Input: Task: corroborate the claim using the given text. Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: The heatmap and PECA results show example genes: the stress response genes HSPA5 (GRP78, BiP) and HSP90B1, the DNA repair gene RAD51, and the aminoacyl-tRNA synthetase WARS. FDR - false discovery rate. Figure 1—figure supplement 1 Download asset Open asset Overview of the statistical workflow for data analysis (PECA). The schematic illustrates the experimental design that maps multiple layers of regulation in response to stress. RNA and protein abundances were measured using RNA-seq and mass spectrometry, respectively. Ribosome footprinting and protein occupancy profiling were used to map the binding of ribosomes and non-ribosomal proteins along mRNAs, respectively. Time points and genes with significant regulation were extracted from each data type with (PECA)(Teo et al. , 2018; Teo et al. , 2014). For changes in RNA concentration, assuming DNA concentration remains constant, PECA reports on transcription and RNA degradation regulation. After factoring out changes that occur in RNA concentrations, the ribosome footprinting, protein occupancy profiling, and mass spectrometry datasets inform on translation, binding of post-transcriptional regulators, and translation/protein degradation changes, respectively. The figure shows the expression patterns for the ER stress response gene IFRD1 as an example of significant regulatory events identified by PECA; layer one represents the changes in molecular abundance on which layer two levels partially depend (false discovery rate <0. 2 in both biological replicates). Solid lines - replicate 1, dashed lines replicate 2. TRXP - transcription; TRL - translation; RNA-DEG - RNA degradation; PROT-DEG - protein degradation. Figure 2 with 5 supplements Download asset Open asset Tunicamycin elicits stress of the endoplasmic reticulum. (A) Reactive oxygen species (ROS) change in HeLa cells after tunicamycin and hydrogen peroxide (left and right, respectively) treatment, as measured for indicated time points. The cells show basal levels of ROS with minimal increase upon tunicamycin treatment, and substantial increase when treated with hydrogen peroxide, consistent with the relationships shown in Figure 1A. (B) The panels show phosphorylation levels of ER stress markers PERK and eIF2α increase after treatment with tunicamycin (left). [SEP] Justify:

Output: The text corroborates the claim by discussing the impact of stress on protein and RNA abundance. It mentions specific genes such as HSPA5 and HSP90B1 related to the stress response, and describes how the experimental design involves measuring changes in protein profiling and ribosome binding in response to mechanical stress. This indicates that mechanical stress can indeed lead to changes in protein conformation and abundance.


Input: Task: contrast the claim using the given text. Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: 68) directly sets out a series of tantalizing questions, and it is clear that a consilience of simulated and reconstructed temperature response has not yet been achieved. Likely explanations for these differences lie at least in part on our representation of the processes governing the climate consequence of eruptions in state-of-the-art GCMs, including aerosol processes, as well as precise knowledge of the timing and magnitude of past events. Paleoclimate proxies are a filter through which we peer into the past, and thus the biological, chemical, and physical mechanisms that give rise to these records need to be better understood. Addressing these myriad and extant uncertainties will require close coordination between those specializing in paleoclimate reconstruction, modeling, and present observations of the climate system: scientists with domain knowledge in aerosol and particulate behavior in the atmosphere, geologists and ice core specialists with knowledge of both atmospheric processes and geochronology, social scientists and engineers who understand the coupled human and natural systems impacted by eruptions, and climate modelers. Volcanic eruptions and their influence on coupled Earth systems cut across traditional disciplinary boundaries, and will continue to require collaboration and a high degree of international cooperation. PAGES has recently organized the “on Climate and Society” (VICS) working group. The principal aims of this group are to improve radiative forcing; understanding of volcanically induced climate variability; and understanding of societal impacts of volcanic eruptions. The group hopes to extend our current volcanic forcing datasets, largely limited to the last millennium back to the beginning of the Holocene. This work will facilitate model-to-data inter comparisons such as those of SSiRC (and its Role in Climate), PMIP4 (Paleoclimate and Project, Phase 4), and VolMIP (Project on the to Volcanic Forcing). In addition to editors Allegra LeGrande and Kevin Anchukaitis, the working group will be lead by Michael Sigl,. affiliations 1for 2School of Geography and Development and Laboratory of Tree-Ring Research, University of Arizona, Tucson, USA contact Allegra N. LeGrande: allegra. n. legrandenasa. gov 10. 1029/2008JD010239 et al. (1996) 42: 233-272 Jungclaus JH et al. (2010) 6: 723-737 Mann ME et al. [SEP] Justify:

Output: The text contrasts the claim by discussing the complexities and uncertainties surrounding the climate consequences of volcanic eruptions. It states that there has not yet been a consilience of simulated and reconstructed temperature responses to volcanic eruptions, indicating that not all eruptions lead directly to global cooling. Additionally, it emphasizes the need to better understand the processes governing climate impacts and mentions that effective modeling of these processes requires collaboration across various scientific disciplines, further suggesting variability in volcanic effects rather than a uniform cooling impact.


Input: Task: pass the claim using the given text. Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: AbbreviationsACR: Acrylamide; GSH: Glutathione; GSH-Px: Glutathione peroxidase; HE: Hematoxylin and eosin; IL-1β: Interleukin-1β; MDA: Malondialdehyde; ROS: Reactive oxygen species; SOD: Superoxide dismutase; TERT: Telomerase reverse transcriptase; TNF-α: Tumor necrosis factor-α; TUNEL: Terminal deoxynucleotidyl transferase mediated dUTP nick end labellingDeclarationsEthics approval and consent to participate Animal experiments were approved by the of Medicine College, of Science and Technology (resolution number 2019078), and accomplished in line with the guidelines of the Council of China. Consent for publication Not applicable. Availability of data and materials The datasets supporting the conclusions of this 57. . Acrylamide in human diet, its metabolism, toxicity, inactivation and the associated legal regulations in food industry. Nutr. 2019 Mar 25:1-16. . Calpeptin is neuroprotective against acrylamide-induced neuropathy in rats. Toxicology. 2018;400-401:1-8. . Neurotoxicity of acrylamide in exposed workers. . 2013; 10(9):3843-54. . Down-regulation of telomerase reverse transcriptase-related anti-apoptotic function in a rat model of acrylamide induced neurobehavioral deficits. Biotech Histochem. 2018;93(7):512-8. . Acrylamide exerts its cytotoxicity in NIH/3T3 fibroblast cells by apoptosis. Health. 2018;34(7):481-9. . Acrylamide-induced apoptosis in rat primary astrocytes and human astrocytoma cell lines. Vitro. 2014;28(4):562-70. . Taurine attenuates acrylamide- induced apoptosis via a PI3K/AKT-dependent manner. Toxicol. 2018;960327118765335. . Roles for Telomerase in the System. Neurosci. 2018;11:160. . [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses acrylamide, its effects, and related ethical approvals, and does not mention curcumin or any anti-inflammatory properties associated with turmeric.


Input: Task: corroborate the claim using the given text. Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: are conventionally viewed as structurally stabilizing elements in proteins but emerging evidence suggests two disulfide subproteomes exist. One group mediates the well known role of structural stabilization. A second redox-active group are best known for their catalytic functions but are increasingly being recognized for their roles in regulation of protein function. Redox-active disulfides are, by their very nature, more susceptible to reduction than structural disulfides; and conversely, the Cys pairs that form them are more susceptible to oxidation. In this study, we searched for potentially redox-active by scanning the Bank for structures of proteins in alternate redox states. The PDB contains over 1134 unique redox pairs of proteins, many of which exhibit conformational differences between alternate redox states. Several classes of structural changes were observed, proteins that exhibit: disulfide oxidation following expulsion of metals such as zinc; major reorganisation of the polypeptide backbone in association with disulfide redox-activity; order/disorder transitions; and changes in quaternary structure. Based on evidence gathered supporting disulfide redox activity, we propose disulfides present in alternate redox states are likely to have physiologically relevant redox activity. evidence supports the concept of two distinct types of disulfides in protein structures which have different functional roles. 1 The best known group act as structural stabilizers in proteins, significantly lowering the Gibb's free energy of the protein chain by crosslinking it, resulting in proteins that are more resistant to denaturation. The second group are redox-active and best known for their catalytic role in proteins such as thiol-disulfide oxidoreductases. An increasing role for the redox-active group in protein redox regulation is emerging. 1, 2 These disulfides act as redox-sensitive switches and are best viewed as post-translational modifications akin to phosphorylation. It has now been established that oxidative regulation: important in processes such as the cell cycle, apoptosis, and response to oxidative stress; is an important control mechanism in the cytosol. Transient oxidation mediates control of enzymes, signaling pathways, as well as transcriptional and translational control. However, these characterized cytosolic proteins likely only represent the tip of the iceberg. Increasingly, reduction of disulfides is also emerging as a key regulator of protein function in oxidizing environments. [SEP] Justify:

Output: The text corroborates the claim by discussing how redox-active disulfides in proteins exhibit conformational differences based on their oxidation states. For instance, it states that 'major reorganisation of the polypeptide backbone in association with disulfide redox-activity' and 'order/disorder transitions' occur, which indicates that mechanisms like mechanical stress can lead to conformational changes in protein structures.


Input: Task: contrast the claim using the given text. Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: Preprints AbstractDiscussion © Author(s) 2024. This work is distributed under the Attribution 4. 0 License. © Author(s) 2024. This work is distributed under the Attribution 4. 0 License. Preprints AbstractDiscussionMetrics 20 Aug 2024 | 20 Aug 2024 Status: this preprint is open for discussion and under review for Climate of the Past (CP). Identifying climate variables that interchange with volcanic eruptions as cooling forces during the Common Era’s ice ages Seip, Øyvind Grøn, and Abstract. Volcanism is known to be an instigating factor for the Age (LALIA, 536–660) and the Age (LIA, 1250–1850), but little is known about when the effect of volcanism ends, and which other mechanisms prolong a cold period that includes the ice-ages’ cold periods, but also continued periods with persistent cooling. Here we show, with a high-resolution lead-lag method, where the stratospheric aerosol optical depth (SAOD) generated by volcanic emissions ceases to precede the summer temperature (NHST). We find that five climate mechanisms cool the (percentage time in parentheses): SAOD (51 %), total solar irradiance (TSI, 2 %), the oscillation (NAO, 11 %), the interdecadal Pacific oscillation (IPO, 28 %) and CO2 (16 %). The last four variables overlap, and altogether the five climate variables cover 89 % of the cold period that includes LALIA and LIA. In contrast, we find an increase in atmospheric CO2 over a brief period just after large volcanic eruptions. During the cold period, the five variables lead NHST, are in a cooling mode, and have sufficient strength to cool the Northern Hemisphere. How to cite. Seip, K. L. , Grøn, Ø. , and Wang, H. : Identifying climate variables that interchange with volcanic eruptions as cooling forces during the Common Era’s ice ages, EGUsphere [preprint], 2024. Received: 21 Jun 2024 – Discussion started: 20 Aug 2024 Publisher's note: remains neutral with regard to jurisdictional claims made in the text, published maps, institutional affiliations, or any other geographical representation in this preprint. The responsibility to include appropriate place names lies with the authors. [SEP] Justify:

Output: The text contrasts the claim by indicating that not all volcanic eruptions lead to immediate global cooling. It discusses the cooling mechanisms associated with volcanic eruptions and specifies that while volcanism can act as a cooling factor, it does not consistently cause immediate cooling events. It mentions findings such as an increase in atmospheric CO2 shortly after large volcanic eruptions, suggesting that the climatic interactions are more complex and not solely reliant on immediate cooling effects from eruptions.


