bluuebunny/crossref_metadata_2025_split huggingface dataset:
A recombinant receptor-binding domain in trimeric form generates completely protective immunity against SARS-CoV-2 infection in nonhuman primates
Authors: Yang Limin , Tian Deyu , Han Jian-bao , Fan Wenhui , Zhang Yuan , Li Yunlong , Sun Wenqiang , Wei Yanqiu , Tian Xiaodong , Yu Dan-dan , Feng Xiao-li , Cheng Gong , Zheng Yong-tang , Bi Yuhai , Liu Wenjun 
Published: March 2021

AbstractSafe and effective vaccination is critical to combatting the COVID-19 pandemic. Here, we developed a trimeric SARS-CoV-2 receptor-binding domain (RBD) subunit vaccine candidate that simulates the natural structure of the spike (S) trimer glycoprotein. Immunization with RBD-trimer induced robust humoral and cellular immune responses and a high level of neutralizing antibodies that were maintained for at least 4 months. Moreover, the antibodies that were produced in response to the vaccine effectively neutralized the SARS-CoV-2 501Y.V2 variant. Of note, when the titers of the antibodies dropped to a sufficiently low level, only one boost quickly activated the anamnestic immune response, resulting in complete protection against the SARS-CoV-2 challenge inrhesus macaqueswithout typical histopathological changes or viral replication in the lungs and other respiratory tissues. Our results indicated that immunization with SARS-CoV-2 RBD-trimer could raise long-term and broad immunity protection in nonhuman primates, thereby offering an optimal vaccination strategy against COVID-19.
High-resolution 3D reconstruction of human oocytes using FIB-SEM
Authors: Trebichalská Zuzana , Javůrek Jakub , Tatíčková Martina , Kyjovská Drahomíra , Kloudová Soňa , Otevřel Pavel , Hampl Aleš , Holubcová Zuzana 
Published: March 2021

AbstractThe oocyte plays a pivotal role in the reproduction of our species. Nevertheless, its biology remains poorly understood. Electron microscopy is traditionally used to inspect the ultrastructure of female gametes. However, two-dimensional micrographs contain only fragmentary information about the spatial organization of the complex oocyte cytoplasm. Here, we employed the Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) to explore human oocyte intracellular morphology in three dimensions (3D). Volume reconstruction from high-resolution image stacks provided an unprecedented view of ooplasmic architecture. Organelle distribution patterns observed in 9 donor oocytes, representing 3 maturational stages, documented structural changes underlying the process by which the egg acquires developmental competence. 3D image segmentation was performed to extract information about distinct organelle populations. The quantitative analysis of the organelle abundance revealed that mitochondrion occupies ~ 4.26 % of the maturing oocyte cytoplasm. This proof-of-concept study demonstrates the potential of FIB-SEM imaging to study human oocyte morphology.
Dissolved organic matter from tropical peatlands impacts shelf sea light availability on coral reefs in the Singapore Strait, Southeast Asia
Authors: Martin Patrick , Sanwlani Nivedita , Lee Tiffany Wan Qi , Wong Joel Meng Cheng , Chang Kristy , Wong Elizabeth Wing-See , Liew Soo Chin 
Published: March 2021

AbstractShelf seas provide valuable ecosystem services, but their productivity and ecological functioning depend critically on sunlight transmitted through the water column. Anthropogenic reductions in underwater light availability are thus recognized as a serious threat to coastal habitats. The flux of strongly light-absorbing coloured dissolved organic matter (CDOM) from land to sea may have increased world-wide, but how this has altered the availability and spectral quality of light in shelf seas remains poorly known. Here, we present time-series data from the Sunda Shelf in Southeast Asia, where the monsoon-driven reversal in ocean currents supplies water enriched in CDOM from tropical peatlands for part of the year, resulting in 5–10-fold seasonal variation in light absorption by CDOM. We show that this terrigenous CDOM can dominate underwater light absorption at wavelengths up to 500 nm, and shift in the underwater irradiance spectrum towards longer wavelengths. The seasonal presence of terrigenous CDOM also causes the depth of 10% light penetration to shoal by 1–5 m, or 10–45%. We further estimate that on average 0.6 m, or 25%, of this terrigenous CDOM-mediated shoaling might be attributable to the enhanced loss of dissolved organic matter caused by peatland disturbance. We show that the seasonal change in the light environment is correlated with photo-acclimation by phytoplankton, and infer that terrigenous CDOM likely contributes to limiting the depth distribution of photosynthetic corals. Our results thus reveal an ecologically important but largely overlooked impact of human modifications to carbon fluxes that is likely becoming increasingly important in coastal seas.
Nuclear export of the pre-60S ribosomal subunit through single nuclear pores observed in real time
Authors: Ruland Jan Andreas , Krüger Annika Marie , Dörner Kerstin , Bhatia Rohan , Wirths Sabine , Pòetes Daniel , Kutay Ulrike , Siebrasse Jan Peter , Kubitscheck Ulrich 
Published: March 2021

