Input: Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: to their strict maternal inheritance in most animals and plants, mitochondrial genomes are predicted to accumulate mutations that are beneficial or neutral in females but harmful in males. Although a few male-harming mtDNA mutations have been identified, consistent with this ‘Mother’s Curse’, their effect on females has been largely unexplored. Here, we identify COIIG177S, a mtDNA hypomorph of cytochrome oxidase II, which specifically impairs male fertility due to defects in sperm development and function without impairing other male or female functions. COIIG177S represents one of the clearest examples of a ‘male-harming’ mtDNA mutation in animals and suggest that the hypomorphic mtDNA mutations like COIIG177S might specifically impair male gametogenesis. Intriguingly, some D. melanogaster nuclear genetic backgrounds can fully rescue COIIG177S -associated sterility, consistent with previously proposed models that nuclear genomes can regulate the phenotypic manifestation of mtDNA mutations. eLife digest Cell compartments called mitochondria are responsible for producing much of the energy that animal and plant cells need. Most of the proteins in mitochondria are produced from genes found in another compartment called the nucleus. However, some mitochondrial proteins are made from genes found in the mitochondria themselves. Unlike the genes in the nucleus, which animals and plants inherit from both their mother and father, the mitochondrial “genome” is only passed on along the female line. Therefore, males represent an evolutionary dead-end for mitochondrial genes. Evolutionary theory predicts that this should result in the evolution and spread of mutations that can be harmful to males, providing they do not reduce the ability of females to survive and reproduce. Although such ‘male-harming’ mutations have been well studied in plants, it is less clear how common they are in animals. Patel, Miriyala, Littleton et al. used fruit flies as a model system to identify and characterize male-harming mutations in the mitochondrial genome. The experiments isolated a mitochondrial genome with a single mutation in a gene that encodes an enzyme called cytochrome oxidase II. The mutation is said to be “hypomorphic” because it lowers the activity of the gene. The fertility of male flies with this mutation rapidly declined as they aged. However, the mutation did not appear to lower the fertility of female flies.

Output: pass


Input: Claim: Urban living always leads to increased stress levels. [SEP] Text: Also, green areas as well as coastal parts of the city have been built over. The green areas in places were observed to be the green alluvial parts along the riverbanks. It has also been observed that development in the last two decades has been in places, where floods tend to accumulate more. A higher correlation exists between the newly built settlements in open areas with the cumulative floods observed (Fig. 14). Fig. 13An overview of the spread of urban growth between 2000 and 2020 and the distribution of floods in Karachi. Development of has taken over on open patches, green areas and water areas both along the streams and coastsFull size imageFig. 14The coefficient of determination for the land area that was converted from open areas to Urban and Green to Urban. A stronger relationship exists between areas that have been converted from Open to Urban. This is because of that these areas were previously attributed to natural streamsFull size imageKarachi is mostly warm and dry with precipitation ranging below 250 mm/year on average. However, the monsoon months are the wettest. It is worth mentioning that monsoon begins towards the last week of July and ends towards the third week of August, over southern Pakistan with some exceptional rainfall towards eastern Sindh province in 2011 and 2012 [103]. Rainfall analysis brought out the fact that Karachi is experiencing short but intense rainfall after every 2–3 years. Urban governance in Karachi has been a matter of grave concern. Of the many problems that Karachi is facing, the marginalization of its poor population is a key factor. Housing and a planned allocation for these communities is missing [104]. Others include ethnic diversity, political violence, and the development of informal economies [105,106,107], that tend to strain the governance structure of a city [108]. These later can be attributed to the post-colonial development trajectory of the city, where the aim was to portray it as a world class city and keeping an exclusive control on development along its central regions [109]. This led to unchecked growth in its peripheries. These communities led development along the natural streamways north of the central old city and landfilling of the existing stream pathways. Even now many marginalised communities inhabit its stream banks in the city [13, 27]. For instance, there is a growing population along the Gujjar Nala, Malir River, and Lyari Rivers. These communities from time to time are under the direct effects of floods.