Input: Task: pass the claim using the given text. Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: Prasad SN, Muralidhara. Neuroprotective effect of geraniol and curcumin in an acrylamide model of neurotoxicity in Drosophila melanogaster: relevance to neuropathy. J Insect Physiol. 2014;60:7-16. . Tau hyperphosphorylation and P-CREB reduction are involved in acrylamide-induced spatial memory impairment: Suppression by curcumin. Immun. 2018; 71:66-80. . Intranasal insulin protects against substantia nigra dopaminergic neuronal loss and alleviatesmotor deficits induced by 6-OHDA in rats. Neuroscience. 2016;318:157-65. -. Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer's disease. Nutr. 2016;115(3):449– Cavallucci V, D'Amelio M. Matter of life and death: the pharmacological approaches targeting apoptosis in brain diseases. Des. 2011;17(3):215-29. . Effects of water extract of Curcuma longa (L. ) roots on immunity and telomerase function. J Med. 2017;14(3). -Soltanahmadi Y, Zarghami N. Adipose Tissue-. (Stuttg). 2018;68(4):213-21. . Curcumin, inflammation, and chronic diseases: how are they linked? Molecules. 2015;20(5):9183-213. . Curcumin: into an against Cancer. Mol Sci. 2019;20(8):1808. . Curcumin-Induced DNA Demethylation in by the DNA-Pathway. Cell Longev. 2020;2020:2543504. Liczbiński P, Michałowicz J, Bukowska B. Molecular mechanism of curcumin action in signaling pathways: Review of the latest research. Phytother Res. 2020;10. 1002/ptr. 6663. . Role of microglial activation and neuroinflammation in neurotoxicity of acrylamide in vivo and in vitro. Arch Toxicol. 2019;93(7):2007-19. TableTable 1. [SEP] Justify:

Output: The text does not provide direct evidence or statements that confirm or refute the claim about curcumin's anti-inflammatory properties. Instead, it contains multiple references and citations related to curcumin's effects on various health aspects, but it fails to explicitly address the claim of anti-inflammatory properties.


Input: Task: corroborate the claim using the given text. Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: 3-5 Importantly, ageing and several major diseases including neurodegenerative diseases such as Alzheimer's disease, type II diabetes, cancer, and cardiovascular disease have been associated with abnormal redox conditions. Structural and redox-active disulfides can be distinguished by their redox potentials. Disulfide redox potentials measured in thiol-disulfide oxidoreductases range from −120 to −270 mV. 6-9 For disulfides serving structural purposes, the redox potential can be as low as −470 mV. 10 Computational methods for distinguishing the two groups would be a boon. Reactivity of a redox-active Cys is modulated by its immediate protein environment. In addition to the effects of the electrostatic environment, physical stress applied to a disulfide bond both through stretching and twisting enhances its reactivity. These forces can be applied to a protein dynamically11 or may be captured during the protein folding process, rendering the disulfide poised to act upon exposure to variations in redox conditions. 12 Because of their enhanced reactivity, redox-active disulfides are also more susceptible to cleavage/oxidation under nonphysiologic conditions. For instance, redox-active disulfides are prone to cleavage by synchrotron radiation during the process of X-ray structure determination. 13-15 Other factors such as the pH of crystallization or the presence of mutations that change the electrostatic environment near a disulfide may also influence reactivity. Here, we mined the Bank (PDB)16 for highly similar proteins that have been solved in multiple redox states, that is, disulfide-bonded in one structure and reduced in another. We present evidence that most of the disulfides present in our dataset are likely to be physiologically redox-active. Many of the proteins have known thiol-based redox activity, while others have a high likelihood of thiol-based redox activity based on their involvement with redox processes. We also observed and classified types of conformational changes which occur during redox transitions. processes are enriched in the redox pair dataset Pairs dataset contains 18,003 pairs of protein structures consisting of 4333 protein chains, of which 1238 (28. 57%) are high-resolution structures (<2. 2 Å). Many structures are of the same protein solved in different redox environments. [SEP] Justify:

Output: The text corroborates the claim by discussing how physical stress, specifically stretching and twisting, applied to disulfide bonds enhances their reactivity. This implies that mechanical forces impact protein structures, suggesting they can induce conformational changes. The mention of reactivity being modulated by the protein environment supports the idea that mechanical stress affects structural dynamics.


Input: Task: contrast the claim using the given text. Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: Download & links Preprint (PDF, 1209 KB) Supplement (678 KB) Download & links Preprint (1209 KB) Metadata XML Supplement (678 KB) Øyvind Grøn, and Status: open (until 20 Nov 2024) Comment types: AC – author | RC – referee | CC – community | EC – editor | CEC – chief editor | : Report abuse Post a comment Subscribe to comment alert RC1: 'Comment on egusphere-2024-1874', #1, 29 Aug 2024 reply This is the third time I have reviewed this paper, earlier versions of which were submitted to Bulletin of Volcanology and Science of the Total Environment. In both cases I recommended rejection, and my recommendation is the same here. Resubmitting papers without fixing them wastes editors’ and reviewers’ time. This may not even be only the third time, as I may have not been sent other versions to review. The fundamental problem is that a purely statistical approach is not correct for this problem. Such a statistical approach ignores the physics of the system and is confusing. Correlation is not causation. The forcing from volcanic eruptions is very short, but the response has a much larger time scale, and is non-linear. In the case of the Age, a resetting of the state of the Arctic climate prolonged the response for decades and centuries. This is already well known. The authors claim “to our knowledge, few studies examine the timings when the effect of volcanism ceases, and other mechanisms continue the cooling effect. ” But to my knowledge there are many papers that address this. For example, look at papers referenced in this submission such as Miller et al. (2012), the title of which is “Abrupt onset of the Age triggered by volcanism and sustained by sea-ice/ocean feedbacks. ” By ignoring the physical system and its response, it is not possible to understand how climate changes. By treating and CO2 as normalized time series, and not with units and actual radiative forcing, the results are meaningless, particularly as NAO and IPO are internal variability and not forcing. The conclusion that CO2 changes are as important as volcanic eruptions is ridiculous, if you account for the magnitude of their forcings, except for the period since 1850 when CO2 and other greenhouse gases dominate. [SEP] Justify:

Output: The text contrasts the claim by stating that the forcing from volcanic eruptions is very short, while the climate response has a much larger time scale, indicating that volcanic eruptions do not cause immediate global cooling. It emphasizes that understanding the response requires consideration of the physical systems involved and their non-linear interactions, rather than a purely statistical approach. This point directly challenges the simplification in the claim.


Input: Task: pass the claim using the given text. Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: Behavioral tests All rats were subjected to behavioral analysis to assess their motor functions. In the hind limb splay examination [3,5], landing foot spread distance was measured as follow: the hind paws of rats were inked, then the rats were placed in a horizontal position of 30 cm high and dropped onto a white paper. The distance between the center points of right and left heels were recorded. In the movement initiation test [5, 24], the rat was held by its hind limbs and its torso, one forelimb was lifted above a table in order that the body weight was supported by the other forelimb alone. Then, rat was allowed to initiate stepping movements for one forelimb, and then the other. The averaged time period to initiate one step was recorded as the response latency for each forelimb. In the gait score test [3,5], animals were placed on the table and were observed for 3 min. Gait was scored as follow: 1: normal gait; 2, slightly abnormal gait characterized by slight ataxia, weakness and foot splay; 3, moderately abnormal gait characterized by obvious ataxia and foot splay with limb spread during ambulation; 4, severely abnormal gait characterized by a combination of all the above symptoms,dragging hind limbs and inability to support body weight. Histopathological analysis The collected brain tissues were fixed with 10% neutral-buffered formalin, subsequently dehydrated and embedded in paraffin. Then, paraffin-embedded brain sections of 5-μm thickness were stained with hematoxylin and eosin (HE) to observe the histopathological changes. The histopathological changes incerebral cortex, hippocampal CA1, CA3, and dentate gyrus regions were analyzed. TUNEL assay The apoptotic neurons in the brain sections were detected using the terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) assay following the instruction manual of (Servicebio, Wuhan, China). Real-time PCR The expression levels of TERT mRNA in cerebral Cortex were measured by real-time PCR using all-in-OneTM qPCR master mix AOPR–1200 (GeneCopoeia, Rockville, MD). [SEP] Justify:

Output: The text does not address curcumin or its properties, including any anti-inflammatory effects. Instead, it focuses on behavioral testing and histopathological analysis of rats, which is unrelated to the claim about curcumin.