AbstractRibosomal subunit biogenesis within mammalian cells initiates in the nucleolus with the assembly of a 90S precursor particle, which is subsequently split into the pre-40S and pre-60S subunits. During further processing steps, pre-ribosomal subunits are loaded with export receptors, which enables their passage through the pore complexes (NPCs) into the cytoplasm. Here export factors are released and both subunits can form a mature ribosome. Ribosomal biogenesis has been studied in great detail by biochemical, genetic and electron microscopic approaches, however, until now live cell data on the in vivo kinetics are still missing.We analysed export kinetics of the large ribosomal subunit (“pre-60S particle”) through single NPCs in living human cells. To assess the in vivo dynamics of this process, we established a stable cell line co-expressing Halo-tagged eIF6 and GFP-fused NTF2 to simultaneously label ribosomal 60S subunits (eIF6) and NPCs (NTF2). By combining single molecule tracking and super resolution confocal microscopy in a highly customized microscopic setup, we visualized the dynamics of single pre-60S particles during the interaction with and export through single NPCs. In this way we obtained unprecedented insights into this key cellular process.Our results revealed that for export events, maximum particle accumulation is found in the centre of the pore, while unsuccessful export terminates within the nuclear basket. The export process takes place with a single rate limiting step and an export dwell time of~24 milliseconds. Only about 1/3 of attempted export events were successful. Given the molecular mass of the pre-60S particles our results show that the mass flux through a single NPC can reach up to ~125 MDa·s−1in vivo.
Conserved organ-specific microbial assemblages in different populations of a terrestrial crab
Authors: Bacci Giovanni , Fratini Sara , Meriggi Niccolò , Cheng Christine L. Y. , Ng Ka Hei , Pindo Massimo , Iannucci Alessio , Mengoni Alessio , Cavalieri Duccio , Cannicci Stefano 
Published: March 2021

AbstractBrachyuran crabs originated in the oceans and evolved specific morphological and physiological adaptations to live in freshwater, intertidal and even terrestrial habitats but the role of a selection mechanism involving symbiotic microorganisms long these colonization processes are not known. In this work we investigated the associated microbiota of three populations of a terrestrial brachyuran crab,Chiromantes haematocheir, to find evidence of a conserved crab-specific microbiome unrelated to the population of origin and dissimilar from environmental microbial assemblages. Bacterial 16S rRNA gene and fungal ITS sequences were obtained from selected crab organs and environmental matrices to profile microbial communities. In spite of the presence of truly marine larval stages and no gregarious behaviour, favouring microbiota exchanges, we found common, organ-specific microbiota, associated to the gut and the gills of the crabs (with more than 15% of the genera detected specifically enriched only in one organ). Our results suggest an early establishment of a new common, stable microbiota in the transition from water to land.
Members of a highly widespread bacteriophage family are hallmarks of metabolic syndrome gut microbiomes
Authors: de Jonge Patrick A. , Wortelboer Koen , Scheithauer Torsten P.M. , van den Born Bert-Jan H. , Zwinderman Aeilko H. , Nobrega Franklin L. , Dutilh Bas E. , Nieuwdorp Max , Herrema Hilde 
Published: March 2021

