bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparable neutralization of SARS-CoV-2 Delta AY.1 and Delta in individuals sera vaccinated with BBV152
Authors: Yadav Pragya D. , Sahay Rima R , Sapkal Gajanan , Nyayanit Dimpal , Shete Anita M. , Deshpande Gururaj , Patil Deepak Y. , Gupta Nivedita , Kumar Sanjay , Abraham Priya , Panda Samiran , Bhargava Balram 
Published: August 2021

AbstractThe recent emergence of the SARS-CoV-2 Variant of Concern, B.1.617.2 (Delta) variant and its high transmissibility has led to the second wave in India. BBV152, a whole-virion inactivated SARS-CoV-2 vaccine used for mass immunization in India, showed a 65.2% protection against the Delta variant in a double-blind, randomized, multicentre, phase 3 clinical trial. Subsequently, Delta has been further mutated to Delta AY.1, AY.2, and AY.3. Of these, AY.1 variant was first detected in India in April 2021 and subsequently from twenty other countries as well. Here, we have evaluated the IgG antibody titer and neutralizing potential of sera of COVID-19 naive individual’s full doses of BBV152 vaccine, COVID-19 recovered cases with full dose vaccines and breakthrough cases post-immunization BBV152 vaccines against Delta, Delta AY.1 and B.1.617.3. A reduction in neutralizing activity was observed with the COVID-19 naive individuals full vaccinated (1.3, 1.5, 1.9-fold), COVID-19 recovered cases with full BBV152 immunization (2.5, 3.5, 3.8-fold) and breakthrough cases post-immunization (1.9, 2.8, 3.5-fold) against Delta, Delta AY.1 and B.1.617.3 respectively compared to B.1 variant. A minor reduction was observed in the neutralizing antibody titer in COVID-19 recovered cases full BBV152 vaccinated and post immunized infected cases compared to COVID-19 naive vaccinated individuals. However, with the observed high titers, the sera of individuals belonging to all the aforementioned groups they would still neutralize the Delta, Delta AY.1 and B.1.617.3 variants effectively.
Neuronal correlates of attentional selectivity and intensity in visual area V4 are invariant of motivational context
Authors: Ghosh Supriya , Maunsell John H.R. 
Published: August 2021

ABSTRACTFlexibly switching attentional strategies is crucial for adaptive behavior in changing environments. Depending on the context, task demand employs different degrees of the two fundamental components of attention– attentional selectivity (preferentially attending to one location in visual space) and effort (the total non-selective intensity of attention). Neuronal responses in the visual cortex that show modulation with changes in either selective attention or effort are reported to partially represent motivational aspect of the task context. The relative contributions and interactions of these two components of attention to modulate neuronal signals and their sensitivity to distinct motivational drives are poorly understood. To address this question, we independently controlled monkeys’ spatially selective attention and non-selective attentional intensity in the same experimental session during a novel visual orientation change detection task. Attention was controlled either by adjusting the relative difficulty of the orientation changes at the two locations or by the reward associated with stimuli at two locations while simultaneously recording spikes from populations of neurons in area V4. We found that V4 neurons are robustly modulated by either selective attention or attentional intensity. Notably, as attentional selectivity for a neuron’s receptive field location decreased, its responses became weaker, despite an increase in the animal’s overall attentional intensity. This strong interaction between attentional selectivity and intensity could be identified in single trial spike trains. A simple divisive normalization of spatially distributed attention performances can explain the interaction between attention components well at the single neuron level. The effects of attentional selectivity and attentional intensity on neuronal responses were the same regardless of whether the changes were motivated by reward or task difficulty. These results provide a detailed cellular-level mechanism of how fundamental components of attention integrate and affect sensory processing in varying motivational and stimulus contexts.
The Effects of Posture on the Three-Dimensional Gait Mechanics of Human Walking in Comparison to Bipedal Chimpanzees
Authors: Johnson Russell T. , O’Neill Matthew C. , Umberger Brian R. 
Published: August 2021

