bluuebunny/crossref_metadata_2025_split huggingface dataset:
Projecting the transition of COVID-19 burden towards the young population while vaccines are rolled out: a modelling study
Authors: Cai Jun , Yang Juan , Deng Xiaowei , Peng Cheng , Chen Xinhua , Wu Qianhui , Liu Hengcong , Zhang Juanjuan , Zheng Wen , Zou Junyi , Zhao Zeyao , Ajelli Marco , Yu Hongjie 
Published: October 2021

AbstractObjectivesSARS-CoV-2 infection causes most cases of severe illness and fatality in older age groups. In China, over 99% of individuals aged ⩾12 years have been fully vaccinated against COVID-19 (albeit with vaccines developed against historical lineages), while 65.0% children aged 3–11 years have been vaccinated their first doses (as of November 12, 2021). Here, we aimed to assess whether, in this vaccination landscape, the importation of Delta variant infections could shift the COVID-19 burden from adults to children.MethodsWe developed an age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission dynamics to simulate epidemics triggered by the importation of Delta variant infections and project the age-specific incidence of SARS-CoV-2 infections, cases, hospitalisations, intensive care unit (ICU) admissions, and deaths.ResultsIn the context of the vaccination programme targeting individuals aged ≥12 years (as it was the case until mid-October 2021), and in the absence of non-pharmaceutical interventions, the importation of Delta variant infections could have led to widespread transmission and substantial disease burden in mainland China, even with vaccination coverage as high as 97% across the eligible age groups. Extending the vaccination roll-out to include children aged 3–11 years (as it was the case since the end of October 2021) is estimated to dramatically decrease the burden of symptomatic infections and hospitalisations within this age group (54% and 81%, respectively, when considering a vaccination coverage of 99%), but would have a low impact on protecting infants (aged 0–2 years).ConclusionsOur findings highlight the importance of including children among the target population and the need to strengthen vaccination efforts by increasing vaccine effectiveness.
Escape from X-inactivation in twins exhibits intra- and inter-individual variability across tissues and is heritable
Authors: Zito A. , Roberts A.L. , Visconti A. , Rossi N. , Andres-Ejarque R. , Nardone S. , Moustafa J.E.S. , Falchi M. , Small K.S. 
Published: October 2021

ABSTRACTX-chromosome inactivation (XCI) silences one X-chromosome in female cells to balance sex-differences in X-dosage. A subset of X-linked genes escape XCI, but the extent to which this phenomenon occurs and how it varies across tissues and in a population is as yet unclear. In order to characterize the incidence and variability of escape across individuals and tissues, we conducted a large scale transcriptomic study of XCI escape in adipose, skin, lymphoblastoid cell lines (LCLs) and immune cells in 248 twins drawn from a healthy population cohort. We identify 159 X-linked genes with detectable escape, of which 54 genes, including 19 lncRNAs, were not previously known to escape XCI. Across tissues we find a range of tissue-specificity, with 11% of genes escaping XCI constitutively across tissues and 24% demonstrating tissue-restricted escape, including genes with cell-type specific escape between immune cell types (B, T-CD4+, T-CD8+ and NK cells) of the same individual. Escape genes interact with autosomal-encoded proteins and are involved in varied biological processes such as gene regulation. We find substantial variability in escape between individuals. 49% of genes show inter-individual variability in escape, indicating escape from XCI is an under-appreciated source of gene expression differences. We utilized twin models to investigate the role of genetics in variable escape. Overall, monozygotic (MZ) twin pairs share more similar escape than dizygotic twin pairs, indicating that genetic factors underlie differences in escape across individuals. However, we also identify instances of discordant XCI within MZ co-twin pairs, suggesting that environmental factors also influence escape. Thus, XCI escape may be shaped by an interplay of genetic factors with tissue- and cell type-specificity, and environment. These results illuminate an intricate phenotype whose characterization aids understanding the basis of variable trait expressivity in females.
Long-term imaging of the ventral nerve cord in behaving adultDrosophila
Authors: Hermans Laura , Kaynak Murat , Braun Jonas , Lobato Ríos Victor , Chen Chin-Lin , Günel Semih , Aymanns Florian , Sakar Mahmut Selman , Ramdya Pavan 
Published: October 2021

