bluuebunny/crossref_metadata_2025_split huggingface dataset:
How immunity from and interaction with seasonal coronaviruses can shape SARS-CoV-2 epidemiology
Authors: Waterlow Naomi R , van Leeuwen Edwin , Davies Nicholas G. ,   CMMID COVID-19 working group, Flasche Stefan , Eggo Rosalind M 
Published: May 2021

AbstractWe hypothesised that cross-protection from seasonal epidemics of human coronaviruses (HCoVs) could have affected SARS-CoV-2 transmission, including generating reduced susceptibility in children. To determine what the pre-pandemic distribution of immunity to HCoVs was, we fitted a mathematical model to 6 years of seasonal coronavirus surveillance data from England and Wales. We estimated a duration of immunity to seasonal HCoVs of 7.3 years (95%CI 6.8 - 7.9) and show that, while cross-protection between HCoV and SARS-CoV-2 may contribute to the age distribution, it is insufficient to explain the age pattern of SARS-CoV-2 infections in the first wave of the pandemic in England and Wales. Projections from our model illustrate how different strengths of cross-protection between circulating coronaviruses could determine the frequency and magnitude of SARS-CoV-2 epidemics over the coming decade, as well as the potential impact of cross-protection on future seasonal coronavirus transmission.Significance statement:Cross-protection from seasonal epidemics of human coronaviruses (HCoVs) has been hypothesised to contribute to the relative sparing of children during the early phase of the pandemic. Testing this relies on understanding the pre-pandemic age-distribution of recent HCoV infections, but little is known about their dynamics. Using England and Wales as a case study, we use a transmission model to estimate the duration of immunity to seasonal coronaviruses, and show how cross-protection could have affected the age distribution of susceptibility during the first wave, and alter SARS-CoV-2 transmission patterns over the coming decade.
Temporal stability and detection sensitivity of the dry swab-based diagnosis of SARS-CoV-2
Authors: Gokulan CG , Kiran Uday , Kuncha Santosh Kumar , Mishra Rakesh K 
Published: May 2021

AbstractThe rapid spread and evolution of various strains of SARS-CoV-2, the virus responsible for COVID-19, continues to challenge the disease controlling measures globally. Alarming concern is, the number of second wave infections surpassed the first wave and the onset of severe symptoms manifesting rapidly. In this scenario, testing of maximum population in less time and minimum cost with existing diagnostic amenities is the only possible way to control the spread of the virus. The previously described RNA extraction-free methods using dry swab have been shown to be advantageous in these critical times by different studies. In this work, we show the temporal stability and performance of the dry swab viral detection method at two different temperatures. Contrived dry swabs holding serially diluted SARS-CoV-2 strains A2a and A3i at 25°C (room temperature; RT) and 4°C were subjected to direct RT-PCR and compared with standard VTM-RNA based method. The results clearly indicate that dry swab method of RNA detection is as efficient as VTM-RNA-based method in both strains, when checked for up to 72 hours. The lesser CT values of dry swab samples in comparison to that of the VTM-RNA samples suggest better sensitivity of the method within 48 hours of time. The results collectively suggest that dry swab samples are stable at RT for 24 hours and the detection of SARS-CoV-2 RNA by RT-PCR do not show variance from VTM-RNA. This extraction free, direct RT-PCR method holds phenomenal standing in the present life-threatening circumstances due to SARS-CoV-2.
Dissecting the loci underlying maturation timing in Atlantic salmon using haplotype and multi-SNP based association methods
Authors: Sinclair-Waters Marion , Nome Torfinn , Wang Jing , Lien Sigbjørn , Kent Matthew P. , Sægrov Harald , Florø-Larsen Bjørn , Bolstad Geir H. , Primmer Craig R. , Barson Nicola J. 
Published: May 2021

