bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pseudomonas aeruginosaisolates defective in function of the LasR quorum sensing regulator are frequent in diverse environmental niches
Authors: Groleau Marie-Christine , Taillefer Hélène , Vincent Antony T. , Constant Philippe , Déziel Eric 
Published: March 2021

ABSTRACTThe saprophytePseudomonas aeruginosais a versatile opportunistic pathogen causing infections in immunocompromised individuals. To facilitate its adaptation to a large variety of niches, this bacterium exploits population density-dependant gene regulation systems called quorum sensing. InP. aeruginosa, three distinct but interrelated quorum sensing systems (las,rhlandpqs) regulate the production of many survival and virulence functions. In prototypical strains, thelassystem, through its transcriptional regulator LasR, is important for the full activation of therhlandpqssystems. Still, LasR-deficient isolates have been reported, mostly sampled from the lungs of people with cystic fibrosis, where they are considered selected by the chronic infection environment. In this study, we show that a defect in LasR activity appears to be an actually widespread mechanism of adaptation in this bacterium. Indeed, we found abundant LasR-defective isolates sampled from hydrocarbon-contaminated soils, hospital sink drains, and meat/fish market environments, using an approach based on phenotypic profiling, supported by gene sequencing. Interestingly, several LasR-defective isolates maintain an activerhlsystem or are deficient inpqssystem signaling. The high prevalence of a LasR-defective phenotype among environmentalP. aeruginosaisolates questions the role of quorum sensing in niche adaptation.
scAmpi - A versatile pipeline for single-cell RNA-seq analysis from basics to clinics
Authors: Bertolini Anne , Prummer Michael , Tuncel Mustafa Anil , Menzel Ulrike , Rosano-González María Lourdes , Kuipers Jack , Stekhoven Daniel Johannes ,   Tumor Profiler consortium, Beerenwinkel Niko , Singer Franziska 
Published: March 2021

AbstractSingle-cell RNA sequencing (scRNA-seq) has emerged as a powerful technique to decipher tissue composition at the single-cell level and to inform on disease mechanisms, tumor heterogeneity, and the state of the immune microenvironment. Although multiple methods for the computational analysis of scRNA-seq data exist, their application in a clinical setting demands standardized and reproducible workflows, targeted to extract, condense, and display the clinically relevant information. To this end, we designed scAmpi (SingleCellAnalysismRNApipeline), a workflow that facilitates scRNA-seq analysis from raw read processing to informing on sample composition, clinically relevant gene and pathway alterations, andin silicoidentification of personalized candidate drug treatments. We demonstrate the value of this workflow for clinical decision making in a molecular tumor board as part of a clinical study.
Combining IP3affinity chromatography and bioinformatics reveals a novel protein-IP3binding site onPlasmodium falciparumMDR1 transporter
Authors: Alves Eduardo , Nakaya Helder , Guimarães Euzébio , Garcia Célia R. S. 
Published: March 2021

AbstractIntracellular Ca2+mobilization induced by second messenger IP3controls many cellular events in most of the eukaryotic groups. Despite the increasing evidence of IP3-induced Ca2+in apicomplexan parasites likePlasmodium, responsible for malaria infection, no protein with potential function as an IP3-receptor has been identified. The use of bioinformatic analyses based on previously known sequences of IP3-receptor failed to identify potential IP3-receptor candidates in anyApicomplexa. In this work, we combine the biochemical approach of an IP3affinity chromatography column with bioinformatic meta-analyses to identified potential vital membrane proteins that present binding with IP3inPlasmodium falciparum. Our analyses reveal that PF3D7_0523000, a gene that codes a transport protein associated with multidrug resistance, as a potential target for IP3. This work provides a new insight for probing potential candidates for IP3-receptor inApicomplexa.
Sulforaphane exhibits in vitro and in vivo antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses
Authors: Ordonez Alvaro A. , Bullen C. Korin , Villabona-Rueda Andres F. , Thompson Elizabeth A. , Turner Mitchell L. , Davis Stephanie L. , Komm Oliver , Powell Jonathan D. , D’Alessio Franco R. , Yolken Robert H. , Jain Sanjay K. , Jones-Brando Lorraine 
Published: March 2021

AbstractSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has incited a global health crisis. Currently, there are no orally available medications for prophylaxis for those exposed to SARS-CoV-2 and limited therapeutic options for those who develop COVID-19. We evaluated the antiviral activity of sulforaphane (SFN), a naturally occurring, orally available, well-tolerated, nutritional supplement present in high concentrations in cruciferous vegetables with limited side effects. SFN inhibited in vitro replication of four strains of SARS-CoV-2 as well as that of the seasonal coronavirus HCoV-OC43. Further, SFN and remdesivir interacted synergistically to inhibit coronavirus infection in vitro. Prophylactic administration of SFN to K18-hACE2 mice prior to intranasal SARS-CoV-2 infection significantly decreased the viral load in the lungs and upper respiratory tract and reduced lung injury and pulmonary pathology compared to untreated infected mice. SFN treatment diminished immune cell activation in the lungs, including significantly lower recruitment of myeloid cells and a reduction in T cell activation and cytokine production. Our results suggest that SFN is a promising treatment for prevention of coronavirus infection or treatment of early disease.
Age-Related Type I Collagen Modifications Reveal Tissue-Defining Differences Between Ligament and Tendon
Authors: Hudson David M. , Archer Marilyn , Rai Jyoti , Weis MaryAnn , Fernandes Russell J. , Eyre David R. 
Published: March 2021

AbstractTendons and ligaments tend to be pooled into a single category as dense elastic bands of collagenous connective tissue. They do have many similar properties, for example both tissues are flexible cords of fibrous tissue that join bone to either muscle or bone. Tendons and ligaments are both prone to degenerate and rupture with only limited capacity to heal, however; healing outcomes for tendons are often faster than ligament injuries. Type I collagen constitutes about 80% of the dry weight of tendons and ligaments and is principally responsible for the core strength of each tissue. Collagen synthesis is a complex process with multiple steps and numerous post-translational modifications including proline and lysine hydroxylation, hydroxylysine glycosylation and covalent cross-linking. The chemistry, placement and quantity of intramolecular and intermolecular cross-links are believed to be key contributors to the tissue-specific variations in material strength and biological properties of collagens. As tendons and ligaments grow and develop, the collagen cross-links are known to chemically mature, strengthen and change in profile. Accordingly, changes in cross-linking and other post-translational modifications are likely associated with tissue development and degeneration. Using mass spectrometry, we have compared tendon and ligaments from fetal and adult bovine knee joints to investigate changes in collagen post-translational properties. Although hydroxylation levels at the type I collagen helical cross-linking lysine residues were similar in all adult tissues, ligaments had significantly higher levels of glycosylation at these sites compared to tendon. Differences in lysine hydroxylation were also found between the tissues at the telopeptide cross-linking sites. Total collagen cross-linking analysis, including mature trivalent cross-links and immature divalent cross-links, revealed unique cross-linking profiles between tendon and ligament tissues. Tendons were found to have a significantly higher frequency of smaller diameter collagen fibrils compared with ligament, which we propose is a consequence of the unique cross-linking profile of each tissue. Understanding the specific molecular characteristics that define and distinguish these specialized tissues will be important for designing improved orthopedic treatment approaches.
Retinal waves but not visual experience are required for development of retinal direction selectivity maps
Authors: Tiriac Alexandre , Bistrong Karina , Feller Marla B. 
Published: March 2021