AbstractHumans walk with an upright posture on extended limbs during stance and with a double-peaked vertical ground reaction force. Our closest living relatives, chimpanzees, are facultative bipeds that walk with a crouched posture on flexed, abducted hind limbs and with a single-peaked vertical ground reaction force. Differences in human and bipedal chimpanzee three-dimensional kinematics have been well quantified; however, it is unclear what the independent effects of using a crouched posture are on three-dimensional gait mechanics for humans, and how they compare with chimpanzees. Understanding the relationships between posture and gait mechanics, with known differences in morphology between species, can help researchers better interpret the effects of trait evolution on bipedal walking. We quantified pelvis and lower limb three-dimensional kinematics and ground reaction forces as humans adopted a series of upright and crouched postures and compared them with data from bipedal chimpanzee walking. Human crouched posture gait mechanics were more similar to bipedal chimpanzee gait than normal human walking, especially in sagittal plane hip and knee angles. However, there were persistent differences between species, as humans walked with less transverse plane pelvis rotation, less hip abduction, and greater peak horizontal ground reaction force in late stance than chimpanzees. Our results suggest that human crouched posture walking reproduces only a small subset of the characteristics of three-dimensional kinematics and ground reaction forces of chimpanzee walking, with the remaining differences likely due in large part to the distinct musculoskeletal morphologies of humans and chimpanzees.Summary StatementDifferences between human crouched posture gait and bipedal chimpanzee gait illustrate the limitations of using modern day humans to infer the evolution of hominin bipedalism.
Quantitative traits under selection: derivations of distributions, higher moments, and the effects of recombination
Authors: Smith Reginald D. 
Published: August 2021

AbstractThe mathematical theory of quantitative traits is over one hundred years old but it is still a fertile area for research and analysis. However, the effects of selection on a quantitative trait, while well understood for the effects on the mean and variance, have traditionally been difficult to attack from the perspective of analyzing the probability density of the breeding values and deriving higher (third and fourth) moments as well as analyzing the impact of recombination. In this paper, the exact formula for the breeding value distribution after selection is derived and, using new integral tables, the first four moments are given exact expressions for the first time. In addition, the effects of recombination on the full distribution of breeding values are demonstrated. Finally, the changes of GXE covariance in the selected parent population caused by factors similar to the Bulmer Effect are also investigated in detail.Mathematics Subject Classification (2020)MSC code 92D10 · MSC code 92D15
Recombinant single-cycle influenza virus as a new tool to augment antitumour immunity with immune checkpoint inhibitors
Authors: Kandasamy Matheswaran , Gileadi Uzi , Rijal Pramila , Tan Tiong Kit , Lee Lian Ni , Chen Jili , Prota Gennaro , Zhang Jing , Rabbitts Terence , Townsend Alain , Cerundolo Vincenzo 
Published: August 2021

AbstractVirus-based tumour vaccines offer many advantages compared to other antigen delivering systems. They generate concerted innate and adaptive immune response, and robust CD8+T cell responses. We engineered a non-replicating pseudotyped influenza virus (S-FLU) to deliver the well-known cancer testis antigen, NY-ESO-1 (S-NY-ESO-1 FLU). Intranasal or intramuscular immunization of NY-ESO-1 S-FLU virus in mice elicited a strong NY-ESO-1 specific CD8+T cell response in lungs and spleen that resulted in the regression of NY-ESO-1 expressing lung tumour and subcutaneous tumour respectively. Combined administration with anti PD-1 antibody, NY-ESO-1 S-FLU virus augmented the tumour protection by reducing the tumour metastasis. We propose that the antigen delivery through S-FLU is highly efficient in inducing antigen specific CD8+T cell response and protection against tumour development in combination with PD-1 blockade.
Within-Arctic horizontal gene transfer as a driver of convergent evolution in distantly related microalgae
Authors: Dorrell Richard G. , Kuo Alan , Füssy Zoltan , Richardson Elisabeth , Salamov Asaf , Zarevski Nikola , Freyria Nastasia J. , Ibarbalz Federico M. , Jenkins Jerry , Karlusich Juan Jose Pierella , Steindorff Andrei Stecca , Edgar Robyn E. , Handley Lori , Lail Kathleen , Lipzen Anna , Lombard Vincent , McFarlane John , Nef Charlotte , Novák Vanclová Anna M.G. , Peng Yi , Plott Chris , Potvin Marianne , Vieira Fabio Rocha Jimenez , Barry Kerrie , Dacks Joel B. , de Vargas Colomban , Henrissat Bernard , Pelletier Eric , Schmutz Jeremy , Wincker Patrick , Bowler Chris , Grigoriev Igor V. , Lovejoy Connie 
Published: August 2021