ABSTRACTResolving the genetic architecture of fitness-related traits is key to understanding the evolution and maintenance of fitness variation. However, well-characterized genetic architectures of such traits in wild populations remain uncommon. In this study, we used haplotype-based and multi-SNP Bayesian association methods with sequencing data for 313 individuals from wild populations to further characterize known candidate regions for sea age at maturation in Atlantic salmon (Salmo salar). We detected an association at five loci (on chromosomesssa06,ssa09,ssa21, andssa25) out of 116 candidates previously identified in an aquaculture strain with maturation timing in wild Atlantic salmon. We found that at each of these five loci, variation explained by the locus was predominantly driven by a single SNP suggesting the genetic architecture of Atlantic salmon maturation includes multiple loci with simple, non-clustered alleles. This highlights the diversity of genetic architectures that can exist for fitness-related traits. Furthermore, this study provides a useful multi-SNP framework for future work using sequencing data to characterize genetic variation underlying phenotypes in wild populations.
Simultaneous fMRI and fast-scan cyclic voltammetry bridges oxygenation and neurotransmitter dynamics across spatiotemporal scales
Authors: Walton Lindsay R , Verber Matthew , Lee Sung-Ho , Chao Tzu-Hao , Wightman R. Mark , Shih Yen-Yu Ian 
Published: May 2021

AbstractThe vascular contributions of neurotransmitters to the hemodynamic response are gaining more attention in neuroimaging studies, as many neurotransmitters are vasomodulatory. To date, well-established electrochemical techniques that detect neurotransmission in high magnetic field environments are limited. Here, we propose an experimental setting enabling simultaneous fast-scan cyclic voltammetry (FSCV) and blood oxygenation-dependent functional magnetic imaging (BOLD fMRI) to measure both local tissue oxygen and dopamine responses, and global BOLD changes, respectively. By using MR-compatible materials and the proposed data acquisition schemes, FSCV detected physiological analyte concentrations with high spatiotemporal resolution inside of a 9.4 T MRI bore. We found that tissue oxygen and BOLD correlate strongly, and brain regions that encode dopamine amplitude differences can be identified via modeling simultaneously acquired dopamine FSCV and BOLD fMRI time-courses. This technique provides complementary neurochemical and hemodynamic information and expands the scope of studying the influence of local neurotransmitter release over the entire brain.
A method to study honeybee foraging regulatory molecules at different times during foraging
Authors: Singh Asem Surindro , Takhellambam Machathoibi Chanu 
Published: May 2021

AbstractThe foraging of honey bees is one of the most well organized and admirable behaviors that exist among social insects. In behavioral studies, these beautiful insects have been extensively used for understanding time-space learning, landmark use and concept of learning etc. Highly organized behaviors such as social interaction and communication are systematically well organized behavioral components of honeybee foraging. Over the last two decades, understanding the regulatory mechanisms underlying honey bee foraging at the cellular and molecular levels has been increasingly interested to several researchers. Upon the search of regulatory genes of brain and behavior, immediate early (IE) genes are considered as tool to begin the investigation. Our two recent studies, have demonstrated three IE genes namely Egr-1, Hr38 and kakusei having a role in the daily foraging of bees and their association with learning and memory during the foraging. These studies further evidence that IE genes can be used as a tool in finding the specific molecular/cellular players of foraging in honey bees and its behavioral components such as learning, memory, social interaction, social communication etc. In this article we provide the details of the method of sample collection at different times during foraging to investigate the foraging regulatory molecules.
BML: a versatile web server for bipartite motif discovery
Authors: Vahed Mohammad , Vahed Majid , Garmire Lana X. 
Published: May 2021

ABSTRACTMotif discovery and characterization are important for gene regulation analysis. The lack of intuitive and integrative web servers impedes effective use of motifs. Here we describe Bipartite Motifs Learning (BML), a web server that provides a user-friendly portal for online discovery and analysis of sequence motifs, using high-throughput sequencing data as the input. BML utilizes both position weight matrix (PWM) and dinucleotide weight matrix (DWM), the latter of which enables the expression of the interdependencies of neighboring bases. With input parameters concerning the motifs are given, the BML achieves significantly higher accuracy than other available tools for motif finding. When no parameters are given by non-expert users, unlike other tools BML employs a learning method to identify motifs automatically and achieve accuracy comparable to the scenario where the parameters are set. The BML web server is freely available at http://motif.t-ridership.com/.
Functional characterization of SARS-CoV-2 vaccine elicited antibodies in immunologically naïve and pre-immune humans
Authors: Forgacs David , Jang Hyesun , Abreu Rodrigo B. , Hanley Hannah B. , Gattiker Jasper L. , Jefferson Alexandria M. , Ross Ted M. 
Published: May 2021