Output: pass


Input: Claim: Sustainable economic growth focuses on balancing development with environmental protection. [SEP] Text: Based on these discussions, our ongoing research on Svalbard (Hovelsrud, Kaltenborn, & Olsen, Reference Hovelsrud, Kaltenborn and Olsen2020; Kaltenborn, Østreng, & Hovelsrud, Reference Kaltenborn, Østreng and Hovelsrud2020; Kelman, Rauken, & Hovelsrud, Reference Kelman, Rauken and Hovelsrud2012; Olsen, Hovelsrud, & ácz, Pavlov and Hänninen2020), and other tourism studies (e. g. Hagen, Vistad, Eide, Flyen, & and Fangel2012; Saville, Reference Saville2019; Sisneros-Kidd, Monz, Hausner, Schmidt, & Clark, Reference Sisneros-Kidd, Monz, Hausner, Schmidt and Clark2019; Van Bets, Lamers, & van Tatenhove, Bets, Lamers and van Tatenhove2017; Viken, Johnston, Nyseth, & Dawson, Reference Viken, Johnston, Nyseth and Dawson2014; Viken, Reference Viken2011), we learned that the tourism industry is struggling with cumulative and cascading effects of changes in policy, economy, and environmental conditions, including climate change (see Fig. 1). Fig. 1 An illustration of the many and scaled processes that the tourism industry needs to balance. Our intention with this commentary is to outline how we address the challenges and opportunities found in the multifaceted landscape of Svalbard tourism. Svalbard’s changing tourism national policy to further develop the tourism industry creates multiple opportunities on Svalbard including local value creation, development of new organisations, and employment opportunities (SSB, 2018). Growth in tourism and culture is reflected in the increased number of guest nights (from 82,831 in 2010 to 162,949 in 2019) (Visit Svalbard, 2020), cruise visitors (from 31,545 in 2010 to 62,342 in 2018) (Epinion, 2019; Port of Longyearbyen, 2018), and increased number of person-years (full-time equivalents) from 291 in 2010 to 518 in 2019 related to accommodation, food service, arts, entertainment, recreation (SSB, 2020).

Output: corroborate


Input: Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: Such combinations have revealed instances of dramatic incompatibility, even within species, which results in male but not female lifespan defects (Camus et al. , 2012). Variation in mtDNA also affects sperm competitiveness in D. melanogaster (Yee et al. , 2013). While these elegant experiments have revealed mtDNA-dependent affects on male lifespan and fertility, they did not comprehensively assess affects on female life-history traits; it is thus unclear whether these mutations are specifically male-harming. One further limitation of such mtDNA ‘swaps’ is that introduced mtDNA often have several co-inherited mutations. This linkage of different mutations makes it nearly impossible to implicate single mutations as being causal for the incompatibility or to understand their biological mechanism. An exception is a single point mutation in D. melanogaster mtDNA that has been causally linked to male sterility (Clancy et al. , 2011). However, recent demonstration of this mtDNA haplotype’s negative pleiotropic effects on fertility and aging, both within and between sexes suggests it is not a specifically male-harming mutation (Camus et al. , 2015). Thus, we currently lack clear examples of specifically male-harming mtDNA mutations in animals. This has also left unanswered the larger question of molecular mechanisms by which mtDNA mutations can manifest their ‘male-harming’ phenotypes. Here, we isolated a mtDNA variant that harbors a single non-synonymous change in subunit II of cytochrome c oxidase (COIIG177S). We find that COIIG177S males have an age– and temperature–dependent decrease in fertility. This decrease in fertility is correlated with a drop in COII enzymatic activity, which remarkably does not result in defects in any other male or female phenotypic traits we measured. Cellular characterization reveals decreased sperm production and function in the mutant males. By combining evolutionary principles with detailed functional characterization, our study thus provides one of the clearest examples of a male-harming mtDNA mutation in animals, and provides insights into the stringent requirements for optimal mtDNA function in sperm development. We further show that the fertility defect in COIIG177S males can be completely suppressed by diverse nuclear backgrounds derived from various D. melanogaster strains, as predicted by the theory of cyto-nuclear genetic conflict.

Output: contrast


Input: Claim: Urban living always leads to increased stress levels. [SEP] Text: In places, where large swaths of lands have been transformed into planned societies, such as Nazimabad, North Nazimabad, Baldia and North Karachi. The natural flow paths of the rivers have been landfilled and flood water in the last few years had accumulated in the streets. Zeiderman et al. [110] suggests that in case of Karachi, there is a challenging urban planning environment that exists. While there is necessity to shift paradigms and adopt a modernist urban planning approach. There is, a need to look beyond the Authority’s (KDA) approach at managing and developing more land. Since the organization is already embattled with various land ownership issues, rapid community growth and sprawling urban societies, that tend to overlook best resource allocation practices and guidelines. An urban resource centre, research on pressing issues of social inclusion, information base creation, monitoring, and modelling growth, both current and future are some of the steps that can be taken to allow for informed decision making [111, 112]. One key aspect of this can also be reestablishment of urban waterways, cleaning of clogged drainage lines and subsequent control on development along these channels. While rehabilitating the communities, in planned areas with adequate amenities and livelihood opportunities [113]. Karachi like many cities of the developing world and region is no different in terms of the issues, faced by it. The city’s growth is dominated by its informal economy which provides vital livelihood for its immigrants. Its, rapid, urban growth being a direct threat, to its sustainability and green spaces [114,115,116]. Also, a myriad of health issues, growing. Of these those related to post flood scenarios being the most common. Incidents of Malaria and Dengue are on the rise, due to conducive, breeding environment and its widespread presence. Water contamination related gastrointestinal issues, diseases of the eyes and skins have been commonly reported in the post flood periods [117]. For a city as big as Karachi one the issues remain solid waste management. Which is usually deposited by its informal settlements in the river channels [118, 119]. And even the waste collected by garbage disposal corporations, has a similar fate, leading to a mixing with floodwaters and higher level of contaminant percolation. As compared to other studies, this research incorporated historical topographic maps in the flood analysis. Making those historical records a baseline, comparison was made to observe the changes in topography, urban development, and protective infrastructure.