AbstractThe Arctic Ocean is being impacted by warming temperatures, increasing freshwater and highly variable ice conditions. The microalgal communities underpinning Arctic marine food webs, once thought to be dominated by diatoms, include a phylogenetically diverse range of small algal species, whose biology remains poorly understood. Here, we present genome sequences of a cryptomonad, a haptophyte, a chrysophyte, and a pelagophyte, isolated from the Arctic water column and ice. Comparing protein family distributions and sequence similarity across a densely-sampled set of algal genomes and transcriptomes, we note striking convergences in the biology of distantly related small Arctic algae, compared to non-Arctic relatives; although this convergence is largely exclusive of Arctic diatoms. Using high-throughput phylogenetic approaches, incorporating environmental sequence data from Tara Oceans, we demonstrate that this convergence was partly explained by horizontal gene transfers (HGT) between Arctic species, in over at least 30 other discrete gene families, and most notably in ice-binding domains (IBD). These Arctic-specific genes have been repeatedly transferred between Arctic algae, and are independent of equivalent HGTs in the Antarctic Southern Ocean. Our data provide insights into the specialized Arctic marine microbiome, and underlines the role of geographically-limited HGT as a driver of environmental adaptation in eukaryotic algae.
HIV-1 drug resistance profiling using amino acid sequence space cartography
Authors: Pikalyova Karina , Orlov Alexey , Lin Arkadii , Tarasova Olga , Marcou Gilles , Horvath Dragos , Poroikov Vladimir , Varnek Alexandre 
Published: August 2021

AbstractHuman immunodeficiency virus (HIV) drug resistance is a global healthcare issue. The emergence of drug resistance demands treatment adaptation. Computational methods predicting the drug resistance profile from genomic data of HIV isolates are advantageous for monitoring drug resistance in patients. Yet, the currently existing computational methods for drug resistance prediction are either not suitable for complex mutational patterns in emerging HIV strains or lack interpretability of prediction results which is of paramount importance in clinical practice. Hence, to overcome these limitations, new approaches for the HIV drug resistance prediction combining high accuracy and interpretability are required. In this work, a new methodology for the analysis of protein sequence data based on the application of generative topographic mapping was developed and applied for HIV drug resistance profiling. It allowed achieving high accuracy of resistance predictions and intuitive interpretation of prediction results. The developed approach was successfully applied for the prediction of HIV resistance towards protease, reverse-transcriptase and integrase inhibitors and in-depth analysis of HIV resistance-inducing mutation patterns. Hence, it can serve as an efficient and interpretable tool to suggest optimal treatment regimens.
Zona Incerta activity dynamics underlying associative fear learning and fear generalization
Authors: Li Zhuoliang , Rizzi Giorgio , Tan Kelly R. 
Published: August 2021

AbstractRecent studies suggest that the Zona Incerta (ZI) plays a role in fear learning and recall. However, there is a clear gap in knowledge as to whether the ZI can encode fear evoking threats and cues that predict them. Here, we subject mice to a classical fear conditioning paradigm while recording the in-vivo calcium dynamics of ZI neurons. We observed that ZI neurons can encode not only a fear evoking stimulus, but can also learn to encode predictive cues, associate them with the unconditioned fear evoking stimulus, and discriminate them from neutral non-predictive cues. While the ZI across all mice learned to become mainly excited by fear predictive cues, only mice that did not generalize fear became largely inhibited by non-predictive cues and better discriminated the two. Together, we provide extensive evidence that the ZI differentially encode fear predictive and non-predictive cues in a generalization dependent manner.
piRNAs of Caenorhabditis elegans broadly silence nonself sequences through functionally random targeting
Authors: McEnany John , Meir Yigal , Wingreen Ned 
Published: August 2021

