bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potassium homeostasis and signaling as a determinant ofEchinaceaspecies tolerance to salinity stress
Authors: Ahmadi Fatemeh , Samadi Abbas , Sepehr Ebrahim , Rahimi Amir , Shabala Sergey 
Published: October 2022

ABSTRACTSalt tolerant is strongly related to potassium (K+) retention in plant tissues under salt stress conditions. However, it is unclear for differentEchinaceaspecies. So, mechanistic basis of fourEchinaceaspecies (i.e.Echinacea purpurea, Echinacea angustifolia, Echinacea pallida, andEchinacea sanguinea) to salinity stress tolerance, and K+retention were assessed in the present study. Non-invasive microelectrode ion flux measuring, DHAR and MDHAR activities, and pharmacological measurements were performed based on the standard methods. Ion flux measurements revealed higher K+efflux inE. pallidaandE. sanguineaspecies compared to theE. purpureaandE. angustifoliaspecies in the elongation zone. Higher salinity-induced H+efflux was found in the elongation zone than mature zone. However,E. angustifoliaandE. purpureahad more Ca2+influx compared toE. pallidaandE. sanguineaspecies. Net K+efflux decreased (> 90%) in the presence of TEA and GdCl3. Increasing of Ca2+uptake and K+loss in fourEchinaceaspecies roots were found in the presence of 0.3 mM Cu/Ascorbate (Cu/Asc). The significant role of H+-ATPase in H+efflux was demonstrated by Sodium orthovanadate. Ultimately, the physiological properties ofEchinaceaspecies have a critical role in salinity-resistant/sensitive differences. Future scientific understanding ofEchinaceaspecies physiognomies may be necessary for better understanding of the plant behavior to salinity stress.One-sentence summaryHigher K+efflux inE. pallidaandE. sanguineaspecies as a result of NaCl and ROS act as a metabolic switch to save energy for adaptations and repairs in salinity stress conditions.
Novel Pore Size-Controlled, Susceptibility Matched, 3D-Printed MRI Phantoms
Authors: Witherspoon Velencia J. , Komlosh Michal E , Benjamini Dan , Özarslan Evren , Lavrik Nickolay , Basser Peter J. 
Published: October 2022

AbstractDiffusion magnetic resonance imaging (dMRI) methods are commonly employed to infer changes in tissue microstructure. Quantities like the apparent diffusion coefficient (mADC), and the fractional anisotropy (FA), derived from diffusion tensor imaging (DTI) data, characterize voxel-averaged diffusion properties, whereas double pulse field gradient (dPFG) or double diffusion encoded (DDE) MR methods can be used to characterize heterogeneous diffusion processes occurring within the voxel. Owing to its unique modular design, our novel 3D-printed dMRI phantom exhibits both macroscopic and microscopic anisotropy and can serve to calibrate measures of them. Our phantom susceptibility is close to that of water’s, enabling fast diffusion weighted echo-planar image (DW-EPI) acquisitions to be used to scan it. 3D printed microstructures offer a new medium with which to vet and validate theoretical models of diffusion and pipelines used to estimate it.HighlightsResearch highlight 1: We report the design concept and fabrication of dimensionally stable, uniformly oriented blocks or modules that can be assembled into large-scale MRI phantoms. Waffle-like structures containing blocks of aligned microcapillaries can be stacked into even larger arrays to construct diameter distribution phantoms, or fractured, to create a “powder-averaged” emulsion of randomly oriented blocks.Research highlight 2: This phantom can be used to vet and calibrate various MRI methods, such as DTI, AxCaliber MRI, MAP-MRI, and various multiple pulsed field gradient (PFG) or multiple diffusion-encoded microstructure imaging methods.Graphical Abstract
On the causes, consequences, and avoidance of PCR duplicates: towards a theory of library complexity
Authors: Rochette Nicolas C. , Rivera-Colón Angel G. , Walsh Jessica , Sanger Thomas J. , Campbell-Staton Shane C. , Catchen Julian M. 
Published: October 2022