Output: pass


Input: Claim: Sustainable economic growth focuses on balancing development with environmental protection. [SEP] Text: Furthermore, Svalbard tourism trends show a shift from seasonal to year-round tourism, from land-based towards marine based tourism and Longyearbyen increasingly becoming a tourist destination rather than a transit hub (Olsen et al. , Reference Olsen, Hovelsrud, Kaltenborn, Pongrácz, Pavlov and Hänninen2020). The revenues from the different segments of the local tourism industry differ greatly, as do their carbon and environmental footprints. The tourist boom in Longyearbyen in the past two decades can be explained by the growing interest in the Arctic in general and in Svalbard in particular, by national and local facilitation of tourism, and by easier access because of reduced sea ice cover (Hovelsrud et al. , Reference Hovelsrud, Kaltenborn and Olsen2020; Palma et al. , and Ronge2019). With retreating sea ice, the tourism industry offers trips to new and previously inaccessible areas, and the cruise ship season is extended (Bystrowska, Reference Bystrowska2019; Olsen, Carter, & Dawson, Reference Olsen, Carter and Dawson2019; Stocker, Renner, & Knol-Kauffman, Reference Stocker, Renner and Knol-Kauffman2020; Øian & Kaltenborn, Reference Øian and Kaltenborn2020). On-land tourism increasingly offers year-around attractions. More tourists boost employment and income, but also result in overcrowding and increasing pressure on the environment and infrastructure. There is concern that Longyearbyen will become a mass tourist destination with a rapid growth in year-round visitors (Olsen et al. , Reference Olsen, Hovelsrud, Kaltenborn, Pongrácz, Pavlov and Hänninen2020). This has prompted community responses designed to limit the impact of tourism on the fragile environment and on Longyearbyen. This concern is reflected in the plans by the tourism organisations, such as the for Tourism on Svalbard (Mimir, 2015) to develop adaptation measures that both meet the demands from increased tourism and from the local population to maintain Longyearbyen as an attractive place to live. From a climate change perspective, the tourism industry faces a greater diversity of risk than other economic sectors (Scott, Hall, & Gössling, Reference Scott, Hall and Gössling2019).

Output: corroborate


Input: Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: Our analyses revealed an approximately 20% decrease in COX enzymatic activity in COIIG177S mutants grown at 29°C in both male and female flies (Figure 5B). Given that the activity of the electron transport chain is coupled to ATP synthesis, we also measured ATP levels at 29°C. In contrast to COX activity, we did not observe a decrease in ATP levels in the COIIG177S mutants (Figure 5C). However, we did observe a mild but significant decrease in reactive oxygen species (ROS) levels (Figure 5D). Thus, impaired COX activity and reduced ROS levels, but not ATP production, appear to correlate with loss of male fertility. Figure 5 Download asset Open asset Biochemical consequences of COIIG177S mtDNA mutation. We measured COX activity from young (3–4 days) or old (21 days) flies raised at 25°C (A), or young flies raised at 29°C (B). (C) We measured ATP levels from 3–4 day old males raised at 29°C. (D) We measured ROS levels from 3–4 day old males raised at 29°C. 4–5 replicates per group for all experiments. Data is normalized to wildtype flies for each group in all experiments. Error bars represent standard error of the mean. 177S mtDNA mutant specifically impairs male fertility Our finding that COIIG177S mutants result in lower COX activity of both males and females prompted us to evaluate several other phenotypes commonly seen in flies with mitochondrial impairment. Mitochondrial dysfunction is often associated with aging defects in many species (Cho et al. , 2011; Tower, 2015). Naturally occurring variation in mtDNA is also known to affect aging in D. melanogaster (Rand et al. , 2006; Clancy, 2008; Camus et al. , 2012). We therefore assayed the lifespan of wildtype and COIIG177S mutant males and females at both 25°C and 29°C. We did not observe any differences in lifespan, even at the sensitized higher temperature between wildtype and mutant flies in either males or females (Figure 6). Figure 6 with 2 supplements see all Download asset Open asset COIIG177S mtDNA mutation does not significantly affect male or female lifespan. We measured average lifespan of males and females at 25°C (A,B) or 29°C (C,D).