ABSTRACTSmall non-coding RNAs such as piRNAs serve as guides for Argonaute proteins, enabling sequence-specific, post-transcriptional regulation of gene expression. The piRNAs of Caenorhabditis elegans have been observed to bind targets with high mismatch tolerance, and appear to lack specific transposon targets, unlike piRNAs in Drosophila melanogaster and other organisms. These observations support a model in which C. elegans piRNAs provide a broad, indiscriminate net of silencing, acting in competition with siRNAs associated with the CSR-1 Argonaute that specifically protect self genes from silencing. However, the breadth of piRNA targeting has not been subject to in-depth quantitative analysis, nor has it been explained how piRNAs are distributed across sequence space to achieve complete coverage. Through a bioinformatic analysis of piRNA sequences, incorporating an original metric of piRNA-target distance, we demonstrate that C. elegans piRNAs are functionally random, in that their coverage of sequence space is comparable to that of random sequences. By possessing a sufficient number of distinct, essentially random piRNAs, C. elegans is able to target arbitrary nonself sequences with high probability. This result elucidates the mechanism by which newly transcribed mRNAs in C. elegans are classified as self or nonself, and has implications for piRNA evolution and biogenesis.
Water soluble, red emitting, carbon nanoparticles stimulate 3D cell invasion via clathrin-mediated endocytic uptake
Authors: Singh Udisha , Teja Aditya Guduru , Walia Shanka , Vaswani Payal , Dalvi Sameer , Bhatia Dhiraj 
Published: August 2021

AbstractBright, fluorescent nanoparticles with excitation and emission towards the red end of the spectrum are highly desirable in the field of bioimaging. We present here a new class of organic carbon-based nanoparticles (CNPs) with robust quantum yield and fluorescence towards the red region of the spectrum. Using organic substrates like para-phenylenediamine (PPDA) dispersed in diphenyl ether and reflux conditions, we achieved scalable amounts of CNPs of the average size of 25 nm. These CNPs were readily uptaken by different mammalian cells, and we show that they prefer clathrin-mediated endocytosis for their cellular entry route. Not only can these CNPs be specifically uptaken in cells, but they also stimulate cellular processes like cell invasion from 3D spheroid models. These new class of CNPs, which have sizes similar to proteinaceous ligands, hold immense potential for their surface functionalization, whereby they could be explored as promising bioimaging agents for biomedical imaging and intracellular drug delivery.
Label-free monitoring of 3D cortical neuronal growth in vitro using optical diffraction tomography
Authors: Lee Ariel J. , Yoon DongJo , Han SeungYun , Hugonnet Herve , Park WeiSun , Park Je-Kyun , Nam YoonKey , Park YongKeun 
Published: August 2021

AbstractThe highly complex central nervous systems of mammals are often studied using three-dimensional (3D) in vitro primary neuronal cultures. A coupled confocal microscopy and immunofluorescence labeling are widely utilized for visualizing the 3D structures of neurons. However, this requires fixation of the neurons and is not suitable for monitoring an identical sample at multiple time points. Thus, we propose a label-free monitoring method for 3D neuronal growth based on refractive index tomograms obtained by optical diffraction tomography. The 3D morphology of the neurons was clearly visualized, and the developmental processes of neurite outgrowth in 3D spaces were analyzed for individual neurons.Abstract Figure
Genomic analyses of human adenoviruses unravel novel recombinant genotypes associated with severe infections in pediatric patients
Authors: Akello Joyce Odeke , Kamgang Richard , Barbani Maria Teresa , Suter-Riniker Franziska , Aebi Christoph , Beuret Christian , Paris Daniel H. , Leib Stephen L , Ramette Alban 
Published: August 2021

AbstractBackgroundHuman Adenoviruses (HAdVs) are highly contagious pathogens of clinical importance, especially among the pediatric population. Studies on comparative viral genomic analysis of cases associated with severe and mild infections due to HAdV are limited. Using whole-genome sequencing (WGS), we investigated whether there were any differences between circulating HAdV strains associated with severe infections (meningitis, sepsis, convulsion, sudden infant death syndrome, death, and hospitalization) and mild clinical presentations in pediatric patients hospitalized between the years 1998 and 2017 in a tertiary care hospital group in Bern, Switzerland covering a population base of approx. 2 million inhabitants. The HAdV species implicated in causing severe infections in this study included HAdV species C genotypes (HAdV1, HAdV2, and HAdV5). Clustering of the HAdV whole-genome sequences of the severe and mild cases did not show any differences except for one sample (isolated from a patient presenting with sepsis, meningitis, and hospitalization) that formed its own cluster with HAdV species C genotypes. This isolate showed intertypic recombination events involving four genotypes, had the highest homology to HAdV89 at complete genome level, but possessed the fiber gene of HAdV1, thereby representing a novel genotype of HAdV species C. The incidence of potential recombination events was higher in severe cases than in mild cases. Our findings confirm that recombination among HAdVs is important for molecular evolution and emergence of new strains. Therefore, further research on HAdVs, particularly among susceptible groups, is needed and continuous surveillance is required for public health preparedness including outbreak investigations.
Coilin oligomerization and remodeling by Nopp140 reveals a hybrid assembly mechanism for Cajal bodies
Authors: Courchaine Edward , Machyna Martin , Straube Korinna , Sauyet Sarah , Enright Jade , Neugebauer Karla M. 
Published: August 2021

