COVID-19 has upended travel across the world, disrupting commute patterns, mode choices, and public transit systems. In the United States, changes to transit service and reductions in passenger ...volume due to COVID-19 are lasting longer than originally anticipated. In this paper we examine the impacts of the COVID-19 pandemic on individual travel behavior across the United States. We analyze mobility data from Janurary to December 2020 from a sample drawn from a nationwide smartphone-based panel curated by a private firm, Embee Mobile. We combine this with a survey that we administered to that sample in August 2020. Our analysis provides insight into travel patterns and the immediate impacts of the COVID-19 pandemic on transit riders.
We investigate three questions. First, how do transit riders differ socio-demographically from non-riders? Second, how has the travel behavior of transit riders changed due to the pandemic in comparison to non-riders, controlling for other factors? And third, how has this travel behavior varied across different types of transit riders?
The travel patterns of transit riders were more significantly disrupted by the pandemic than the travel of non-riders, as measured by the average weekly number of trips and distance traveled before and after the onset of the pandemic. This was calculated using GPS traces from panel member smartphones. Our survey of the panel revealed that of transit riders, 75% reported taking transit less since the pandemic, likely due to a combination of being affected by transit service changes, concerns about infection risk on transit, and trip reductions due to shelter-in-place rules. Less than 10 percent of transit riders in our sample reported that they were comfortable using transit despite COVID-19 infection risk, and were not affected by transit service reductions. Transit riders were also more likely to have changed their travel behavior in other ways, including reporting an increase in walking. However, lower-income transit riders were different from higher-income riders in that they had a significantly smaller reduction in the number of trips and distance traveled, suggesting that these lower-income households had less discretion over the amount of travel they carried out during the pandemic. These results have significant implications for understanding the way welfare has been affected for transportation-disadvantaged populations during the course of the pandemic, and insight into the recovery of U.S. transit systems.
The evidence from this unique dataset helps us understand the future effects of the pandemic on transit riders in the United States, either in further recovery from the pandemic with the anticipated effects of mass vaccination, or in response to additional waves of COVID-19 and other pandemics.
•The COVID-19 pandemic significantly disrupted travel for public transit users.•Transit riders reduced their travel more than non-riders.•Among transit riders, those of lower income reduced their travel less than others.•The majority of transit riders were hesitant to use transit due to infection risk.•Less crowding, and enforcing mask use, could increase willingness to use transit.
Brain circuits endow behavioral flexibility. Here, we study circuits encoding flexible chemotaxis in C. elegans, where the animal navigates up or down NaCl gradients (positive or negative chemotaxis) ...to reach the salt concentration of previous growth (the set point). The ASER sensory neuron mediates positive and negative chemotaxis by regulating the frequency and direction of reorientation movements in response to salt gradients. Both salt gradients and set point memory are encoded in ASER temporal activity patterns. Distinct temporal activity patterns in interneurons immediately downstream of ASER encode chemotactic movement decisions. Different interneuron combinations regulate positive versus negative chemotaxis. We conclude that sensorimotor pathways are segregated immediately after the primary sensory neuron in the chemotaxis circuit, and sensory representation is rapidly transformed to motor representation at the first interneuron layer. Our study reveals compact encoding of perception, memory, and locomotion in an experience-dependent navigational behavior in C. elegans.
•Compact encoding of perception, memory, and movement for chemotaxis•Temporal activity patterns of a sensory neuron encodes perception and memory•Flexible relays of interneuronal network•Rapid synaptic transformation of sensory representation to motor representation
Luo et al. explore a chemotaxis circuit in C. elegans and find that it encodes behavior and plasticity via complex activity patterns in single sensory neurons representing both perception and experience, transforming these patterns into representations of motor decisions at the first postsynaptic relays.
Health traits are of significant economic importance to the dairy industry due to their effects on milk production and associated treatment costs. Genome-wide association studies (GWAS) provide a ...means to identify associated genomic variants and thus reveal insights into the genetic architecture of complex traits and diseases. The objective of this study is to investigate the genetic basis of seven health traits in dairy cattle and to identify potential candidate genes associated with cattle health using GWAS, fine mapping, and analyses of multi-tissue transcriptome data.
We studied cow livability and six direct disease traits, mastitis, ketosis, hypocalcemia, displaced abomasum, metritis, and retained placenta, using de-regressed breeding values and more than three million imputed DNA sequence variants. After data edits and filtering on reliability, the number of bulls included in the analyses ranged from 11,880 (hypocalcemia) to 24,699 (livability). GWAS was performed using a mixed-model association test, and a Bayesian fine-mapping procedure was conducted to calculate a posterior probability of causality to each variant and gene in the candidate regions. The GWAS detected a total of eight genome-wide significant associations for three traits, cow livability, ketosis, and hypocalcemia, including the bovine Major Histocompatibility Complex (MHC) region associated with livability. Our fine-mapping of associated regions reported 20 candidate genes with the highest posterior probabilities of causality for cattle health. Combined with transcriptome data across multiple tissues in cattle, we further exploited these candidate genes to identify specific expression patterns in disease-related tissues and relevant biological explanations such as the expression of Group-specific Component (GC) in the liver and association with mastitis as well as the Coiled-Coil Domain Containing 88C (CCDC88C) expression in CD8 cells and association with cow livability.