Output: contrast


Input: Claim: Urban living always leads to increased stress levels. [SEP] Text: Analysis was done based on this comparison and results were drawn. While the development before 1980s was not large scale, there has been a massive increase in urban growth since then. By year 2000, Karachi had experienced 286% increase in urban extent that was caused by various factors like lack of oversight on management of land, absence of urban planning etc. Relationship between urbanization and economic growth should be positive, ideally [120]. However, in Pakistan, this relationship shows that GDP growth has decreased between 2015 and 2021 while urban population percentage is constantly increasing. Thus, increase in urban extent from 1980s to 2000 is massive as in compared to the size of the economy of Pakistan and the state’s ability to invest in sustainable development at such a massive scale. Unregulated and unchecked allocation of parcels for development of housing societies also contributed towards rapid sprawl. Temporal LULC analysis shows that increase in urban extent was mostly at the expense of decrease in agricultural land. This type of urban extent and downward natural slope of core urban area (Fig. 1) rendered this urban development susceptible to the negative effects of urban floods. Rapid urbanization also affected city’s natural drainage system. This natural drainage/stream network was either removed or damaged due to rapid urban development over the years. Both urban development (Table 3) and stream network covered or damaged by urban development (Table 4) shows an increasing trend. By year 2020, Stream network in 12 out of 24 towns is more than 70% as compared to more than 50% in year 2000 (Table 4). Most of the streams have been removed and the little natural streams that are left, are clogged with sewage and industrial and household waste. This continue to be a major problem as water does not get its natural flow and tends to inundate the roads or houses nearby these drains. Analysis from 2000 to 2020 showed that during urban floods, same areas are inundated repeatedly, where stream blockage/damage is maximum. Although the drainage network has been cleaned many times, especially after year 2020, but this temporary measure needs to be replaced with some permanent structural changes. Urban settlements developed on banks of drainage/stream networks are a major concern during floods. Due to their proximity and structure, they are badly affected during each urban flood event. Analysis showed that these settlements are increasing at a high rate, and block flood water flow towards Arabian Sea.

Output: pass


Input: Claim: Sustainable economic growth focuses on balancing development with environmental protection. [SEP] Text: In Svalbard, tourists often arrive by cruise ships, which is an even more carbon-intensive way of travel than aviation (Walnum et al. , Reference Walnum, Gössling, Simonsen, Iversen, Hem, Dybedal and Jacobsen2019). Therefore, mitigation policies may affect Svalbard tourism, which relies on long haul travellers. This is exemplified by Norway’s announcement in November 2020 to prohibit Oil for all vessels operating around Svalbard. Increasing ocean temperature, rapid decline in winter sea ice, and other environmental changes influence ecosystem functions (Meier et al. , Reference Meier, Hovelsrud, van Oort, Key, Kovacs, Michel and Reist2014). The ecosystem services such as sea ice, permafrost, flora, and fauna are directly or indirectly affected by climate change (AMAP, 2017b; Hanssen-Bauer et al. , Reference Hanssen-Bauer, Førland, Hisdal, Mayer, Sandø and Sorteberg2019; Hovelsrud, Poppel, Oort, & Reist, Reference Hovelsrud, Poppel, Oort and Reist2011), thereby affecting the infrastructure and products at the heart of Svalbard tourism. Further, climate change is also causing an emergency response crisis in Longyearbyen due to avalanches threatening homes and thawing permafrost causing severe damage to roads and other infrastructure. Recently, a portion of the Longyearbyen population were evacuated from their homes due to avalanche threats. Theoretical and methodological approaches To study the balancing of competing and sometimes conflicting demands and goals, we approach the societal, economic, and environmental sustainability of Svalbard tourism through the frames of adaptation to multiple stressors and societal transformation to a low-emission society. Adaptation is a context-dependent process shaped by the structure of the community and the exposure-sensitivities to multiple stressors, such as the consequences of climate change and outmigration, and cumulative consequences of change, affecting societal vulnerability (e. g. Hovelsrud & Smit, and Smit2010). Adaptation processes can be reactive or proactive and include barriers, limits, and opportunities across scales (e. g. governance, sectors) and actors (AMAP, 2017a). This means that there is a potential for conflict between the different actors’ interests.

Output: corroborate


Input: Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: N = 100 flies per group. Sensitivity to physiological stress and neuronal function are also associated with mitochondrial dysfunction (Fergestad et al. , 2006; Pieczenik and Neustadt, 2007; Ugalde et al. , 2007; Distelmaier et al. , 2009; Celotto et al. , 2011). We therefore assayed heat intolerance, and ‘bang sensitivity’, a measure of neuronal dysfunction (Burman et al. , 2014). There were no statistically significant differences in these traits in either males or females, even in aged flies grown at 29°C, the highly sensitized and susceptible condition (Figure 6—figure supplements 1, 2). Thus, despite the 20% reduction in COX activity in both males and females, the phenotypic consequences of COIIG177S in D. melanogaster appear to be largely benign, with deleterious effects confined to male fertility alone. COIIG177S impairs sperm development and motility We next investigated the biological basis of the decreased male fertility in COIIG177S mtDNA-bearing males. Male sterility could either result from defects in the ability of males to mate or can be a result of defective sperm development/function or a combination of both. In order to distinguish between these two possibilities, we took advantage of the fact that transfer of male accessory gland peptides during mating induces egg-laying in females (Wolfner, 1997). We find that mating wildtype females with COIIG177S males induces egg-laying just as robustly as in females mated with males carrying wildtype mtDNA (Figure 7A). However, almost all of the eggs laid by females mated with COIIG177S mutant males were unfertilized and failed to hatch (Figure 7A). Taken together, these data suggest that the decreased fertility in COIIG177S males occurs due to defects in sperm development or function, and not due to mating ability. We therefore sought to determine the nature of cellular defects in COIIG177S male testes. Figure 7 with 1 supplement see all Download asset Open asset Normal mating but defective sperm development in COIIG177S mutant mtDNA males. (A) We measured whether the COIIG177S mtDNA mutation affected the mating success of males.