AbstractCajal bodies (CBs) are ubiquitous nuclear membraneless organelles (MLOs) that promote efficient biogenesis of RNA-protein complexes. Depletion of the CB scaffolding protein coilin is lethal for vertebrate embryogenesis, making CBs a strong model for understanding the structure and function of MLOs. Although it is assumed that CBs form through biomolecular condensation, the biochemical and biophysical principles that govern CB dynamics have eluded study. Here, we identify features of the coilin protein that drive CB assembly and shape. Focusing on coilin’s N-terminal domain (NTD), we discovered its unexpected capacity for oligomerization in vivo. Single amino acid mutational analysis of coilin revealed distinct molecular interactions required for oligomerization and binding to the Nopp140 ligand, which facilitates CB assembly. We demonstrate that the intrinsically disordered regions of Nopp140 have substantial condensation properties and suggest that Nopp140 binding thereby remodels stable coilin oligomers to form a particle that recruits other functional components.
Large differences in carbohydrate degradation and transport potential in the genomes of lichen fungal symbionts
Authors: Resl Philipp , Bujold Adina R. , Tagirdzhanova Gulnara , Meidl Peter , Rallo Sandra Freire , Kono Mieko , Fernández-Brime Samantha , Guðmundsson Hörður , Andrésson Ólafur Sigmar , Muggia Lucia , Mayrhofer Helmut , McCutcheon John P. , Wedin Mats , Werth Silke , Willis Lisa M. , Spribille Toby 
Published: August 2021

AbstractLichen symbioses are generally thought to be stabilized by the transfer of fixed carbon compounds from a photosynthesizing unicellular symbiont to a fungus. In other fungal symbioses, carbohydrate subsidies correlate with genomic reductions in the number of genes for plant cell wall-degrading enzymes (PCWDEs), but whether this is the case with lichen fungal symbionts (LFSs) is unknown. We predicted genes encoding carbohydrate-active enzymes (CAZymes) and sugar transporters in 17 existing and 29 newly sequenced genomes from across the class Lecanoromycetes, the largest extant clade of LFSs. Despite possessing lower mean numbers of PCWDE genes compared to non-symbiont Ascomycota, all LFS genomes possessed a robust suite of predicted PCWDEs. The largest CAZyme gene numbers, on par with model species such as Penicillium, were retained in genomes from the subclass Ostropomycetidae, which are found in crust lichens with highly specific ecologies. The lowest numbers were in the subclass Lecanoromycetidae, which are symbionts of many generalist macrolichens. Our results suggest that association with phototroph symbionts does not in itself result in functional loss of PCWDEs and that PCWDE losses may have been driven by adaptive processes within the evolution of specific LFS lineages. The inferred capability of some LFSs to access a wide range of carbohydrates suggests that some lichen symbioses may augment fixed CO2 with carbon from external sources.SignificanceLichen symbioses are considered self-contained autotrophic systems in which the total carbon economy is the sum of phototroph-fixed CO2, supplied to a fungus as sugars. In other fungal-plant symbioses, such as mycorrhizae, plant-derived sugar subsidies are associated with loss of plant cell wall-degrading enzymes (PCWDEs). We compared PCWDE inventories in 46 genomes from the largest group of lichen fungal symbionts (LFSs) with non-symbionts from across Ascomycota. We found that despite lower overall gene numbers, all LFSs retain PCWDEs, and some possess gene numbers and functional diversity on par with non-symbionts. Our results suggest that association with a phototroph does not necessarily result in PCWDE loss, and some lichens may obtain carbon from sources other than CO2 fixation.