AbstractLibrary preparation protocols for most sequencing technologies involve PCR amplification of the template DNA, which open the possibility that a given template DNA molecule is sequenced multiple times. Reads arising from this phenomenon, known as PCR duplicates, inflate the cost of sequencing and can jeopardize the reliability of affected experiments. Despite the pervasiveness of this artifact, our understanding of its causes and of its impact on downstream statistical analyses remains essentially empirical. Here, we develop a general quantitative model of amplification distortions in sequencing datasets, which we leverage to investigate the factors controlling the occurrence of PCR duplicates. We show that the PCR duplicate rate is determined by the ratio between library complexity and sequencing depth, and that amplification noise (including in its dependence on the number of PCR cycles) only plays a minor role for this artifact. We confirm our predictions using new and published RAD-seq libraries and provide a method to estimate library complexity and amplification noise in any dataset containing PCR duplicates. We discuss how amplification-related artifacts impact downstream analyses, and in particular genotyping accuracy. The proposed framework unites the numerous observations made on PCR duplicates and will be useful to experimenters of all sequencing technologies where DNA availability is a concern.
Deodorize with Bugs: Inoculation with black soldier fly larvae alters the microbiome and volatile organic compound profile of decomposing food waste
Authors: Michishita Rena , Shimoda Masami , Furukawa Seiichi , Uehara Takuya 
Published: October 2022

AbstractThe black soldier fly (BSF;Hermetia illucens) is used in sustainable processing of many types of organic waste. However, organic waste being decomposed by BSF produces strong odors, hindering more widespread application. The odor components and how they are produced have yet to be characterized. We found that digestion of food waste by BSF significantly alters the microbial flora, based on metagenomic analyses, and the odor components generated, as shown by thermal desorption gas chromatography mass spectrometry analysis. Inoculation with BSF significantly decreased production of volatile organic sulfur compounds (dimethyl disulfide and dimethyl trisulfide), which are known to be released during methionine and cysteine metabolism byLactobacillusandEnterococcusbacteria. BSF inoculation significantly changed the abundance ofLactobacillusandEnterococcusand decreased microbial diversity overall. These findings may help in optimizing use of BSF for deodorization of composting food waste.
Characterization of the HHV-6 U20 immunoevasin
Authors: Schneider Christine L. , Whyte Melissa L. , Konrad Sheryl L. , Hudson Amy W. 
Published: October 2022

AbstractRoseoloviruses (HHV-6A, -6B, and -7) infect >90% of the human population during early childhood, and are thought to remain latent or persistent throughout the life of the host. As such,these viruses are among the most pervasive and stealthy of all viruses;they must necessarily excel at escaping immune detection throughout the life of the host, and yet very little is known about how these viruses so successfully escape host defenses. Herein, we characterize the HHV6A and HHV6B U20 gene products, which are encoded within a block of genes unique to the roseoloviruses, and therefore of particular interest. Despite 92% amino acid identity, U20 proteins from HHV6A and 6B have been shown to possess different host evasion functions. Here we characterize expression, trafficking, and post-translational modifications of U20 during HHV6A infection. While U20 localized to lysosomes in HHV-6A-infected cells, HHV-6B U20 trafficked to the cell surface and was rapidly internalized. HHV-6B U20 trafficked slowly through the secretory system, receiving several post translational modifications to its N-linked glycans indicative of surface expressed glycoproteins. Interestingly, U20 is also phosphorylated on at least one Ser, Thr, or Tyr residue. These results provide a framework to understand the role(s) of U20 in evading host defenses.ImportanceHHV6A and HHV6B U20 proteins are virus-encoded integral membrane glycoproteins possessing class I MHC-like folds. As such, it is tempting to speculate that they are involved in host evasion. Indeed, although they share 92% identity, HHV6A U20 has been shown to target NK activating ligands (1) and HHV6B U20 has been shown to inhibit TNF receptor signaling and apoptosis (2). Here, we have performed cell biological and biochemical characterization of the trafficking, glycosylation, and post-translational modifications occurring on HHV6A and -6B U20, and we demonstrate U20 expression in the context of HHV6 infection.
Galectin-3 is Associated with Heart Failure Incidence: A Meta-Analysis
Authors: Baccouche Basil M. , Mahmoud Mattia A. , Nief Corrine , Patel Karan , Natterson-Horowitz B. 
Published: October 2022