Output: contrast


Input: Claim: Urban living always leads to increased stress levels. [SEP] Text: Major urban settlements affected by flood water were present in Gadap town, followed by Korangi town, Faisal Cantonment, town and Gulshan-e-Iqbal. These settlements need to be relocated to alternate locations to provide easy passage to flood water. Data availability and dissemination is a major issue in Pakistan. In the absence of modern data keeping, dissemination and analysis by the authorities. It was necessary to look for alternatives, such as published public map records and satellite remote sensing data. Moreover, statistical records and data on streams, stream flow rates, environmental data such as rainfall and temperature records are extremely limited, and some are impossible to find. Published records are mostly in the form of news archive, but they seldom have a spatial component associated. It would be therefore important to lead this work into databasing all forms of published records on urban growth and make it available to the research community. Another important analysis can be the effect of the loss of natural water conveyance on disease prevalence and urban heat accumulation. 6 Conclusionin Pakistan is a recurring phenomenon. Raid urban sprawl and poor maintenance of natural drainage system make flooding further worse necessitating identification of flood prone urban areas during floods. LULC information show that Karachi experienced rapid urban grown over the years. This rapid sprawl linked with poor management of water channels cause urban flooding in the city of Karachi during short but heavy rainfall. SAR imagery is an effective data source for detection of flood water in urban areas as it is not affected by weather conditions thus providing better identification of flooded areas. Using thresholding, flood water was extracted from SAR imagery. LULC classification was carried out using Landsat imagery. This classification information shows that natural streams and flood protection structures were replaced with urbanization with the passage of time. This stream blockage is almost 100% in core urban areas of the city. When overlaid both LULC information and urban flood water, analysis showed that urban development has blocked stream network of the city. Due to this blockage, low lying urban areas face flood inundation during rainfall. It was also observed that town with the highest number of natural streams filled up are the ones that were worst affected recently. Examples are that of and Orangi. A visual analysis of topographic sheets showed several embankments along these streams. And we assume that the streams must have been filled, with soil from the very embankments. Hence leading to easy and cheap preparation of land for construction.

Output: pass


Input: Claim: Sustainable economic growth focuses on balancing development with environmental protection. [SEP] Text: Nevertheless, recent assessments of adaptation in the Barents Region, where Longyearbyen is located, show that proactive adaptation by local governments and business organisations, such as adaptive responses to avalanche, mudslides, sea level rise, sea ice reduction, and thawing permafrost in practice, is ahead of national guidelines (AMAP, 2017a). Adaptation, whether reactive or proactive, takes many forms depending on the interactive and multiple effects. It may reduce vulnerability (Adger et al. , and Wreford2009), increase resilience, and enable transformation (Pelling, Reference Pelling2011). Engineering and new infrastructure may be developed to reduce the effects of thawing permafrost and avalanche; other adaptive responses may include new or changed institutional structures, economic mechanisms, and innovations (AMAP, 2017a). These are already at play in Svalbard, evidenced by the multitude of new tourism operators and products adjusted to the more recent climate change effects. Societal transformation is a concept closely related to adaptation and is taking hold as a theoretical framing for analysing how society can address the call for substantial greenhouse gas emission (GHG) cuts and the implementation of the SDGs (Veland et al. in press; Few, Morchain, Spear, Mensah, & and Bendapudi2017; O’Brien, Reference O’Brien2016, Reference O’Brien2012). While transformational adaptation may be required where incremental adaptation is insufficient (Kates, Travis, & Wilbanks, Reference Kates, Travis and Wilbanks2012), the concept of transformation is unsettled and ambiguous in theory as well as in policy and practice and requires explorative and transdisciplinary research (Scoones, Leach, & Newell, Reference Scoones, Leach and Newell2015). Major changes, inherent in ambitious sustainability targets, come with trade-offs between different values, groups, and activities, and therefore point to investigations on who prioritises what to understand what transformation may demand of different segments of society. Recent findings show that there is an obvious gap between how transformation is portrayed and pursued at the international level, at the national sectoral levels, and in locally based sectors (Amundsen & Hermansen, and Hermansen2020).

