bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virus-host interactions and genetic diversity of Antarctic sea ice bacteriophages
Authors: Demina Tatiana A. , Luhtanen Anne-Mari , Roux Simon , Oksanen Hanna M. 
Published: May 2021

AbstractDespite generally appreciated significant roles of microbes in sea ice and polar waters, detailed studies of virus-host systems from such environments have been so far limited by only a few isolates. Here, we investigated infectivity under various conditions, infection cycles, and genetic diversity of Antarctic sea ice bacteriophages: PANV1, PANV2, OANV1, and OANV2. The phages infect common sea ice bacteria belonging to the generaParaglaciecolaorOctadecabacter. Although the phages are marine and cold-active, replicating at 0-5 °C, they all survived temporal incubations at ≥30 °C and remained infectious without any salts or supplemented only with magnesium, suggesting a robust virion assembly maintaining integrity under a wide range of conditions. Host recognition in the cold proved to be effective, and the release of progeny viruses occurred as a result of cell lysis. The analysis of viral genome sequences showed that nearly half of the gene products of each virus are unique, highlighting that sea ice harbors unexplored virus diversity. Based on predicted genes typical for tailed double-stranded DNA phages, we suggest placing the four studied viruses in the classCaudoviricetes. Searching against viral sequences from metagenomic assemblies revealed that related viruses are not restricted to Antarctica, but also found in distant marine environments.ImportanceVery little is known about sea ice microbes despite the significant role of sea ice in the global oceans as well as microbial input into biogeochemical cycling. Studies on the sea ice viruses have been typically limited to -omics-based approaches and microscopic examinations of sea ice samples. Up to date, only four cultivable viruses have been isolated from Antarctic sea ice. Our study of these unique isolates advances the understanding of the genetic diversity of viruses in sea ice environments, their interactions with host microbes, and possible links to other biomes. Such information contributes to more accurate future sea ice biogeochemical models.
Detecting effective starting point of genomic selection by divergent trends from BLUP and ssGBLUP in pigs, beef cattle, and broilers
Authors: Abdollahi-Arpanahi Rostam , Lourenco Daniela , Misztal Ignacy 
Published: May 2021

AbstractGenomic selection has been adopted nationally and internationally in different livestock and plant species. However, understanding whether genomic selection has been effective or not is an essential question for both industry and academia. Once genomic evaluation started being used, estimation of breeding values with pedigree BLUP became biased because this method does not consider selection using genomic information. Hence, the effective start point of genomic selection can be detected in two possible ways including the divergence of genetic trends and Realized Mendelian sampling (RMS) trends obtained with BLUP and Single-step genomic BLUP (ssGBLUP). This study aimed to find the start date of genomic selection for a set of economically important traits in three livestock species by comparing trends obtained using BLUP and ssGBLUP. For this purpose, three datasets comprised a pig dataset with 117k genotypes and 1.3M animals in pedigree, Angus cattle dataset consisted of ~842k genotypes and 11.5M animals in pedigree, and a purebred broiler chicken dataset included ~154k genotypes and 1.3M birds in pedigree were used. The genetic trends for pigs diverged for the genotyped animals born in 2014 for average daily gain and backfat. In beef cattle, the trends started diverging in 2009 for weaning weight and in 2016 for postweaning gain, with little diverging for birth weight. In broiler chickens, the genetic trends estimated by ssGBLUP and BLUP diverged at breeding cycle 6 for two out of three production traits. The RMS trends for the genotyped pigs diverged for animals born in 2014, more for average daily gain than for backfat. In beef cattle, the RMS trends started diverging in 2009 for weaning weight and in 2016 for postweaning gain, with a trivial trend for birth weight. In broiler chickens, the RMS trends from ssGBLUP and BLUP diverged strongly for two production traits at breeding cycle 6, with a slight divergence for another trait. Divergence of the genetic trends from ssGBLUP and BLUP indicates onset of the genomic selection. Presence of trends for RMS indicates selective genotyping, with or without the genomic selection. The onset of genomic selection and genotyping strategies agree with industry practices across the 3 species. In summary, the effective start of genomic selection can be detected by the divergence between genetic and RMS trends from BLUP and ssGBLUP.
Differences in social brain function in autism spectrum disorder are linked to the serotonin transporter
Authors: Wong Nichol M.L. , Dipasquale Ottavia , Turkheimer Federico , Findon James L. , Wichers Robert H. , Dimitrov Mihail , Murphy Clodagh M. , Stoencheva Vladimira , Robertson Dene M. , Murphy Declan G. , Daly Eileen , McAlonan Grainne M. 
Published: May 2021

