bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histologic safety of transcranial focused ultrasound neuromodulation and magnetic resonance acoustic radiation force imaging in rhesus macaques and sheep
Authors: Gaur Pooja , Casey Kerriann M. , Kubanek Jan , Li Ningrui , Mohammadjavadi Morteza , Saenz Yamil , Glover Gary H. , Bouley Donna M. , Pauly Kim Butts 
Published: November 2019

AbstractBackgroundNeuromodulation by transcranial focused ultrasound (FUS) offers the potential to non-invasively treat specific brain regions, with treatment location verified by magnetic resonance acoustic radiation force imaging (MR-ARFI).ObjectiveTo investigate the safety of these methods prior to widespread clinical use, we report histologic findings in two large animal models following FUS neuromodulation and MR-ARFI.MethodsTwo rhesus macaques and thirteen Dorset sheep were studied. FUS neuromodulation was targeted to the primary visual cortex in rhesus macaques and to subcortical locations, verified by MR-ARFI, in eleven sheep. Both rhesus macaques and five sheep received a single FUS session, whereas six sheep received repeated sessions three to six days apart. The remaining two control sheep did not receive ultrasound but otherwise underwent the same anesthetic and MRI procedures as the eleven experimental sheep. Hematoxylin and eosin-stained sections of brain tissue (harvested zero to eleven days following FUS) were evaluated for tissue damage at FUS and control locations as well as tissue within the path of the FUS beam. TUNEL staining was used to evaluate for the presence of apoptosis in sheep receiving high dose FUS.ResultsNo FUS-related pre-mortem histologic findings were observed in the rhesus macaques or in any of the examined sheep. Extravascular red blood cells (RBCs) were present within the meninges of all sheep, regardless of treatment group. Similarly, small aggregates of perivascular RBCs were rarely noted in non-target regions of neural parenchyma of FUS-treated (8/11) and untreated (2/2) sheep. However, no concurrent histologic abnormalities were observed, consistent with RBC extravasation occurring as post-mortem artifact following brain extraction. Sheep within the high dose FUS group were TUNEL-negative at the targeted site of FUS.ConclusionsThe absence of FUS-related histologic findings suggests that the neuromodulation and MR-ARFI protocols evaluated do not cause tissue damage.
First evidence of production of the lantibiotic nisin P
Authors: Garcia-Gutierrez Enriqueta , O’Connor Paula M. , Saalbach Gerhard , Walsh Calum J. , Hegarty James W. , Guinane Caitriona M. , Mayer Melinda J. , Narbad Arjan , Cotter Paul D. 
Published: November 2019

AbstractNisin P is a natural nisin variant, the genetic determinants for which were previously identified in the genomes of twoStreptococcusspecies, albeit with no confirmed evidence of production. Here we describeStreptococcus agalactiaeDPC7040, a human fecal isolate, which exhibits antimicrobial activity against a panel of gut and food isolates by virtue of producing nisin P. Nisin P was purified, and its predicted structure was confirmed by nanoLC-MS/MS, with both the fully modified peptide and a variant without rings B and E being identified. Additionally, we compared its spectrum of inhibition and minimum inhibitory concentration (MIC) with that of nisin A and its antimicrobial effect in a fecal fermentation in comparison with nisin A and H. We found that its antimicrobial activity was less potent than nisin A and H, and we propose a link between this reduced activity and the peptide structure.
Relating the strength of density dependence and the spatial distribution of individuals
Authors: Brush Micah , Harte John 
Published: November 2019

