bluuebunny/crossref_metadata_2025_split huggingface dataset:
Micapipe: A Pipeline for Multimodal Neuroimaging and Connectome Analysis
Authors: Cruces Raúl R. , Royer Jessica , Herholz Peer , Larivière Sara , Vos de Wael Reinder , Paquola Casey , Benkarim Oualid , Park Bo-yong , Degré-Pelletier Janie , Nelson Mark , DeKraker Jordan , Tardif Christine , Poline Jean-Baptiste , Concha Luis , Bernhardt Boris C. 
Published: February 2022

AbstractMultimodal magnetic resonance imaging (MRI) has accelerated human neuroscience by fostering the analysis of brain structure, function, and connectivity across multiple scales and in living brains. The richness and complexity of multimodal neuroimaging, however, demands processing methods to integrate information across modalities and different spatial scales. Here, we present micapipe, an open processing pipeline for BIDS-conform multimodal MRI datasets. micapipe can generate i) structural connectomes derived from diffusion tractography, ii) functional connectomes derived from resting-state signal correlations, iii) geodesic distance matrices that quantify cortico-cortical proximity, and iv) microstructural profile covariance matrices that assess inter-regional similarity in cortical myelin proxies. These matrices are routinely generated across established 18 cortical parcellations (100-1000 parcels), in addition to subcortical and cerebellar parcellations. Results are represented on three different surface spaces (native, conte69, fsaverage5), and outputs are BIDS-conform. Processed outputs can be quality controlled at the individual and group level. micapipe was tested on several datasets and is available at https://github.com/MICA-MNI/micapipe, documented at https://micapipe.readthedocs.io/, and containerized as a BIDS App http://bids-apps.neuroimaging.io/apps/. We hope that micapipe will foster robust and integrative studies of human brain microstructure, morphology, and connectivity.
Gut-liver-axis microphysiological system for studying cellular fluidic shear stress and inter-tissue interaction
Authors: Yang Jiandong , Hirai Yoshikazu , Imamura Satoshi , Tsuchiya Toshiyuki , Tabata Osamu , Kamei Ken-ichiro 
Published: February 2022

AbstractGut-liver-axis (GLA) is a fundamental interaction between the gut and liver for maintaining human health. To clarify the physiological and pathological roles of GLA in the human body, a GLA microphysiological system (GLA-MPS) holds great potential. However, in current GLA-MPS, the importance of a physiologically relevant flow for gut and liver cells’ cultivation is not fully addressed. In addition, the integration of individual organ perfusion, circulation flow, and organ tissue functions in a single device has not been achieved. Here, we introduce a GLA-MPS by integrating two cell culture chambers with individually applied perfusion flows and a circulation channel with an on-chip pneumatic micropump under cell culture chambers via a porous membrane for interconnecting them. We analyzed the fluid shear stress (FSS) with computational fluid dynamics simulations and confirmed that the physiologically relevant FSS (i.e., 8 × 10−3 and 1.2 × 10−7 dyne cm−2) could be applied for the gut (Caco-2) and liver (HepG2) cells, respectively. Under physiologically relevant flow, the Caco-2 and HepG2 cells in the GLA-MPS maintained a cell survival rate of 95% and 92%, respectively; further, they enhanced the expression of functional proteins such as zonula occludens 1 (ZO-1) and albumin (ALB), respectively. Thus, the presented GLA-MPS can be adapted as an advanced in vitro model in a wide range of applications for disease modeling associated with inter-tissue interactions, such as fatty liver diseases.
Understanding Chicks’ Emotions: Are Eye Blinks & Facial Temperatures Reliable Indicators?
Authors: Pijpers Naomi , van den Heuvel Huib , Duncan Ian H. , Yorzinski Jessica , Neethirajan Suresh 
Published: February 2022