AbstractRetinal waves and visual experience have been implicated in the formation of retinotopic and eye-specific maps throughout the visual system, but whether either play a role in the development of the maps within the retina itself is unknown. We explore this question using direction-selective retinal ganglion cells, which are organized into a map that aligns to the body and gravitational axes of optic flow. Using two-photon population calcium imaging, we find that the direction selectivity map is present at eye opening and is unaltered by dark-rearing. Remarkably, the horizontal component of the direction selectivity map is absent in mice lacking normal retinal waves, whereas the vertical component remains normal. These results indicate that intrinsic patterns of activity, rather than extrinsic motion signals are critical for the establishment of direction selectivity maps in the retina.One Sentence SummaryHorizontal direction selectivity in the retina is absent in mice lacking normal retinal waves.
Unlimited cooperativity ofBetatectivirusSSB, a novel DNA binding protein related to an atypical group of SSBs from protein-primed replicating bacterial viruses
Authors: Lechuga A. , Kazlauskas D. , Salas M. , Redrejo-Rodríguez M. 
Published: March 2021

AbstractBam35 and related betatectiviruses are tail-less bacteriophages that prey on members of theBacillus cereusgroup. These temperate viruses replicate their linear genome by a protein-primed mechanism. In this work, we have identified and characterized the product of the viral ORF2 as a single-stranded DNA binding protein (hereafter B35SSB). B35SSB binds ssDNA with great preference over dsDNA or RNA in a sequence-independent, highly cooperative manner that results in a non-specific stimulation of DNA replication. We have also identified several aromatic and basic residues, involved in base-stacking and electrostatic interactions, respectively, that are required for effective protein-ssDNA interaction.Although SSBs are essential for DNA replication in all domains of life as well as many viruses, they are very diverse proteins. However, most SSBs share a common structural domain, named OB-fold. Protein-primed viruses could constitute an exception, as no OB-fold DNA binding protein has been reported. Based on databases searches as well as phylogenetic and structural analyses, we showed that B35SSB belongs to a novel and independent group of SSBs. This group contains proteins encoded by protein-primed viral genomes from unrelated viruses, spanning betatectiviruses and Φ29 and close podoviruses, and they share a conserved pattern of secondary structure. Sensitive searches and structural predictions indicate that B35SSB contains a conserved domain resembling a divergent OB-fold, which would constitute the first occurrence of an OB-fold-like domain in a protein-primed genome.HighlightsBam35 ORF 2 product encodes a viral single-stranded DNA binding protein (B35SSB).B35SSB binds ssDNA in a highly cooperative manner but with no sequence specificity.B35SSB-ssDNA binding is mediated by base-stacking and ionic interactions.Bam35 and Φ29-related SSBs form a novel group of SSBs from protein-primed viruses.The B35-Φ29 SSBs group shares a highly divergent OB-fold-like domain.
Demonstration of local adaptation of maize landraces by reciprocal transplantation
Authors: Janzen Garrett M. , Aguilar-Rangel María Rocío , Cíntora-Martínez Carolina , Blöcher-Juárez Karla Azucena , González-Segovia Eric , Studer Anthony J. , Runcie Daniel E. , Flint-Garcia Sherry A. , Rellán-Álvarez Rubén , Sawers Ruairidh J. H. , Hufford Matthew B. 
Published: March 2021

AbstractPopulations are locally adapted when they exhibit higher fitness than foreign populations in their native habitat. Maize landrace adaptations to highland and lowland conditions are of interest to researchers and breeders. To determine the prevalence and strength of local adaptation in maize landraces, we performed a reciprocal transplant experiment across an elevational gradient in Mexico. We grew 120 landraces, grouped into four populations (Mexican Highland, Mexican Lowland, South American Highland, South American Lowland), in Mexican highland and lowland common gardens and collected phenotypes relevant to fitness, as well as reported highland-adaptive traits such as anthocyanin pigmentation and macrohair density. 67k DArTseq markers were generated from field specimens to allow comparison between phenotypic patterns and population genetic structure.We found phenotypic patterns consistent with local adaptation, though these patterns differ between the Mexican and South American populations. While population genetic structure largely recapitulates drift during post-domestication dispersal, landrace phenotypes reflect adaptations to native elevation. Quantitative traitQSTwas greater than neutralFSTfor many traits, signaling divergent directional selection between pairs of populations. All populations exhibited higher fitness metric values when grown at their native elevation, and Mexican landraces had higher fitness than South American landraces when grown in our Mexican sites. Highland populations expressed generally higher anthocyanin pigmentation than lowland populations, and more so in the highland site than in the lowland site. Macrohair density was largely non-plastic, and Mexican landraces and highland landraces were generally more pilose. Analysis ofδ13C indicated that lowland populations may have lower WUE. Each population demonstrated garden-specific correlations between highland trait expression and fitness, with stronger positive correlations in the highland site.These results give substance to the long-held presumption of local adaptation of New World maize landraces to elevation and other environmental variables across North and South America.
Symbiodiniaceae conduct under natural bleaching stress during advanced gametogenesis stages of the mesophotic coralAlveopora allingi
Authors: Eyal Gal , Eyal-Shaham Lee , Loya Yossi 
Published: March 2021