SummaryThere is significant interest in altering the course of cardiometabolic disease development via the gut microbiome. Nevertheless, the highly abundant phage members -which impact gut bacteria- of the complex gut ecosystem remain understudied. Here, we characterized gut phageome changes associated with metabolic syndrome (MetS), a highly prevalent clinical condition preceding cardiometabolic disease. MetS gut phageome populations exhibited decreased richness and diversity, but larger inter-individual variation. These populations were enriched in phages infectingBacteroidaceaeand depleted in those infectingRuminococcaeae. Differential abundance analysis identified eighteen viral clusters (VCs) as significantly associated with either MetS or healthy phageomes. Among these are a MetS-associatedRoseburiaVC that is related to healthy control-associatedFaecalibacteriumandOscillibacterVCs. Further analysis of these VCs revealed theCandidatus Heliusviridae, a highly widespread gut phage lineage found in 90+% of the participants. The identification of the temperateCa. Heliusviridaeprovides a novel starting point to a better understanding of the effect that phages have on their bacterial hosts and the role that this plays in MetS.
Taming strong selection with large sample sizes
Authors: Krukov Ivan , Gravel Simon 
Published: March 2021

1AbstractThe fate of mutations and the genetic load of populations depend on the relative importance of genetic drift and natural selection. In addition, the accuracy of numerical models of evolution depends on the strength of both selection and drift: strong selection breaks the assumptions of the nearly neutral model, and drift coupled with large sample sizes breaks Kingman’s coalescent model.Thus, the regime with strong selection and large sample sizes, relevant to the study of pathogenic variation, appears particularly daunting. Surprisingly, we find that the interplay of drift and selection in that regime can be used to define asymptotically closed recursions for the distribution of allele frequencies that are accurate well beyond the strong selection limit.Selection becomes more analytically tractable when the sample sizenis larger than twice the population-scaled selection coefficient:n≥ 2Ns(4Nsin diploids). That is, when the expected number of coalescent events in the sample is larger than the number of selective events. We construct the relevant transition matrices, show how they can be used to accurately compute distributions of allele frequencies, and show that the distribution of deleterious allele frequencies is sensitive to details of the evolutionary model.
Activity ofPlasmodium vivaxpromoter elements inPlasmodium knowlesi, and a centromere-containing plasmid that expresses NanoLuc throughout the parasite life cycle
Authors: Moraes Barros Roberto R. , Thawnashom Kittisak , Gibson Tyler J. , Armistead Jennifer S. , Caleon Ramoncito L. , Kaneko Miho , Kite Whitney A. , Mershon J. Patrick , Brockhurst Jacqueline K. , Engels Theresa , Lambert Lynn , Orr-Gonzalez Sachy , Adams John H. , Sá Juliana M. , Kaneko Osamu , Wellems Thomas E. 
Published: March 2021

AbstractBackgroundPlasmodium knowlesiis now the major cause of human malaria in Malaysia, complicating malaria control efforts that must attend to the elimination of multiplePlasmodiumspecies. Recent advances in the cultivation ofP. knowlesierythrocytic-stage parasitesin vitro, transformation with exogenous DNA, and infection of mosquitoes with gametocytes from culture have opened up studies of this pathogen without the need for resource-intensive and costly non-human primate (NHP) models. For further understanding and development of methods for parasite transformation in malaria research, this study examined the activity of various trans-species transcriptional control sequences and the influence ofPlasmodium vivaxcentromeric (pvcen) repeats in plasmid-transfectedP. knowlesiparasites.MethodsIn vitrocultivatedP. knowlesiparasites were transfected with plasmid constructs that incorporatedP. vivaxorPlasmodium falciparum5’ UTRs driving the expression of bioluminescence markers (firefly luciferase or Nanoluc). Promoter activities were assessed by bioluminescence, and parasites transformed with human resistant allele dihydrofolate reductase-expressing plasmids were selected using antifolates. The stability of transformants carryingpvcen-stabilized episomes was assessed by bioluminescence over a complete parasite life cycle through a rhesus macaque monkey, mosquitoes, and a second rhesus monkey.ResultsLuciferase expression assessments show that certainP. vivaxpromoter regions, not functional in the more evolutionarily-distantP. falciparum, can drive transgene expression inP. knowlesi. Further,pvcenrepeats may improve the stability of episomal plasmids inP. knowlesiand support detection of NanoLuc-expressing elements over the full parasite life cycle from rhesus macaque monkeys toAnopheles dirusmosquitoes and back again to monkeys. In assays of drug responses to chloroquine, G418 and WR9910, antimalarial half-inhibitory concentration (IC50) values of blood stages measured by NanoLuc activity proved comparable to IC50values measured by the standard SYBR Green method.ConclusionAll threeP. vivaxpromoters tested in this study functioned inP. knowlesiwhereas two of the three were inactive inP. falciparum. NanoLuc-expressing, centromere-stabilized plasmids may support high-throughput screenings ofP. knowlesifor new antimalarial agents, including compounds that can block the development of mosquito- and/or liver-stage parasites.
Comparative analysis of public RNA-sequencing data from human intestinal enteroid (HIEs) infected with enteric RNA viruses identifies universal and virus-specific epithelial responses
Authors: Cieza RJ , Golob JL , Colacino JA , Wobus CE 
Published: March 2021