Input: Task: corroborate the claim using the given text. Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: Key to Groups: A, ion channel, ion pump modifier; B, protein folding, isomerization; C, cell cycle; D, Calvin cycle; E, photosynthesis, respiration, transport, maturation of proteins involved in these processes; F, destruction of oxygen radicals; G, redox metal homeostasis; H, amino acid metabolism; I, sulfur metabolism; J, nucleotide metabolism/homeostasis; K, isoprenoid biosynthesis; L, RNA-interacting; M, proteases; N, DNA repair; O, actin-related; P, carrier proteins; Q, other metabolism; R, NADP+-dependent oxidoreductase; S, other oxidoreductase; T, signaling; U, development; V, cell growth pathways; W, enzyme inhibitors; X, redox homeostasis; Y, ROS generating; Z, apoptosis; a, protein fate; b, cell entry; c, cell adhesion; d, DNA-interacting proteins; e, translation; f, immunity; g, carbohydrate metabolism; h, NAD+-dependent oxidoreductases; i, Ca handling; j, methyltransferase; k, other. To further assess the likelihood that the presence of proteins in the PDB with disulfides in both redox states is an indicator of physiological disulfide redox activity, we looked for (GO) terms overrepresented in the dataset compared to the entire PDB. GO is a dynamic controlled vocabulary of over 16,000 terms used to describe molecular function, process and location of action of a protein in a generic cell. 28 The analysis revealed many GO terms consistent with redox function, including cell redox homeostasis and multiple pathways of cysteine biosynthesis (Table 2). Interestingly, several of the enriched GO terms are linked to proteins mediating cell entry, including bacterial toxins and viral entry proteins. Reduction of disulfides, often accompanied by irreversible conformational changes, have previously been implicated as a general mechanism in cell entry proteins of diverse types. 27 Experimental evidence directly supporting such a general process exists for HIV gp120, Newcastle disease virus, SARS coronavirus and Chlamydia. 29-32 Thus the GO terms support redox roles for proteins in the dataset. [SEP] Justify:

Output: The text corroborates the claim by suggesting that the reduction of disulfides in proteins can lead to irreversible conformational changes, which aligns with the idea that mechanical stress can induce changes in protein structures. The text indicates that such changes are a common mechanism found in cell entry proteins of various types, providing a clear link to the claim.


Input: Task: contrast the claim using the given text. Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: The claim on lines 529-530 that “Volcanic eruptions instigated directly or indirectly increases in atmospheric CO2 concentrations for 136 ±42 years” is completely wrong, and based on statistical artifacts of the analysis that have no basis in physics. CO2 emissions from volcanic eruptions for the past 2000 years have been very small. They have been important for massive flood basalt eruptions, but the contribution from eruptions during the period studied is trivial. The authors mix up external forcing and the internal climate system. Oceanic and atmospheric variations (such as the NAO) are internal responses to external forcings, such as volcanic eruptions and solar variations. Some of the 10. 5194/egusphere-2024-1874-RC1 AC1: 'Response to -2024-1874', Knut Seip, 02 Sep 2024 reply R … Resubmitting papers without fixing them wastes editors’ and reviewers’ time. Response. I find the introduction to the review personal, and to me this contrast with the reviewer choosing to be anonymous. Second, we have “fixed” the paper, partly based on the present reviewer’s recommendations. However, there are issues the reviewer pointed to that we do not agree with. We appreciate the opportunity to respond to the reviewer’s – sometimes harsh (the term ridiculous was used! ) –comments. And for the record, there have been other reviewers that have been positive to the study. R The fundamental problem is that a purely statistical approach is not correct for this problem. Such a statistical approach ignores the physics of the system and is confusing. Response. The paper is basically statistical, but we invoke time series, e. g. , the Oscillation (NAO) and other ocean variability series that have been discussed extensively in physical terms. The ocean variability series has been shown to impact global temperature. Wu et al. (2019) is cited in the paper line 537, but a new 235. R. In the case of the Age, a resetting of the state of the Arctic climate prolonged the response for decades and centuries. This is already well known. Response. We are not sure what the reviewer means by “resetting”. There is a large literature on ocean teleconnections across the globe, and changes in the Arctic climate is one element. [SEP] Justify:

Output: The text contrasts the claim by disputing a related assertion that volcanic eruptions lead to increases in atmospheric CO2, stating instead that 'CO2 emissions from volcanic eruptions for the past 2000 years have been very small.' This indicates that volcanic eruptions do not contribute significantly to atmospheric changes, which challenges the implication that they cause immediate global cooling.


Input: Task: pass the claim using the given text. Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: The sequences of primer sets for TERT were 5’-- 3’(forward) and 5’-–3’ (reverse). β-actin gene was applied as a reference. Immunohistochemistry Paraffin-embedded brain sections of 5-μm thickness were incubated with a rabbit anti-TERT antibody (Servicebio, Wuhan, China), then a biotinylated goat anti-rabbit secondary antibody (Servicebio, Wuhan, China). Immune complexes were visualized using 3,3’-diaminobenzidine tetrachloride (DAB). Then, sections were counter-stained with hematoxylin. Measurement of parameters related to oxidative stress in cerebral homogenates The brain tissue homogenates were made by homogenizing each cerebral cortex tissue with 9 times volume of PBS on ice, then centrifuging. The contents of malondialdehyde (MDA) and glutathione (GSH) as well as the activities of SOD and GSH-Px in the cerebral homogenates were measured according to their respective manufacturer’s instructions (Bio-Engineering Co. , Ltd. , Nanjing, China). The protein contents in cerebral homogenates were detected using the bicinchoninic acid assay kit (Bio-Engineering Co. , Ltd. , Nanjing, China). Measurement of IL–1β and TNF-ɑ levels in cerebral homogenates The concentrations of IL–1β and TNF-ɑ in cerebral homogenates were determined using using ELISA kits according to the manufacturer’s instructions (IL–1β: PeproTech Inc. , NJ, USA TNF-ɑ: R&). Statistical analysis All data were expressed as the mean ± SD, and analyzed using one-way analysis of variance (ANOVA) with post hoc Tukey test by SPSS 22. 0 software. P < 0. 05 or P < 0. 01 was considered statistically significant. ResultsEffect of curcumin on ACR-induced body weight and neurobehavioral changes As shown in Fig. 1A, the animals in the ACR group began to show slow growth compared to the normal control group since 2 weeks of exposure (P < 0. 05). [SEP] Justify:

Output: The text does not address the claim directly; it focuses on specific laboratory procedures and measurements related to oxidative stress and neurobehavioral changes without mentioning or providing evidence regarding the anti-inflammatory properties of curcumin. Therefore, it is irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: Disulfides were tested computationally for likely redox activity by screening the dataset for oxidized structures where the disulfide had particular properties previously associated with redox activity. Flagged disulfides were those (a) with high torsional energies; (b) found in known redox-active sequence motifs; or (c) which disobeyed known rules of protein stereochemistry. 12 Studies of disulfide-bonds in model proteins have shown that those bonds with high torsional energies are more easily cleaved than disulfide-bonds with lower stored energy. 33-36 148 disulfides in 139 proteins have torsional energies >15 kJ mol−1: a conservative threshold associated with redox activity. 27 These are designated by “H” in Table 1. Redox-pair disulfides were also found in sequence motifs previously shown to be associated with redox activity. 67 proteins, designated by “M” in Table S1, contain known redox-active motifs such as the CXXC motif: a redox-active disulfide motif commonly found in the thioredoxin fold, but which has also arisen convergently in other folds. A further 65 proteins, designated by “F” in Table S1, contain disulfides in protein structures that disobey known rules of protein stereochemistry. 37, 38 These disulfides, which we refer to as “forbidden” disulfides, conform to canonical structural motifs. Deformation of the resident structure enhances disulfide reactivity by inducing stress in the protein chain. 37, 38 Forbidden disulfides are proposed to have a functional role through redox activity. 12 In summary, a total of 226 proteins in the dataset contain disulfides predicted to be redox-active by a second independent bioinformatic analysis method. Nonetheless, it is possible that some proteins with alternate Cys-Pair redox states are non-native, that is, not encountered under normal, or abnormal, physiological conditions. We reasoned that proteins demonstrated selective reduction of disulfides were more likely to represent physiological states. Accordingly, for proteins with more than one disulfide, the dataset was partitioned into pairs where all the disulfides were reduced and those where some disulfides were selectively reduced while others remained intact, to further test the likelihood of involvement in physiological redox processes. [SEP] Justify:

Output: The text corroborates the claim by stating that 'deformation of the resident structure enhances disulfide reactivity by inducing stress in the protein chain.' This indicates that mechanical stress can indeed lead to changes in the conformation of protein structures, thus supporting the claim.


Input: Task: contrast the claim using the given text. Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: Other variabilities have also been given prominent roles, like El Niño and the Pacific decadal oscillation. R The authors claim, “to our knowledge, few studies examine the timings when the effect of volcanism ceases, and other mechanisms continue the cooling effect. ” But to my knowledge there are many papers that address this. …” Miller et al. (2012) is given as an example. Response. The study by Miller et al. (2012) identify when summer cold begins (1275), but not when it ends. There are several studies that suggest mechanisms that would continue the cooling effect, but they are generic. et al. (2012, p. 5) study says: “Climate modeling reveals one such possible feedback mechanism. ” Modeling studies have their advantage in being mechanistically driven, but also their drawbacks. Examples on this were given on Line 60. In contrast, the time series we use are observed series, although often based on proxies. R By ignoring the physical system and its response, it is not possible to understand how climate changes. Response. “To understand” is a complex and interesting expression. For example, you understand a phenomenon if you can refer to something well known (freezing water increase in volume, IPO gets warmer) and accepted a causal link between the familiar and what you want to understand (the water bottle breaks, GTA increases). The water bottle example is from Campbell (1952). R. By treating and CO2as normalized time series, and not with units and actual radiative forcing, the results are meaningless. Response. We treat the series in a normalized form to identify correlations and lead-lag relations. We also distinguish components of the series. To convert the series to a common unit is a challenge, but we refer to studies that suggest that e. g. NAO and IPO would have the strength to affect the global temperature, line 535. Presently we could have added a study by Samset et al. (2024) who focus on ocean basins having positive anomalies at the same time and on upwelling of previously stored deeper water with high temperatures. Text will be changed, a reference to Samset et al. (2024) will be added. R particularly as NAO and IPO are internal variability and not forcing. Response. [SEP] Justify:

Output: The text contrasts the claim by discussing the complexities of climate change and cooling effects, stating that 'few studies examine the timings when the effect of volcanism ceases, and other mechanisms continue the cooling effect.' This implies that not all volcanic eruptions result in immediate cooling, as other mechanisms could persist and influence climate after volcanic activity, which contradicts the absolute nature of the claim.