Collectively, our analyses report six significant associations and 20 candidate genes of cattle health. With the integration of multi-tissue transcriptome data, our results provide useful information for future functional studies and better understanding of the biological relationship between genetics and disease susceptibility in cattle.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Most cases of adult myeloid neoplasms are routinely assumed to be sporadic. Here, we describe an adult familial acute myeloid leukemia (AML) syndrome caused by germline mutations in the DEAD/H-box ...helicase gene DDX41. DDX41 was also found to be affected by somatic mutations in sporadic cases of myeloid neoplasms as well as in a biallelic fashion in 50% of patients with germline DDX41 mutations. Moreover, corresponding deletions on 5q35.3 present in 6% of cases led to haploinsufficient DDX41 expression. DDX41 lesions caused altered pre-mRNA splicing and RNA processing. DDX41 is exemplary of other RNA helicase genes also affected by somatic mutations, suggesting that they constitute a family of tumor suppressor genes.
ABSTRACT
Since the early 1990s, ecologists and evolutionary biologists have aggregated primary research using meta‐analytic methods to understand ecological and evolutionary phenomena. Meta‐analyses ...can resolve long‐standing disputes, dispel spurious claims, and generate new research questions. At their worst, however, meta‐analysis publications are wolves in sheep's clothing: subjective with biased conclusions, hidden under coats of objective authority. Conclusions can be rendered unreliable by inappropriate statistical methods, problems with the methods used to select primary research, or problems within the primary research itself. Because of these risks, meta‐analyses are increasingly conducted as part of systematic reviews, which use structured, transparent, and reproducible methods to collate and summarise evidence. For readers to determine whether the conclusions from a systematic review or meta‐analysis should be trusted – and to be able to build upon the review – authors need to report what they did, why they did it, and what they found. Complete, transparent, and reproducible reporting is measured by ‘reporting quality’. To assess perceptions and standards of reporting quality of systematic reviews and meta‐analyses published in ecology and evolutionary biology, we surveyed 208 researchers with relevant experience (as authors, reviewers, or editors), and conducted detailed evaluations of 102 systematic review and meta‐analysis papers published between 2010 and 2019. Reporting quality was far below optimal and approximately normally distributed. Measured reporting quality was lower than what the community perceived, particularly for the systematic review methods required to measure trustworthiness. The minority of assessed papers that referenced a guideline (~16%) showed substantially higher reporting quality than average, and surveyed researchers showed interest in using a reporting guideline to improve reporting quality. The leading guideline for improving reporting quality of systematic reviews is the Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) statement. Here we unveil an extension of PRISMA to serve the meta‐analysis community in ecology and evolutionary biology: PRISMA‐EcoEvo (version 1.0). PRISMA‐EcoEvo is a checklist of 27 main items that, when applicable, should be reported in systematic review and meta‐analysis publications summarising primary research in ecology and evolutionary biology. In this explanation and elaboration document, we provide guidance for authors, reviewers, and editors, with explanations for each item on the checklist, including supplementary examples from published papers. Authors can consult this PRISMA‐EcoEvo guideline both in the planning and writing stages of a systematic review and meta‐analysis, to increase reporting quality of submitted manuscripts. Reviewers and editors can use the checklist to assess reporting quality in the manuscripts they review. Overall, PRISMA‐EcoEvo is a resource for the ecology and evolutionary biology community to facilitate transparent and comprehensively reported systematic reviews and meta‐analyses.