Output: corroborate


Input: Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: Hence, mitochondria, because of their involvement in ageing (Martin & Grotewiel 2006; Yu & Chung 2006), are a good system in which to study the putative relationship existing between the connection (and level of connection) of replication and transcription with ageing processes. 1. 2. Mitochondria and ageing Several properties of mitochondrial genomes have already been shown to associate with lifespan, presumably because of cumulative DNA damage due to free radicals produced by the normal function of mitochondria in the cell’s energetic metabolism (Wiesner et al. , 2006). It seems that evolution of vertebrate longevities (and in general, the associated evolution of their life history strategies) causes accelerated rates of amino acid replacements in mitochondrion-encoded protein coding genes (Rottenberg, 2006, 2007). Mutagenesis independent of free oxidative radicals also affects mitochondrion-associated ageing: in mitochondrial genomes, the number of direct repeats, a factor causing deletions, correlates negatively with mammalian lifespan (Samuels, 2004; Samuels et al. , 2004; Khaidakov et al. , 2006). Using a similar comparative approach, Samuels (2005) showed that lifespan increases proportionally to the stability of hybridization between complementary mitochondrial DNA strands, estimated by free energies. This property is proportional to the probability of opening up and expansion of single-stranded mtDNA bubbles. Negative selection on repeats (Samuels, 2005; Khaidakov et al. , 2006) explains the exceptional status of most vertebrate mitochondrial genomes as breaking Chargaff’s second parity rule (complementary nucleotides are met with almost equal frequencies in single stranded DNA), fitting the hypothesis that inversions and inverted transposition could be a major contributing if not dominant factor in the almost universal validity of this rule (Albrecht-Buehler, 2006). These single stranded bubbles are more likely to occur where direct repeats exist, causing deletions (Khaidakov et al. , 2006), but this probably also increases mutation rates in the single stranded sequences forming the bubble when the bubble is not enzymatically excised. This is because hydrolytic deaminations of cytosine to thymine and adenine to guanine, both transitions, occur proportionally to time spent single stranded (Dssh) by the genome (as shown for example during replication in primate mitochondrial genomes, Krishnan et al.

Output: contrast


Input: Claim: Urban living always leads to increased stress levels. [SEP] Text: One of the limitations of the study was small scale historical topographic maps. Although information extracted from these historical records like elevation, urban extent, stream network and embankments etc. was effectively utilized in the analysis, however same analysis could have been performed with more accuracy if large scale historical records were available. Sentinel 1 SAR imagery is an excellent source to extract water extent of an area. In this study, open-source data of 10 m resolution was used. Better water extraction can be done if higher resolution SAR imagery was available, which is mostly not available as open source.

Output: pass


Input: Claim: Sustainable economic growth focuses on balancing development with environmental protection. [SEP] Text: Understanding and applying local perceptions of societal transformation may be useful for revealing what different local actors view as meaningful and acceptable transformation directions (Karlsson & Hovelsrud, and Hovelsrud2020). Transformation necessitates integrated approaches spanning divisions between and within sectors and social groups (Moloney & Horne, and Horne2015), as well as across scales (Kates et al. , Reference Kates, Travis and Wilbanks2012). Societal transformation requires large and cross-scale changes (from global to individual) and interconnections in technologies, politics, economic mechanisms, and social values (Kates et al. , Reference Kates, Travis and Wilbanks2012; O’Brien, Reference O’Brien2016). The lack of consistent theories and practices guiding transformation may therefore involve uncertainties in terms of outcomes for sustainability when transferred into policy and practice (Blythe et al. , and Brown2018; Leach et al. , Reference Leach, Rockström, Raskin, Scoones, Stirling, Smith and Olsson2012). In Svalbard, there are two key levels of potentially transformative change: (1) Svalbard’s economic and policy portfolio transforming from coal to tourism, research, and education, driven by the Norwegian state; and (2) the tourism industry’s responses to multiple pressures and demands, and to the opportunities and challenges that may arise in developing new tourism products both in response to a changing market and to change the traditional tourist demands. Tourism operators have ambitions to expand the tourism industry, shifting its focus from the traditional products of ice and polar bears towards more localised products with a lower carbon footprint, while ensuring that the transition is sustainable. Through the application of two interlinked theoretical perspectives, it is possible to investigate whether the tourism industry’s responses are transformational or adaptive or both. This comes with implications for how to develop a sustainable tourism industry. defines sustainable tourism as taking “full account of its current and future economic, social, and environmental impacts, addressing the needs of visitors, the industry, the environment, and the host communities” (UNEP-WTO, 2005, p. 12). We approach sustainability as an interlinked concept where socio-ecological sustainability depends on an acceptable balance, according to public judgement, between pressures and responses in coupled environmental, economic, and socio-cultural domains (Petrov et al.