ABSTRACTSpatial patterns in ecology contain useful information about underlying mechanisms and processes. Although there are many summary statistics used to quantify these spatial patterns, there are far fewer models that directly link explicit ecological mechanisms to observed patterns easily derived from available data. We present a model of intraspecific spatial aggregation that quantitatively relates static spatial patterning to negative density dependence. Individuals are placed according to the colonization rule consistent with the Maximum Entropy Theory of Ecology (METE), and die with probability proportional to their abundance raised to a powerα, a parameter indicating the degree of density dependence. Our model shows quantitatively and generally that increasing density dependence randomizes spatial patterning.α= 1 recovers the strongly aggregated METE distribution that is consistent with many ecosystems empirically, and asα →2 our prediction approaches the binomial distribution consistent with random placement. In between our model predicts less aggregation than METE, but more than random placement. We additionally relate our mechanistic parameterαto the statistical aggregation parameterkin the negative binomial distribution, giving it an ecological interpretation in the context of density dependence. We use our model to analyze two contrasting datasets, a 50 ha tropical forest and a 64 m2serpentine grassland plot. For each dataset, we inferαfor individual species as well as a communityαparameter. We find thatαis generally larger in the tightly packed forest than the sparse grassland, and the degree of density dependence increases at smaller scales. These results are consistent with current understanding in both ecosystems, and we infer this underlying density dependence using only empirical spatial patterns. Our model can easily be applied to other datasets where spatially explicit data are available.
Resolvin D-series regulates Phospholipase D both during inflammation and resolution by modulating phagocyte functions
Authors: Ganesan Ramya , Henkels Karen M. , Shah Krushangi , de la Rosa Xavier , Libreros Stephania , Cheemarla Nagarjuna R , Serhan Charles N. , Gomez-Cambronero Julian 
Published: November 2019

ABSTRACTA successful acute inflammatory response results in the elimination of infectious agents by neutrophils and monocytes, followed by resolution and repair by tissue-resident and recruited macrophages. D-series resolvins are pro-resolving mediators involved in resolution and tissue repair, their intracellular signaling mechanism(s) are of interest. Here, we report that D-series resolvins activate phospholipase D (PLD), a ubiquitously expressed membrane lipase in modulating phagocyte functions. The mechanism for PLD-mediated actions of RvD5 in polarizing macrophages (M1-M2) was found to be two-pronged: (a) RvD5 inhibits post-transcriptional modifications, by miRs and 3’exonulceases that process PLD2 mRNA, thus increasing PLD2 expression and activity; (b) RvD5 enhances PLD2-S6K signaling and Actin expression required for membrane expansion and efferocytosis. In addition, investigating RvD5’s actions in second organ reflow injury, we found that RvD5 did not reduce lung neutrophil myeloperoxidase levels in PLD2-/- mice compared to WT and PLD1-/- mice, pointing to a unique role of PLD2 as the relevant isoform in RvD5-mediated resolution. These results demonstrate that RvD5-PLD2 are attractive targets for therapeutic interventions in vascular inflammation such as I/R injury and cardiovascular diseases.
Measuring three-dimensional dynamics of platelet activation using 3-D quantitative phase imaging
Authors: Lee SangYun , Jang Seongsoo , Park YongKeun 
Published: November 2019

AbstractPlatelets, or thrombocytes, are anucleated tiny blood cells with an indispensable contribution to the hemostatic properties of whole blood, detecting injured sites at the surface of blood vessels and forming blood clots. Here, we quantitatively and non-invasively investigated the morphological and biochemical alterations of individual platelets during activation in the absence of exogenous agents by employing 3-D quantitative phase imaging (QPI). By reconstructing 3-D refractive index (RI) tomograms of individual platelets, we investigated alterations in platelet activation before and after the administration of various platelet agonists. Our results showed that while the integrity of collagen-stimulated platelets was preserved despite the existence of a few degranulated platelets with developed pseudopods, platelets stimulated by thrombin or thrombin receptor-activating peptide (TRAP) exhibited significantly lower cellular concentration and dry mass than did resting platelets. Our work provides a means to systematically investigate drug-respondents of individual platelets in a label-free and quantitative manner, and open a new avenue to the study of the activation of platelets.Abstract Figure
Neutralizing antibody responses to an HIV envelope glycan hole are not easily broadened
Authors: Yang Yuhe R. , McCoy Laura E. , van Gils Marit J. , Andrabi Raiees , Turner Hannah L. , Yuan Meng , Cottrell Christopher A. , Ozorowski Gabriel , Voss James , Pauthner Matthias , Polveroni Thomas M. , Messmer Terrence , Wilson Ian A. , Sanders Rogier W. , Burton Dennis R. , Ward Andrew B. 
Published: November 2019