Input: Task: pass the claim using the given text. Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: Skip to main content Explore journals Get published About BMC My account Search all BMC 0. 1 M PBS (pH 7. 4, final methanol concentration was < 1%) and injected (i. p. , at 50 mg/kg) one a day to mice in groups: and VIII. The same volume of vehicle (PBS) was injected to WT (Group I) and 5xFAD mice (Group-IV), as summarized in Table 1. Table 1 Summary of the different animal groups and treatment regimens used in this studyFull size table Tissue processingAll mice were deeply anaesthetized with an overdose of sodium pentobarbital (i. p. ), and transcardially perfused with 0. 1 M cold PBS at pH 7. 4, followed by 4% paraformaldehyde (diluted in 0. 1 M PBS at pH 7. 4) to fix the brains. The brains were then removed, suspended in 4% paraformaldehyde for 24 h at 4 °C, and transferred to the graded sucrose solutions (10, 20 and 30%). When brains were completely immersed in the 30% sucrose solution, they were stored at 4 °C until being sectioned coronally at 40 µm on a Cryostat (Leica, Germany). Cur and SLCP permeability studyTo investigate whether sufficient amounts of Cur or SLCP crossed the blood brain barrier (BBB) and reached to the regions of interest in the brain, the Cur- and the SLCP-injected 5xFAD mice (Group V–VIII) were sacrificed and their brain tissue was processed, as described above. Coronal sections (40 μM) were cut and imaged using a fluorescent microscope (Leica, Germany) to assess the amount of Cur or SLCP bound to the Aβ plaques, which was confirmed by co-localization of either the Cur or the SLCP to Aβ-specific antibody (6E10) in Aβ-plaques, as described previously [32]. To compare the permeability of Cur and SLCP in vitro, mouse neuroblastoma cells (N2a, ATCC, Catalog no: Neuro2a (ATCC® CCL131™) and the primary hippocampal neurons from a 5xFAD mouse were used. [SEP] Justify:

Output: The text does not address the claim regarding the anti-inflammatory properties of curcumin. Instead, it focuses on the methodology for examining the permeability of curcumin in the brain and its binding to Aβ plaques, which is unrelated to inflammation.


Input: Task: corroborate the claim using the given text. Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: The enriched GO terms for both the partially and fully reduced sets contained terms previously associated with thiol-based redox regulation indicating both the fully and partially reduced sets have likely redox activity (Table 2). Conformational changes associated with redox activity Having established the Redox-Pair dataset is enriched in proteins involved in redox-regulated processes, we studied conformational changes between redox pairs of proteins. For many proteins in the data set there were negligible conformational differences between the SG atoms of each Cys residue of the reduced and oxidized states (see Fig. 2). For this group, other factors may be required for, or preclude, conformational changes in these proteins. Crystal packing forces, for example, may prevent a subsequent conformational change after cleavage of the disulfide by synchrotron radiation. For another group, the small distance changes of 2–4 Å observed are most likely due to rotation of one or both Cys sidechains toward each other to form the SS bond. Some of the proteins exhibiting these small conformational changes are oxidoreductases with catalytic thiols such as thioredoxin, thioredoxin reductase, and protein disulfide isomerase. Figure 2Open in figure viewerPowerin disulfide separation in protein Redox Pairs. Excluding interchain disulfides, around 21% of redox structure pairs have a change of over 1 Å in the sulfur atom separation between the oxidized and reduced structures. Maximal intrachain differences of up to 18. 8 Å were apparent in 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXP reductoisomerase) and the RNA sulfuration enzyme TrmU. 39 For proteins which exhibit major conformational changes, four classes were identified based on the nature of the change. These groups were: proteins that oxidize disulfides following expulsion of metals such as Zn; proteins that exhibited major reorganization or “morphing” of portions of the polypeptide backbone in association with disulfide redox-activity; proteins that exhibited order/disorder transitions; and proteins that exhibited changes in quaternary structure. Redox sites associated with zinc and other metals Redox regulation of proteins that form disulfides following expulsion of Zn is an emerging area of signaling. [SEP] Justify:

Output: The text corroborates the claim by discussing how conformational changes in proteins can occur due to redox activity, which can be influenced by mechanical stress. It indicates that while some proteins show negligible conformational differences, others exhibit significant changes associated with their structural properties, including factors like disulfide bonds and interactions like folding or morphing. Specifically, the text states, 'four classes were identified based on the nature of the change,' which implies that mechanical stressors and redox reactions can lead to various types of conformational changes in proteins.


Input: Task: contrast the claim using the given text. Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: NAO (indirectly) and IPO show characteristics of surface water temperatures in the Atlantic and the Pacific respectively, but they are also part of a teleconnection system and therefore exert force on other part of the global surface temperature system. (NAO is measured as sea surface pressure difference, but it is associated with sea surface temperatures in the literature). If GTA is restricted to the surface system, the oceanic deep waters will be a force outside this system. However, the referee is right, presently all the ocean waters are treated as one system. Text will be changed. R. The conclusion that CO2changes are as important as volcanic eruptions is ridiculous, if your account for the magnitude of their forcings, except for the period since 1850 when CO2and other greenhouse gases dominate. Response. The role of CO2 in the atmosphere before, say 1850, has been revised in recent literature. It is probably not as small as previously believed. For example, Hansen et al. (2023) states that “We infer from paleoclimate data that aerosol cooling offset GHG warming for several millennia as civilization developed” The authors suggest that the effects of aerosols and GHG were comparable. However, their suggestions are discussed further in subsequent literature. R. The claim on lines 529-530 that “Volcanic eruptions instigated directly or indirectly increases in atmospheric CO2concentrations for 136 ±42 years” is completely wrong and based on statistical artifacts of the analysis that have no basis in physics. Response. We give the source for the time series for CO2 around line 140. To our knowledge, it is developed without 0. 1,2) smoothed version of the raw curve (Line 228, to avoid possible high frequency noise) and the droplines shows volcanic eruptions. KLS remade the calculations the result is correct, and the calculations are available from him. ) We do not know what artefacts the referee refers to. R CO2 emissions from volcanic eruptions for the past 2000 years have been very small. They have been important for massive flood basalt eruptions, but the contribution from eruptions during the period studied is trivial. Response. We quote Werner et al. (2019) and Buono et al. (2023). We should not have restricted the Werner reference to one figure. Did we misunderstand the information in the Werner 401. N. R. (1952). What is science? [SEP] Justify:

Output: The text contrasts the claim by stating that CO2 emissions from volcanic eruptions for the past 2000 years have been very small and that their contribution is trivial, particularly in the context of atmospheric changes. It emphasizes that while massive flood basalt eruptions may have had significant effects, typical eruptions do not contribute meaningfully to global cooling. This directly counters the assertion that all volcanic eruptions induce immediate cooling effects.


Input: Task: pass the claim using the given text. Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: The N2a cells were grown with minimum essential medium () containing 10% heat-inactivated fetal bovine serum (FBS), and penicillin and streptomycin (100 I. U. /mL and 100 μg/mL). The culture was maintained at 37 °C in a humidified atmosphere at 5% CO2. The primary hippocampal neurons were taken from embryonic-16 (E16) mouse pups and grown in neurobasal media containing B27 supplementation for 7 days in vitro (7-DIV), as described previously [42]. Prior to the experiment, the cells were grown in either in 60 mm Petri dishes or on glass coverslips, using fresh MEM or neurobasal media that lacked growth factors. The cells were then treated with 100 μM of either Cur or SLCP for 2 h, after which the media was removed, and the cells were fixed with 4% paraformaldehyde solution. Microphotographic images were taken using a fluorescent microscope (Leica, Germany) with appropriate excitation/emission filters for analyses. Aβ plaque load in 5xFAD after treatment with Cur or SLCPTo check the effects of acute treatment of Cur or SLCP on Aβ plaque burden, the 5xFAD brain sections were stained with Cur and the number of Aβ plaques were counted in these sections. Cur was used to label Aβ plaques, because it labels plaques as efficiently as Aβ-specific antibody [32]. Using Image-J software ( the total area of each image was measured and the numbers of Aβ plaques were counted manually in PFC and DG area of hippocampus and expressed as number of Aβ plaques per 100 µm2 area. Only clearly visible, large fluorescent signals were considered as Aβ plaques. A minimum of 10 serial sections, with forty different fields were used to count the number of Aβ plaques in each group (n = 4), with the experimenters blinded to the group identity of the specimens analyzed. Neuronal morphology by cresyl violet stainingOne of the aims of this study was to investigate whether short-term treatment of Cur or SLCP can protect the neuronal morphology, especially in hippocampal subfields and in the PFC area. To this end, the tissue from 5xFAD mice that were treated with Cur or SLCP was stained with 0. [SEP] Justify:

Output: The text does not provide information that directly supports or contradicts the claim regarding curcumin's anti-inflammatory properties. It mainly describes the experimental setup and methodology relating to the treatment of N2a cells and the examination of Aβ plaques without specifically addressing the anti-inflammatory effects of curcumin.


Input: Task: corroborate the claim using the given text. Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: Further inspection of proteins with likely redox-active Zn sites reveals that two forbidden disulfide motifs, the Disulfide (JSD) and a type of β-diagonal disulfide (BDD),12 are repetitively associated with redox-active Zn-binding sites in the dataset. Oxidized structures that contain a BDD include isoleucyl tRNA synthetase (1ile 180–184, 502–504), the apoptosis-related proteins birc8 and survivin (1xb1, 300–303;1f3h, 57–60), aspartate transcarbamylase (1r0b, 138–141) and the DNA repair enzyme RecR (1vdd, 57–60). Oxidized structures that contain a JSD include the amino-acyl tRNA synthetases for Leu and Ile (1obh, 439–484; 1jzs, 461–502), the enzymes of sulfur metabolism MetH and BHMT (1q7m, 207–273; 1lt7, 217–300) and GTP hydrolase GTPhI (1gtp, 110–181). Morphing transitions in the dataset A large group of proteins in the dataset were observed to undergo plastic deformations involving large scale rearrangements of the polypeptide backbone. We refer to these conformational changes as morphing transitions. These transitions, which typically involve unraveling portions of secondary structure, are illustrated in Figure 4 and in animations in the Supporting Information. The well known redox-sensitive protein OxyR belongs to this group. In OxyR, a protein of 305 residues, significant refolding of the C-terminus occurs involving residues 196–221. 23 In the reduced structure, residues 200–204 form a short 310 helix flanked by regions of coil. Upon oxidation, residues 196–221 adopt a different fold with residues 189–193 and 213–218 forming two parallel β-strands joined by a loop with a disulfide-linkage between Cys199 and Cys208. In the reduced OxyR structure, the two Cys that form the disulfide are separated by almost 13 Å. Cys 199 in OxyR is known to undergo alternate modifications such as glutathionylation. [SEP] Justify:

Output: The text corroborates the claim by describing how proteins undergo 'morphing transitions,' which involve 'plastic deformations' and 'large scale rearrangements of the polypeptide backbone.' This emphasizes that mechanical or external stress can indeed lead to conformational changes in the protein structures, supporting the idea that such stress results in structural alterations.