AbstractThe dynamics and connectivity of neural circuits continuously change during an animal’s lifetime on timescales ranging from milliseconds to days. Therefore, to investigate how biological networks accomplish remarkable cognitive and behavioral tasks, minimally invasive methods are needed to perform repeated measurements, or perturbations of neural circuits in behaving animals across time. Such tools have been developed to investigate the brain but similar approaches are lacking for comprehensively and repeatedly recording motor circuits in behaving animals. Here we describe a suite of microfabricated technologies that enable long-term, minimally invasive optical recordings of the adultDrosophila melanogasterventral nerve cord (VNC)—neural tissues that are functionally equivalent to the vertebrate spinal cord. These tools consist of (i) a manipulator arm that permits the insertion of (ii) a compliant implant into the thorax to expose the imaging region of interest; (iii) a numbered, transparent polymer window that encloses and provides optical access to the inside of the thorax, and (iv) a hinged remounting stage that allows gentle and repeated tethering of an implanted animal for two-photon imaging. We validate and illustrate the utility of our toolkit in several ways. First, we show that the thoracic implant and window have minimal impact on animal behavior and survival while also enabling neural recordings from individual animals across at least one month. Second, we follow the degradation of chordotonal organ mechanosensory nerve terminals in the VNC over weeks after leg amputation. Third, because our tools allow recordings of the VNC with the gut intact, we discover waves of neural population activity following ingestion of a high-concentration caffeine solution. In summary, our microfabricated toolkit makes it possible to longitudinally monitor anatomical and functional changes in premotor and motor neural circuits, and more generally opens up the long-term investigation of thoracic tissues.
Sex Differences in Pubertal Circadian and Ultradian Rhythmic Development Under Naturalistic Conditions
Authors: Grant Azure D. , Wilbrecht Linda , Kriegsfeld Lance J. 
Published: October 2021

AbstractBiological rhythms in core body temperature (CBT) provide informative markers of adolescent development under controlled laboratory conditions. However, it is unknown if these markers are preserved under more variable naturalistic conditions, and if CBT may therefore prove useful in a real-world setting. To evaluate this possibility, we examined fecal steroid concentrations and CBT rhythms from pre-adolescence (p26) through early adulthood (p76) in intact male and female rats under natural light and climate at the University of California, Berkeley Field Station. Despite greater environmental variability, CBT markers of pubertal onset and its rhythmic progression were comparable to those previously reported in laboratory conditions in female rats and extend actigraphy-based findings in males. Specifically, sex differences emerged in circadian rhythm (CR) power and temperature amplitude prior to pubertal onset and persisted into early adulthood, with females exhibiting elevated CBT and decreased CR power compared to males. Within-day (ultradian rhythm; UR) patterns also exhibited a pronounced sex difference associated with estrous cyclicity. Pubertal onset, defined by vaginal opening, preputial separation, and sex steroid concentrations, occurred later than previously reported under lab conditions for both sexes. Vaginal opening and increased fecal estradiol concentrations were closely tied to the commencement of 4-day oscillations in CBT and UR power in female rats. By contrast, preputial separation and the first rise in testosterone concentration were not associated with adolescent changes to CBT rhythms in male rats. Together, males and females exhibited unique temporal patterning of CBT and sex steroids across pubertal development, with tractable associations between hormonal concentrations, external development, and temporal structure in females. The preservation of these features outside the laboratory supports CBT as a strong candidate for translational pubertal monitoring under naturalistic conditions in females.
Population-specific patterns of toxin sequestration in monarch butterflies from around the world
Authors: Freedman Micah G. , Choquette Sue-Ling , Ramírez Santiago R. , Strauss Sharon Y. , Hunter Mark D. , Vannette Rachel L. 
Published: October 2021