ABSTRACTExtensive studies with subtype A BG505-derived HIV envelope glycoprotein (Env) SOSIP immunogens have revealed that the dominant autologous neutralizing site in rabbits is located in an exposed region of the heavily glycosylated trimer that lacks potential N-linked glycosylation sites at positions 230, 241, and 289. The Env derived from B41, a subtype B virus, shares a glycan hole centered on positions 230 and 289. BG505 and B41 SOSIP immunogens were combined to test whether immunization in rabbits could induce broader Tier 2 neutralizing responses to the common glycan hole shared between BG505 and B41. Here we isolated autologous neutralizing antibodies (nAbs) that were induced by immunization with B41 SOSIP alone, as well as B41 and BG505 co-immunization, and describe their structure in complex with the B41 SOSIP trimer. Our data suggest that distinct autologous nAb lineages are induced by BG505 and B41 immunogens, even when both immunogens were administered together. In contrast to previously described BG505 glycan hole antibodies, the B41-specific nAbs accommodate the highly conserved N241 glycan (>97% conserved), which is present in B41. Single particle cryo-electron microscopy (cryoEM) studies confirmed that B41 and BG505-specific nAbs bind to overlapping glycan hole epitopes. In an attempt to broaden the reactivity of a B41-specific nAb, mutations in the BG505 glycan hole epitope guided by our high-resolution data only recovered partial binding. Overall, designing prime-boost immunogens to increase the breath of nAb responses directed at glycan holes epitopes remains challenging even when the typically immunodominant glycan holes despite overlap with different Envs.IMPORTANCEA glycan hole is one of the most dominant autologous neutralizing epitopes targeted on BG505 and B41 SOSIP trimer immunized rabbits. Our high-resolution cryoEM studies of B41 in complex with a B41-specific antibody complex elucidate the molecular basis of this strain-specific glycan hole response. We conclude that eliciting cross-reactive responses to this region would likely require hybrid immunogens that bridge between BG505 and B41.
Aggressive Periodontitis with Neutropenia Caused byMMD2Mutation
Authors: Mizuno Noriyoshi , Morino Hiroyuki , Mihara Keichiro , Iwata Tomoyuki , Ohno Yoshinori , Matsuda Shinji , Ouhara Kazuhisa , Kajiya Mikihito , Suzuki-Takedachi Kyoko , Sotomaru Yusuke , Takeda Katsuhiro , Sasaki Shinya , Okanobu Ai , Sakuma Tetsushi , Yamamoto Takashi , Matsuda Yukiko , Ohsawa Ryousuke , Fujita Tsuyoshi , Shiba Hideki , Kawakami Hideshi , Kurihara Hidemi 
Published: November 2019

AbstractAggressive periodontitis causes rapid periodontal tissue destruction and is a disease that occurs at a young age and runs in the patient’s family. Here, we revealed a heterozygous A116V missense mutation in the gene encoding monocyte to macrophage differentiation associated 2 (MMD2) protein in a Japanese family with aggressive periodontitis and neutropenia. Analyses of patients’ peripheral blood revealed a low number of neutrophils but abundant quantity of CD34+hematopoietic stem and progenitor cells (HSPCs). Moreover, mutantMmd2mice showed severe alveolar bone loss and neutropenia. In patients and mutantMmd2mice, differentiation of HSPCs into granulocytes was also impeded, and their granulocytes were functionally impaired. Taken together, A116V mutation inMMD2gene induced mild neutropenia and slightly limited the immune defense response. Our studies suggested that aggressive periodontitis in association with A116VMMD2mutation constitutes a new immune system defect that belongs to the same spectrum of severe congenital neutropenia.
Identification of Potential Dual-Targets Anti-Toxoplasma gondii Compounds Through Structure-Based Virtual Screening and In-Vitro Studies
Authors: Salin Nurul Hanim , Noordin Rahmah , Najjar Belal Omar Al , Kamarulzaman Ezatul Ezleen , Yunus Muhammad Hafiznur , Karim Izzati Zahidah Abdul , Nasim Nurul Nadieya Mohd , Zakaria Iffah Izzati , Wahab Habibah A. 
Published: November 2019

