COVID survivors frequently experience lingering neurological symptoms that resemble cancer therapy-related cognitive impairment, a syndrome for which white-matter microglial reactivity and consequent ...neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared to SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis and elevated CCL11 at early timepoints, but after influenza only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.
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Purpose
The nutritional quality of final products is attracting an increased level of attention within life cycle assessment (LCA) literature of agri-food systems. The majority of these studies, ...however, are based on comparisons at the dietary level and, therefore, are unable to offer immediate implications for farmers as to how best to produce food. This article evaluates recent literature examining the nutrition-environment nexus at the commodity level, with the aim to identify potential pathways towards sustainability analysis that can inform both consumers and producers.
Methods
A systematic search of literature was carried out to produce a shortlist of studies, and strict exclusion criteria were applied to them afterwards to eliminate irrelevant material. The studies thus selected were classified into one of three tiers based on the level of complexity with regard to their functional units: (1) based on single nutrients, (2) based on composite indicators derived from multiple nutrients and (3) based on commodity-level analysis in a dietary context.
Results and discussion
Sixteen papers were identified for inclusion in the review. All of them accounted for climate change either directly or indirectly, whilst only five addressed different impact categories at the same time. Nine studies estimated environmental impacts under functional units associated with nutrient density scores, and the others utilised alternative approaches to account for nutritional value such as linear programming and end-point modelling combined with epidemiological data. A recently developed method to calculate the marginal contribution of a commodity to the overall nutritional value of a specific diet was considered to be a successful first step in bridging the aforementioned knowledge gap.
Conclusions
The LCA community should continue the ongoing effort to link farm management decisions to diet-level environmental impacts through an enhanced focus on human nutrition across the entire value chain. Future research comparing environmental performances of multiple food groups or multiple production systems should acknowledge differences in nutritional composition and bioavailability between the final products and, ideally, the effects of these nutrients on overall dietary quality.
Delays in peer reviewed publication may have consequences for both assessment of scientific prowess in academics as well as communication of important information to the knowledge receptor community. ...We present an analysis on the perspectives of authors publishing in conservation biology journals regarding their opinions on the importance of speed in peer-review as well as how to improve review times. Authors were invited to take part in an online questionnaire, of which the data was subjected to both qualitative (open coding, categorizing) and quantitative analyses (generalized linear models). We received 637 responses to a total of 6,547 e-mail invitations sent. Peer-review speed was generally perceived as slow, with authors experiencing a typical turnaround time of 14 weeks while their perceived optimal review time is six weeks. Male and younger respondents seem to have higher expectations of review speed than females and older respondents. Majority of participants attributed lengthy review times to the 'stress' on the peer-review system (i.e., reviewer and editor fatigue), while editor persistence and journal prestige were believed to speed up the review process. Negative consequences of lengthy review times appear to be greater for early career researchers and can also have impact on author morale (e.g. motivation or frustration). Competition among colleagues were also of concern to respondents. Incentivizing peer review was among the top suggested alterations to the system along with training graduate students in peer review, increased editorial persistence, and changes to the norms of peer-review such as opening the peer-review process to the public. It is clear that authors surveyed in this study view the peer-review system as under stress and we encourage scientists and publishers to push the envelope for new peer review models.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Complex interactions between host immunity and the microbiome regulate norovirus infection. However, the mechanism of host immune promotion of enteric virus infection remains obscure. The cellular ...tropism of noroviruses is also unknown. Recently, we identified CD300lf as a murine norovirus (MNoV) receptor. In this study, we have shown that tuft cells, a rare type of intestinal epithelial cell, express CD300lf and are the target cell for MNoV in the mouse intestine. We found that type 2 cytokines, which induce tuft cell proliferation, promote MNoV infection in vivo. These cytokines can replace the effect of commensal microbiota in promoting virus infection. Our work thus provides insight into how the immune system and microbes can coordinately promote enteric viral infection.
Prognostic systems for myelodysplasia rely on clinical factors, but particular genetic lesions can influence relapse rate, overall survival, and nonrelapse-related mortality as well as the choice of ...conditioning regimen for hematopoietic stem-cell transplantation.
The myelodysplastic syndrome (MDS) is clinically and biologically heterogeneous. In children and young adults, MDS can arise in the context of congenital mutations that cause bone marrow failure syndromes or inherited predisposition to myeloid cancers.
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Therapy-related MDS develops as a late complication in patients with previous exposure to chemotherapy, radiation therapy, or both.
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In most patients, however, primary MDS arises in the absence of an identified exposure, prodromal bone marrow failure syndrome, or inherited predisposition.
Although allogeneic hematopoietic stem-cell transplantation is the only curative therapy for MDS, mortality after transplantation is high, with deaths attributable to relapsed disease and to . . .
Mutation accumulation in somatic cells contributes to cancer development and is proposed as a cause of aging. DNA polymerases Pol ε and Pol δ replicate DNA during cell division. However, in some ...cancers, defective proofreading due to acquired POLE/POLD1 exonuclease domain mutations causes markedly elevated somatic mutation burdens with distinctive mutational signatures. Germline POLE/POLD1 mutations cause familial cancer predisposition. Here, we sequenced normal tissue and tumor DNA from individuals with germline POLE/POLD1 mutations. Increased mutation burdens with characteristic mutational signatures were found in normal adult somatic cell types, during early embryogenesis and in sperm. Thus human physiology can tolerate ubiquitously elevated mutation burdens. Except for increased cancer risk, individuals with germline POLE/POLD1 mutations do not exhibit overt features of premature aging. These results do not support a model in which all features of aging are attributable to widespread cell malfunction directly resulting from somatic mutation burdens accrued during life.