Input: Task: pass the claim using the given text. Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: Dover Publications. Cheng, L. J. , Abraham, J. , Trenberth, K. E. , Boyer, T. , Mann, M. E. , Zhu, J. , Wang, F. , Yu, F. J. , Locarnini, R. , Fasullo, J. , Zheng, F. , Li, Y. L. , Zhang, B. ,. . . Lu, Y. Y. (2024). Indicators in 2023. Advances in Atmospheric Sciences, 41(6), 1068-1082. J. E. , Sato, M. , Simons, L. , Nazarenko, L. S. , von Schuckmann, K. , Loeb, N. G. , Osman, M. B. , 9, Gary Russell, Junji Cao, & Li11, J. (2023). Global warming in the pipeline. Climate Change, 3. . , & Trenberth, K. E. (2013). and with the Oscillation. Journal of Climate, 26(18), 7298-7310. G. H. , Geirsdóttir, A. , Zhong, Y. F. , Larsen, D. J. , Otto-. , Björnsson, H. , & Thordarson, T. (2012). Abrupt onset of the Age triggered by volcanism and sustained by sea-ice/ocean feedbacks. Letters, 39. L02708 10. 1029/2011gl050168& Wilcox, L. J. (2024). 2023 temperatures reflect steady global warming and internal sea surface temperature variability. & Environment, 5(1). 460 10. 1038/s43247-024-01637-8Werner, C. , Fischer, T. , Aiuppa, A. , Edmonds, M. , Cardellini, C. , Carn, S. , & Allard, P. (2019). Emissions from Regions: in Review. In B. Orcutt, I. Daniel, & R. Dasgupta (Eds. ), Deep Carbon: Past to Present (2. 18 10. [SEP] Justify:

Output: The text does not address the claim regarding volcanic eruptions and their impact on global cooling. Instead, it appears to be a bibliographic citation comprised largely of names and publication details, lacking relevant information to support, contrast, or clarify the claim.


Input: Task: pass the claim using the given text. Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: 1% cresyl violet, as described previously [43]. The sections were washed, dehydrated, cleared, mounted, and coverslipped using DePex mounting media (). The slides were dried, after which photomicrographs were taken using a compound light microscope (Olympus, Japan) with 100× objectives (total magnification of 1000×). The number of pyknotic, or tangle-like, cells were counted manually using Image-J software ( and were expressed as number of pyknotic cells per 100 µm2 area. A minimum of 5 serial sections, each with 10 different fields, were used for counting the number of pyknotic cells in each group (n = 4), with the experimenters blinded to the group identity of the specimens being analyzed. Neuroinflammation study by immunohistochemistryTo compare the anti-inflammatory effects of Cur or SLCP in 5xFAD mice, the brain tissue from each mouse was labeled with GFAP and Iba-1, which are the markers for activated astrocytes and microglia, respectively. GFAP-immunohistochemistryA subset of brain sections were rinsed three times with 0. 1 M PBS (pH 7. 4) for 5 min each. The sections were then blocked with 10% normal goat serum for 1 h at room temperature with gentle shaking. The tissue was incubated overnight on a shaker at 4 °C with GFAP antibody (rabbit polyclonal, 1:500). On the next day, the sections were thoroughly washed with PBS, three times, for 10 min each. The sections were incubated with anti-rabbit secondary antibody (1:1000), tagged with Alexa-594 (Molecular Probes, OR), for 30 min at room temperature. Then sections were washed thoroughly with distilled water, dehydrated, cleared and mounted on slides using anti-fading Fluoro-mount aqueous mounting media (Sigma) prior to microscopic examination using a fluorescence microscope (Leica, Germany) with the appropriate excitation/emission filters. Iba-1 immunohistochemistrySimilarly, for Iba-1 immunohistochemistry, another subset of brain section were thoroughly rinsed, three times with 0. 1 M PBS (pH 7. 4) for 5 min each. [SEP] Justify:

Output: The text does not address the claim regarding curcumin's anti-inflammatory properties. Instead, it focuses on experimental procedures related to neuroinflammation studies, mentioning immunohistochemistry techniques and markers for activated astrocytes and microglia without any reference to curcumin or turmeric.


Input: Task: corroborate the claim using the given text. Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: coli DNA polymerase III τ 20-1xxh; Rhodobacter capsulatus xanthine dehydrogenase 21-1jrp. Metal in all structures is Zn unless specified otherwise. Metal atoms in structure 21 are Fe atoms in Fe-S cluster. Figure 4Open in figure viewerPowertransitions in protein Redox Pairs. A: A large morphing transition in the chloride channel CLIC1: a protein that forms ion channels by inserting itself into membranes in response to oxidation. B: A smaller morphing transition in cyclic phosphodiesterase (CPDase) a protein involved in the tRNA splicing pathway of yeast, plants and vertebrates. Redox activity of the disulfide modulates access to the active site. 59 Oxidized structures are shown on the left. Reduced structures are on the right. The region of the polypeptide chain between the two redox-active Cys is shown in green in the oxidized structure and red in the reduced structure. Other morphing regions are shown in blue. C: Flocco-Mowbray diagram for CLIC1 (left) and CPDase (right). Y-axis SFMI-Smoothed Flocco-Mowbray Index. The polypeptide chain is coloured according to the corresponding oxidized structure. Redox-active thiols are indicated with open squares. Animations of the conformational changes in CLIC1 and CPDase are included in the Supporting Information. To determine whether the oxidized structure of OxyR is indeed an oddity, or if other proteins exhibit similar conformational changes, we systematically searched for morphing proteins in the dataset by scanning for protein structure pairs that exhibited large differences of the backbone torsional angles over at least seven contiguous residues. Changes in pseudo-dihedral angles calculated using four consecutive Cα atoms exceeding a summed threshold of 1000 degrees over seven consecutive residues were used to detect changes in secondary structure. Twenty-two parents were found in the fully reduced set and four in the partially reduced set (designated m in Table 1). Proteins showing the largest conformational changes are in Table II. [SEP] Justify:

Output: The text provides insight into conformational changes in proteins, specifically mentioning 'a large morphing transition' in the chloride channel CLIC1 and a 'smaller morphing transition' in cyclic phosphodiesterase (CPDase). Furthermore, it discusses how redox activity modulates access to active sites, suggesting that external factors, potentially including mechanical stress, can influence structural changes in proteins. This supports the claim that such changes can be induced.


Input: Task: contrast the claim using the given text. Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: These responses are partly dependent on the climate state prior to an eruption, as well as the location of the volcano and the season of eruption (Stevenson et al. 2017). While much attention has focused on short-term variability, less is known about the influence of longer-term changes in the background climate (Zanchettin et al. 2013). The future response to an eruption may be different because of changes in the climate system caused by anthropogenic warming. Aubry et al. (2016) have recently shown that warming-induced changes in the vertical structure of atmosphere (particularly changes in the tropopause height) would impact on the rise of volcanic plumes, but the impact of future changes on the radiative forcing and response to a volcanic eruption has not been quantified. Here we analyse an ensemble of comprehensive model simulations of a large volcanic eruption to evaluate the climate system response to a large volcanic eruption in a future climate state. We performed an ensemble of simulations with the HadGEM2-ES model (HadGEM2 2011; Collins et al. 2011) of a Tambora 1815 -like eruption in pre-industrial (Kandlbauer et al. 2013) and Pathway 6. 0 (RCP 6. 0) conditions for the years AD1860 and AD2045, respectively. Tambora was chosen because it provides a very strong forcing which can be more easily separated from simulated internal variability. 2 MethodsTo simulate the climatic impact of a volcanic eruption we use the 2 (HadGEM2-ES). This a coupled atmosphere-ocean general circulation model (GCM), which includes terrestrial and ocean carbon cycle components, interactive tropospheric aerosols and an interactive tropospheric chemistry scheme (HadGEM2 2011; Collins et al. 2011). The atmospheric resolution of the model is 1. 875 × 1. 25° (longitude-latitude), with 38 vertical levels reaching to just over 39 km, with 11 levels above 15 km and resolving the lower stratosphere. The ocean resolution is 1° horizontally, but this increases in the latitudinal direction to 1/3° in the tropics, and has 40 unequally spaced vertical levels. HadGEM2-ES includes an interactive sulphur cycle as well as representations of biomass burning, sea-salt, mineral dust and fossil fuel black and organic carbon aerosols (Bellouin et al. 2011). [SEP] Justify:

Output: The text contrasts the claim by discussing the dependency of climate responses to volcanic eruptions on various factors, such as the climate state prior to an eruption, the volcano's location, and the season of eruption. It implies that not all eruptions lead to uniform climatic impacts or immediate global cooling, acknowledging complexities such as anthropogenic warming that may alter responses to eruptions.


Input: Task: pass the claim using the given text. Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: The sections were then immersed in a solution of 3% hydrogen peroxide and 0. 1 M PBS (pH 7. 4) for 30 min at room temperature to inhibit endogenous peroxidase. Then the sections were rinsed with PBS and blocked with 10% normal goat serum (NGS), which underwent gently shaking for 1 h at room temperature. The tissue was then incubated with Iba-1 antibody (rabbit, monoclonal, 1:4000) with gentle shaking for 4 h at room temperature and then for overnight at 4 °C. On the next day, the sections were thoroughly washed 3 times for 5 min each, and incubated with biotinylated anti-rabbit secondary antibody (1:250) for 1 h at room temperature. Finally, the sections were incubated with peroxidase substrate solution, supplied with the ABC kit (Vector Laboratory, CA), and the signal was developed using diaminobenzidine (DAB) until the desired staining intensity emerged. The tissue was then washed, dehydrated with graded alcohol, cleared with xylene, mounted on slides, coverslipped with DePex (), air dried, and visualized using a compound light microscope (Olympus, Japan) with 20× objectives (total magnification 200×). Quantification of GFAP-IR and Iba-1-IR cellsFor quantification of GFAP-IR and Iba-1-IR cells, the sections were imaged using a fluorescent microscope (Leica, Germany) and a compound light microscope (Olympus, Japan), respectively. The number of GFAP-IR and Iba-1-IR were counted manually using Image-J software ( Briefly, the images were taken from randomly selected regions of the layer IV/V of PFC (bregma +3. 20 mm), striatum (bregma +1. 00 mm), subicular complex, hippocampus (CA1, CA3 and dentate gyrus) at bregma −3. 30 mm, and the entorhinal cortex (bregma −3. 30 mm), using 20× objectives (total magnification at 200×). The total area of each image was measured and the numbers of GFAP-IR and Iba-1-IR cells were counted manually in those areas. [SEP] Justify:

Output: The text is irrelevant to the claim because it provides a detailed description of a laboratory procedure for tissue processing and quantification of specific immunoreactive cells but does not mention curcumin, turmeric, or any anti-inflammatory properties.