AbstractAlterations in the serotonergic control of brain pathways responsible for facial-emotion processing in people with autism spectrum disorder (ASD) may be a target for intervention. However, the molecular underpinnings of autistic-neurotypical serotonergic differences are challenging to access in vivo. Receptor-Enriched Analysis of functional Connectivity by Targets (REACT) has helped define molecular-enriched fMRI brain networks based on a priori information about the spatial distribution of neurochemical systems from available PET templates. Here, we used REACT to estimate the dominant fMRI signal related to the serotonin transporter (5-HTT) distribution during processing of aversive facial expressions of emotion processing in adults with and without ASD. We first predicted a group difference in baseline (placebo) functioning of this system. We next used a single 20 mg oral dose of citalopram, i.e. a serotonin reuptake inhibitor, to test the hypothesis that network activity in people with and without ASD would respond differently to inhibition of 5-HTT. To confirm the specificity of our findings, we also repeated the analysis with 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 receptor maps.We found a baseline group difference in the 5-HTT-enriched response to faces in the ventromedial prefrontal cortex. A single oral dose of citalopram ‘shifted’ the response in the ASD group towards the neurotypical baseline but did not alter response in the control group.Our findings suggest that the 5HTT-enriched functional network is dynamically different in ASD during processing of socially relevant stimuli. Whether this acute neurobiological response to citalopram in ASD translates to a clinical target will be an important next step.
Mild traumatic brain injury/ concussion initiates an atypical astrocyte response caused by blood-brain barrier dysfunction
Authors: Heithoff Benjamin P. , George Kijana K. , Shandra Oleksii , Robel Stefanie 
Published: May 2021

AbstractMild traumatic brain injury/ concussion (mTBI) account for 70-90% of all reported TBI cases and cause long lasting neurological consequences in 10 to 40% of patients. Recent clinical studies revealed increased blood-brain barrier (BBB) permeability in mTBI patients, which correlated with secondary damage after mTBI. However, the cascade of cellular events initiated by exposure to blood-borne factors resulting in sustained damage are not fully resolved. We previously reported that astrocytes respond atypically to mTBI rapidly downregulating many proteins essential to their homeostatic function while classic scar formation does not occur. Here, we tested the hypothesis that mTBI -induced BBB damage causes atypical astrocytes through exposure to blood-borne factors. Using a mTBI mouse model, 2-photon imaging, an endothelial cell-specific genetic ablation approach, and serum-free primary astrocyte cultures, we demonstrated that areas with atypical astrocytes coincide with BBB damage and that exposure of astrocytes to plasma proteins is sufficient to initiate downregulation of astrocyte homeostatic proteins. While mTBI resulted in frequent impairment of both physical and metabolic BBB properties and leakage of small-sized blood-borne factors, deposition of the coagulation factor fibrinogen or vessel rupture were rare. Surprisingly, even months after mTBI BBB repair did not occur in areas with atypical astrocytes. Together, these findings implicate that even relatively small BBB disturbances are sustained long-term and render nearby astrocytes dysfunctional, likely at the cost of neuronal health and function.
The outward Shaker channel OsK5.2 is beneficial to the plant salt tolerance through its role in K+ translocation and its control of leaf transpiration
Authors: Zhou Jing , Nguyen Thanh Hao , Luu Doan Trung , Sentenac Hervé , Véry Anne-Aliénor 
Published: May 2021

AbstractHigh soil salinity constitutes a major environmental constraint to crop production worldwide, and the identification of genetic determinants of plant salt tolerance is awaited by breeders. While the leaf K+ to Na+ homeostasis is considered as key parameter of plant salt tolerance, the underlying mechanisms are not fully identified. Especially, the contribution of K+ channels to this homeostasis has been scarcely examined. Here, we show, using a reverse genetics approach, that the outwardly-rectifying K+ channel OsK5.2, involved in K+ translocation to the shoot and K+ release by guard cells for stomatal closure, is a strong determinant of rice salt tolerance. Upon saline treatment, OsK5.2 function in xylem sap K+ load was maintained, and even transiently increased, in roots. OsK5.2 selectively handled K+ in roots and was not involved in xylem sap Na+ load. In shoots, OsK5.2 expression was up-regulated from the onset of the saline treatment, enabling fast reduction of stomatal aperture, decreased transpirational water flow and therefore decreased trans-plant Na+ flux and reduced leaf Na+ accumulation. Thus, the OsK5.2 functions allowed shoot K+ nutrition while minimizing arrival of Na+, and appeared highly beneficial to the leaf K+ to Na+ homeostasis, the avoidance of salt toxicity and plant growth maintaining.
Contribution of metal transporters of the ABC, ZIP, and NRAMP families to manganese uptake and infective endocarditis virulence in Streptococcus sanguinis
Authors: Puccio Tanya , Kunka Karina S. , Kitten Todd 
Published: May 2021