Eukaryotic cells contain assemblies of RNAs and proteins termed RNA granules. Many proteins within these bodies contain KH or RRM RNA-binding domains as well as low complexity (LC) sequences of ...unknown function. We discovered that exposure of cell or tissue lysates to a biotinylated isoxazole (b-isox) chemical precipitated hundreds of RNA-binding proteins with significant overlap to the constituents of RNA granules. The LC sequences within these proteins are both necessary and sufficient for b-isox-mediated aggregation, and these domains can undergo a concentration-dependent phase transition to a hydrogel-like state in the absence of the chemical. X-ray diffraction and EM studies revealed the hydrogels to be composed of uniformly polymerized amyloid-like fibers. Unlike pathogenic fibers, the LC sequence-based polymers described here are dynamic and accommodate heterotypic polymerization. These observations offer a framework for understanding the function of LC sequences as well as an organizing principle for cellular structures that are not membrane bound.
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► A biotinylated small molecule precipitates RNA granule proteins from cell lysates ► Low complexity sequences in these proteins form hydrogels ► Amyloid-like fibers within the gels can trap LCS domains from other proteins ► The cell-free in vitro reactions model RNA granule architecture and formation
RNA-binding proteins with regions of low complexity sequence can form hydrogels in vitro comprised of amyloid-like fibers either via nucleation by a small molecule or by self-organization. Unlike pathologic amyloids, the fibers are dynamic and can incorporate low complexity domains from different proteins, suggesting a basis for assembly of RNA granules within cells.
Tobacco smoking causes lung cancer
, a process that is driven by more than 60 carcinogens in cigarette smoke that directly damage and mutate DNA
. The profound effects of tobacco on the genome of ...lung cancer cells are well-documented
, but equivalent data for normal bronchial cells are lacking. Here we sequenced whole genomes of 632 colonies derived from single bronchial epithelial cells across 16 subjects. Tobacco smoking was the major influence on mutational burden, typically adding from 1,000 to 10,000 mutations per cell; massively increasing the variance both within and between subjects; and generating several distinct mutational signatures of substitutions and of insertions and deletions. A population of cells in individuals with a history of smoking had mutational burdens that were equivalent to those expected for people who had never smoked: these cells had less damage from tobacco-specific mutational processes, were fourfold more frequent in ex-smokers than current smokers and had considerably longer telomeres than their more-mutated counterparts. Driver mutations increased in frequency with age, affecting 4-14% of cells in middle-aged subjects who had never smoked. In current smokers, at least 25% of cells carried driver mutations and 0-6% of cells had two or even three drivers. Thus, tobacco smoking increases mutational burden, cell-to-cell heterogeneity and driver mutations, but quitting promotes replenishment of the bronchial epithelium from mitotically quiescent cells that have avoided tobacco mutagenesis.
ABSTRACT
Ultra-hot Jupiters are tidally locked gas giants with dayside temperatures high enough to dissociate hydrogen and other molecules. Their atmospheres are vastly non-uniform in terms of ...chemistry, temperature, and dynamics, and this makes their high-resolution transmission spectra and cross-correlation signal difficult to interpret. In this work, we use the SPARC/MITgcm global circulation model to simulate the atmosphere of the ultra-hot Jupiter WASP-76b under different conditions, such as atmospheric drag and the absence of TiO and VO. We then employ a 3D Monte Carlo radiative transfer code, hires-mcrt, to self-consistently model high-resolution transmission spectra with iron (Fe i) lines at different phases during the transit. To untangle the structure of the resulting cross-correlation map, we decompose the limb of the planet into four sectors, and we analyse each of their contributions separately. Our experiments demonstrate that the cross-correlation signal of an ultra-hot Jupiter is primarily driven by its temperature structure, rotation, and dynamics, while being less sensitive to the precise distribution of iron across the atmosphere. We also show that the previously published iron signal of WASP-76b can be reproduced by a model featuring iron condensation on the leading limb. Alternatively, the signal may be explained by a substantial temperature asymmetry between the trailing and leading limb, where iron condensation is not strictly required to match the data. Finally, we compute the Kp–Vsys maps of the simulated WASP-76b atmospheres, and we show that rotation and dynamics can lead to multiple peaks that are displaced from zero in the planetary rest frame.
Somatic mutations drive the development of cancer and may contribute to ageing and other diseases
. Despite their importance, the difficulty of detecting mutations that are only present in single ...cells or small clones has limited our knowledge of somatic mutagenesis to a minority of tissues. Here, to overcome these limitations, we developed nanorate sequencing (NanoSeq), a duplex sequencing protocol with error rates of less than five errors per billion base pairs in single DNA molecules from cell populations. This rate is two orders of magnitude lower than typical somatic mutation loads, enabling the study of somatic mutations in any tissue independently of clonality. We used this single-molecule sensitivity to study somatic mutations in non-dividing cells across several tissues, comparing stem cells to differentiated cells and studying mutagenesis in the absence of cell division. Differentiated cells in blood and colon displayed remarkably similar mutation loads and signatures to their corresponding stem cells, despite mature blood cells having undergone considerably more divisions. We then characterized the mutational landscape of post-mitotic neurons and polyclonal smooth muscle, confirming that neurons accumulate somatic mutations at a constant rate throughout life without cell division, with similar rates to mitotically active tissues. Together, our results suggest that mutational processes that are independent of cell division are important contributors to somatic mutagenesis. We anticipate that the ability to reliably detect mutations in single DNA molecules could transform our understanding of somatic mutagenesis and enable non-invasive studies on large-scale cohorts.
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