AbstractAcute gastroenteritis (AGE) has a significant disease burden on society. Noroviruses, rotaviruses and astroviruses are important viral causes of AGE but are relatively understudied enteric pathogens. Recent developments in novel biomimetic human models of enteric disease are opening new possibilities for studying human-specific hostmicrobe interactions. Human intestinal enteroids (HIE), which are epithelium-only intestinal organoids derived from stem cells isolated from human intestinal biopsy tissues, have been successfully used to culture representative norovirus, rotavirus and astrovirus strains. Previous studies investigated host-virus interactions at the intestinal epithelial interface by individually profiling the epithelial transcriptional response to a member of each virus family by RNA sequencing (RNA-seq). We used these publicly available datasets to uniformly analyze these data and identify shared and unique transcriptional changes in the human intestinal epithelium upon human enteric virus infections.
Osteoblast-Specific Wnt Secretion is Required for Skeletal Homeostasis and Loading-Induced Bone Formation in Adult Mice
Authors: Lawson Lisa Y. , Brodt Michael D. , Migotsky Nicole , Chermside-Scabbo Christopher , Palaniappan Ramya , Silva Matthew J. 
Published: March 2021

AbstractWnt signaling is critical to many aspects of skeletal regulation, but the importance of Wnt ligands in adult bone homeostasis and the anabolic response to mechanical loading is not well documented. We inhibited Wnt ligand secretion in adult (5-mo) mice using a systemic (drug) and a bone-targeted (genetic) approach, and subjected them to axial tibial loading to induce lamellar bone formation. Mice treated with the porcupine inhibitor WNT974 exhibited a decrease in bone formation in non-loaded limbs as well as a 54% decline in the periosteal bone formation response to tibial loading. Similarly, within 1-2 weeks of Wls deletion in osteoblasts (Osx-CreERT2;WlsF/Fmice), skeletal homeostasis was altered with decreased bone formation and increased resorption, and the anabolic response to loading was reduced 65% compared to control (WlsF/F). These findings establish a requirement for Wnt ligand secretion by osteoblasts for adult bone homeostasis and the anabolic response to mechanical loading.
Modulation of taste sensitivity by the olfactory system inDrosophila
Authors: Junca Pierre , Stanley Molly , Musso Pierre-Yves , Gordon Michael D 
Published: March 2021

AbstractAn animal’s sensory percepts are not raw representations of the outside world. Rather, they are constructs influenced by many factors including the species, past experiences, and internal states. One source of perceptual variability that has fascinated researchers for decades is the effect of losing one sensory modality on the performance of another1. Typically, dysfunction of one sense has been associated with elevated function of others, creating a type of sensory homeostasis2. For example, people with vision loss have been reported to demonstrate enhanced tactile and auditory functions, and deafness has been associated with heightened attention to visual inputs for communication3,4. By contrast, smell and taste—the two chemosensory modalities—are so intrinsically linked in their contributions to flavor that loss of smell is often anecdotally reported as leading to deficiencies in taste5–8. However, human studies specifically examining taste are mixed and generally do not support this widely-held belief, and data from animal models is largely lacking9. Here, we examine the impact of olfactory dysfunction on taste sensitivity inDrosophila melanogaster. We find that partial loss of olfactory input (hyposmia) dramatically enhances flies’ sensitivity to both appetitive (sugar, low salt) and aversive (bitter, high salt) tastes. This taste enhancement is starvation-independent and occurs following suppression of either first- or second-order olfactory neurons. Moreover, optogenetically increasing olfactory inputs reduces taste sensitivity. Finally, we observed that taste enhancement is not encoded in the activity of peripheral gustatory sensory neurons, but is associated with elevated sugar responses in protocerebrum anterior medial (PAM) dopaminergic neurons of the mushroom bodies. These results suggest a level of homeostatic control over chemosensation, where flies compensate for lack of olfactory input by increasing the salience of taste information.
Population codes enable learning from few examples by shaping inductive bias
Authors: Bordelon Blake , Pehlevan Cengiz 
Published: March 2021

