bluuebunny/crossref_metadata_2025_split huggingface dataset:
Library preparation method and DNA source influence endogenous DNA recovery from 100-year-old avian museum specimens
Authors: Settlecowski Amie E. , Marks Ben D. , Manthey Joseph D. 
Published: February 2023

AbstractMuseum specimens collected prior to cryogenic tissue storage are increasingly being used as genetic resources, and though high throughput sequencing is becoming more cost-efficient, whole genome sequencing (WGS) of historical DNA (hDNA) remains inefficient and costly due to its short fragment sizes and high loads of exogenous DNA, among other factors. It is also unclear how sequencing efficiency is influenced by DNA source. We aimed to identify the most efficient method and DNA source for collecting WGS data from avian museum specimens. We analyzed low-coverage WGS from 60 DNA libraries prepared from four American Robin (Turdus migratorius) and four Abyssinian Thrush (Turdus abyssinicus) specimens collected in the 1920s. We compared DNA source (toepad versus incision-line skin clip) and three library preparation methods: 1) double-stranded, single tube (KAPA); 2) single-stranded, multi-tube (IDT); and 3) single-stranded, single-tube (Claret Bioscience). We found that the multi-tube ssDNA method resulted in significantly greater endogenous DNA content, average read length, and sequencing efficiency than the other tested methods. We also tested whether a predigestion step reduced exogenous DNA in libraries from one specimen per species and found promising results that warrant further study. The ~10% increase in average sequencing efficiency of the best performing method over a commonly implemented dsDNA library preparation method has the potential to significantly increase WGS coverage of hDNA from bird specimens. Future work should evaluate the threshold for specimen age at which these results hold and how the combination of library preparation method and DNA source influence WGS in other taxa.
Mono-ADP-ribosyltransferase 1 (Artc1)-deficiency decreases tumorigenesis, increases inflammation, decreases cardiac contractility, and reduces survival
Authors: Ishiwata-Endo Hiroko , Kato Jiro , Oda Hirotake , Sun Junhui , Yu Zu-Xi , Liu Chengyu , Springer Danielle A. , Dagur Pradeep , Lizak Martin J. , Murphy Elizabeth , Moss Joel 
Published: February 2023

AbstractArginine-specific mono-ADP-ribosylation is a reversible post-translational modification; arginine-specific, cholera toxin-like mono-ADP-ribosyltransferases (ARTCs) transfer ADP-ribose from NAD+to arginine, followed by cleavage of ADP-ribose-(arginine)protein bond by ADP-ribosylarginine hydrolase 1 (ARH1), generating unmodified (arginine)protein. ARTC1 has been shown to enhance tumorigenicity as doesArh1deficiency. In this study,Artc1-KO andArtc1/Arh1-double-KO mice showed decreased spontaneous tumorigenesis and increased age-dependent, multi-organ inflammation with upregulation of pro-inflammatory cytokine TNF-α. In a xenograft model using tumorigenicArh1-KO mouse embryonic fibroblasts (MEFs), tumorigenicity was decreased inArtc1-KO and heterozygous recipient mice, with tumor infiltration by CD8+T cells and macrophages, leading to necroptosis, suggesting that ARTC1 promotes the tumor microenvironment. Furthermore,Artc1/Arh1-double-KO MEFs showed decreased tumorigenesis in nude mice, showing that tumor cells as well as tumor microenvironment require ARTC1. By echocardiography and MRI,Artc1-KO and heterozygous mice showed male-specific, reduced myocardial contractility. Furthermore,Artc1-KO male hearts exhibited enhanced susceptibility to myocardial ischemia-reperfusion-induced injury with increased receptor-interacting protein kinase 3 (RIP3) protein levels compared to WT mice, suggesting that ARTC1 suppresses necroptosis. Overall survival rate ofArtc1-KO was less than theirArtc1-WT counterparts, primarily due to enhanced immune response and inflammation. Thus, anti-ARTC1 agents may reduce tumorigenesis but may increase multi-organ inflammation and decrease cardiac contractility.Graphical Abstract
A SARS-CoV-2 vaccine designed for manufacturability results in unexpected potency and non-waning humoral response
Authors: Campbell Elliot , Dobkin Julie , Osorio Louis , Kolloli Afsal , Ramasamy Santhamani , Kumar Ranjeet , Sant’Angelo Derek B. , Subbian Selvakumar , Denzin Lisa K. , Anderson Stephen 
Published: February 2023