Background & Aims Aerobic exercise reduces liver fat and visceral adipose tissue (VAT). However, there is limited data from randomized trials to inform exercise programming recommendations. This ...study examined the efficacy of commonly prescribed exercise doses for reducing liver fat and VAT using a randomized placebo-controlled design. Methods Inactive and overweight/obese adults received 8 weeks of either; i) low to moderate intensity, high volume aerobic exercise (LO:HI, 50% VO2peak , 60 min, 4 d/week); ii) high intensity, low volume aerobic exercise (HI:LO, 70% VO2peak , 45 min, 3 d/week); iii) low to moderate intensity, low volume aerobic exercise (LO:LO, 50% VO2peak, 45 min, 3 d/week); or iv) placebo (PLA). Liver fat (spectroscopy) and VAT (magnetic resonance imaging) were measured before and after intervention. Results Forty-seven of the 48 (n = 12 in each group) participants completed the trial. There were no serious adverse events. There was a significant change in group × time interaction in liver fat, which reduced in HI:LO by 2.38 ± 0.73%, in LO:HI by 2.62 ± 1.00%, and in LO:LO by 0.84 ± 0.47% but not in PLA (increase of 1.10 ± 0.62%) ( p = 0.04). There was a significant reduction in VAT in HI:LO (−258.38 ± 87.78 cm3 ), in LO:HI (−386.80 ± 119.5 cm3 ), and in LO:LO (−212.96 ± 105.54 cm3 ), but not in PLA (92.64 ± 83.46 cm3 ) ( p = 0.03). There were no significant differences between the dose or intensity of the exercise regimen and reductions in liver fat or VAT ( p >0.05). Conclusion The study found no difference in efficacy of liver fat reduction by either aerobic exercise dose or intensity. All of the aerobic exercise regimens employed reduced liver fat and VAT by a small amount without clinically significant weight loss.
The tricarboxylic acid (TCA) cycle is a central metabolic pathway responsible for supplying reducing potential for oxidative phosphorylation and anabolic substrates for cell growth, repair and ...proliferation. As such it thought to be essential for cell proliferation and tissue homeostasis. However, since the initial report of an inactivating mutation in the TCA cycle enzyme complex, succinate dehydrogenase (SDH) in paraganglioma (PGL), it has become clear that some cells and tissues are not only able to survive with a truncated TCA cycle, but that they are also able of supporting proliferative phenotype observed in tumours. Here, we show that loss of SDH activity leads to changes in the metabolism of non-essential amino acids. In particular, we demonstrate that pyruvate carboxylase is essential to re-supply the depleted pool of aspartate in SDH-deficient cells. Our results demonstrate that the loss of SDH reduces the metabolic plasticity of cells, suggesting vulnerabilities that can be targeted therapeutically.
Regulation of gene expression is integral to the development and survival of all organisms. Transcription begins with the assembly of a pre-initiation complex at the gene promoter, followed by ...initiation of RNA synthesis and the transition to productive elongation. In many cases, recruitment of RNA polymerase II (Pol II) to a promoter is necessary and sufficient for activation of genes. However, there are a few notable exceptions to this paradigm, including heat shock genes and several proto-oncogenes, whose expression is attenuated by regulated stalling of polymerase elongation within the promoter-proximal region. To determine the importance of polymerase stalling for transcription regulation, we carried out a genome-wide search for Drosophila melanogaster genes with Pol II stalled within the promoter-proximal region. Our data show that stalling is widespread, occurring at hundreds of genes that respond to stimuli and developmental signals. This finding indicates a role for regulation of polymerase elongation in the transcriptional responses to dynamic environmental and developmental cues.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Garlic has been used for centuries for its flavour and health promoting properties that include protection against cancer. The vinyl disulfide-sulfoxide ajoene is one of the phytochemicals found in ...crushed cloves, hypothesised to act by S-thiolating reactive cysteines in target proteins.
Using our fluorescently labelled ajoene analogue called dansyl-ajoene, ajoene's protein targets in MDA-MB-231 breast cancer cells were tagged and separated by 2D electrophoresis. A predominant band was identified by MALDI-TOF MS/MS to be vimentin. Target validation experiments were performed using pure recombinant vimentin protein. Computational modelling of vimentin bound to ajoene was performed using Schrödinger and pK
calculations by Epik software. Cytotoxicity of ajoene in MDA-MB-231 and HeLa cells was measured by the MTT assay. The vimentin filament network was visualised in ajoene-treated and non-treated cells by immunofluorescence and vimentin protein expression was determined by immunoblot. The invasion and migration activity was measured by wound healing and transwell assays using wildtype cells and cells in which the vimentin protein had been transiently knocked down by siRNA or overexpressed.
The dominant protein tagged by dansyl-ajoene was identified to be the 57 kDa protein vimentin. The vimentin target was validated to reveal that ajoene and dansyl-ajoene covalently bind to recombinant vimentin via a disulfide linkage at Cys-328. Computational modelling showed Cys-328 to be exposed at the termini of the vimentin tetramer. Treatment of MDA-MB-231 or HeLa cells with a non-cytotoxic concentration of ajoene caused the vimentin filament network to condense; and to increase vimentin protein expression. Ajoene inhibited the invasion and migration of both cancer cell lines which was found to be dependent on the presence of vimentin. Vimentin overexpression caused cells to become more migratory, an effect that was completely rescued by ajoene.
The garlic-derived phytochemical ajoene targets and covalently modifies vimentin in cancer cells by S-thiolating Cys-328. This interaction results in the disruption of the vimentin filament network and contributes to the anti-metastatic activity of ajoene in cancer cells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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