ABSTRACTIntroductionHeart failure (HF) is a leading cause of death worldwide. The global prevalence of heart failure is projected to increase rapidly in the coming decades, and significant attention has turned to improving biomarker-based risk prediction of incident HF. The aim of this paper was to qualitatively and quantitatively evaluate the evidence associating levels of galectin-3 with risk of incident HF.MethodsA review of PUBMED-indexed peer-reviewed literature was performed. Nine studies met inclusion criteria, and all nine had data eligible for conversion and pooling. A random-effects meta-analysis was performed using hazard ratios and 95% confidence intervals from a minimally adjusted model, a further adjusted model, and from subgroups within the further-adjusted model.ResultsThe minimally-adjusted model provided a HR of 1.97 (95% CI 1.74-2.23) when comparing the top quartile of log-gal-3 to the bottom quartile. The further-adjusted model provided a HR of 1.32 (95% CI 1.21-1.44) for the same comparison. The positive, significant association was conserved during sensitivity analysis.ConclusionThere is a significant positive association between levels of circulating galectin-3 and risk of incident heart failure. Given the complex mechanistic relationship between galectin-3 and cardiovascular pathophysiology, further investigation is recommended for possible implementation of galectin-3 into clinical risk prediction models.
An epigenetic basis of adaptive plasticity inDrosophila melanogaster
Authors: DiVito Evans Abigail , Fairbanks Regina A. , Schmidt Paul , Levine Mia T. 
Published: October 2022

ABSTRACTFluctuating environments threaten fertility and viability. To better match the immediate, local environment, many organisms adopt alternative phenotypic states, a phenomenon called “phenotypic plasticity”. Local adaptation shapes phenotypic plasticity: natural populations that predictably encounter fluctuating environments tend to be more plastic than conspecific populations that encounter a constant environment. Despite pervasive evidence of such “adaptive phenotypic plasticity,” the evolution of the gene regulatory mechanisms underlying plasticity remains poorly understood. Here we test the hypothesis that environment-dependent phenotypic plasticity is mediated by epigenetic factors and that these epigenetic factors vary across naturally occurring genotypes. To test these hypotheses, we exploit the adaptive reproductive arrest ofDrosophila melanogasterfemales, called diapause. Using an inbred line from a natural population with high diapause plasticity, we demonstrate that diapause is determined epigenetically: only a subset of genetically identical individuals enter diapause and this diapause plasticity is epigenetically transmitted for at least three generations. Upon screening a suite of epigenetic marks, we discovered that the active histone marks H3K4me3 and H3K36me1 are depleted in diapausing ovaries. Using ovary-specific knockdown of histone mark writers and erasers, we demonstrate that H3K4me3 and H3K36me1 depletion promotes diapause. Given that diapause is highly polygenic – distinct suites of alleles mediate diapause plasticity across distinct genotypes – we investigated the potential for genetic variation in diapause-determining epigenetic marks. Specifically, we asked if these histone marks were similarly depleted in diapause of a geographically distinct, comparatively less plastic genotype. We found evidence of genotypic divergence in both the gene expression program and histone mark abundance. This study reveals chromatin determinants of adaptive plasticity and suggests that these determinants are genotype-dependent, offering new insight into how organisms may exploit and evolve epigenetic mechanisms to persist in fluctuating environments.
Quantification of differential toxin expressions and their relation to distinct lifespans of bacterial subpopulations associated with diverse host immune mechanisms
Authors: Santra Shweta , Nayak Indrani , Das Dibyendu , Banerjee Anirban 
Published: October 2022

AbstractAn assortment of robust intracellular defence mechanisms are critical for restricting proliferation of pathogens and maintaining sanctity of the cytosol. Defect in these mechanisms could be exploited by the pathogens for creation of a safe sanctuary which can act as a transient reservoir for periodic dissemination into the host. While residing inside the host cell, pore forming toxins secreted by the pathogens compromises the integrity of the vacuole and exposes the microbe to diverse intracellular defence mechanisms. However, the correlation between toxin expression levels and consequent pore dynamics, fostering pathogen’s intracellular life, remains largely unexplored. In this study, usingStreptococcus pneumoniae(SPN) and its secreted pore forming toxin pneumolysin (Ply), as model systems, we explored various facets of host-pathogen interactions in host cytosol, governed by the toxin expression and the resultant pore formation. The extent of damage on the endosomal membrane was found to dictate subsequent interaction with different host endosomal damage sensors. This in turn governed the routes of SPN clearance, revealing multiple layers of defence mechanisms at host’s disposal for counteracting invaded pathogens. A subset of SPN population producing extremely low amount of Ply inflicted minimal damage to the endomembrane, precluding decoration by endomembrane damage sensors and significantly prolonging its intracellular persistence. Such long persisting bacterial population could be key for pathogenic transmission or ensuing invasive disease. Using time-lapse fluorescence imaging, we monitored lifespans of different pneumococcal population subsets inside host cells. After quantitative analysis of various timescales such as pore formation time, vacuolar or cytosolic residence time and total degradation time, we developed a mathematical model that could correlate these to intravacuolar accumulation of Ply monomers. By proposing events like pore formation and vacuolar degradation of SPN as first passage processes, our theoretical modelling yields estimates of Ply production rate, burst size, and threshold Ply quantities which triggers these outcomes. Collectively, we present a general method by which intracellular lifespans of pathogens could be correlated to differential levels of toxins that they produce.
Population structure and genetic variance among local populations of an non-native earthworm species in Minnesota, USA
Authors: Heimburger Bastian , Klein Andreas , Roth Alex , Scheu Stefan , Eisenhauer Nico , Schaefer Ina 
Published: October 2022