ABSTRACTThe rapid development of several highly efficacious SARS-CoV-2 vaccines was an unprecedented scientific achievement that saved millions of lives. However, now that SARS-CoV-2 is transitioning to the endemic stage, there exists an unmet need for new vaccines that provide durable immunity, protection against variants, and can be more easily manufactured and distributed. Here we describe a novel protein component vaccine candidate, MT-001, based on a fragment of the SARS-CoV-2 spike protein that encompasses the receptor binding domain (RBD). Mice and hamsters immunized with a prime-boost regimen of MT-001 demonstrated extremely high anti-spike IgG titers, and remarkably this humoral response did not appreciably wane for up to 12 months following vaccination. Further, virus neutralization titers, including titers against variants such as Delta and Omicron BA.1, remained high without the requirement for subsequent boosting. MT-001 was designed for manufacturability and ease of distribution, and we demonstrate that these attributes are not inconsistent with a highly immunogenic vaccine that confers durable and broad immunity to SARS-CoV-2 and its emerging variants. These properties suggest MT-001 could be a valuable new addition to the toolbox of SARS-CoV-2 vaccines and other interventions to prevent infection and curtail additional morbidity and mortality from the ongoing worldwide pandemic.
Boundary stacking interactions enable cross-TAD enhancer-promoter communication during limb development
Authors: Hung Tzu-Chiao , Kingsley David M. , Boettiger Alistair 
Published: February 2023

AbstractWhile long-range enhancers and their target promoters are frequently contained within a TAD, many developmentally important genes have their promoter and enhancers within different TADs. Hypotheses about molecular mechanisms enabling such cross-TAD interactions remain to be assessed. To test these hypotheses, we use Optical Reconstruction of Chromatin Architecture (ORCA) to characterize the conformations of thePitx1locus on thousands of single chromosomes in developing mouse limbs. Our data supports a model in which neighboring boundaries are stacked with each other as a result of loop-extrusion, bringing boundary-proximalcis-elements into contact. This stacking interaction also explains the appearance of architectural stripes in the population average maps (e.g. Hi-C data). Through molecular dynamics simulations, we further propose that increasing boundary strengths facilitates the formation of the stacked boundary conformation, counter-intuitively facilitating border bypass. This work provides a revised view of the TAD borders’ function, both facilitating as well as preventingcis-regulatory interactions, and introduces a framework to distinguish border-crossing from border-respecting enhancer-promoter pairs.
A fast, robust method for quantitative assessment of collagen fibril architecture from transmission electron micrographs
Authors: Rego Bruno V. , Weiss Dar , Humphrey Jay D. 
Published: February 2023

ABSTRACTCollagen is the most abundant protein in mammals; it exhibits a hierarchical organization and provides structural support to a wide range of soft tissues, including blood vessels. The architecture of collagen fibrils dictates vascular stiffness and strength, and changes therein can contribute to disease progression. While transmission electron microscopy (TEM) is routinely used to examine collagen fibrils under normal and pathological conditions, computational tools that enable fast and minimally subjective quantitative assessment remain lacking. In the present study, we describe a novel semi-automated image processing and statistical modeling pipeline for segmenting individual collagen fibrils from TEM images and quantifying key metrics of interest, including fibril crosssectional area and aspect ratio. For validation, we show illustrative results for adventitial collagen in the thoracic aorta from three different mouse models.
Inferring context-dependent computations through linear approximations of prefrontal cortex dynamics
Authors: Soldado-Magraner Joana , Mante Valerio , Sahani Maneesh 
Published: February 2023