AbstractIn commercial farming systems, chicks are reared without a mother. This absence of maternal influence can cause welfare problems when the chicks become older. Chicks imprint on their mothers they are young, and this mediates their stress and fear response. It is important to recognise problems early in the development of chicks to avoid welfare issues when they are older. One way to assess welfare is by measuring affective states. Research has shown chickens can display empathy, both towards their offspring and towards conspecifics. Measures of negative and positive affective states, either behavioural or physiological, could be good welfare indicators. This study employed non-invasive methods to measure affective states in laying hen chicks. Using video and thermal imaging, it analysed temperature changes in the peripheral areas and head region as well as changes in blinking behaviour before and after exposure to a stressor. The prediction was that the temperature would decrease in the eye and peripheral regions in response to a stressor and that the blinking rate would decrease. These changes would be indicative of a negative affective state. The results showed that the eye temperature as well as the blinking rate both decreased, whereas the temperature in the head region and the beak area increased. These results could be indicative of a negative affective state.
Human immunodeficiency virus type 2 capsid protein mutagenesis reveals amino acid residues important for virus particle assembly
Authors: Yang Huixin , Talledge Nathaniel , Arndt William G. , Zhang Wei , Mansky Louis M. 
Published: February 2022

AbstractHuman immunodeficiency virus (HIV) Gag drives virus particle assembly. The capsid (CA) domain is critical for Gag multimerization mediated by protein-protein interactions. The Gag protein interaction network defines critical aspects of the retroviral lifecycle at steps such as particle assembly and maturation. Previous studies have demonstrated that the immature particle morphology of HIV-2 is intriguingly distinct relative to that of HIV-1. Based upon this observation, we sought to determine the amino acid residues important for virus assembly that might help explain the differences between HIV-1 and HIV-2. To do this, we conducted site-directed mutagenesis of targeted locations in the HIV-2 CA domain of Gag and analyzed various aspects of virus particle assembly. A panel of 31 site-directed mutants of residues that reside at the HIV-2 CA inter-hexamer interface, intra-hexamer interface and CA inter-domain linker were created and analyzed for their effects on the efficiency of particle production, particle morphology, particle infectivity, Gag subcellular distribution and in vitro protein assembly. Seven conserved residues between HIV-1 and HIV-2 (L19, A41, I152, K153, K157, N194, D196) and two non-conserved residues (G38, N127) were found to significantly impact Gag multimerization and particle assembly. Taken together, these observations complement structural analyses of immature HIV-2 particle morphology and Gag lattice organization as well as provide important comparative insights into the key amino acid residues that can help explain the observed differences between HIV immature particle morphology and its association with virus replication and particle infectivity.
SleepMat: A New Behavioral Analysis Software Program for Sleep and Circadian Rhythms
Authors: Sisobhan Shiju , Rosensweig Clark , Lear Bridget C , Allada Ravi 
Published: February 2022

AbstractDrosophila is a premier model for the study of circadian rhythms and sleep, revealing molecular mechanisms that are conserved with vertebrates, including humans. The Drosophila Activity Monitoring (DAM) system has been employed for automated, high throughput analyses, enabling measures of a wide range of measures of circadian and sleep, including period, rhythmicity, anticipation, sleep amount, bout length, and bout number. Yet there are no publicly available programs that capture the full breadth of these measures. Here we develop a new program SleepMat that analyzes a uniquely broader range of circadian and sleep parameters. The program is built on a Matlab platform, employs an easy-to-use graphic user interface, and is highly flexible to customize data inputs. This program will enable a user-friendly high throughput analysis of a broad range of sleep and circadian parameters that can be coupled to the power of Drosophila genetics.
Egg-adaptation pathway of human influenza H3N2 virus is contingent on natural evolution
Authors: Liang Weiwen , Tan Timothy J.C. , Wang Yiquan , Lv Huibin , Sun Yuanxin , Bruzzone Roberto , Mok Chris K.P. , Wu Nicholas C. 
Published: February 2022

ABSTRACTEgg-adaptive mutations in influenza hemagglutinin (HA) often emerge during the production of egg-based seasonal influenza vaccines, which contribute to the largest share in the global influenza vaccine market. While some egg-adaptive mutations have minimal impact on the HA antigenicity (e.g. G186V), others can alter it (e.g. L194P). Here, we show that the preference of egg-adaptation pathway in human H3N2 HA is strain-dependent. In particular, Thr160 and Asn190, which are found in many recent H3N2 strains, restrict the emergence of L194P but not G186V. Our results further suggest that natural amino acid variants at other HA residues also play a role in determining the egg-adaptation pathway. Consistently, recent human H3N2 strains from different clades acquire different mutations during egg passaging. Overall, these results demonstrate that natural mutations in human H3N2 HA can influence the egg-adaption pathway, which has important implications in seed strain selection for egg-based influenza vaccine.
Detection of prevalent SARS-CoV-2 variant lineages in wastewater and clinical sequences from cities in Québec, Canada
Authors: N’Guessan Arnaud , Tsitouras Alexandra , Sanchez-Quete Fernando , Goitom Eyerusalem , Reiling Sarah J. , Galvez Jose Hector , Nguyen Thanh Luan , Loan Nguyen Ha Thanh , Visentin Flavia , Hachad Mounia , Krylova Kateryna , Matthews Sara , Kraemer Susanne A. , Stretenowich Paul , Bourgey Mathieu , Djambazian Haig , Chen Shu-Huang , Roy Anne-Marie , Brookes Brent , Lee Sally , Simon Marie-Michelle , Maere Thomas , Vanrolleghem Peter A. , Labelle Marc-Andre , Moreira Sandrine , Levade Inès , Bourque Guillaume , Ragoussis Jiannis , Dorner Sarah , Frigon Dominic , Shapiro B. Jesse 
Published: February 2022