SummaryStreptococcus sanguinis is an important cause of infective endocarditis. In strain SK36, the ABC-family manganese transporter, SsaACB, is essential for virulence. We have now identified a ZIP-family protein, TmpA, as a secondary manganese transporter. A tmpA mutant had no phenotype, but a ΔssaACB ΔtmpA mutant was far more attenuated for serum growth and somewhat more attenuated for virulence in a rabbit model than its ΔssaACB parent. The growth of both mutants was restored by supplemental manganese, but the ΔssaACB ΔtmpA mutant required twenty-fold more and accumulated less. Although ZIP-family proteins are known for zinc and iron transport, TmpA-mediated transport of either metal was minimal. In contrast to ssaACB and tmpA, which appear ubiquitous in S. sanguinis, a mntH gene encoding an NRAMP-family transporter has been identified in relatively few strains, including VMC66. As in SK36, deletion of ssaACB greatly diminished VMC66 endocarditis virulence and serum growth, and deletion of tmpA from this mutant diminished virulence further. Virulence was not significantly altered by deletion of mntH from either VMC66 or its ΔssaACB mutant. This and the accompanying paper together suggest that SsaACB is of primary importance for endocarditis virulence while secondary transporters TmpA and MntH contribute to growth under differing conditions.
High-throughput, multiplex microfluidic test strip for the determination of antibiotic susceptibility in uropathogenic E. coli with smartphone detection
Authors: Needs Sarah H. , Rafaque Zara , Imtiaz Wajiha , Ray Partha , Andrews Simon , Edwards Alexander D. 
Published: May 2021

AbstractAntibiotic resistance in urinary tract infections is a major global challenge and improved cost-effective and high throughput antibiotic susceptibility tests (AST) are urgently needed to inform correct antibiotic selection. We evaluated a high throughput microfluidic test strip for AST and minimum inhibitory concentration (MIC) determination in 20 urinary pathogenic E. coli (UPEC) isolates using six commonly prescribed or therapeutically beneficial antibiotics. The microfluidic MIC performs broth microdilution in 1 microliter volume capillaries, 100 X smaller than standard broth microdilution. Each test strip contains 10 parallel capillaries which are dipped into a single well of a 96 well plate, significantly increasing throughput over a microtitre plate. When tested with clinical UPEC isolates at standardised inoculum density, these devices gave 100% essential agreement (+/- 1 doubling dilution of antibiotic) to the gold standard microplate broth microdilution method described by CLSI. Although for some antibiotic/isolate combinations an earlier endpoint readout reduced accuracy, MIC test strips read at a 6h endpoint still gave 69 – 100 % essential agreement depending on the antibiotic. Growth could be detected significantly earlier than 6h, but with a trade-off between speed vs accuracy. These high-throughput, multiplexed test strips could be used to increase throughput and give faster results than microplates while retaining the core broth microdilution methodology of gold standard techniques for AST and MIC determination.
Regulation of osteoblast autophagy based on PI3K/AKT/mTOR signaling pathway study on the effect of β-ecdysterone on fracture healing
Authors: Tang Yanghua , Mo Yafeng , Xin Dawei , Xiong Zhenfei , Zeng Linru , Luo Gan 
Published: May 2021