AbstractThe complex neural population activity of prefrontal cortex (PFC) is a hallmark of cognitive processes. How these rich dynamics emerge and support neural computations is largely unknown. Here, we infer mechanisms underlying the context-dependent selection and integration of sensory inputs by fitting dynamical models to PFC population responses of behaving monkeys. A class of models implementing linear dynamics driven by external inputs accurately captured the PFC responses within each context, achieving performance comparable to models without linear constraints. Two distinct mechanisms of input selection and integration were equally consistent with the data. One implemented context-dependent recurrent dynamics, as previously proposed, and relied on transient input amplification. The other relied on the subtle contextual modulation of the inputs, providing quantitative constraints on the attentional effects in sensory areas required to explain flexible PFC responses and behavior. Both mechanisms consistently revealed properties of inputs and recurrent dynamics missing in more simplified, incomplete descriptions of PFC responses. By revealing mechanisms consistent with rich cortical dynamics, our modeling approach provides a principled and general framework to link neural population activity and computation.
C3 in the 10-20 system may not be the best target for the motor hand area
Authors: Kim Hakjoo , Wright David L. , Rhee Joohyun , Kim Taewon 
Published: February 2023

ABSTRACTThe C3 region in the international 10-20 system for electroencephalography (EEG) recording is assumed to represent the right motor hand area. Therefore, in the absence of transcranial magnetic stimulation (TMS) or a neuronavigational system, neuromodulation methods, such as transcranial direct current stimulation, target C3 or C4, based on the international 10-20 system, to influence the cortical excitability of the right and left hand, respectively. The purpose of this study is to compare the peak-to-peak motor evoked potential (MEP) amplitudes of the right first dorsal interosseus (FDI) muscle after single-pulse TMS at C3, C3h, and C1. Using an intensity of 110% of the resting motor threshold, 15 individual MEPs from each of C3, C3h, C1, and hotspots were randomly recorded from FDI for sixteen right-handed undergraduate students. Average MEPs were greatest at C3h and C1, with both being larger than those recorded at C3. These data are congruent with recent findings using topographic analysis of individual MRIs that revealed poor correspondence between C3/C4 and the respective hand knob. Implications for the use of scalp locations determined using the 10-20 system for localizing the hand area are highlighted.HighlightsMEPs recorded at C3h and C1 were larger than those recorded at C3.Scalp locations other than C3 offer a more accurate estimation of human hand area.
Phenotype switching of the mutation rate facilitates adaptive evolution
Authors: Lobinska Gabriela , Pilpel Yitzhak , Ram Yoav 
Published: February 2023

AbstractThe mutation rate plays an important role in adaptive evolution. It can be modified by mutator and anti-mutator alleles. Recent empirical evidence hints that the mutation rate may vary among genetically identical individuals: empirical evidence from bacteria suggests that the mutation rate can be affected by translation errors and expression noise in various proteins. Importantly, this non-genetic variation may be heritable via a transgenerational epigenetic mode of inheritance, giving rise to a mutator phenotype that is independent from mutator alleles. Here we investigate mathematically how the rate of adaptive evolution is affected by the rate of mutation rate phenotype switching. We model an asexual population with two mutation rate phenotypes, non-mutator and mutator. An offspring may switch from its parental phenotype to the other phenotype. We find that switching rates that correspond to so-far empirically described non-genetic systems of inheritance of the mutation rate lead to higher rates of adaptation on various fitness landscapes. These switching rates can maintain within the same individuals both a mutator phenotype and pre-existing mutations, a combination that facilitates adaptation. Moreover, non-genetic inheritance increases the proportion of mutators in the population, which in turn increases the probability of hitchhiking of the mutator phenotype with adaptive mutations. This in turns facilitates the acquisition of additional adaptive mutations. Our results rationalize recently observed noise in the expression of proteins that affect the mutation rate and suggest that non-genetic inheritance of this phenotype may facilitate evolutionary adaptive processes.
Transferrin-induced signaling through transferrin receptor and AKT kinase mediates formation of Rab8- and MICAL-L1-positive tubules involved in receptor recycling
Authors: Rangaraj Nandini , Vaibhava Vipul , Sudhakar Cherukuri , Moharir Shivranjani C , Swarup Ghanshyam 
Published: February 2023