ABSTRACTWastewater-based epidemiology has emerged as a promising tool to monitor pathogens in a population, particularly when clinical diagnostic capacities become overwhelmed. During the ongoing COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), several jurisdictions have tracked viral concentrations in wastewater to inform public health authorities. While some studies have also sequenced SARS-CoV-2 genomes from wastewater, there have been relatively few direct comparisons between viral genetic diversity in wastewater and matched clinical samples from the same region and time period. Here we report sequencing and inference of SARS-CoV-2 mutations and variant lineages (including variants of concern) in 936 wastewater samples and thousands of matched clinical sequences collected between March 2020 and July 2021 in the cities of Montreal, Quebec City, and Laval, representing almost half the population of the Canadian province of Quebec. We benchmarked our sequencing and variant-calling methods on known viral genome sequences to establish thresholds for inferring variants in wastewater with confidence. We found that variant frequency estimates in wastewater and clinical samples are correlated over time in each city, with similar dates of first detection. Across all variant lineages, wastewater detection is more concordant with targeted outbreak sequencing than with semi-random clinical swab sampling. Most variants were first observed in clinical and outbreak data due to higher sequencing rate. However, wastewater sequencing is highly efficient, detecting more variants for a given sampling effort. This shows the potential for wastewater sequencing to provide useful public health data, especially at places or times when sufficient clinical sampling is infrequent or infeasible.
The Nicaraguan Pediatric Influenza Cohort Study, 2011-2019: influenza incidence, seasonality, and transmission
Authors: Maier Hannah E. , Kuan Guillermina , Gresh Lionel , Chowell Gerardo , Bakker Kevin , Lopez Roger , Sanchez Nery , Lopez Brenda , Schiller Amy , Ojeda Sergio , Harris Eva , Balmaseda Angel , Gordon Aubree 
Published: February 2022

ABSTRACTBackgroundChildren account for a large portion of global influenza burden and transmission, and a better understanding of influenza in children is needed to improve prevention and control strategies.MethodsTo examine the incidence and transmission of influenza we conducted a prospective community-based study of children aged 0-14 years in Managua, Nicaragua between 2011 and 2019. Participants were provided with medical care through study physicians and symptomatic influenza was confirmed by RT-PCR. Wavelet analyses were used to examine seasonality. Generalized growth models (GGMs) were used to estimate effective reproduction numbers.ResultsFrom 2011-2019, 3,016 children participated, with an average of ∼1,800 participants per year and median follow-up time of 5 years per child, and 48.3% of the cohort in 2019 had been enrolled their entire lives. The overall incidence rates per 100 person-years were 14.5 symptomatic influenza cases (95%CI: 13.9-15.1) and 1.0 influenza-associated ALRI case (95%CI: 0.8-1.1). Symptomatic influenza incidence peaked at age 9-11 months. Infants born during peak influenza circulation had lower incidence in the first year of their lives. The mean effective reproduction number was 1.2 (range 1.02-1.49), and we observed significant annual patterns for influenza and influenza A, and a 2.5-year period for influenza B.ConclusionsThis study provides important information for understanding influenza epidemiology and informing influenza vaccine policy. These results will aid in informing strategies to reduce the burden of influenza.SummaryIn this long-running influenza cohort, we found a substantial incidence of RT-PCR-confirmed influenza, and report by subtype/lineage. Infants born during influenza epidemics were protected from infection that first year. The mean effective reproduction number across years was 1.2.
Neutralization profile of Omicron variant convalescent individuals
Authors: Rössler Annika , Knabl Ludwig , Laer Dorothee von , Kimpel Janine 
Published: February 2022