AbstractThe mesophotic coralAlveopora allingifrom the northern Gulf of Eilat/Aqaba, Red Sea, is affected by year-round partial coral-bleaching events. During these events, the migration of Symbiodiniaceae takes place from the coral-host mesoglea to the developed oocytes in bleached parts of colonies ofA. allingibut not in the non-bleached parts. Additionally, these oocytes are abnormal, missing part of the structural material of the peripheral areas and are also significantly larger in the bleached areas of the colonies. Hence, we suggest a parasitic behavior of the symbionts or a commensalism relationship which enhance symbionts’ needs during bleaching periods and may boost the gametogenesis development in these corals. We propose that evolutionarily, this behavior may greatly contribute to the symbiont community survival throughout the bleaching period, and it can also be beneficial for the host’s persistence and adaptation to bleaching through the acquisition of a specific symbiont community following the bleaching event.
Parallel and recurrent cascade models as a unifying force for understanding sub-cellular computation
Authors: Harkin Emerson F. , Shen Peter R. , Goel Anish , Richards Blake A. , Naud Richard 
Published: March 2021

AbstractNeurons are very complicated computational devices, incorporating numerous non-linear processes, particularly in their dendrites. Biophysical models capture these processes directly by explicitly modelling physiological variables, such as ion channels, current flow, membrane capacitance, etc. However, another option for capturing the complexities of real neural computation is to use cascade models, which treat individual neurons as a cascade of linear and non-linear operations, akin to a multi-layer artificial neural network. Recent research has shown that cascade models can capture single-cell computation well, but there are still a number of sub-cellular, regenerative dendritic phenomena that they cannot capture, such as the interaction between sodium, calcium, and NMDA spikes in different compartments. Here, we propose that it is possible to capture these additional phenomena usingparallel, recurrentcascade models, wherein an individual neuron is modelled as a cascade of parallel linear and non-linear operations that can be connected recurrently, akin to a multi-layer, recurrent, artificial neural network. Given their tractable mathematical structure, we show that neuron models expressed in terms of parallel recurrent cascades can themselves be integrated into multi-layered artificial neural networks and trained to perform complex tasks. We go on to discuss potential implications and uses of these models for artificial intelligence. Overall, we argue that parallel, recurrent cascade models provide an important, unifying tool for capturing single-cell computation and exploring the algorithmic implications of physiological phenomena.
Quantitative blood flow estimationin vivoby optical speckle image velocimetry
Authors: Qureshi Muhammad Mohsin , Liu Yan , Mac Khuong Duy , Kim Minsung , Safi Abdul Mohaimen , Chung Euiheon 
Published: March 2021