Input: Task: corroborate the claim using the given text. Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: These proteins include the Cl− channel CLIC1: a protein that forms ion channels by inserting itself into membranes in response to oxidation; the detoxification enzyme arsenate reductase, which undergoes multiple conformational changes associated with a disulfide relay as part of its reaction cycle17, 61 and cyclic phosphodiesterase, a tRNA-splicing enzyme where the disulfide modulates access to the active site. 59 Like OxyR, several of these proteins exhibit large changes in Cα separations of the two Cys between alternate redox states (Table II). Thus large physical separation of the reduced Cys pair seems to be a common feature of many of these proteins and does not preclude disulfide formation. Table II. Proteins with region ΔSG Å → Oxidized ox re EcOxyR 199–208 1i6a 1i69 281–298 15. 9 Helix, coil to sheet HsCLIC1 24–59 1rk4 1k0m 27–56 13. 5 Sheet to helix, coil VpChpP 424–493 1v7v 1v7w 483–499 10. 8 Strand to coil SaArsC 82–89 1lju 1jf8 81–95 10. 7 Helix to coil AtCPDase 104–110 1fsi 1jh6 99–119 9. 0 C-term of helix to coil Aebcp 49–54 2cx3 2cx4 44–60 7. 6 Helix to β-hairpin Hs/RnPhe hydroxylase 203–334 1tdw 1phz 131–149 7. 2 Helix to coil HsAKT 60–77 1unr 1unq 39–53 6. 8 Helix to coil SaArsC 10–82 1lk0 1jf8 80–94 5. 7 Helix to coil HsSSAT 120–122 2b5g 2g3t 145–147,155–170 5. 2 Coil to strand transition HsIL2 58–105 1m48 1m4a 29–36, 71–87 5. 1 Coil to N-term of helix 26–459 1meh 1pvn 317–327,412–435 5. [SEP] Justify:

Output: The text corroborates the claim by discussing several proteins, including the Cl− channel CLIC1 and arsenate reductase, that undergo multiple conformational changes associated with physical and redox states. It indicates that the large physical separation of certain cysteine pairs in these proteins is commonplace, which implies a response to mechanical or oxidative stress, thus supporting the idea that mechanical stress can induce conformational changes.


Input: Task: contrast the claim using the given text. Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: The fields have been masked (grey shading) where they are not significant at the 95% level according to a 2-sided Student’s t-test. For the transient RCP6 simulations, the same years (i. e. with the same greenhouse gas concentrations) are comparedFull size image There are also significant changes in the SW cloud response over the same ocean basins (Fig. 3i). Comparing the no-eruption pre-industrial and RCP6 simulations, the cloud coverage is generally reduced by around 2–3%. The removal of high albedo cloud reveals darker underlying surface and hence would increase the effective volcanic forcing, because it makes the troposphere darker and so more prone to the influence from increases in stratospheric aerosols. This is the opposite of the modelled response over the Atlantic and basins. These regions correspond with the areas of largest relative increase in sulphate aerosol loading and biomass burning aerosol, as indicated by increased aerosol optical depth shown in Fig. 4. Since both sulphate and biomass burning aerosols can influence the cloud properties via parameterised indirect aerosol effects in HadGEM2-ES, the simulated changes in cloud properties between the pre-industrial and RCP6 are consistent with the large increase in aerosol loading over these regions. Therefore, changes in cloud top effective p3. is an updated version of the radiation code used in the Unified Model, including in HadGEM2-ES (Edwards and Slingo 1996). As the largest change in the SW flux is over the Indian and Atlantic oceans, we configured a single column profile with appropriate conditions. We prescribed a uniform cloud layer from 400–150 mbar, with optical properties derived from HadGEM2-ES effective cloud top radius and liquid water content. A single uniform layer of tropospheric sulphate [partitioned into aitken and accumulation modes with a ratio of 3:2, as in Fig. 5 of Bellouin et al. (2007)] is distributed from the surface to 500 mbar. The solar zenith angle is set to 55\(^\circ\), corresponding to the insolation weighted-mean (Cronin 2014). Paired simulations are performed with the second including a single volcanic stratospheric aerosol layer with a mixing ratio chosen to represent the volcanic aerosol layer of approximately the density of Tambora eruption as simulated with HadGEM2-ES. [SEP] Justify:

Output: The text contrasts the claim by discussing changes in cloud properties and aerosol loading in response to volcanic eruptions, specifically mentioning how volcanic aerosols can influence climate by altering cloud coverage and effective volcanic forcing. It indicates complex interactions and suggests that not all responses lead to the immediate global cooling implied in the claim.


Input: Task: pass the claim using the given text. Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: Only clearly visible fluorescent signals or brown DAB color were considered as GFAP-IR and Iba-1-IR cells, respectively. The GFAP-IR and Iba-1-IR cells were expressed as number of cells per 100 µm2 area. A minimum of 10 serial sections, from which thirty different fields were used to count the number of GFAP-IR and Iba-1-IR cells in each group, using four different animals in each group with the experimenter blinded to the group identity of the specimens analyzed. Comparative study of inhibition of Aβ42 aggregation by Cur or SLCPTo compare the anti-amyloid activity, such as inhibition of Aβ42 oligomer and fibril formation by Cur or SLCP, the dot blot assay was used [14]. Briefly, Aβ42 peptide was dissolved in HFIP, vortexed for 1 min and allowed to solubilize for 30 min at room temperature. Then, the HFIP was evaporated under laminar hood, until the peptide was completely dried to make a thin film. This was followed by speed-vacuuming for 10 min [42, 44], after which the film was stored at − 20 °C. Each HFIP film was dissolved in 60 mM NaOH (final concentration 6 mM) and diluted with Tris-buffer saline (TBS, 0. 1 M, pH 7. 4, 0. 025% NaN3) to get the desired peptide concentration (10 μM). Then 50 μL of peptide solution (10 μM) was taken in Eppendorf tube and incubated, with or without different concentrations of Cur or SLCP (in μM: 1, 0. 1, 0. 01, 0. 001), for 8-, and 24-h at 37 °C, with gentle shaking (200 rpm). After the stipulated period of incubation, about 10 μL of peptide solution was spotted on nitrocellulose membrane (Bio-). [SEP] Justify:

Output: The text does not provide information relevant to the claim about curcumin's anti-inflammatory properties. Instead, it focuses on experimental methods for analyzing the inhibition of amyloid beta aggregation by curcumin, but does not explicitly mention any anti-inflammatory effects.


Input: Task: corroborate the claim using the given text. Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: 0 Helical phase shift, helix to coil RnPR-1 Ppase 49–104 1x24 12cl 20–30,46–56,103–110 4. 9 R1 helix to coil, R3 coil to helix EcMurD 208–227 1uag 1eeh 345–354 4. 6 Helix to coil transition HepCRNA polymerase 1a 303–311 1nhu 1c2p 303–318 3. 8 β-hairpin straddled by disulfide (motif C) curls in oxidized structure TtLeu-tRNAs 439–484 1obh 1h3n 150–193, 436–447, 539–546 3. 8 Sheet melts, helical phase shift EcATCase 114–141 1tug 1d09 45–58 3. 7 Coil to helix transition HepCRNA polymerase 2b 316–366 1yvx 1yuy 19–38, 445–451, 539–546 3. 6 Helix to coil HsTSP1 153–214 2es3 1za4 17–29 3. 1 Coil to helix transition MmActivin receptor 86–91 1bte 2goo 58–73, 87–94 3. 0 R1 helix to coil, R2 coil to helix Schem13 193–193a 1txn 1tkl 40–60, 187–202 NA R1 coil to strand, R2 coil to helix/strand HsDNA pol III λ 543–543a 1xsl 1xsn 460–474 NA Strand to coil HsActivin 80–80a 2arv 2arp 20–27, 65–79 NA R1 helix to coil transition R2 coil to extension of C-term helix HsRXR 269–269a 1g5y 1fm9 242–264,433–451 NA Coil to helix R2 Transitions are expressed from reduced to oxidized but are likely to be reversible. Structures where change in SG separation is caused by quaternary structure changes are indicated as NA. [SEP] Justify:

Output: The text corroborates the claim by detailing various transitions in protein structures under mechanical stress, including 'Helical phase shift' and transitions from 'helix to coil' and 'coil to helix.' These descriptions indicate that mechanical stress can indeed lead to conformational changes, supporting the claim.


Input: Task: contrast the claim using the given text. Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: The emergence of mid-latitude warming in the second half of winter only in response to the future eruption is replicated here as in the fully coupled simulations. We therefore conclude that changes in surface conditions, most likely the relatively extreme high-latitude sea-ice expansion in the early winter in the future eruption may be responsible for this behaviour in the model. However, more model ensemble members are required to comprehensively evaluate the robustness of the results in the coupled model, and to clarify the mechanisms underlying this aspect of the model’s response (Pausata et al. 2016; Bittner et al. 2016) (Table 1). Fig. 10Summer (JJA) sea-surface temperature anomalies (\(^\circ\)C) for the past (left) and future (right) ensemble-mean 5-year mean eruption responseFull size image These simulations show that the different spatial patterns of sea-ice expansion may be able to explain the post-eruption winter warming response simulated in response to the future eruption. Since the winter-warming persists for at least 5 years after the future eruption, it suggests that the mechanism involved is distinct [e. g. Zanchettin et al. (2012, 2013)] from that which causes the 1-year post-eruption winter-warming observed during the past century (Robock and Mao 1992; Zambri and Robock 2016). This mechanism requires further evaluation with a larger ensemble of eruption simulations. 3. 6 Other earth system impactsAlthough cooling is reduced for a future volcanic eruption, much of any societally-relevant climatic impact stems from changes to the hydrological cycle. Thermodynamic arguments would predict a reduced hydrological response in the future eruption because of the more limited cooling, but the precipitation change is more complex, reflecting the role of dynamical changes. In central Europe the pre-industrial eruption simulation shows increased summer cloudiness and precipitation in agreement with observations from 1816 (Auchmann et al. 2012) and mechanistic arguments (Wegmann et al. 2014). The future simulation shows a similar though less widespread response (Fig. 9). In contrast, a significant precipitation reduction over tropical after the pre-industrial eruption is not simulated in the future eruption response, because of a more muted sea-surface temperature response in the tropical Atlantic (Fig. 10). This is caused by the reduced effective volcanic forcing in this region discussed in Sect. 3. 3. [SEP] Justify:

Output: The text contrasts the claim by discussing scenarios where the climatic impact of volcanic eruptions is more complex than just immediate global cooling. It indicates that while some cooling occurs, future volcanic eruptions may show reduced cooling effects and can lead to warming responses, particularly highlighted by the statement that 'cooling is reduced for a future volcanic eruption.' This implies that not all volcanic eruptions lead to immediate global cooling, challenging the absolute nature of the claim.