AbstractRecently, the Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been described as immune escape variant.Here, we analyzed samples from BA.1 (Omicron) convalescent patients with different constellations of prior SARS-CoV-2 immunity regarding vaccination and previous infection with a non-Omicron variant and determined titers of neutralizing antibodies against different SARS-CoV-2 variants (D614G, Alpha, Beta, Delta, Gamma, Omicron).We found high neutralizing antibody titers against all variants for vaccinated individuals after BA.1 breakthrough infection or for individuals after infection with a pre-omicron variant followed by BA.1 infection. In contrast, samples from naive unvaccinated individuals after BA.1 infection mainly contained neutralizing antibodies against BA.1 but only occasionally against the other variants.
3D printed bioreactor enabling the physiological culture and the study of pathological processes in large vessels
Authors: Matos Rolando S , Maselli Davide , McVey John H , Heiss Christian , Campagnolo Paola 
Published: February 2022

AbstractRoutine cardiovascular interventions such as balloon angioplasty, result in vascular activation and remodeling, often requiring re-intervention. 2D in vitro culture models and small animal experiments have enabled the discovery of important molecular and cellular pathways involved in this process, however the clinical translation of these results is often underwhelming. There is a critical need for an ex vivo model representative of the human vascular physiology and encompassing the complexity of the vascular wall and the physical forces regulating its function. Vascular bioreactors for ex vivo culture of large vessels are viable alternatives, but their custom-made design and insufficient characterization often hinders the reproducibility of the experiments.The objective of the study was to design and validate a novel 3D printed cost-efficient and versatile perfusion system, capable of sustaining the viability and functionality of large porcine arteries for 7 days and enabling monitoring of post-injury remodeling.MultiJet Fusion 3D printing technology was used to engineer the ‘EasyFlow’ insert, converting a conventional 50 ml centrifuge tube into a mini bioreactor. Porcine carotid arteries either left untreated or injured with a conventional angioplasty balloon, were cultured under pulsatile flow for up to 7 days. Pressure, heart rate, medium viscosity and shear conditions were adjusted to represent the typical arterial physiology. Tissue viability, cell activation and matrix remodeling were analyzed by immunohistochemistry, and vascular function was monitored by duplex ultrasound.Physiological blood flow conditions in the EasyFlow bioreactor preserved endothelial coverage and smooth muscle organization and extracellular matrix structure in the vessel wall, as compared to static culture. Injured arteries presented hallmarks of early remodeling, such as intimal denudation, smooth muscle cell disarray and media/adventitia activation in flow culture. Duplex ultrasound confirmed physiological hemodynamic conditions, dose-dependent vasodilator response to nitroglycerin in untreated vessels and impaired dilator response in angioplastied vessels. We here validate a low-cost, robust and reproducible system to study vascular physiopathology, laying the basis for future investigations into the pathological remodeling of blood vessels and creating a platform to test novel therapies and devices ex vivo, in a patient relevant system.
Deep Mendelian Randomization: Investigating the Causal Knowledge of Genomic Deep Learning Models
Authors: Malina Stephen , Cizin Daniel , Knowles David A. 
Published: February 2022

AbstractMulti-task deep learning (DL) models can accurately predict diverse genomic marks from sequence, but whether these models learn the causal relationships between genomic marks is unknown. Here, we describe Deep Mendelian Randomization (DeepMR), a method for estimating causal relationships between genomic marks learned by genomic DL models. By combining Mendelian Randomization with in silico mutagenesis, DeepMR obtains local (locus specific) and global estimates of (an assumed) linear causal relationship between marks. In a simulation designed to test recovery of pairwise causal relations between transcription factors (TFs), DeepMR gives accurate and unbiased estimates of the ‘true’ global causal effect, but its coverage decays in the presence of sequence-dependent confounding. We then apply DeepMR to examine the global relationships learned by a state-of-the-art DL model, BPNet [Avsec et al., 2020], between TFs involved in reprogramming. DeepMR’s causal effect estimates validate previously hypothesized relationships between TFs and suggest new relationships for future investigation.
ReadBouncer: Precise and Scalable Adaptive Sampling for Nanopore Sequencing
Authors: Ulrich Jens-Uwe , Lutfi Ahmad , Rutzen Kilian , Renard Bernhard Y. 
Published: February 2022