AbstractPurposeTo investigate the effects of β-ecdysterone on fracture healing and the underlying mechanism.MethodsMTT assay was used to detect the cell viability and alkaline phosphatase (ALP) activity was measured using a commercial kit. AO/PI and flow cytometry assays were used to determine the state of apoptosis of osteoblasts. The expression level of RunX2, ATG7 and LC3 was evaluated by qRT-PCR and Western blot assays. X-ray and HE staining were conducted on the fractured femur to evaluate the pathological state. Immunohistochemical assay was used to detect the expression level of Beclin-1 and immunofluorescence assay was used to measure the expression level of LC3 in the fractured femurs. Western blot was utilized to determine the expression level of PI3K, p-AKT1, AKT1, p-mTOR, mTOR, p-p70S6K, and p70S6K.ResultsThe ALP activity and expression of RunX2 in fractured osteoblasts were significantly suppressed by 3-methyladenine and elevated by rapamycin, 60, and 80 μM β-ecdysterone. The apoptotic state of fractured osteoblasts was enhanced by 3-methyladenine and alleviated by rapamycin, 60, and 80 μM β-ecdysterone. The state of autophagy both in fractured osteoblasts and femurs was inhibited by 3-methyladenine and facilitated by rapamycin and β-ecdysterone. Compared to control, Garrett score in 3-methyladenine group was significantly decreased and promoted in rapamycin and β-ecdysterone groups, accompanied by ameliorated pathological state. Lastly, the PI3K/AKT/mTOR pathway both in fractured osteoblasts and femurs was activated by 3-methyladenine and inhibited by rapamycin and β-ecdysterone.Conclusionβ-ecdysterone might facilitate fracture healing by activating autophagy through suppressing PI3K/AKT/mTOR signal pathway.
In-Cell Sensitivity-Enhanced NMR of Intact Living Mammalian Cells
Authors: Ghosh Rupam , Xiao Yiling , Kragelj Jaka , Frederick Kendra K. 
Published: May 2021

AbstractNMR has the resolution and specificity to determine atomic-level protein structures of isotopically-labeled proteins in complex environments and, with the sensitivity gains conferred by dynamic nuclear polarization (DNP), NMR has the sensitivity to detect proteins at their endogenous concentrations. However, DNP sensitivity enhancements are critically dependent on experimental conditions and sample composition. While some of these conditions are theoretically compatible with cellular viability, the effects of others on cellular sample integrity are unknown. Uncertainty about the integrity of cellular samples limits the utility of experimental outputs. Using several measures, we establish conditions that support DNP enhancements that can enable detection of micromolar concentrations of proteins in experimentally tractable times that are compatible with cellular viability. Taken together, we establish DNP assisted MAS NMR as a technique for structural investigations of biomolecules in intact viable cells that can be phenotyped both before and after NMR experiments.ClassificationBiophysics and Structural Biology
Development and applications of sialoglycan-recognizing probes (SGRPs) with defined specificities: exploring the dynamic mammalian sialoglycome
Authors: Srivastava Saurabh , Verhagen Andrea , Sasmal Aniruddha , Wasik Brian R. , Diaz Sandra , Yu Hai , Bensing Barbara A. , Khan Naazneen , Khedri Zahra , Secrest Patrick , Sullam Paul , Varki Nissi , Chen Xi , Parrish Colin R. , Varki Ajit 
Published: May 2021

AbstractGlycans that are abundantly displayed on vertebrate cell surface and secreted molecules are often capped with terminal sialic acids (Sias). These diverse 9-carbon-backbone monosaccharides are involved in numerous intrinsic biological processes. They also interact with commensals and pathogens, while undergoing dynamic changes in time and space, often influenced by environmental conditions. However, most of this sialoglycan complexity and variation remains poorly characterized by conventional techniques, which often tend to destroy or overlook crucial aspects of Sia diversity and/or fail to elucidate native structures in biological systems i.e., in the intact sialome. To date, in situ detection and analysis of sialoglycans has largely relied on the use of plant lectins, sialidases or antibodies, whose preferences (with certain exceptions) are limited and/or uncertain. We took advantage of naturally-evolved microbial molecules (bacterial adhesins, toxin subunits and viral hemagglutinin-esterases) that recognize sialoglycans with defined specificity to delineate 9 classes of Sialoglycan Recognizing Probes (SGRPs: SGRP1–SGRP9) that can be used to explore mammalian sialome changes in a simple and systematic manner, using techniques common in most laboratories. SGRP candidates with specificity defined by sialoglycan microarray studies were engineered as tagged probes, each with a corresponding non-binding mutant probe as a simple and reliable negative control. The optimized panel of SGRPs can be used in methods commonly available in most bioscience labs, such as ELISA, Western Blot, flow cytometry and histochemistry. To demonstrate the utility of this approach, we provide examples of sialoglycome differences in tissues from C57BL/6 wild type mice and human-like Cmah−/− mice.
Differential transcriptomic response ofAnopheles arabiensistoPlasmodium vivaxandPlasmodium falciparuminfection
Authors: Tsapi Majoline Tchioffo , Kornobis Etienne , Puchot Nicolas , English Solomon , Proux Caroline , Goupeyou-Youmsi Jessy , Sakuntabhai Anavaj , Marie-Agnes-Dillies  , Milijaona Randrianarivelojosia , Girod Romain , Ndiath Mamadou Ousmane , Bourgouin Catherine 
Published: May 2021