AbstractAs the COVID-19 pandemic continues, the authorization of vaccines for emergency use has been crucial in slowing down the rate of infection and transmission of the SARS-CoV-2 virus that causes COVID-19. In order to investigate the longitudinal serological responses to SARS-CoV-2 natural infection and vaccination, a large-scale, multi-year serosurveillance program entitled SPARTA (SARS SeroPrevalence and Respiratory Tract Assessment) was initiated at 4 locations in the U.S. The serological assay presented here measuring IgG binding to the SARS-CoV-2 receptor binding domain (RBD) detected antibodies elicited by SARS-CoV-2 infection or vaccination with a 95.5% sensitivity and a 95.9% specificity. We used this assay to screen more than 3100 participants and selected 20 previously infected pre-immune and 32 immunologically naïve participants to analyze their antibody binding to RBD and viral neutralization (VN) responses following vaccination with two doses of either the Pfizer-BioNTech BNT162b2 or the Moderna mRNA-1273 vaccine. Vaccination not only elicited a more robust immune reaction than natural infection, but the level of neutralizing and anti-RBD antibody binding after vaccination is also significantly higher in pre-immune participants compared to immunologically naïve participants (p<0.0033). Furthermore, the administration of the second vaccination did not further increase the neutralizing or binding antibody levels in pre-immune participants (p=0.69). However, ~46% of the immunologically naïve participants required both vaccinations to seroconvert.
Cell-autonomous timing drives the vertebrate segmentation clock’s wave pattern
Authors: Rohde Laurel A. , Bercowsky-Rama Arianne , Valentin Guillaume , Naganathan Sundar Ram , Desai Ravi A. , Strnad Petr , Soroldoni Daniele , Oates Andrew C. 
Published: May 2021

AbstractRhythmic and sequential segmentation of the growing vertebrate body relies on the segmentation clock, a multi-cellular oscillating genetic network. The clock is visible as tissue-level kinematic waves of gene expression that travel through the pre-somitic mesoderm (PSM) and arrest at the position of each forming segment. Here we test how this hallmark wave pattern is driven by culturing single maturing PSM cells. We compare their cell-autonomous oscillatory and arrest dynamics to those we observe in the embryo at cellular resolution, finding similarity in the relative slowing of oscillations and arrest in concert with differentiation. This shows that cell-extrinsic signals are not required by the cells to instruct the developmental program underlying the wave pattern. We show that a cell-autonomous timing activity initiates during cell exit from the tailbud, then runs down in the anterior-ward cell flow in the PSM, thereby using elapsed time to provide positional information to the clock. Exogenous FGF lengthens the duration of the cell-intrinsic timer, indicating extrinsic factors in the embryo may regulate the segmentation clock via the timer. In sum, our work suggests that a noisy cell-autonomous, intrinsic timer drives the slowing and arrest of oscillations underlying the wave pattern, while extrinsic factors in the embryo tune this timer’s duration and precision. This is a new insight into the balance of cell-intrinsic and -extrinsic mechanisms driving tissue patterning in development.
Decentralizing cell-free RNA sensing with the use of low-cost cell extracts
Authors: Arce Anibal , Chavez Fernando Guzman , Gandini Chiara , Puig Juan , Matute Tamara , Haseloff Jim , Dalchau Neil , Molloy Jenny , Pardee Keith , Federici Fernán 
Published: May 2021

