Marine heatwaves (MHWs) have occurred in all ocean basins with severe negative impacts on coastal and ocean ecosystems. The northeast Pacific 2013-2015 MHW in particular received major societal ...concerns. Yet, our knowledge about how MHWs impact fish stocks is limited. Here, we combine outputs from a large ensemble simulation of an Earth system model with a fish impact model to simulate responses of major northeast Pacific fish stocks to MHWs. We show that MHWs cause biomass decrease and shifts in biogeography of fish stocks that are at least four times faster and bigger in magnitude than the effects of decadal-scale mean changes throughout the 21st century. With MHWs, we project a doubling of impact levels by 2050 amongst the most important fisheries species over previous assessments that focus only on long-term climate change. Our results underscore the additional challenges from MHWs for fisheries and their management under climate change.
Human occupants are an important source of microbes in indoor environments. In this study, we used DNA sequencing of filter samples to assess the fungal and bacterial composition of air in an ...environmental chamber under different levels of occupancy, activity, and exposed or covered carpeting. In this office-like, mechanically ventilated environment, results showed a strong influence of outdoor-derived particles, with the indoor microbial composition tracking that of outdoor air for the 2-hour sampling periods. The number of occupants and their activity played a significant but smaller role influencing the composition of indoor bioaerosols. Human-associated taxa were observed but were not particularly abundant, except in the case of one fungus that appeared to be transported into the chamber on the clothing of a study participant. Overall, this study revealed a smaller signature of human body-associated taxa than had been expected based on recent studies of indoor microbiomes, suggesting that occupants may not exert a strong influence on bioaerosol microbial composition in a space that, like many offices, is well ventilated with air that is moderately filtered and moderately occupied.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Future projections of potential ocean ecosystem stressors, such as acidification, warming, deoxygenation, and changes in ocean productivity, are uncertain due to incomplete understanding of ...fundamental processes, internal climate variability, and divergent carbon emission scenarios. This complicates climate change impact assessments. We evaluate the relative importance of these uncertainty sources in projections of potential stressors as a function of projection lead time and spatial scale. Internally generated climate variability is the dominant source of uncertainty in middle‐to‐low latitudes and in most coastal large marine ecosystems over the next few decades, suggesting irreducible uncertainty inherent in these short projections. Uncertainty in projections of century‐scale global sea surface temperature (SST), global thermocline oxygen, and regional surface pH is dominated by scenario uncertainty, highlighting the critical importance of policy decisions on carbon emissions. In contrast, uncertainty in century‐scale projections of net primary productivity, low‐oxygen waters, and Southern Ocean SST is dominated by model uncertainty, underscoring that the importance of overcoming deficiencies in scientific understanding and improved process representation in Earth system models are critical for making more robust projections these potential stressors. We also show that changes in the combined potential stressors emerge from the noise in 39% (34–44%) of the ocean by 2016–2035 relative to the 1986–2005 reference period and in 54% (50–60%) of the ocean by 2076–2095 following a high‐carbon emission scenario. Projected large changes in surface pH and SST can be reduced substantially and rapidly with aggressive carbon emission mitigation but only marginally for oxygen. The regional importance of model uncertainty and internal variability underscores the need for expanded and improved multimodel and large initial condition ensemble projections with Earth system models for evaluating regional marine resource impacts.
Key Points
The sources of uncertainty in global and regional projections are quantified
Internal variability uncertainty is dominant on small spatial scales and short time horizons
Model and scenario uncertainties become dominant in end‐of‐century projections
Translating the Paris Agreement to limit global warming to 1.5°C above preindustrial level into impactrelated targets facilitates communication of the benefits of mitigating climate change to ...policymakers and stakeholders. Developing ecologically relevant impact-related targets for marine ecosystem services, such as fisheries, is an important step. Here, we use maximum catch potential and species turnover as climate-risk indicators for fisheries. We project that potential catches will decrease by more than 3 million metric tons per degree Celsius of warming. Species turnover is more than halved when warming is lowered from 3.5° to 1.5°C above the preindustrial level. Regionally, changes in maximum catch potential and species turnover vary across ecosystems, with the biggest risk reduction in the Indo-Pacific and Arctic regions when the Paris Agreement target is achieved.