AbstractTransferrin and its receptor play an important role in iron homeostasis. Binding of transferrin to its receptor (TFRC, transferrin receptor protein 1) initiates endocytic trafficking and subsequent recycling of TFRC to the plasma membrane. RAB8-positive tubules emanating from the endocytic recycling compartment play an important role in receptor recycling. However, the signaling pathways or mechanisms that mediate formation of RAB8-positive tubules are not clear. Here, we have investigated the role of transferrin-induced signaling in the regulation of RAB8- and MICAL-L1-positive tubules. Addition of transferrin to the serum starved HeLa cells resulted in enhanced recruitment of RAB8 as well as MICAL-L1 to the tubules, which was mediated by TFRC. Dynasore, an inhibitor of dynamin and endocytosis, completely blocked transferrin-induced formation of RAB8/MICAL-L1-positive tubules. RAB8 showed strong colocalization with MICAL-L1 on the tubules. Blocking of SRC or AKT kinase activity by specific inhibitors abolished transferrin-induced recruitment of RAB8 and MICAL-L1 to the tubules. Recycling of transferrin receptor was inhibited by blocking of AKT activity. TBC1D17, a GTPase activating protein for RAB8, inhibited RAB8/MICAL-L1-positive tubule formation. A phospho-mimicking mutant S366D of TBC1D17 did not inhibit formation of RAB8-positive tubules. Overall, these results show that transferrin induces TFRC mediated signaling dependent on endocytosis that is essential for the formation of RAB8- and MICAL-L1-positive tubules involved in recycling of transferrin receptor. Our results also show that AKT regulates transferrin-induced formation of RAB8- and MICAL-L1-positive tubules, which might be mediated by phosphorylation of TBC1D17.
The representational dynamics of the animal appearance bias in human visual cortex are indicative of fast feedforward processing
Authors: Chen Chiu-Yueh , Leys Gaëlle , Bracci Stefania , de Beeck Hans Op 
Published: February 2023

AbstractThe human visual system has a seemingly unique tendency to interpret zoomorphic objects as animals, not as objects. This animal appearance bias is very strong in the ventral visual pathway as measured through functional magnetic resonance imaging (fMRI), but it is absent in feedforward deep convolutional neural networks. Here we investigate how this bias emerges over time by probing its representational dynamics through multivariate electroencephalography (EEG). The initially activated representations to lookalike zoomorphic objects are very similar to the representations activated by animal pictures and very different from the neural responses to regular objects. Neural responses that reflect the true identity of the zoomorphic objects as inanimate objects are weaker and appear later, as do effects of task context. The strong early emergence of an animal appearance bias strongly supports a feedforward explanation, indicating that lack of recurrence in deep neural networks is not an explanation for their failure to show this bias.
Unraveling codon usage ofEscherichia coliusing machine learning
Authors: Huang Bifang , Hu Yunzhuo , Chen Xuanyang , Lin Shiqiang 
Published: February 2023

AbstractMachine learning is used to investigate the codon usage of protein-encoding genes, which is one of the fundamental questions of molecular biology. The presentation, parameter learning, and decoding of the conditional random field (CRF) model are implemented and then utilized to analyze the codon usage of the genes ofEscherichia coliand its phages. Most genes ofE. coliuse codons conforming to the weights of the model determined by allE. coligenes. Phages use the codons like their hostE. coli. Finally, the study evaluates the codon usage of several example genes in the context of the model. These results help to understand the codon usage inE. coli.
Bio-Heat Transfer and Monte Carlo Measurement of Near-Infrared Transcranial Stimulation of Human Brain
Authors: Ibrahimi Faezeh , Delrobaei Mehdi 
Published: February 2023

ABSTRACTTranscranial photobiomodulation is an optical method for non-invasive brain stimulation. The method projects red and near-infrared light through the scalp within 600-1100 nm and low energy within the 1-20J/cm2range. Recent studies have been optimistic about replacing this method with pharmacotherapy and invasive brain stimulation. However, concerns and ambiguities exist regarding the light penetration depth and possible thermal side effects. While the literature survey indicates that the skin temperature rises after experimental optical brain stimulation, inadequate evidence supports a safe increase in temperature or the amount of light penetration in the cortex. Therefore, we aimed to conduct a comprehensive study on the heat transfer of near-infrared stimulation for the human brain. Our research considers the transcranial photobiomodulation over the human brain model by projecting 810 nm light with 100mW/cm2power density to evaluate its thermal and optical effects using bioheat transfer and radiative transfer equation. Our results confirm that the near-infrared light spectrum has a small incremental impact on temperature and approximately penetrates 1 cm, reaching the cortex. A time-variant study of the heat transfer was also carried out to measure the temperature changes during optical stimulation.
Assessing vector competence of mosquitoes from northeastern France to West Nile virus and Usutu virus
Authors: Martinet Jean-Philippe , Bohers Chloé , Vazeille Marie , Ferté Hubert , Mousson Laurence , Mathieu Bruno , Depaquit Jérôme , Failloux Anna-Bella 
Published: February 2023