Output: corroborate


Input: Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: In fact, the deamination gradients detected by comparative analyses are considered as strong evidence in favor of the unidirectional replication mechanisms (Gibson, 2005). My interpretation is that the unidirectional replication is relatively rare, but it leaves at evolutionary scales a clear imprint on genomes because it causes biases in mutation patterns, and that at least one other replication process, putatively similar to the one in nuclei, exists. That process is more frequent and effective, affecting less the genome at evolutionary scale. Indeed, some evidence on mitochondrial transcription factors suggests that two replication modes coexist, and that the modes of mitochondrial replication are regulated by mitochondrial metabolism (Pohjoismaki et al. , 2006). Results and conclusions will be also interpreted according to this hypothesis, considering that only one replication mechanism, the unidirectional one, creates replication deamination gradients. 1. 7. Lifespan and convergence of replication and transcription Heavy strand sequences of mitochondrial tRNA genes tend to form OL-like structures and seem to assist the “recognized” vertebrate mitochondrial OL in the WANCY region (Seligmann & Krishnan, 2006). DsshrX resembles Dssht more than does DsshrW (see Figure 1, and Seligmann et al. , 2006b). Pathogenic mutations, as compared to non-pathogenic polymorphisms in human mitochondrial tRNAs, disturb the fine balance of DsshrX by altering which tRNAs function and which do not function as alternative OLs (Seligmann et al. , 2006b). These observations strengthen the hypothesis that collinearity between these processes increases longevity by slowing ageing. A further observation in line with this hypothesis is that nucleotide contents of heavy strand DNA sequences coding for the first and second positions of tRNA anticodons in vertebrate mitochondrial genomes correlate with Dssht calculated according to the highly conserved tRNA arrangement along the vertebrate mitochondrial genome. When mitochondrial replication and transcription are collinear, as observed in Homo sapiens after integrating all putative OLs in DsshrX calculations, overall deamination risks at sites coding for the first two anticodon positions are minimized (Seligmann et al. , 2006b), not only during transcription, but also during replication because replication is collinear with transcription in this case.

Output: contrast


Input: Claim: Urban living always leads to increased stress levels. [SEP] Text: Skip to Content eLife home page your research Search by keyword or author Reset form my search to Research 10. 7554/eLife. 40396 Open access Copyright information Version of RecordApril 25, 2019 Accepted ManuscriptApril 16, 2019 Open annotations (there are currently 0 annotations on this page). 2,878 views 430 downloads 29 0396. Copy to clipboard Download BibTeX Download. RIS Full text Figures and data Peer review Side by side Additional files 9 figures, 1 table and 2 additional files 1 with 1 supplement Download asset Open asset NLRP12 negatively regulates hepatocellular carcinoma. (A) Analysis of genetic association of NLRP12 in HCC using the TCGA database through the cBioportal online platform. (B) Analysis of NLRP12 expression in human normal liver and -seq data in the TCGA database through the web-portal. Data are presented in a box plot where whiskers represent maximum and minimum variables. (C) WT mice were injected with DEN (25 mg/kg i. p. ) at the age of 14 days or left untreated. Livers from DEN-treated (n = 10) and untreated mice (n = 6) were analyzed for the expression of Nlrp12 by real-time qPCR. Data represent means ± SEM. (D–H) WT mice (n = 20) and Nlrp12-/- (n = 20) were injected with DEN (25 mg/kg i. p. ) at the age of 14 days and sacrificed at 10 months after DEN injection. (D) Representative images of liver tumors are shown. (E) The number of tumors per liver, tumor sizes, and liver to body weight ratios were measured. Data represent means ± SEM (n = 20). Statistical difference was determined by two-tailed unpaired t-test. (F) Livers from mice described in D were stained for H and E. and E-stained sections are shown. (G) H and E-stained liver sections were histopathologically examined for adenoma development. Data represent means ± SEM (n = 15). Statistical difference was determined by two-tailed unpaired t-test. (H) Serum ALT and AST levels in tumor-bearing mice. Data represent means ± SEM (n = 15). Statistical difference was determined by two-tailed unpaired t-test.

Output: pass


Input: Claim: Sustainable economic growth focuses on balancing development with environmental protection. [SEP] Text: , and Schweitzer2016). We understand this balancing act as being to some extent scaled along institutional levels. When national and international governing bodies set targets for sustaining key aspects of societies or the environment (Protection Act), they are potentially placing demands for transformation at other societal levels. The progress towards sustainability is linked to the debates in climate change research on how to conceptually distinguish between adaptation to multiple stressors and societal transformation. We firmly believe that without an understanding of the local perspectives and needs, we cannot develop the theoretical foundations of adaptation and transformation, which after all are inextricably linked to the practical and physical actualities of local context. Co-production of knowledge has become the new buzzword in the global environmental change literature and is listed as a requirement in many calls for research or assessment proposals. Such co-production underpins the theoretical and methodological approach of our study, where the boundaries between domain of science and non-science ideally will be dissolved and not actively maintained. For co-production of usable knowledge to occur the boundaries must be kept open and porous in the right places, through communication, translation and mediation, to ensure legitimate, salient, and credible knowledge (e. g. Cash et al. , and Mitchell2003). The concept of co-production, first coined by in the 1970s, has many applications and definitions as outlined in the overview by Bremer and Meisch (and Meisch2017). They identify two main focal areas in research on co-production of knowledge, descriptive and prescriptive. The first area of co-production of knowledge pertains to the description and analysis of how knowledge is generated and sustained within power relations and social order. The focus is on understanding how the products of science and technology flow across societal boundaries. This descriptive perspective is represented by scholars such as Sheila Jasanoff, Bruno Latour, and Bryan Wynne, who are on a quest to understand how science, technology, and society interact to make and remake each other (Bremer & Meisch, and Meisch2017, p. 2). Here we align largely with the second area, which pertains to co-production as deliberate collaboration between different knowledge systems and stakeholder groups towards a common goal of generating knowledge on policy-relevant topic. In practice, this means that the researcher and industry operators in BalancingAct will discuss what we know and how we know the tourism industry and the potential for developing new and sustainable tourism products.

