related functions of proteins and mitochondrial dysfunction with age, but does not support the idea that biohacking guarantees longevity or doubles lifespan. Instead, it highlights complexities and the uncertainties regarding the contributions of specific proteins to longevity, suggesting that while certain mechanisms and proteins may play a role in aging, they do not guarantee significant increases in lifespan.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: 001. Statistical difference was determined by two-tailed unpaired t-test. (D) Nlrp12-/- primary hepatocytes were stimulated with LPS in the presences or absence of JNK inhibitor. The levels of cMyc, P-cJun, and P-JNK were measured by Western blotting. (E) NLRP12 was knocked down in HepG2 cells usingCas9 technology. Cells were then stimulated with LPS (1 ug/ml) and the activation of JNK was measured by Western blotting. Figure 6—figure supplement 1—source data 1 NLRP12 downregulates inflammatory responses in hepatocytes in responses to multiple stimuli. Download elife-40396-fig6-figsupp1-data1-v2. zip Figure 7 with 1 supplement Download asset Open asset NLRP12 regulates hepatocyte proliferation via JNK activation. (A–B) Primary hepatocytes from WT and Nlrp12-/- mouse livers were treated with LPS in the presence or absence of a JNK inhibitor. The proliferation of hepatocytes was monitored in real-time by IncuCyte live cell image analyzer. (A) Representative images of hepatocytes captured by IncuCyte are shown. (B) The changes in cell confluence were used as a surrogate marker of cell proliferation. Data represent means ± SD (n = 5 replicates) and is representative of three independent experiments. Statistical difference was determined by two-tailed unpaired t-test. (C) WT and Nlrp12-/- hepatocytes were treated with LPS for 24 hr followed by 1 hr incubation with BrdU. Cells were then immunostained with anti-BrdU antibody and BrdU incorporation (S phase) was analyzed by flow cytometry. (D) Percentage of S phase cells as analyzed by flow cytometry was quantitatively analyzed. Data represent means ± SD (n = 3 replicates) and is representative of two independent experiments. Statistical difference was determined by two-tailed unpaired t-test. (E–F) Hepatocytes stained with anti-BrdU (green) were observed and counted under the 20X microscopic objective. DAPI (blue) was used for nucleus staining. Data represent means ± SD (n = 30 replicates) and is representative of two independent experiments. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses scientific experiments related to hepatocytes, JNK activation, and the effects of LPS on cell proliferation. It does not mention urban living or stress levels, nor does it provide any information that can support or contradict the claim.


Input: Task: corroborate the claim using the given text. Claim: Quantum biology is a relatively new field that merges principles of quantum mechanics and biology. [SEP] Text: Multidimensional equilibrium of bipolar quantum agents ∀(x, y), (u, v) ∈ B∞ = [−∞, 0] × [0, +∞], we have Bipolar Addition: (x, y) + (u, v) ≡ (x + u, y + v). (2a) Bipolar Multiplication: (x, y) × (u, v) ≡ (xv + yu, xu + yv); (2b) Algebra: E(t+1) = M(t)´ E(t). (2c) Power Law: E(t+n) = Mn(t) ´ E(t). (2d) In Eq. (2c) M(t) is a bipolar quantum logic gate matrix [18] that characterizes the nucleus bipolar regulation center of the electron-positron pairs of a matter or antimatter atom; E(t) is the bipolar energy vector of the pairs of an atom. The unification is realized in the background independent BQG (cf. Part I). Figure 2 shows an equilibrium-based unification of matter and antimatter atoms as a bipolar quantum cellular automaton (BQCA) – a multidimensional bipolar dynamic equilibrium emerged from bipolar interaction and bipolar quantum superposition. The matter-antimatter BQCA unification can be deemed a result of self-organization of multiple BQAs through bipolar quantum superposition in BQG. It is shown that the BQCA also leads to the unification of wave-p2. (a) Matter atom as bipolar quantum agent; (b) Antimatter atom as bipolar quantum agent; (c) Bipolar equilibrium-based unification of matter and antimatter into a bipolar cellular automaton (adapted from [2,16]) Toward an analytical paradigm of quantum mechanics and quantum biology In this section we show that the BQCA model for matter-antimatter unification presented in last section can be scaled to physical and biological system models with conservational, regenerating, degenerating or repression and activation properties. These properties make it possible to describe different biological systems as BQAs at the molecular, cell and organism levels. [SEP] Justify:

Output: The text corroborates the claim by discussing the relationship between quantum mechanics and biological systems. It explains that the bipolar quantum cellular automaton (BQCA) model can be scaled to physical and biological systems, indicating a merge of principles from quantum mechanics with biology. The mention of describing different biological systems as bipolar quantum agents at various levels supports the idea that quantum biology integrates these two fields.


Input: Task: contrast the claim using the given text. Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: Thus, it is tempting to speculate that a stable pool of mitochondrial LLPs provides structural support for the maintenance of mitochondrial structure and function early during the reproductive lifespan. However, turnover of mitochondrial LLPs later in the reproductive lifespan may serve as a biological timer of aging. Because mitochondria are maternally inherited, these mitochondrial LLPs formed during fetal development of the mother are likely transferred to the embryo and impact subsequent generations (48). AcknowledgementsFundingThis research was supported by 21HD098498 to JNS and 21AG072343 to JNS. EKBW was supported by the 32 NS106812 and 99NS126639. Author contributionsConceptualization: Methodology: : Visualization: Funding acquisition: Project administration: Supervision: Writing – original draft: Writing – review & editing: all authors. Competing interestsThe authors declare no competing interests. Data and materials availabilityAll data generated or analyzed during this study are included in the manuscript and supporting files. RAW MS data has also been deposited at MassIVE under the accession number MSV000092217Supplementary MaterialsMaterials and MethodsFigs. S1 to S3Tables S1 and S2Table S1. Summary of proteins identified in 6- and 10-month chase ovaries. Table S2. Summary of proteins identified in 6 and 10-month chase oocytes. Fig. S1:Multi-generational whole animal pulse-chase labeling design along the reproductive aging continuum. (A) Wild-type female FVB mice (n=3) were fed a 15N-diet for 13 weeks and were maintained on a 15N-labeled diet through breeding, pregnancy, and weaning to produce 15N-labeled pups. Labeled pups were sacrificed after switching over to a 14N-diet for a chase period of 6- or 10-months. Ovaries and oocytes were designated for NanoSIMS, or liquid-chromatography/mass spectrometry. Female FVB mice experience age-associated changes in ovarian reserve, ovarian microenvironment, and gamete quality. (B) Representative images of each follicle class from mice of 6 weeks old and 6 months old. (C) Average follicle number per area of ovarian section from mice of the following ages: 6 weeks, 6 months, and 10 months (N= 3 mice per age cohort). [SEP] Justify:

Output: The text contrasts the claim by discussing biological processes related to mitochondrial function and reproductive aging without supporting the idea that biohacking can guarantee longevity or significantly double human lifespan. Instead of providing evidence for longevity through biohacking, it describes how mitochondrial LLPs may act as a biological timer of aging, suggesting that aging is influenced by underlying biological mechanisms rather than interventions that guarantee lifespan extension.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: Statistical difference was determined by two-tailed unpaired t-test. (G) The proposed mechanism of NLRP12-mediated regulation of HCC. Figure 7—source data 1 Assesment of the role of Nlrp12 in hepatocyte proliferation. Download elife-40396-fig7-data1-v2. zip Figure 7—figure supplement 1 Download asset Open asset JNK-dependent hepatocyte proliferation is regulated by NLRP12. (A) Primary hepatocytes from WT and Nlrp12-/- mouse livers were treated with LPS in the presence or absence of JNK inhibitor. The cellular proliferation was monitored in real time with the continuous presence of indicated treatments until the end of each experiment by IncuCyte live cell image analyzer. Representative images of hepatocytes captured by IncuCyte. (B) The hepatocytes from healthy WT and Nlrp12-/- mice were cultured and treated with LPS for 24 hr in the presence or absence of JNK inhibitor. Hepatocytes were immunostained for Ki67 (green) and F-actin (red), and counterstained with DAPI (blue). (C) Percentage of Ki67-positive cells per field under 20X objective. 10 independent fields were counted from each experiment and representative of three independent experiments. Data represent means ± SD (n = 10). *p<0. 05. **p<0. 01, ***p<0. 001. Statistical difference was determined by two-tailed unpaired t-test. Figure 7—figure supplement 1—source data 1 Analysis of Ki67-positive cells in LPS-stimulated hepatocytes. Download elife-40396-fig7-figsupp1-data1-v2. zip Author response image 1 Download asset Open asset Analysis of gene alterations of different innate immune genes using cBioportal. Author response image 2 Download asset Open asset Gross anatomy of DEN and DEN plus CCL4-treated mice. resources table Reagent type or resourceDesignationSource or referenceIdentifiersAdditional informationGenetic reagent (M. musculus)C57BL/6:MGI:3028467 JAX:000664Genetic reagent (M. [SEP] Justify:

Output: The text is irrelevant to the claim regarding urban living and stress levels, as it discusses scientific experiments and data related to hepatocyte proliferation and immune gene alterations, with no mention of urban living or stress.


Input: Task: corroborate the claim using the given text. Claim: Quantum biology is a relatively new field that merges principles of quantum mechanics and biology. [SEP] Text: Scalable fractality of BQCA Without a formal geometrical and logical basis for quantum mechanics, after seven decades since its inception, quantum biology [20] is still a research area in its infancy. Although the Yin and Yang of Nature have been recognized as fundamental and ubiquitous bipolar coexistence in biology [21] and genomics [22], no formal geometrical and logical model had been available for reasoning on the Yin and Yang for thousands of years until recently. It is a living proof to Einstein’s assertion [23] that “the axiomatic basis of theoretical physics cannot be extracted from experience but must be freely invented. ” The above dilemma can be best illustrated with two mysteries. One is in the process of photosynthesis where “P3. Equilibrium-based bipolar scalability and fractality of BQCA: (a) Bipolar scalability and fractality; (b) BQG as a background independent bipolar fractal geometry With complete background independence, BQG makes bipolar quantum cellular automaton-based fractal emergence, branching, regulation, and communication possible through bipolar quantum superposition and entanglement. In BQG, spacetime can emerge and disappear following the arrivals and departures of BQAs or fractals. A BQA as a dynamic equilibrium is to the Yin and the Yang of bipolar relativity as gravity is to space and time of general relativity but with fundamentally different syntax, semantics, and basic postulates. While space and time are not direct opposites and cannot form a bipolar dynamic equilibrium, bipolar interaction and complementarity is posited to cause the emergence of BQAs as well as spacetime through bipolar quantum superposition and entanglement in a bipolar dynamic equilibrium process [1,2]. Since the Yin and the Yang are two reciprocal and interdependent opposites of a dynamic equilibrium that are completely background independent and ubiquitous, BQG is fundamentally different from Euclidian, Hilbert, and spacetime geometries. The new geometry is quadrant-irrelevant and shape-free because bipolar identity, interaction, superposition, separation, and entanglement can be accounted for in the geometry without quadrants. With the shape-free and quadrant-irrelevant properties, BQG can support bipolar fractality anywhere in any amount of bipolar energy or information for investigating into the quantum nature of shaped fractals in micro and meso scales. [SEP] Justify:

Output: The text corroborates the claim by noting that quantum biology is still in its infancy, indicating it is a relatively new area of research. It suggests that quantum biology merges principles of quantum mechanics with biological processes, evidenced by discussions on quantum superposition and entanglement in biological and genomic contexts. This supports the notion that quantum biology integrates quantum mechanics with biology, reaffirming the claim.