AbstractWest Nile virus (WNV) and Usutu virus (USUV) are two arthropod-borne viruses that circulate in mainland France. Assessing vector competence has only been conducted so far with mosquitoes from southern France while an increasingly active circulation of WNV and USUV has been reported in the last years. The main vectors are mosquitoes of theCulexgenus and the common mosquitoCulex pipiens. Here, we measure the vector competence of five mosquito species (Aedes rusticus, Aedes albopictus, Anopheles plumbeus, Culex pipiensandCuliseta longiareolata) present in northeastern France. Field-collected populations were exposed to artificial infectious blood meal containing WNV or USUV and examined at different days post-infection. We show that (i)Cx. pipienstransmitted WNV and USUV, (ii)Ae. rusticusonly WNV, and (iii) unexpectedly,Ae. albopictustransmitted both WNV and USUV. Less surprising,An. plumbeuswas not competent for both viruses. Combined with data on distribution and population dynamics, these assessments of vector competence will help in developing a risk map and implementing appropriate prevention and control measures.Author summaryWest Nile virus (WNV) and Usutu virus (USUV) are on the rise in Europe and in France. WNV is reported in France as early as the 1960s in the Camargue and USUV more recently, in 2015 in eastern France. The re-emergence of WNV infections in the Camargue is associated with an expansion towards the North which is also favorable to maintain a viral transmission cycle. USUV frequently co-circulates with WNV sharing the same mosquito vectors.Culex pipiens, able to feed on birds and humans, is considered to be the main vector in France. Our study is the first to investigate the vector competence to WNV and USUV of five different mosquito species collected in northeastern France. We ascertain that FrenchCx. pipiensmosquitoes are competent to both WNV and USUV. More surprisingly, the mosquitoAedes albopictusfrom northeastern France was able to transmit WNV and USUV. Based on our result, we propose that surveillance of mosquitoes combined with viral detections must be implemented in northeastern France to allow early viral detection and timely intervention to prevent outbreaks of these two neurological diseases.
Bacterial suppressor-of-copper-sensitivity (Scs) proteins exhibit diverse thiol-disulfide oxidoreductase cellular functions
Authors: Hong Yaoqin , Qin Jilong , Mitchell Lachlan , Paxman Jason J. , Heras Begoña , Totsika Makrina 
Published: February 2023

ABSTRACTDisulfide bond (Dsb) proteins catalyse oxidative protein folding governing bacterial survival and virulence. Dsb systems inEscherichia coliK-12 are well-studied, yet what determines dithiol oxidase or disulfide reductase activity remains unknown. Past studies suggest oligomerisation of periplasmic thiol oxidoreductases dictates the direction of thiol catalytic activity. Here, we studied three suppressor-of-copper-sensitivity C (ScsC) Dsb-like proteins known to exist in the reduced state and bind to copper. These proteins adopt different quaternary structures:Salmonella entericaScsC (StScsC) is monomeric, while ScsC fromProteus mirabilis(PmScsC) andCaulobacter crescentus(CcScsC) are trimeric. When expressed in the model organismE. coliK-12, we showed that all three ScsC proteins exhibit both dithiol oxidation and disulfide reduction activity, despite structural differences. Interestingly, while ScsC reductase function was supported by the canonicalE. coliDsbD reductase, oxidase activity depended on environmental oxidation. However, an engineered monomeric PmScsC synergises withE. coliDsbB to gain dithiol oxidase activity at the expense of reductase function. Thus, oligomerisation could be one mechanism by which ScsC proteins avoid interactions with the periplasmic thiol oxidase pathway. This tightly controls their re-oxidation and maintains ScsC proteins in the reduced state required for binding and sequestering toxic levels of cellular copper.