Input: Task: pass the claim using the given text. Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: Then, the membrane was blocked with 5% nonfat milk in TBS-Tween-20 (TBS-T) at room temperature for 1 h, washed with TBS-T, and probed with Aβ-oligomer (A11) and Aβ fibril (OC) specific antibodies (rabbit polyclonal, 1: 1000) in 5% non-fat milk powder in TBS-T overnight at 4 °C. After washing, it was probed with anti-rabbit horseradish-peroxidase (HRP) conjugated secondary antibody solution (1: 25,000, ) for 1 h at room temperature. After washing three times, the blot was developed with (GE-) for 2–5 min. The dot blots were scanned using gel documentation system (Bio-), and the optical density of each dot was measured using Image-J software ( analysisThe morphometric data for GFAP-IR and Iba-1-IR in different brain areas were expressed as mean ± SEM. All data were analyzed using one way analysis of variance (ANOVA) with Tukey HSD (honest significant difference) post-hoc tests being conducted when appropriate. A probability value ≤ 0. 05 was considered as statistically significant. ResultsComparison of permeability of Cur or SLCP to the brain tissueTo compare the permeability of Cur or SLCP after their injections (i. p. ) for 2 or 5 days, the 5xFAD mouse brains were sectioned and observed under a fluorescent microscope. We observed that both Cur and SLCP crossed the BBB and bound with Aβ plaques after 2- and 5-days of injections (Fig. 1a) and co-localized with Aβ-specific antibody (6E10) (Fig. 1b). We also found that SLCP showed more permeability than Cur, as assessed by intensity of fluorescent signals that were bound with Aβ plaques. In addition, those mice receiving 5 days of treatment showed increased Aβ plaque labeling when compared to those receiving 2 days of treatment for both the Cur and SLCP groups (Fig. 1a). Similarly, a trend towards more solubility and greater permeability was observed after 2 h exposure of SLCP over Cur with N2a and primary hippocampal neurons at 7 days in vitro (Additional file 1: Fig. S1). [SEP] Justify:

Output: The text does not address the claim about curcumin's anti-inflammatory properties. Instead, it discusses the permeability of curcumin (Cur) and a specific formulation (SLCP) across the blood-brain barrier (BBB) and their binding to Aβ plaques without making any claims about anti-inflammatory effects. Thus, the text is irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: ox, oxidized structure; re, reduced structure; AKT, Rac-alpha serine/threonine kinase; ArsC, arsenate reductase; ATCase, aspartate carbamoyltransferase; bcp, bacterioferritin comigratory protein; ChpP, chitobiose phosphorylase; CLIC1, chloride intracellular channel protein 1; CPDase, cyclic nucleotide phosphodiesterase; DNA pol III λ, DNA polymerase III λ; hem13, coproporphyrinogen III oxidase; IL2, interleukin 2; IMPDH, inosine monophosphate dehydrogenase; Leu-tRNAs, leucyl-tRNA synthetase; MurD, UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase; OxyR, hydrogen peroxide-inducible genes activator; PR-1 Ppase, protein tyrosine phosphatase 4a1; RXR, retinoic acid receptor; SSAT, spermidine/spermine N1-acetyltransferase; TSP1, thrombospondin-1; Ae, Aeropyrum pernix, At, Arabidopsis thaliana; Ec, E. coli; HepC, Hepatitis C; Hs, Homo sapiens; Mm, Mus musculus; Rn, Rattus norvegus; Sa, Staphylococcus aureus; Sc, Saccharomyces cerevisiae; Tf, Tritrichomonas foetus; Tt, Thermus thermophilus; Vp, Vibrio proteolyticus. a 2nd Cys residue is in another chain (interchain disulfide). Order/disorder transitions Another recognizable group of conformational changes involves order/disorder transitions. In these transitions, alternate redox states of the protein correlated with differing amounts of disorder in the protein structure, as evidenced by missing electron density. A total of 282 redox pair structures in 27 parents exhibited order/disorder transitions correlated with the redox state of the disulfide (Table III, Fig. 5). [SEP] Justify:

Output: The text corroborates the claim by discussing 'order/disorder transitions' as a form of conformational change in proteins that is correlated with differing amounts of disorder. It mentions that 'alternate redox states of the protein' are linked to these transitions, implying that external factors such as mechanical stress can indeed induce changes in protein structures.


Input: Task: contrast the claim using the given text. Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: The nature of the aerosol-cloud interaction strength is also highly uncertain (Carslaw et al. 2013). Although, HadGEM2-ES is one of the best models in CMIP5 [see Fig. 9. 7 by Flato et al. (2013)], and is close to the mean response (in terms of aerosol effects) when compared with 8 other models used in CMIP5 (Zelinka et al. 2014), the strength of the aerosol-cloud interactions in the model are controversial (Booth et al. 2012; Zhang et al. 2012). A newer version of the Unified model which predicts p1. 5 km, so that smaller more frequent eruptions would more easily penetrate the stratosphere, following the mechanism outlined by Aubry et al. (2016). Summers are nearly ice-free under RCP6 in 2050 in these simulations. Further into the future, the sea-ice response to an eruption will be larger given projected further reductions in annual sea-ice extent (Stroeve et al. 2012). In a sufficiently warm future state with no sea-ice year-round, an eruption might not cause any significant sea-ice formation. In this case, other cloud-related climate feedbacks may instead be more important (Abbot and Tziperman 2008). Our conclusions regarding the dynamical post-eruption response are supported by separate atmosphere-only simulations. Despite this, the small ensemble size of our study, hinders comprehensive conclusions regarding the dynamical responses in the northern hemisphere extra-tropics. Whilst the differences in temperature anomalies between the pre-industrial and future (as shown in Fig. 2) strongly suggest dynamical differences between the two time periods, the limited size of our ensemble does not allow us to unequivocally rule out internal model variability. Therefore, a more thorough analysis of this aspect of the modelled response would require further simulations to produce a larger ensemble size (Pausata et al. 2015; Bittner et al. 2016). There are a limited number of observed large eruptions, as well as difficulties in separating El Niño-(ENSO) related climate effects from volcanic eruptions. Further, general circulation models (including HadGEM2-ES) had been thought to under-estimate the observed post-eruption northern hemisphere winter dynamical response (Driscoll et al. 2012; Charlton-Perez et al. [SEP] Justify:

Output: The text contrasts the claim by discussing the uncertainty surrounding the aerosol-cloud interaction strength following volcanic eruptions and emphasizes that not all eruptions have the same effects on climate. It mentions that the model's predictions indicate that smaller, more frequent eruptions may not cause significant impacts, especially in a future state where sea-ice formations are minimal. This suggests variability in the effects of volcanic eruptions, contradicting the assertion that all such events cause immediate global cooling.


Input: Task: pass the claim using the given text. Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: 3a–c) and fibril formation (Fig. 3d–f). However, SLCP treatment showed significantly greater inhibition (p < 0. 01) of Aβ42 fibril formation after 24 h of treatment than did Cur (Fig. 3d–f). Fig. 2Acute treatment of either Cur or SLCP reduced Aβ plaque loads in 5xFAD mice brain. a The 5xFAD mice were treated with Cur or SLCP for 2- or 5-days, sacrificed, and their brains were sectioned on a cryostat and stained with Cur, which labeled the Aβ plaques that were observed in the PFC and the DG area of the hippocampus. Scale bar indicates 250 µm and is applicable to the other images. b Cur binds to Aβ plaques in a manner similar to Aβ-specific antibody (6E10), so it was used for labeling and counting Aβ plaques in this study. Scale bar indicates 100 µm and is applicable to the other images. c, d The number of Aβ plaques were significantly decreased (**p < 0. 01) in both the PFC (c) and the DG area of the hippocampus (d) in comparison to untreated 5xFAD miceFull size image Fig. 3SLCP inhibits Aβ fibril formation greater than does Cur. Aβ42 peptide was dissolved in HFIP, and after being completely dried, it was dissolved in 60 mM NaOH and diluted with Tris buffer saline (1 mM, pH 7. 4), yielding a 10 μM concentration. Fifty microliter of peptide solution was incubated with, or without, different concentrations of Cur or SLCP for 8- and 24-h. After the stipulated period for each experiment, about 10 μL of peptide solution was spotted on the nitrocellulose membrane. The blots were probed with Aβ-oligomer specific (A11) and fibril specific (OC) antibodies. a–c inhibition of Aβ42-oligomer formation by Cur and SLCP. d–f Aβ42 fibril formation was attenuated by Cur and SLCP after 24 h of incubation. Note that SLCP showed greater inhibition of Aβ42 fibril formation than dietary Cur (d, e). [SEP] Justify:

Output: The text does not directly address the claim regarding the anti-inflammatory properties of curcumin. Instead, it discusses the effects of curcumin (Cur) and a compound identified as SLCP on Aβ fibril formation and plaque loads in 5xFAD mice, focusing on these specific biochemical interactions. Therefore, the text is irrelevant to the claim, which centers on the anti-inflammatory properties rather than the effects on Aβ plaques.


Input: Task: corroborate the claim using the given text. Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: coli oxidoreductase ghdB,74, 80 where helices are lost upon reduction; and the bacteriophage cell entry protein PRD181 where a small β-sheet disappears upon reduction. The amount of disorder in the chains is also of interest. For most reduced structures, the disorder introduced upon reduction of the disulfide affects less than 10% of the polypeptide chain. However, three of the four group D proteins exhibited large regions of disorder in excess of 20% of the involved protein chain. Interestingly, all were associated with a second more-ordered monomer that was oxidized. For example, the Thermotoga maritima tRNA-processing enzyme, Psi55s undergoes a spectacular loss of secondary structure in one monomer upon binding of RNA. 75 It is possible that the fully reduced state of these protein dimers is uncrystallisable and that only partially and fully oxidized oligomers are sufficiently ordered to enable structure solution. Changes in quaternary structure We also investigated whether formation of interchain disulfide bonds altered the quaternary state of proteins. Different redox states of the interchain disulfides are associated with two general types of quaternary interaction: those where the number of oligomers differs between the reduced and oxidized state; and those where the number of subunits involved in the oligomer stays constant, but the oligomerization interface changes. Pairs exhibit a mixture of the two types of quaternary change. For example, disulfide-bonded dimers of the macrophage sialoadhesin form an interface distinct from that found in trimers formed upon binding of sialosides,82 and may negatively regulate ligand binding. Twenty-nine protein clusters with intermolecular disulfide bonds exhibit changes in quaternary structure upon oxidation/reduction. Redox regulation of the quaternary state has previously been associated with cooperative behavior in proteins. For example, the HoxB5 protein binds DNA in vitro when either oxidized or reduced but formation of an intramolecular disulfide between HoxB5 monomers is necessary for co-operative binding. 83 Other well-known examples are OxyR23 and p53. 84 Several other proteins in the dataset exhibit co-operative behavior. [SEP] Justify:

Output: The text corroborates the claim by discussing various proteins that undergo conformational changes due to alterations in their redox state, which can be viewed as a form of mechanical stress. Notably, it mentions the loss of secondary structure and changes in quaternary structure in proteins as a result of oxidative and reductive states, indicating that these changes in state can induce conformational alterations in protein structures.