AbstractLearning from a limited number of experiences requires suitable inductive biases. To identify how inductive biases are implemented in and shaped by neural codes, we analyze sample-efficient learning of arbitrary stimulus-response maps from arbitrary neural codes with biologically-plausible readouts. We develop an analytical theory that predicts the generalization error of the readout as a function of the number of observed examples. Our theory illustrates in a mathematically precise way how the structure of population codes shapes inductive bias, and how a match between the code and the task is crucial for sample-efficient learning. We observe that many different codes can support the same inductive bias. By analyzing recordings from the mouse primary visual cortex, we demonstrate that biological codes have lower total activity than other codes with identical bias. Using these mouse primary visual cortex responses, we demonstrate the existence of an efficiency bias towards low frequency orientation discrimination tasks for grating stimuli and low spatial frequency reconstruction tasks for natural images. We reproduce the discrimination bias in a simple model of primary visual cortex, and further show how invariances in the code to certain stimulus variations alter learning performance. We extend our methods to time-dependent neural codes and predict the sample efficiency of readouts from recurrent networks. Finally, we discuss implications of our theory in the context of recent developments in neuroscience and artificial intelligence. Overall, our study provides a concrete method for elucidating inductive biases of the brain and promotes sample-efficient learning as a general normative coding principle.
A systematic structural comparison of all solved small proteins (4-6 kDa) reveals the weight of disulfide bonds in proteins’ foldability
Authors: Moreira Mariana H. , Almeida Fabio C. L. , Domitrovic Tatiana , Palhano Fernando L. 
Published: March 2021

AbstractDefensins are small proteins, usually ranging from 4 to 6 kDa, amphipathic, disulfide-rich, and with a small or even absent hydrophobic core. Since a hydrophobic core is generally found in globular proteins that fold in an aqueous solvent, the peculiar fold of defensins can challenge tertiary protein structure predictors. We performed a PDB-wide survey of small proteins (4-6 kDa) to understand the similarities of defensins with other small disulfide-rich proteins. We found no differences when we compared defensins with non-defensins regarding the proportion and exposition to the solvent of apolar, polar, and charged residues. Then we divided all small proteins (4-6 kDa) deposited in PDB into two groups, one group with at least one disulfide bond (bonded, defensins included) and another group without any disulfide bond (unbonded). The group of bonded proteins presented apolar residues more exposed to the solvent than the unbonded group. Theab initioalgorithm for tertiary protein structure prediction Robetta was more accurate to predict unbonded than bonded proteins. Our work highlights one more layer of complexity for the tertiary protein prediction structure: small disulfide-rich proteins’ ability to fold even with a poor hydrophobic core.
Coughs, Colds and “Freshers’ Flu” Survey in the University of Cambridge, 2007-2008
Authors: Eames Ken TD , Tang Maria L , Hill Edward M , Tildesley Michael J , Read Jonathan M , Keeling Matt J , Gog Julia R 
Published: March 2021

AbstractUniversities provide many opportunities for the spread of infectious respiratory illnesses. Students are brought together into close proximity from all across the world and interact with one another in their accommodation, through lectures and small group teaching and in social settings. The COVID-19 global pandemic has highlighted the need for sufficient data to help determine which of these factors are important for infectious disease transmission in universities and hence control university morbidity as well as community spillover. We describe the data from a previously unpublished self-reported university survey of coughs, colds and flu-like symptoms collected in Cambridge, UK, during winter 2007-2008. The online survey collected information on symptoms and socio-demographic, academic and lifestyle factors. There were 1076 responses, 97% from University of Cambridge students (5.7% of the total university student population), 3% from staff and <1% from other participants, reporting onset of symptoms between September 2007 and March 2008. Undergraduates are seen to report symptoms earlier in the term than postgraduates; differences in reported date of symptoms are also seen between subjects and accommodation types, although these descriptive results could be confounded by survey biases. Despite the historic and exploratory nature of the study, this is one of few recent detailed datasets of flu-like infection in a university context and is especially valuable to share now to improve understanding of potential transmission dynamics in universities during the current COVID-19 pandemic.