AbstractSpeckle based methods are popular non-invasive, label-free full-field optical techniques for imaging blood flow maps at single vessel resolution with a high temporal resolution. However, conventional speckle approach cannot provide an absolute velocity map with magnitude and direction. Here, we report a novel optical speckle image velocimetry (OSIV) technique for measuring the quantitative blood flow vector map by utilizing particle image velocimetry with speckle cross-correlations. We demonstrate that our OSIV instrument has a linearity range up to 7 mm/s, higher than conventional optical methods. Our method can measure the absolute flow vector map at up to 190 Hz without sacrificing the image size, and it eliminates the need for a high-speed camera/detector. We applied OSIV to image the blood flow in a mouse brain, and as a proof of concept, imaged the real-time dynamic changes in the cortical blood flow field during the stroke processin vivo. Our wide-field quantitative flow measurement OSIV method without the need of tracers provides a valuable tool for studying the healthy and diseased brain.
Defining Vascular Cognitive Impairment in India—A Descriptive Study of MRI Volumetry vs. Cognition in ‘Normal’ Adults
Authors: Sundar Uma , Mukhopadhyay Amita , Raghavan Sheelakumari , Menon Ramshekhar N. , Kesavadas Chandrasekharan , Shah Nilesh , Adsul Balkrishna B. , Joshi Anagha R. 
Published: March 2021

AbstractBackgroundIt is important to establish criteria to define Vascular Cognitive Impairment (VCI) in India as VCI is an image-based diagnosis and MRI changes resulting from age with prevalent vascular risk factors may confound MRI interpretation.ObjectiveTo establish normative community data for MRI volumetry including white matter hyperintensity volume (WMHV), correlated with age-stratified cognitive scores and vascular risk factors in adults ≥40 years old.Materials and MethodsWe screened 2651 individuals without known neurological morbidity, living in Mumbai and nearby rural areas, using validated Marathi translations of Kolkata Cognitive Battery (KCB) and Geriatric depression score (GDS). We stratified 1961 persons with GDS ≤9 by age and cognitive score, and randomly selected ten percent from each subgroup for MRI brain volumetry. Crude volumes were standardized to reflect percentage of intracranial volume.ResultsMRI volumetry studies were done in 199 individuals (F/M = 90/109; 73 with BMI ≥25; 44 hypertensives; 29 diabetics; mean cognitive score 76.5). Both grey and white matter volumes decreased with increasing age. WMHV increased with age and hypertension. Grey matter volume decreased with increasing WMHV. Positive predictors of cognition included standardized hippocampal volume (HCV), urban living, education, and BMI, while WMHV and age were negative predictors. Urban dwellers had higher cognitive scores than rural, and (paradoxically) smaller HCV.ConclusionsFurther study is warranted into sociodemographic and biological factors that mutually influence cognition. Our findings contribute to baseline diagnostic criteria for VCI and could help in early diagnosis and control of cognitive decline and its key risk factors.
Factors confounding the athlete biological passport: a systematic narrative review
Authors: Krumm Bastien , Faiss Raphael 
Published: March 2021

AbstractBackgroundThrough longitudinal, individual and adaptive monitoring of blood biomarkers, the haematological module of the athlete biological passport (ABP) has become a valuable tool in anti-doping efforts. The composition of blood as a vector of oxygen in the human body varies in athletes with the influence of multiple intrinsic (genetic) or extrinsic (training or environmental conditions) factors. In this context, it is fundamental to establish a comprehensive understanding of the various causes that may affect blood variables and thereby alter a fair interpretation of ABP profiles.MethodsThis literature review described the potential factors confounding the ABP to outline influencing factors altering haematological profiles acutely or chronically.ResultsOur investigation confirmed that natural variations in ABP variables appear relatively small, likely—at least in part—because of strong human homeostasis. Furthermore, the significant effects on haematological variations of environmental conditions (e.g. exposure to heat or hypoxia) remain debatable. The current ABP paradigm seems rather robust in view of the existing literature that aims to delineate adaptive individual limits. Nevertheless, its objective sensitivity may be further improved.ConclusionsThis narrative review contributes to disentangling the numerous confounding factors of the ABP to gather the available scientific evidence and help interpret individual athlete profiles.Key pointsThrough longitudinal, individual and adaptive monitoring of blood biomarkers, the haematological module of the athlete biological passport (ABP) has become a valuable tool in anti-doping efforts.This literature review described the potential factors confounding the ABP to outline influencing factors altering haematological profiles acutely or chronically.While our results support the current ABP paradigm as rather robust to delineate adaptive individual limits, our work may contribute to disentangling the numerous confounding factors of the ABP to gather the available scientific