Input: Task: contrast the claim using the given text. Claim: All volcanic eruptions cause immediate global cooling. [SEP] Text: 2013; Bittner et al. 2016), but restricting the analysis to the first post-eruption winter and only the strongest volcanic eruptions alters this (Bittner et al. 2016; Zambri and Robock 2016). Nevertheless, an improved understanding of the dynamical response to volcanic eruptions is required to clarify the possibility of enhanced winter warming in response to future eruptions. Idealised eruption simulations with a larger range of models (Zanchettin et al. 2016) will contribute to this issue. 5 ConclusionsIndependent of several uncertainties associated with the winter warming response or the exact timing of future warming and sea-ice decline, our results show for the first time that a future large eruption will have a smaller cooling signal than would be expected in a pre-industrial state. The dominant contributing factors to the reduced cooling (increased tropospheric planetary albedo and sea-ice reduction) are both robust features of climate model projections across a range of different coupled models (Stroeve et al. 2012). However, they have not been evaluated in the context of future climate response. The lack of previous climate model-based analysis is partly because future climate change scenarios do not include volcanic eruptions despite there being about a 30% probability of a Tambora-scale eruption by 2100 (Deligne et al. 2010). The interaction between tropospheric planetary albedo and the magnitude of the direct volcanic aerosol radiative forcing has not been reported previously to our knowledge. This diminished volcanic response may, depending on the eruption magnitude, be further enhanced by the proposed effect of the tropopause height on the penetration of smaller eruption plumes (Aubry et al. 2016). Even given a reduced cooling signal, the impacts on society and ecosystems from a large eruption are in places likely to be stronger in the future because of the intensified hydrological response. More detailed assessments of the likely climate-induced impacts are required to translate the identified mechanisms into appropriate adaptation strategies. 2. 73(2011) Aerosol forcing in the CMIP5 simulations by HadGEM2-ES and the role of ammonium nitrate. J 116(D20206)(2016) The impact of wave-mean flow interaction on the polar vortex after tropical volcanic eruptions. J 121(2012) Aerosols implicated as a prime driver of twentieth-century climate variability. Nature 484(7393):228–2322300. [SEP] Justify:

Output: The text contrasts the claim by indicating that a future large volcanic eruption may have a smaller cooling signal than expected. It mentions that the dynamics of the response to volcanic eruptions can lead to variations in cooling, particularly highlighting that 'the dominant contributing factors to the reduced cooling' are linked to increased tropospheric planetary albedo and sea-ice reduction. Thus, it implies that not all volcanic eruptions necessarily cause immediate global cooling and that the impact can vary significantly depending on various climatic factors.


Input: Task: pass the claim using the given text. Claim: Curcumin, found in turmeric, has anti-inflammatory properties. [SEP] Text: Scale bar indicates 250 µm and is applicable to other imagesFull size image Cur and SLCP treatments decreased Iba-1-IR and GFAP-IR in entorhinal cortex of 5xFAD miceThe entorhinal cortex is the major input and output structure of the hippocampal formation and is involved in the maintenance of cortico-hippocampal circuits. The number of Iba-1-IR microglia were significantly decreased (p < 0. 01) in both the 2- and 5-day Cur or SLCP treatment groups (Fig. 13a, b). Significant decreases (p < 0. 01) of Iba-1-IR cells were observed in the 5-day group in comparison to 2-day group, with the SLCP-treated mice having fewer Iba-1-IR cells than those receiving Cur (Fig. 13a, b). In contrast, 2 days Cur treatment did not reduce the number of GFAP-IR astrocytes, whereas both Cur and SLCP significantly decreased (p < 0. 01) GFAP-IR after 5 days of treatment. We also found there was a significant decrease (p < 0. 01) in the GFAP-IR between the Cur and SLCP groups after 5 days of treatment (Fig. 13a, c). Fig. 13Cur and SLCP reduce neuroinflammation in entorhinal cortex in 5xFAD mice. The 5xFAD mice were treated with Cur or SLCP for 2- or 5-days, sacrificed, and their brain sections were collected and immunolabeled for Iba-1 and GFAP. The number of labeled Iba-1-IR (a, b) and GFAP-IR (a, c) cells was significantly reduced (**p < 0. 01) in the entorhinal cortex in comparison to vehicle-treated 5xFAD mice. Significant reduction in both GFAP-IR and Iba-1-IR was observed after 5 days, in comparison to those receiving 2 days, of treatment (b, c). [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses experimental results concerning the effects of Cur and SLCP treatments on Iba-1-IR and GFAP-IR in the entorhinal cortex of 5xFAD mice. While it mentions Cur (curcumin), it does not provide conclusive evidence or information specifically supporting or contrasting the claim about its anti-inflammatory properties.


Input: Task: corroborate the claim using the given text. Claim: Mechanical stress can induce conformational changes in protein structures. [SEP] Text: For example in Leu-tRNA synthetase, part of the protein chain becomes disordered upon Zn expulsion but this is not the case for all proteins with labile Zn. Redox regulation of proteins that form disulfides following expulsion of Zn is an emerging area of signaling. Well known and characterized examples including Hsp33 which is activated by Zn expulsion as part of the oxidative stress response99; and the small Tim proteins which are kept in a transport-competent state in the cytosol by conjugation with Zn. 41 Upon delivery to mitochondria, Zn is expelled from small Tim proteins which are activated by disulfide formation. Zn is not expelled from all protein Zn-binding sites with equal facility, and is probably not expelled from some sites at all under physiologic conditions. For structural Zn sites an analogous situation may exist to the bipartite distribution of redox-active and structural disulfides in proteins, with labile Zn sites being redox-active and inert Zn sites corresponding to the purely structural group. Key to Zn expulsion under oxidizing conditions is the presence of oxidation-prone Cys as a Zn ligand. Sites with more Cys are likely to be more facile. Based on the number and nature of ligands, the Zn sites detected in the dataset likely belong to the redox-active group. The repeated association of forbidden disulfides of the BDD type with labile Zn binding sites is particularly interesting because of the recent characterization of the oxidative process that leads to activation of the bacterial chaperone Hsp33. 99 The presence of the Zn center keeps Hsp33 monomeric and functionally inactive. Upon exposure to elevated temperatures, the C-terminal domain swings away from the protein's center of mass, exposing the Zn centre. The N-terminal thiols in the Zn site, Cys 232 and Cys 234, are preferentially oxidatively modified. The remaining two Cys, 269 and 272, form a disulfide of the BDD type, releasing Zn and unfolding the C-terminal domain. Unfolding the C-terminus removes a steric barrier to dimerization, activating the protein's chaperone function. The function of disulfide formation between Cys 269 and 272 in the Zn binding site has not been fully delineated. [SEP] Justify:

Output: The text corroborates the claim by discussing how mechanical stress, in the form of elevated temperatures, induces conformational changes in the protein Hsp33. Specifically, it explains that upon exposure to such stress, the C-terminal domain of Hsp33 unfolds, leading to its dimerization and activation. This demonstrates a clear example of how external mechanical factors can lead to significant structural changes in protein conformation.


Input: Task: contrast the claim using the given text. Claim: All volcanoes are formed on land and never underwater. [SEP] Text: Skip to content (Set) PUSH (Seismic Hazard) STAMP (SiTe AMPlification) and (Web) Temblor (iOS) Temblor (Android) Insurance & a retrofit my building? buy insurance? Living with a safe home in earthquake country How to prepare for an earthquake How to get involved Underwater volcanoes are difficult to monitor. Tonga eruption shows why Posted on March 9, 2022March 18, 2022 by Temblor Tonga’s underwater eruption hints at need for more seismic stations near such active, submarine volcanoes located near populated parts of the Pacific. Retailleau, Ph. D. , du Piton de la Fournaise, Institut de Physique du Globe de Paris (@RetailleauLise) Citation: Retailleau, L. , 2022, Underwater volcanoes are difficult to monitor. Tonga eruption shows why, Temblor, One of the largest explosive volcanic eruptions in recent decades occurred on January 15, 2022, at Hunga Tonga–Hunga Haʻapai volcano in the Pacific Ocean, in the Kingdom of Tonga. It generated worldwide interest and concern because of the profusion of ash that exploded into the atmosphere, and the accompanying shock wave, tsunamis and isolation of the people of Tonga as their communications systems were cut and ash hampered rescue and first aid efforts. In the aftermath, scientists must consider what happened, what can be learned and how the island kingdom can prepare for future eruptions. Satellite image of Hunga Tonga–Hunga Haʻapai eruption on January 15, 2022. Credit: Agency (CC BY 4. 0), via Two islands become one… Hunga Tonga–Hunga Haʻapai is a mostly submarine volcano in the Ocean located about 65 kilometers (40 miles) north of Tongatapu, Tonga’s main island. Tonga’s islands form part of the Tonga-Kermadec arc, which sits above a subduction zone where the Pacific plate rapidly plunges under the Indo-Australian plate at a rate of around 20 centimeters (0. 8 inches) per year. This subduction generates numerous earthquakes, with each year bringing more than ten magnitude-6 and a few magnitude-7 events. A magnitude-8 earthquake typically strikes every few years, according to the U. S. earthquake browser. [SEP] Justify:

Output: The text contrasts the claim by providing information about underwater volcanoes, specifically noting that Hunga Tonga–Hunga Haʻapai is 'a mostly submarine volcano.' This directly contradicts the assertion that all volcanoes are formed on land, highlighting the existence of volcanic formations underwater.