AbstractCell-free gene expression systems have emerged as a promising platform for field-deployed biosensing and diagnostics. When combined with programmable toehold switch-based RNA sensors, these systems can be used to detect arbitrary RNAs and freeze-dried for room temperature transport to the point-of-need. These sensors, however, have been implemented using reconstituted PURE cell-free protein expression systems that are difficult to source in the Global South due to their high commercial cost and cold-chain shipping requirements. Here, we describe the implementation of RNA toehold switch-based sensors using E. coli cell lysate-based cell-free protein expression systems, which can be produced locally and reduce the cost of sensors by two orders of magnitude. We then demonstrate that these in-house cell lysates provide sensor performance comparable to commercial PURE cell-free systems. We further optimize use of these lysates with a CRISPRi strategy to enhance the stability of linear DNAs, enabling the direct use of PCR products for fast screening of new designs. As a proof-of-concept, we develop novel toehold sensors for the plant pathogen Potato Virus Y (PVY), which dramatically reduces the yield of this important staple crop. The local implementation of low-cost cell-free toehold sensors could enable biosensing capacity at the regional level and lead to more decentralized models for global surveillance of infectious disease.
Classification of Pacemaker Dynamics in the Mouse Intestine by Field Potential Microimaging
Authors: Iwata Naoko , Takai Chiho , Mochizuki Naoto , Yamauchi Mariko , Kaji Noriyuki , Kasahara Yoshiyuki , Nakayama Shinsuke 
Published: May 2021

AbstractThe flexible and sophisticated movement of the gastrointestinal (GI) tract implies the involvement of mechanisms other than enteric neural circuits, to coordinate excitation in microregions. We thus performed microimaging of pacemaker dynamics in the small intestine of mice since it contains typical network-forming pacemaker cells. A dialysis membrane-reinforced low-impedance microelectrode array (MEA) enabled field potentials over a wide frequency range to be stably measured in microregions. The pacemaker dynamics were classified into basic patterns despite large variations. In the developmental process, pacemaker activity was categorized as either an ‘expanding’ or a ‘migrating’ pattern that was initiated in or propagated to the MEA sensing area, respectively. The intercellular current of the volume conductor complicated the waveform of both activities. The existence of ‘expanding’ and ‘migrating’ patterns was attributable to duplicated pacemaker systems such as intracellular Ca2+oscillation-activated and voltage-gated mechanisms. Additionally, from the spatio-temporal feature during the period of pacemaker events, the ‘bumpy/aberrant’ pattern was defined by aberrant, incoherent propagation, and associated with local impairment of excitability, while the ‘colliding/converging’ pattern involved the interaction of multiple activities in the MEA area. Interconversion between the four micro-coordination patterns occurred in the same microregion. 5-Hydroxytryptamine (5-HT) promoted ‘migrating’ activity, implying an improvement or restoration of spatial conductivity. These results agree well with the action of 5-HT to change GI movement toward propulsion. In conclusion, our MEA method of microimaging classification enables the quantitative assessment of spatio-temporal electric coordination underlying GI motility, suggesting its application to small model animals.
The role of visual and olfactory cues in social decisions of guppies and zebrafish
Authors: Santacà Maria , Dadda Marco , Bisazza Angelo 
Published: May 2021

ABSTRACTVision and olfaction are expensive to maintain, and in many taxa there appears to be a trade-off in investment between the two sensory systems. Previous work has suggested that guppies (Poecilia reticulata) and zebrafish (Danio rerio) may differ in the relative importance they place on these two senses in social interactions. In this study, we directly examined this issue by experimentally contrasting olfactory and visual information in social situations. In the first experiment, we found that guppies spent more time where conspecifics were visible than where they could smell them. On the contrary, zebrafish spent significantly more time in an empty compartment containing smell of conspecifics than in a compartment in which they only saw them. The difference was not large, suggesting that both species integrate various types of information to locate a nearby shoal. In two subsequent experiments, we studied the role of vision and smell in the discrimination of the quality of the social group, namely the number and the familiarity of its members. Zebrafish and guppies were confirmed to rely on different senses to estimate the size of a social group, whereas they did not differ in the discrimination of familiar and non-familiar conspecifics which appears to be based equally on the two senses. Similarly to what happens in other vertebrate clades, we suggest that, among teleosts, there are large differences in the relative importance of the different senses in the perception of the external world.
The haplotype-based analysis ofAegilops tauschiiintrogression into hard red winter wheat and its impact on productivity traits
Authors: Nyine Moses , Adhikari Elina , Clinesmith Marshall , Aiken Robert , Betzen Bliss , Wang Wei , Davidson Dwight , Yu Zitong , Guo Yuanwen , He Fei , Akhunova Alina , Jordan Katherine W , Fritz Allan K , Akhunov Eduard 
Published: May 2021