AbstractA variety of human activities have been identified as driving factors for the release and spread of invasive earthworm species in North America. Population genetic markers can help to identify locally relevant anthropogenic vectors and provide insights into the processes of population dispersal and establishment. We sampled the invasive European earthworm speciesLumbricus terrestrisat nine sites and several bait shops within the metropolitan area of Minneapolis-St. Paul in Minnesota, USA. We used microsatellite markers to infer genetic diversity and population structure, and 16S rDNA to address multiple introduction events, including bait dumping, which is a common source ofL. terrestrisintroductions into the wild. Our results indicate multiple introductions but not from current bait dumping. Overall, genetic structure was low and earthworms >5000 m apart were genetically differentiated, except for one sampling location, indicating jump-dispersal followed by population establishment. Further, earthworms at one location north of Minneapolis established from one or few founder individuals, suggesting that earthworm invasions are ongoing. We therefore encourage further monitoring of earthworm populations using molecular markers, in order to disentangle the different human-related vectors contributing to the spread of earthworms and their establishment, which is essential to develop adequate management strategies.
Designed active-site library reveals thousands of functional GFP variants
Authors: Weinstein Jonathan Yaacov , Martí-Gómez Carlos , Lipsh-Sokolik Rosalie , Hoch Shlomo Yakir , Liebermann Demian , Nevo Reinat , Weissman Haim , Petrovich-Kopitman Ekaterina , Margulies David , Ivankov Dmitry , McCandlish David , Fleishman Sarel Jacob 
Published: October 2022

AbstractMutations in a protein active site can lead to dramatic and useful changes in protein activity. The active site, however, is extremely sensitive to mutations due to a high density of molecular interactions, drastically reducing the likelihood of obtaining functional multipoint mutants. We introduce an atomistic and machine-learning-based approach, called htFuncLib, to design a sequence space in which mutations form low-energy combinations that mitigate the risk of incompatible interactions. We applied htFuncLib to the GFP chromophore-binding pocket, and, using fluorescence readout, recovered >16,000 unique designs encoding as many as eight active-site mutations. Many designs exhibit substantial and useful diversity in functional thermostability (up to 96 °C), fluorescence lifetime, and quantum yield. By eliminating incompatible active-site mutations, htFuncLib generates a large diversity of functional sequences. We envision that htFuncLib will be useful for one-shot optimization of activity in enzymes, binders, and other proteins.
FBXL4 deficiency promotes mitophagy by elevating NIX
Authors: Elcocks Hannah , Brazel Ailbhe J. , McCarron Katy R. , Kaulich Manuel , Husnjak Koraljka , Mortiboys Heather , Clague Michael J. , Urbé Sylvie 
Published: October 2022