IMPORTANCE: Positron emission tomography (PET) may increase the diagnostic accuracy and confirm the underlying neuropathologic changes of Alzheimer disease (AD). OBJECTIVE: To determine the accuracy ...of antemortem 18Fflortaucipir PET images for predicting the presence of AD-type tau pathology at autopsy. DESIGN, SETTING, AND PARTICIPANTS: This diagnostic study (A16 primary cohort) was conducted from October 2015 to June 2018 at 28 study sites (27 in US sites and 1 in Australia). Individuals with a terminal illness who were older than 50 years and had a projected life expectancy of less than 6 months were enrolled. All participants underwent 18Fflortaucipir PET imaging, and scans were interpreted by 5 independent nuclear medicine physicians or radiologists. Supplemental autopsy 18Fflortaucipir images and pathological samples were also collected from 16 historically collected cases. A second study (FR01 validation study) was conducted from March 26 to April 26, 2019, in which 5 new readers assessed the original PET images for comparison to autopsy. MAIN OUTCOMES AND MEASURES: 18Fflortaucipir PET images were visually assessed and compared with immunohistochemical tau pathology. An AD tau pattern of flortaucipir retention was assessed for correspondence with a postmortem B3-level (Braak stage V or VI) pathological pattern of tau accumulation and to the presence of amyloid-β plaques sufficient to meet the criteria for high levels of AD neuropathological change. Success was defined as having at least 3 of the 5 readers above the lower bounds of the 95% CI for both sensitivity and specificity of 50% or greater. RESULTS: A total of 156 patients were enrolled in the A16 study and underwent 18Fflortaucipir PET imaging. Of these, 73 died during the study, and valid autopsies were performed for 67 of these patients. Three autopsies were evaluated as test cases and removed from the primary cohort (n = 64). Of the 64 primary cohort patients, 34 (53%) were women and 62 (97%) were white; mean (SD) age was 82.5 (9.6) years; and 49 (77%) had dementia, 1 (2%) had mild cognitive impairment, and 14 (22%) had normal cognition. Prespecified success criteria were met for the A16 primary cohort. The flortaucipir PET scans predicted a B3 level of tau pathology, with sensitivity ranging from 92.3% (95% CI, 79.7%-97.3%) to 100.0% (95% CI, 91.0%-100.0%) and specificity ranging from 52.0% (95% CI, 33.5%-70.0%) to 92.0% (95% CI, 75.0%-97.8%). A high level of AD neuropathological change was predicted with sensitivity of 94.7% (95% CI, 82.7%-98.5%) to 100.0% (95% CI, 90.8%-100.0%) and specificity of 50.0% (95% CI, 32.1%-67.9%) to 92.3% (95% CI, 75.9%-97.9%). The FR01 validation study also met prespecified success criteria. Addition of the supplemental autopsy data set and 3 test cases, which comprised a total of 82 patients and autopsies for both the A16 and FR01 studies, resulted in improved specificity and comparable overall accuracy. Among the 156 enrolled participants, 14 (9%) experienced at least 1 treatment-emergent adverse event. CONCLUSIONS AND RELEVANCE: This study’s findings suggest that PET imaging with 18Fflortaucipir could be used to identify the density and distribution of AD-type tau pathology and the presence of high levels of AD neuropathological change, supporting a neuropathological diagnosis of AD.
Gut-associated lymphoid tissues (GALT) are the key antigen sampling and adaptive immune inductive sites within the intestinal wall. Human GALT includes the multi-follicular Peyer's patches of the ...ileum, the vermiform appendix, and the numerous isolated lymphoid follicles (ILF) which are distributed along the length of the intestine. Our current understanding of GALT diversity and function derives primarily from studies in mice, and the relevance of many of these findings to human GALT remains unclear. Here we review our current understanding of human GALT diversity, structure, and composition as well as their potential for regulating intestinal immune responses during homeostasis and inflammatory bowel disease (IBD). Finally, we outline some key remaining questions regarding human GALT, the answers to which will advance our understanding of intestinal immune responses and provide potential opportunities to improve the treatment of intestinal diseases.
Increasingly, evidence argues that many neurodegenerative diseases, including progressive supranuclear palsy (PSP), are caused by prions, which are alternatively folded proteins undergoing ...selfpropagation. In earlier studies, PSP prions were detected by infecting human embryonic kidney (HEK) cells expressing a tau fragment TauRD(LM) fused to yellow fluorescent protein (YFP). Here, we report on an improved bioassay using selective precipitation of tau prions from human PSP brain homogenates before infection of the HEK cells. Tau prions were measured by counting the number of cells with TauRD(LM)–YFP aggregates using confocal fluorescence microscopy. In parallel studies, we fused α-synuclein to YFP to bioassay α-synuclein prions in the brains of patients who died of multiple system atrophy (MSA). Previously, MSA prion detection required ∼120 d for transmission into transgenic mice, whereas our cultured cell assay needed only 4 d. Variation in MSA prion levels in four different brain regions from three patients provided evidence for three different MSA prion strains. Attempts to demonstrate α-synuclein prions in brain homogenates from Parkinson’s disease patients were unsuccessful, identifying an important biological difference between the two synucleinopathies. Partial purification of tau and α-synuclein prions facilitated measuring the levels of these protein pathogens in human brains. Our studies should facilitate investigations of the pathogenesis of both tau and α-synuclein prion disorders as well as help decipher the basic biology of those prions that attack the CNS.