AbstractPlasmodium vivaxmalaria is now recognized as the second most dangerous parasitic threat to human health with the regular decrease ofPlasmodium falciparumworldwide over recent decades. A very limited numbers of studies address the interaction ofP. vivaxwith itsAnophelesmosquito vectors. Those studies were conducted inP. vivaxendemic countries withP.vivaxlocal major vectors for which limited genomic and genetic tools are available. Despite the presence ofP. vivaxin several African countries and increasing reports on its occurrence in many others, there is virtually no data on the molecular responses ofAnopheles arabiensis,a major African mosquito vector, toP. vivax, which limits the development of further “mosquito-targeted” interventions aimed at reducingP. vivaxtransmission. Taking advantage of the situation of Madagascar whereP. falciparum,P. vivaxandAn. arabiensisare present, we explore the molecular responses ofAn. arabiensistowards these two human malaria parasites. RNA sequencing on RNAs isolated from mosquito midguts dissected at the early stage of infection (24 hours) was performed using mosquitoes fed on the blood ofP. vivaxandP. falciparumgametocyte carriers in a field station. From ade novoassembly ofAn. arabiensismidgut total RNA transcriptome, the comparative analysis revealed that a greater number of genes were differentially expressed in the mosquito midgut in response toP. vivax(209) than toP. falciparum(81). Among these, 15 common genes were identified to be significantly expressed in mosquito midgut 24 hours after ingestingP. vivaxandP. falciparumgametocytes, including immune responsive genes and genes involved in amino-acid detoxification pathways. Importantly, working with both wild mosquitoes and field circulating parasites, our analysis revealed a strong mosquito genotype by parasite genotype interaction. Our study also identified 51 putative long non-coding RNAs differentially expressed inAn. arabiensismosquito infected midgut. Among these, several mapped to the publishedAn. arabiensisgenome at genes coding immune responsive genes such as gambicin 1, leucine-rich repeat containing genes, either on sense or antisense strands.This study constitutes the first comparison ofAn. arabiensismolecular interaction withP. vivaxandP. falciparum, investigating both coding and long non-coding RNAs for the identification of potential transcripts, that could lead to the development of novel approaches to simultaneously block the transmission ofvivaxandfalciparummalaria.
Elucidating Tumor-stromal Metabolic Crosstalk in Colorectal Cancer through Integration of Constraint-Based Models and LC-MS Metabolomics
Authors: Wang Junmin , Delfarah Alireza , Gelbach Patrick , Fong Emma , Macklin Paul , Mumenthaler Shannon M. , Graham Nicholas A. , Finley Stacey 
Published: May 2021

AbstractColorectal cancer (CRC) is a major cause of morbidity and mortality in the United States. Tumor-stromal metabolic crosstalk in the tumor microenvironment promotes CRC development and progression, but exactly how stromal cells, in particular cancer-associated fibroblasts (CAFs), affect the metabolism of tumor cells remains unknown. Here we take a data-driven approach to investigate the metabolic interactions between CRC cells and CAFs, integrating constraint-based modeling and metabolomic profiling. Using metabolomics data, we perform unsteady-state parsimonious flux balance analysis to infer flux distributions for central carbon metabolism in CRC cells treated with or without CAF-conditioned media. We find that CAFs reprogram CRC metabolism through stimulation of glycolysis, the oxidative arm of the pentose phosphate pathway (PPP), and glutaminolysis as well as inhibition of the tricarboxylic acid cycle. To identify potential therapeutic targets, we simulate enzyme knockouts and find that inhibiting the hexokinase and glucose-6-phosphate dehydrogenase reactions exploits the CAF-induced dependence of CRC cells on glycolysis and oxidative PPP. Our work gives mechanistic insights into the metabolic interactions between CRC cells and CAFs and provides a framework for testing hypotheses towards CRC-targeted therapies.