AbstractAnimals frequently defend themselves against predators using diet-derived toxins. Monarch butterflies are a preeminent example of toxin sequestration, gaining protection via cardenolides in their milkweed hosts. Few studies have considered genetic variation in sequestration ability, in monarchs or other species. Here, we use two approaches to study natural selection on cardenolide sequestration in monarchs. First, we conducted a reciprocal rearing experiment with six monarch populations and six associated host species from around the world to determine whether sequestration is higher in monarchs reared on sympatric host species. Second, we compared sequestered cardenolides in wild-caught monarchs from Guam—an island where bird predators have been functionally extirpated for >40 years—to a nearby island with intact birds. We found substantial genetic variation in sequestration ability, though no consistent sequestration advantage in sympatric combinations. One monarch population from Puerto Rico showed greatly reduced sequestration fromAsclepias syriaca, likely reflecting a lack of evolutionary association with this host. Monarchs from Guam showed reduced sequestration fromA. curassavica, both in a cross-island comparison and when reared under controlled conditions. Our results suggest that processes involved in toxin sequestration are subject to natural selection and may evolve in response to contemporary changes in species interactions.
Mapping enzyme catalysis with metabolomic biosensing
Authors: Xu Linfeng , Chang Kai-Chun , Payne Emory M. , Modavi Cyrus , Liu Leqian , Palmer Claire M. , Tao Nannan , Alper Hal S. , Kennedy Robert T. , Cornett Dale S. , Abate Adam R. 
Published: October 2021

AbstractEnzymes are represented across a vast space of protein sequences and structural forms and have activities that far exceed the best chemical catalysts; however, engineering them to have novel or enhanced activity is limited by technologies for sensing product formation. Here, we describe a general and scalable approach for characterizing enzyme activity that uses the metabolism of the host cell as a biosensor by which to infer product formation. Since different products consume different molecules in their synthesis, they perturb host metabolism in unique ways that can be measured by mass spectrometry. This provides a general way by which to sense product formation, to discover unexpected products and map the effects of mutagenesis.
Cholinergic modulation of distinct inhibitory domains in granule cells of the olfactory bulb
Authors: Villar Pablo S. , Hu Ruilong , Teitz Batya , Araneda Ricardo C. 
Published: October 2021

SUMMARYEarly olfactory processing relies on a large population of inhibitory neurons in the olfactory bulb (OB), the granule cells (GCs). GCs inhibit the OB output neurons, the mitral and tufted cells (M/TCs), shaping their responses to odors both in the spatial and temporal domains, therefore, the activity of GCs is finely tuned by local and centrifugal excitatory and inhibitory inputs. While the circuit substrates underlying regulatory inputs onto GCs are well-established, how they are locally modulated remains unclear. Here, we examine the regulation of GABAergic inhibition onto GCs by acetylcholine, a main neuromodulatory transmitter released in the OB, by basal forebrain (BF) neurons. In acute brain slices from male and female mice, we show that activation of muscarinic acetylcholine receptors (mAChRs) produces opposing effects on local and centrifugal inhibition onto GCs. By using electrophysiology, laser uncaging and optogenetics we show that the kinetics of GABAergic currents in GCs could be correlated with distal and proximal spatial domains from where they originate, along the GC somatodendritic axis. Proximal inhibition from BF afferents, is suppressed by activation of M2/M4-mAChRs. In contrast, distal local inhibition from deep short axon cells (dSACs) is enhanced by activation of M3-mAChRs. Furthermore, we show that the cholinergic enhancement of distal inhibition in GCs reduces the extent of dendrodendritic inhibition in MCs. Interestingly, the excitatory cortical feedback, which also targets the proximal region of GCs, was not modulated by acetylcholine, suggesting that muscarinic activation shifts the synaptic balance towards excitation in GCs. Together, these results suggest that BF cholinergic inputs to the OB fine tune GC-mediated inhibition of M/TCs by differentially modulating the proximal and distal domains of inhibition in GCs.
Estimating global variation in the maximum growth rates of eukaryotic microbes from cultures and metagenomes via codon usage patterns
Authors: Weissman JL , Dimbo Edward-Robert O. , Krinos Arianna I. , Neely Christopher , Yagües Yuniba , Nolin Delaney , Hou Shengwei , Laperriere Sarah , Caron David A. , Tully Benjamin , Alexander Harriet , Fuhrman Jed A. 
Published: October 2021