Output: corroborate


Input: Claim: Biohacking guarantees longevity by doubling the average human lifespan. [SEP] Text: This suggests that at high Dsshr->Dssht convergence levels, another factor decreases lifespan. It is plausible that collinearity between the processes increases the frequency of collisions between replication and transcription forks. This decreases the respective rates of these processes, increasing the overall time spent single stranded, causing more mutations. This increase might be greater than the relative decrease in mutation rate due to collinearity between the processes, especially at high collinearity levels. Figure 5 plots lifespan in Figure 5. Maximal lifespan as a function of a measure of convergence between replication and transcription in mitochondrial genomes in Cetacea. Axes are as in Figure 3. Species names are followed by NCBI (genbank) entries: Balaena mysticetus, NC_005268; Balaenoptera acutorostrata, NC_005271; Balaenoptera borealis, NC_006929; Balaenoptera edeni, NC_007938; Balaenoptera musculus, NC_001601; Balaenoptera physalus, NC_001321 Balaenoptera bairdii, NC_005274; Eschrichtius robustus, NC_005279; Eubalaena australis, NC_006930; Hyperoodon ampullatus, NC_005273; Inia geoffrensis, NC_005276; Kogia breviceps, NC_005272; Lipotes vexillifer, NC_007629; Megaptera novaeangliae, NC_006927; Monodon monoceros, NC_005279; Phocoena phocoena, NC_005280; Physeter catodon, NC_002503; Pontoporia blainvillei, NC_005277. Cetacea as a function of Dsshr->Dssht convergence. At low convergence levels, lifespan increases with convergence until a threshold region in Dsshr->Dssht convergence. Beyond that threshold, lifespan decreases with Dsshr->Dssht convergence. It is hence not a surprise to find a negative correlation between Dsshr->Dssht convergence and maximal lifespans in lizards (Figure 6).

Output: contrast


Input: Claim: Urban living always leads to increased stress levels. [SEP] Text: (I–J) WT (n = 6) and Nlrp12-/- (n = 6) mice were injected with DEN (25 mg/kg i. p. ) at the age of 14 days followed by eight weekly injections of CCl4 (0. 5 ml/kg i. p. , dissolved in corn oil) starting at 10 weeks of age and euthanized at the age of 6 months. (I) Representative images of liver tumors are shown. (J) The numbers, sizes, and liver to body weight ratio were measured. Data represent means ± SEM. Statistical difference was determined by two-tailed unpaired t-test. Figure 1—source data 1 NLRP12 negatively regulates hepatocellular carcinoma. Download elife-40396-fig1-data1-v2. zip Figure 1—figure supplement 1 Download asset Open asset Nlrp12-deficiency doesn’t induce HCC in healthy untreated control mice. (A) A model for DEN-induced liver carcinogenesis. Mice are injected with DEN (25 mg/kg) at the age of 14 days after birth. 10 months following DEN injection, mice were scarified to measure tumor burden. (B) A dodel for DEN plus CCl4-induced HCC. Mice were injected with DEN (25 mg/kg) at the age of 14 days followed by eight weekly injections of CCl4 (0. 5 ml/kg i. p. , dissolved in corn oil) starting at 10 weeks of age. Mice were euthanized at the age of 6 months. (C–E) WT and Nlrp12-/- healthy mice were sacrificed at 10 months after birth and livers were examined. (C) Representative images of the liver from healthy 10 month-old WT and Nlrp12-/- mice. (D) Liver sections were examined following H and E staining. (E) Serum ALT and AST levels of 10-month-old untreated control mice. Data represent means ± SEM (n = 5). Figure 1—figure supplement 1—source data 1 Nlrp12-deficiency doesn’t alter liver fucntion in healthy mice. Download elife-40396-fig1-figsupp1-data1-v2.

Output: pass


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

Output: corroborate


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

Output: contrast


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

Output: pass


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

Output: corroborate


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

Output: contrast


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

Output: pass


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

Output: corroborate


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

Output: contrast


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

Output: pass


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

Output: corroborate


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

Output: contrast


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

Output: pass


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

Output: corroborate


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

Output: contrast


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

Output: pass


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

Output: corroborate


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

Output: contrast


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

Output: pass


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

Output: corroborate


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

Output: pass


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

Output: pass


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

Output: corroborate