Nanopore sequencers allow targeted sequencing of interesting nucleotide sequences by rejecting other sequences from individual pores. This feature facilitates the enrichment of low-abundant sequences by depleting overrepresented ones in-silico. Existing tools for adaptive sampling either apply signal alignment, which cannot handle human-sized reference sequences, or apply read mapping in sequence space relying on fast GPU base callers for real-time read rejection. Using nanopore long-read mapping tools is also not optimal when mapping shorter reads as usually analyzed in adaptive sampling applications. Here we present a new approach for nanopore adaptive sampling that combines fast CPU and GPU base calling with read classification based on Interleaved Bloom Filters (IBF). Read-Bouncer improves the potential enrichment of low abundance sequences by its high read classification sensitivity and specificity, outperforming existing tools in the field. It robustly removes even reads belonging to large reference sequences while running on commodity hardware without graphical processing units (GPUs), making adaptive sampling accessible for in-field researchers. Readbouncer also provides a user-friendly interface and installer files for end-users without a bioinformatics background.AvailabilityThe C++ source code of ReadBouncer is available at (https://gitlab.com/dacs-hpi/readbouncer).
Optimization of NLS Composition Improves CRISPR-Cas12a Editing Rates in Human Primary Cells
Authors: Luk Kevin , Liu Pengpeng , Zeng Jing , Wang Yetao , Maitland Stacy A. , Idrizi Feston , Ponnienselvan Karthikeyan , Zhu Lihua Julie , Luban Jeremy , Bauer Daniel E. , Wolfe Scot A. 
Published: February 2022

AbstractType V CRISPR–Cas12a systems are an attractive alternative nuclease platform for specific genome editing applications. However, previous studies demonstrate that there is a gap in overall activity between Cas12a and Cas9 in primary cells. Here we describe optimization to the nuclear localization signal composition and architecture of Cas12a to facilitate highly efficient targeted mutagenesis in mammalian cell lines (HEK293T, Jurkat, and K562 cells) and primary cells (NK cells and CD34+ HSPCs), regardless of Cas12a ortholog. A 3xNLS Cas12a architecture resulted in the most robust editing platform. The improved editing activity of Cas12a in both NK cells and CD34+ HSPCs resulted in pronounced phenotypic changes associated with target gene editing. Lastly, we demonstrated that optimization of the NLS composition and architecture of Cas12a did not decrease the specificity of editing in HEK293T and CD34+ HSPCs. Our new Cas12a NLS variant provides an improved nuclease platform for therapeutic genome editing.
Autophagy receptor NDP52 alters DNA conformation to modulate RNA Polymerase II transcription
Authors: dos Santos Ália , Rollins Daniel E. , Hari-Gupta Yukti , Reed Hannah C. W. , Du Mingxue , Ru Sabrina Yong Zi , Pidlisna Kseniia , Stranger Ane , Lorgat Faeeza , Brown Ian , Howland Kevin , Aaron Jesse , Wang Lin , Ellis Peter J. I. , Chew Teng-Leong , Martin-Fernandez Marisa , Pyne Alice L. B. , Toseland Christopher P. 
Published: February 2022

ABSTRACTNDP52 is an autophagy receptor involved in the recognition and degradation of invading pathogens and damaged organelles. Although NDP52 was first identified in the nucleus and is expressed throughout the cell, to date, there is no clear nuclear function for NDP52. Here, we use a multidisciplinary approach to characterise the biochemical properties and nuclear roles of NDP52. We found that NDP52 clusters with RNA Polymerase II (RNAPII) at transcription initiation sites and that its overexpression promotes the formation of additional transcriptional clusters. We also show that depletion of NDP52 impacts overall gene-expression levels in two model mammalian cells, and that transcription inhibition affects the spatial organisation and molecular dynamics of NDP52 in the nucleus. This directly links NDP52 to a role in RNAPII-dependent transcription. Furthermore, we also show that NDP52 binds specifically and with high affinity to double-stranded DNA (dsDNA) and that this interaction leads to changes in DNA structure in vitro. This, together with our proteomics data indicating enrichment for interactions with nucleosome remodelling proteins and DNA structure regulators, suggests a possible function for NDP52 in chromatin regulation. Overall, here we uncover novel nuclear roles for NDP52 in gene expression and DNA structure regulation.