AbstractMicrobial eukaryotes are ubiquitous in the environment and play important roles in key ecosystem processes, including accounting for a significant portion of global primary production. Yet, our tools for assessing the functional capabilities of eukaryotic microbes in the environment are quite limited because many microbes have yet to be grown in culture. Maximum growth rate is a fundamental parameter of microbial lifestyle that reveals important information about an organism’s functional role in a community. We developed and validated a genomic estimator of maximum growth rate for eukaryotic microbes, enabling the assessment of growth potential for organisms and communities directly in the environment. We produced a database of over 700 maximum growth rate predictions from genomes, transcriptomes, and metagenome-assembled genomes. By comparing the maximal growth rates of existing culture collections with environmentally-derived genomes we found that, unlike for prokaryotes, culture collections of microbial eukaryotes are only minimally biased in terms of growth potential. We then extended our tool to make community-wide estimates of growth potential from over 500 marine metagenomes, mapping growth potential across the global oceans. We found that prokaryotic and eukaryotic communities have highly correlated growth potentials near the ocean surface, but there is no correlation in their genomic potentials deeper in the water column. This suggests that fast growing eukaryotes and prokaryotes thrive under similar conditions at the ocean surface, but that there is a decoupling of these communities as resources become scarce deeper in the water column.
When are bacteria really gazelles? Comparing patchy ecologies with dimensionless numbers
Authors: Urmy Samuel S. , Cramer Alli N. , Rogers Tanya L. , Sullivan-Stack Jenna , Schmidt Marian , Stewart Simon D. , Symons Celia C. 
Published: October 2021

AbstractFrom micro to planetary scales, spatial heterogeneity—patchiness—is ubiquitous in ecological systems, defining the environments in which organisms move and interact. While this fact has been recognized for decades, most large-scale ecosystem models still use spatially averaged “mean fields” to represent natural populations, while fine-scale, spatially explicit models are mostly restricted to particular organisms or systems. In a conceptual paper, Grünbaum (2012,Interface Focus2: 150-155) introduced a heuristic framework, based on three dimensionless ratios quantifying movement, reproduction, and resource consumption, to characterize patchy ecological interactions and identify when mean-field assumptions are justifiable. In this paper, we calculated Grünbaum’s dimensionless numbers for 33 real interactions between consumers and their resource patches in terrestrial, aquatic, and aerial environments. Consumers ranged in size from bacteria to blue whales, and patches lasted from minutes to millennia, spanning spatial scales of mm to hundreds of km. We found that none of the interactions could be accurately represented by a purely mean-field model, though 26 of them (79%) could be partially simplified by averaging out movement, reproductive, or consumption dynamics. Clustering consumer-resource pairs by their non-dimensional ratios revealed several unexpected dynamic similarities between disparate interactions. For example, bacterialPseudoalteromonasexploit nutrient plumes in a similar manner to Mongolian gazelles grazing on ephemeral patches of steppe vegetation. Our findings suggest that dimensional analysis is a valuable tool for characterizing ecological patchiness, and can link the dynamics of widely different systems into a single quantitative framework.
Kernel-based genetic association analysis for microbiome phenotypes identifies host genetic drivers of beta-diversity
Authors: Liu Hongjiao , Ling Wodan , Hua Xing , Moon Jee-Young , Williams-Nguyen Jessica S. , Zhan Xiang , Plantinga Anna M. , Zhao Ni , Zhang Angela , Knight Rob , Qi Qibin , Burk Robert D. , Kaplan Robert C. , Wu Michael C. 
Published: October 2021