AbstractIntrogression from wild relatives have a great potential to broaden beneficial allelic diversity available for crop improvement in breeding programs. Here, we assessed the impact of introgression from 21 diverse accessions ofAegilops tauschii, the diploid ancestor of the wheat D genome, into six hard red winter wheat cultivars on yield and yield component traits. We used 5.2 million imputed D genome SNPs identified by whole-genome sequencing of parental lines and the sequence-based genotyping of introgression population including 351 BC1F3:5lines. Phenotyping data collected from the irrigated and non-irrigated field trials revealed that up to 23% of the introgression lines produce more grain than the parents and check cultivars. Based on sixteen yield stability statistics, the yield of twelve introgression lines (3.4%) was stable across treatments, years and locations; five of these lines were also high yielding, producing 9.8% more grain than the average yield of check cultivars. The most significant SNP-trait and haplotype-trait associations were identified on chromosome arms 2DS and 6DL for spikelet number per spike (SNS), on chromosome arms 2DS, 3DS, 5DS and 7DS for grain length and on chromosome arms 1DL, 2DS, 6DL and 7DS for grain width. Introgression of haplotypes fromAe. tauschiiparents was associated with increase in SNS, which positively correlated with heading date, whereas haplotypes from hexaploid wheat parents were associated with increased grain width. We show that haplotypes on 2DS associated with increased spikelet number and heading date are linked with multiple introgressed alleles ofPpd-D1identified by the whole-genome sequencing of theAe. tauschiiparents. While some introgressed haplotypes exhibited significant pleiotropic effects with the direction of effects on the yield component traits being largely consistent with the previously reported trade-offs, there were haplotype combinations associated with the positive trends in yield. The characterized repertoire of the introgressed haplotypes derived fromAe. tauschiiaccessions with the combined positive effects on yield and yield components traits in elite germplasm provides a valuable source of alleles for improving the productivity of winter wheat by optimizing the contribution of component traits to yield.
NetTIME: a Multitask and Base-pair Resolution Framework for Improved Transcription Factor Binding Site Prediction
Authors: Yi Ren , Cho Kyunghyun , Bonneau Richard 
Published: May 2021

AbstractMotivationMachine learning models for predicting cell-type-specific transcription factor (TF) binding sites have become increasingly more accurate thanks to the increased availability of next-generation sequencing data and more standardized model evaluation criteria. However, knowledge transfer from data-rich to data-limited TFs and cell types remains crucial for improving TF binding prediction models because available binding labels are highly skewed towards a small collection of TFs and cell types. Transfer prediction of TF binding sites can potentially benefit from a multitask learning approach; however, existing methods typically use shallow single-task models to generate low-resolution predictions. Here we propose NetTIME, a multitask learning framework for predicting cell-type-specific transcription factor binding sites with base-pair resolution.ResultsWe show that the multitask learning strategy for TF binding prediction is more efficient than the single-task approach due to the increased data availability. NetTIME trains high-dimensional embedding vectors to distinguish TF and cell-type identities. We show that this approach is critical for the success of the multitask learning strategy and allows our model to make accurate transfer predictions within and beyond the training panels of TFs and cell types. We additionally train a linear-chain conditional random field (CRF) to classify binding predictions and show that this CRF eliminates the need for setting a probability threshold and reduces classification noise. We compare our method’s predictive performance with two state-of-the-art methods, Catchitt and Leopard, and show that our method outperforms previous methods under both supervised and transfer learning settings.AvailabilityNetTIME is freely available athttps://github.com/ryi06/NetTIMEand the code is also archived athttps://doi.org/10.5281/zenodo.6994897Contactrb133@nyu.edu