Global climate change is affecting the distribution of marine species and is thought to represent a threat to biodiversity. Previous studies project expansion of species range for some species and ...local extinction elsewhere under climate change. Such range shifts raise concern for species whose long-term persistence is already threatened by other human disturbances such as fishing. However, few studies have attempted to assess the effects of future climate change on threatened vertebrate marine species using a multi-model approach. There has also been a recent surge of interest in climate change impacts on protected areas. This study applies three species distribution models and two sets of climate model projections to explore the potential impacts of climate change on marine species by 2050. A set of species in the North Sea, including seven threatened and ten major commercial species were used as a case study. Changes in habitat suitability in selected candidate protected areas around the UK under future climatic scenarios were assessed for these species. Moreover, change in the degree of overlap between commercial and threatened species ranges was calculated as a proxy of the potential threat posed by overfishing through bycatch. The ensemble projections suggest northward shifts in species at an average rate of 27 km per decade, resulting in small average changes in range overlap between threatened and commercially exploited species. Furthermore, the adverse consequences of climate change on the habitat suitability of protected areas were projected to be small. Although the models show large variation in the predicted consequences of climate change, the multi-model approach helps identify the potential risk of increased exposure to human stressors of critically endangered species such as common skate (Dipturus batis) and angelshark (Squatina squatina).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gene amplification is a tumor-specific event during malignant transformation. Recent studies have proposed a lineage-dependency (addiction) model of human cancer whereby amplification of certain ...lineage transcription factors predisposes a survival mechanism in tumor cells. These tumor cells are derived from tissues where the lineage factors play essential developmental and maintenance roles. Here, we show that recurrent amplification at 18q11.2 occurs in 21% of esophageal adenocarcinomas (EAC). Utilization of an integrative genomic strategy reveals a single gene, the embryonic endoderm transcription factor GATA6, as the selected target of the amplification. Overexpression of GATA6 is found in EACs that contain gene amplification. We find that EAC patients whose tumors carry GATA6 amplification have a poorer survival. We show that ectopic expression of GATA6, together with FGFR2 isoform IIIb, increases anchorage-independent growth in immortalized Barrett's esophageal cells. Conversely, siRNA-mediated silencing of GATA6 significantly reduces both cell proliferation and anchorage-independent growth in EAC cells. We further demonstrate that induction of apoptotic/anoikis pathways is triggered upon silencing of GATA6 in EAC cells but not in esophageal squamous cells. We show that activation of p38α signaling and up-regulation of TNF-related apoptosis-inducing ligand are detected in apoptotic EAC cells upon GATA6 deprivation. We conclude that selective gene amplification of GATA6 during EAC development sustains oncogenic lineage-survival of esophageal adenocarcinoma.
The biological production of methane is vital to the global carbon cycle and accounts for ca. 74% of total methane emissions. The organisms that facilitate this process, methanogenic archaea, belong ...to a large and phylogenetically diverse group that thrives in a wide range of anaerobic environments. Two main subgroups exist within methanogenic archaea: those with and those without cytochromes. Although a variety of metabolisms exist within this group, the reduction of growth substrates to methane using electrons from molecular hydrogen is, in a phylogenetic sense, the most widespread methanogenic pathway. Methanogens without cytochromes typically generate methane by the reduction of CO
with electrons derived from H
, formate, or secondary alcohols, generating a transmembrane ion gradient for ATP production via an Na
-translocating methyltransferase (Mtr). These organisms also conserve energy with a novel flavin-based electron bifurcation mechanism, wherein the endergonic reduction of ferredoxin is facilitated by the exergonic reduction of a disulfide terminal electron acceptor coupled to either H
or formate oxidation. Methanogens that utilize cytochromes have a broader substrate range, and can convert acetate and methylated compounds to methane, in addition to the ability to reduce CO
Cytochrome-containing methanogens are able to supplement the ion motive force generated by Mtr with an H
-translocating electron transport system. In both groups, enzymes known as hydrogenases, which reversibly interconvert protons and electrons to molecular hydrogen, play a central role in the methanogenic process. This review discusses recent insight into methanogen metabolism and energy conservation mechanisms with a particular focus on the genus
.