AbstractUnderstanding human genetic influences on the gut microbiota helps elucidate the mechanisms by which genetics affects health outcomes. We propose a novel approach, the covariate-adjusted kernel RV (KRV) framework, to map genetic variants associated with microbiome beta-diversity, which focuses on overall shifts in the microbiota. The proposed KRV framework improves statistical power by capturing intrinsic structure within the genetic and microbiome data while reducing the multiple-testing burden. We apply the covariate-adjusted KRV test to the Hispanic Community Health Study/Study of Latinos in a genome-wide association analysis (first gene-level, then variant-level) for microbiome beta-diversity. We have identified an immunity-related gene,IL23R, reported in previous association studies and discovered 3 other novel genes, 2 of which are involved in immune functions or autoimmune disorders. Our findings highlight the value of the KRV as a powerful microbiome GWAS approach and support an important role of immunity-related genes in shaping the gut microbiome composition.
Individual differences in visual search performance extend from artificial arrays to naturalistic environments
Authors: Botch Thomas L. , Garcia Brenda D. , Choi Yeo Bi , Robertson Caroline E. 
Published: October 2021

AbstractVisual search is a universal human activity in naturalistic environments. Traditionally, visual search is investigated under tightly controlled conditions, where head-restricted participants locate a minimalistic target in a cluttered array presented on a computer screen. Do classic findings of visual search extend to naturalistic settings, where participants actively explore complex, real-world scenes? Here, we leverage advances in virtual reality (VR) technology to relate individual differences in classic visual search paradigms to naturalistic search behavior. In a naturalistic visual search task, participants looked for an object within their environment via a combination of head-turns and eye-movements using a head-mounted display. Then, in a classic visual search task, participants searched for a target within a simple array of colored letters using only eye-movements. We tested how set size, a property known to limit visual search within computer displays, predicts the efficiency of search behavior inside immersive, real-world scenes that vary in levels of visual clutter. We found that participants’ search performance was impacted by the level of visual clutter within real-world scenes. Critically, we also observed that individual differences in vi1–3sual search efficiency in classic search predicted efficiency in real-world search, but only when the comparison was limited to the forward-facing field of view for real-world search. These results demonstrate that set size is a reliable predictor of individual performance across computer-based and active, real-world visual search behavior.
The nitrogen phosphotransferase regulator PtsN (EIIANtr) regulates inorganic polyphosphate production inEscherichia coli
Authors: Bowlin Marvin Q. , Long Abagail R. , Huffines Joshua T. , Gray Michael J. 
Published: October 2021

ABSTRACTInorganic polyphosphate (polyP) is synthesized by bacteria under stressful environmental conditions and acts by a variety of mechanisms to promote cell survival. While the kinase that synthesizes polyP (PPK, enocoded by theppkgene) is well known, little is understood about how environmental stress signals lead to activation of this enzyme. Previous work has shown that the transcriptional regulators DksA, RpoN (σ54), and RpoE (σ24) positively regulate polyP production, but notppktranscription, inEscherichia coli. In this work, we set out to examine the role of the alternative sigma factor RpoN and nitrogen starvation stress response pathways in controlling polyP synthesis in more detail. In the course of these experiments, we identified GlnG, GlrR, PhoP, PhoQ, RapZ, and GlmS as proteins that affect polyP production, and uncovered a central role for the nitrogen phosphotransferase regulator PtsN (EIIANtr) in a polyP regulatory pathway, acting upstream of DksA, downstream of RpoN, and apparently independently of RpoE. However, none of these regulators appears to act directly on PPK, and the mechanism(s) by which they modulate polyP production remain unclear. Unexpectedly, we also found that the pathways that regulate polyP production vary depending not only on the stress condition applied, but also on the composition of the media in which the cells were grown before exposure to polyP-inducing stress. These results constitute substantial progress towards deciphering the regulatory networks driving polyP production under stress, but highlight the remarkable complexity of this regulation and its connections to a broad range of stress-sensing pathways.IMPORTANCEBacteria respond to changes in their environments with a complex regulatory network that controls the expression and activity of a wide range of effectors important for their survival. This stress response network is critical for the virulence of pathogenic bacteria and for the ability of all bacteria to grow in natural environments. Inorganic polyphosphate (polyP) is an evolutionarily ancient and almost universally conserved stress response effector that plays multiple roles in virulence, stress response, and survival in diverse organisms. This work provides new insights into the connections between well characterized nitrogen starvation and cell envelope stress response signaling pathways and the production of polyP inEscherichia coli.