Input: Task: contrast the claim using the given text. Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: In humans, oocytes initiate meiosis during fetal development, and by birth, all oocytes are arrested at prophase of meiosis I (17, 18). This cell cycle arrest is maintained until ovulation, which occurs any time between puberty and menopause, and thus can span decades. The oocytes are particularly sensitive to protein metabolism alterations because they contribute the bulk cytoplasm to the embryo following fertilization. Thus, maternal proteins produced during oogenesis are essential to generate high-quality gametes (9). The ovarian microenvironment is a critical determinant of gamete quality and has been shown to become fibro-inflamed and stiff with age (19-21). Although a small number of oocyte-specific proteins have been identified as long-lived, including cohesins and several centromere-specific histones, there has not been a discovery-based approach to define the long-lived proteome of the ovary and oocyte. Thus, the potential contribution of LLPs to the age-related deterioration of the reproductive system in mammals remains to be elucidated. In this study we used multi-generational whole animal metabolic stable isotope labeling and leading mass spectrometry (MS)-based quantitative proteomic approaches to visualize and identify ovarian and oocyte long lived macromolecules in vivo during milestones relevant to the reproductive system. Exceptional longevity of ovarian structures and molecules in mammalsThe mammalian ovary is a structurally complex, heterogenous, and dynamic organ with follicles at different stages of development, remnants of ovulation (corpora lutea), and a heterogeneous stroma (22) (Fig. 1A). Very little is known about the long-term homeostasis and relative turnover of the ovarian tissue components during aging. To address this, we visualized the lifespan of ovarian macromolecules in mammals using a combination of stable isotope labelling and multi-isotope imaging mass spectrometry (MIMS) (fig. S1A). First, using a two-generational metabolic labelling of animals with 15N, we generated a cohort of fully 15N-labelled pups. After birth, labelled females were kept with the labelled dam until weaning, at which time their food source was switched to the 14N-chow chase. [SEP] Justify:

Output: The text contrasts the claim by focusing on the complexities of oocyte biology and aging in mammals. It discusses factors influencing the quality of gametes and the limited understanding of longevity in reproductive systems, suggesting that there isn't clear evidence demonstrating that biohacking, as defined in the claim, guarantees longevity or doubling human lifespan.


Input: Task: pass the claim using the given text. Claim: Urban living always leads to increased stress levels. [SEP] Text: musculus)Nlrp12-/- C57BL/6JPMID:12563287RRID: MGI:2676630Cell line (Homo Sapiens)HepG2:CVCL_0027Recombinant DNA reagentpcDNA4/TOInvitrogenCat#V1020-20Recombinant DNA reagentpcDNA4/TO-Nlrp12This paperFull length Nlrp12 (mouse) cDNA was cloned into pcDNA4/reagentpcDNA4/TO-NLRP12This paperFull length NLRP12 (human) cDNA was cloned into pcDNA4/reagentNLRP12 sg/Cas9 All-in-(Human)ABM IncCat # K1434706Recombinant DNA reagentScrambled sg/Cas9 All-in-one # K010AntibodyRabbit polyclonal anti-NLRP12:SCR_001456 Cat # OAAB04256WB: 1:500AntibodyRabbit monoclonal anti-p44/42 (Erk1/2):AB_390779 Cat # 4695,WB: 1:2000AntibodyRabbit monoclonal anti-Phospho- SAPK/:AB_823588 Cat # 4668WB: 1:1000AntibodyRabbit monoclonal anti-p38 :AB_10999090 Cat # 8690WB: 1:1000AntibodyRabbit monoclonal anti-Phospho-:AB_2315049 Cat # 4060WB: 1:1000AntibodyRabbit monoclonal anti-c:AB_1903938 Cat # 5605WB: 1:1000, IF:1:100AntibodyMouse monoclonal anti b-actinSigmaRRID:AB_476697. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses various reagents and antibodies related to NLRP12 and does not address the topic of urban living or stress levels in any way. There is no mention of urban living or its effects on stress, making it unrelated to the claim.