AbstractThe selective autophagy of mitochondria is linked to mitochondrial quality control and is critical to a healthy organism. We have conducted a CRISPR/Cas9 screen of human E3 ubiquitin ligases for influence on mitophagy under both basal cell culture conditions and following acute mitochondrial depolarisation. We identify two Cullin RING ligases, VHL and FBXL4 as the most profound negative regulators of basal mitophagy. We show that these converge through control of the mitophagy adaptors BNIP3 and BNIP3L/NIX through different mechanisms. FBXL4 suppression of BNIP3 and NIX levels is mediated via direct interaction and protein destabilisation rather than suppression of HIF1α-mediated transcription. Depletion of NIX but not BNIP3 is sufficient to restore mitophagy levels. Our study enables a full understanding of the aetiology of early onset mitochondrial encephalomyopathy that is supported by analysis of a disease associated mutation. We further show that the compound MLN4924, which globally interferes with Cullin RING ligase activity, is a strong inducer of mitophagy providing a research tool in this context and a candidate therapeutic agent for conditions linked to mitochondrial dysfunction.
Distinct roles for canonical and variant histone H3 lysine 36 in Polycomb silencing
Authors: Salzler Harmony R. , Vandadi Vasudha , McMichael Benjamin D. , Brown John C. , Boerma Sally A. , Leatham-Jensen Mary P. , Adams Kirsten M. , Meers Michael P. , Simon Jeremy M. , Duronio Robert J. , McKay Daniel J. , Matera A. Gregory 
Published: October 2022

AbstractPolycomb complexes regulate cell-type specific gene expression programs through heritable silencing of target genes. Trimethylation of histone H3 lysine 27 (H3K27me3) is essential for this process. Perturbation of H3K36 is thought to interfere with H3K27me3. We show that mutants ofDrosophilareplication-dependent(H3.2K36R)or -independent(H3.3K36R)histone H3 genes generally maintain Polycomb silencing and reach later stages of development. In contrast, combined(H3.3K36RH3.2K36R)mutants display widespread Hox gene misexpression and fail to develop past the first larval stage. Chromatin profiling revealed that theH3.2K36Rmutation disrupts H3K27me3 levels broadly throughout silenced domains, whereas these regions are mostly unaffected inH3.3K36Ranimals. Analysis of H3.3 distributions showed that this histone is enriched at presumptive PREs (Polycomb Response Elements) located outside of silenced domains but relatively depleted from those inside. We conclude that H3.2 and H3.3 K36 residues collaborate to repress Hox genes using different mechanisms.Short summaryHistone H3.2 and H3.3 K36 residues ensure Hox gene silencing and enable development by different, but synergistic mechanisms.
A novel Single Alpha-Helix-DNA-binding domain in CAF-1 promotes gene silencing and DNA damage survival through tetrasome-length DNA selectivity and spacer function
Authors: Rosas Ruben , Aguilar Rhiannon R. , Arslanovic Nina , Tyler Jessica K. , Churchill Mair E. A. 
Published: October 2022

AbstractThe histone chaperone chromatin assembly factor 1 (CAF-1) deposits nascent histone H3/H4 dimers onto newly replicated DNA forming the central core of the nucleosome known as the tetrasome. How CAF-1 ensures there is sufficient space for the assembly of tetrasomes remains unknown. Structural and biophysical characterization of the lysine/glutamic acid/arginine-rich (KER) region of CAF-1 revealed a 128 Å single alpha helix (SAH) motif with unprecedented DNA binding properties. Distinct KER sequence features and length of the SAH drive the selectivity of CAF-1 for tetrasome-length DNA and facilitate function in budding yeast.In vivo, the KER cooperates with the DNA-binding winged helix domain in CAF-1 to overcome DNA damage sensitivity and maintain silencing of gene expression. We propose that the KER SAH links functional domains within CAF-1 with structural precision, acting as a DNA binding spacer element during chromatin assembly.
Breadth of Fc-mediated effector function delineates grades of clinical immunity following human malaria challenge
Authors: Nkumama Irene N. , Odera Dennis , Musasia Fauzia , Mwai Kennedy , Nyamako Lydia , Murungi Linda , Tuju James , Fürle Kristin , Rosenkranz Micha , Kimathi Rinter , Njuguna Patricia , Hamaluba Mainga , Kapulu Melissa C. , Frank Roland ,   CHMI-SIKA study Team, Osier Faith H. A. 
Published: October 2022

SUMMARYControlled human malaria challenge studies in semi-immune volunteers provide an unparalleled opportunity to robustly identify mechanistic correlates of protection. We leveraged this platform to undertake a head-to-head comparison of seven functional antibody assays that are relevant to immunity against the erythrocytic merozoite stage ofPlasmodium falciparum. Fc-mediated effector functions were strongly associated with protection from clinical symptoms of malaria and exponential parasite multiplication while the gold standard growth inhibition assay was not. The breadth of Fc-mediated effector function clearly discriminated grades of clinical immunity following challenge. These findings present a paradigm shift in the understanding of the mechanisms that underpin immunity to malaria and have important implications for vaccine development.