AbstractToxoplasma gondiiis the etiologic agent of toxoplasmosis, a disease which can lead to morbidity and mortality of the fetus and immunocompromised individuals. Due to the limited effectiveness or side effects of existing drugs, the search for better drug can didates is still ongoing. In this study, we performed structure-based screening of potential dual-targets inhibitors of active sites ofT. gondiidrug targets such as uracil phosphoribosyltransferase (UPRTase) and adenosine kinase (AK). First screening of virtual compounds from the National Cancer Institute (NCI) was performedviamolecular docking. Subsequently, the hit compounds were testedin-vitrofor anti-T. gondiieffect using cell viability assay with Vero cells as host to determine cytotoxicity effects and drug selectivities. Clindamycin, as positive control, showed a selectivity index (SI) of 10.9, thus compounds with SI > 10.9 specifically targetT. gondiiproliferation with no significant effect on the host cells. Good anti-T. gondiieffects were observed with NSC77468 (7-ethoxy-4-methyl-6,7-dihydro-5H-thiopyrano[2,3-d] pyrimidin-2-amine) which showed SI values of 25. This study showed thatin-silicoselection can serve as an effective way to discover potentially potent and selective compounds againstT. gondii.
The complete mitochondrial genome of endangered Assam Roofed Turtle,Pangshura sylhetensis(Testudines: Geoemydidae): Genomic features and Phylogeny
Authors: Kundu Shantanu , Kumar Vikas , Tyagi Kaomud , Chandra Kailash 
Published: November 2019

AbstractAssam Roofed Turtle,Pangshura sylhetensisis an endangered and least studied species endemic to India and Bangladesh. The genomic feature ofP. sylhetensismitogenome is still anonymous to the scientific community. The present study decodes the first complete mitochondrial genome ofP. sylhetensis(16,568 bp) by using next-generation sequencing. Thisde novoassembly encodes 13 Protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs), and one control region (CR). Most of the genes were encoded on the majority strand, except NADH dehydrogenase subunit 6 (nad6) and eight tRNAs. Most of the PCGs were started with an ATG initiation codon, except for Cytochrome oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 5 (nad5) with GTG. The study also found the typical cloverleaf secondary structure in most of the tRNA genes, except for serine (trnS1) with lack of conventional DHU arm and loop. Both, Bayesian and Maximum-likelihood topologies showed distinct clustering of all the Testudines species with their respective taxonomic ranks and congruent with the previous phylogenetic hypotheses (PangshuraandBatagursister taxa). Nevertheless, the mitogenomic phylogeny with other amniotes corroborated the sister relationship of Testudines with Archosaurians (Birds and Crocodilians). Additionally, the mitochondrial Gene Order (GO) analysis indicated that, most of the Testudines species showed plesiomorphy with typical vertebrate GO.
Inference of Population Genetic Structure and High Linkage Disequilibrium AmongAlternariaspp. Collected from Tomato and Potato Using Genotyping by Sequencing
Authors: Adhikari Tika B. , Knaus Brian J. , Grünwald Niklaus J. , Halterman Dennis , Louws Frank J. 
Published: November 2019

ABSTRACTGenotyping by sequencing (GBS) is considered a powerful tool to discover single nucleotide polymorphisms (SNPs), which are useful to characterize closely related genomes of plant species and plant pathogens. We applied GBS to determine genome-wide variations in a panel of 187 isolates of three closely relatedAlternariaspp. that cause diseases on tomato and potato in North Carolina (NC) and Wisconsin (WI). To compare genetic variations, reads were mapped to bothA. alternataandA. solanidraft reference genomes and detected dramatic differences in SNPs among them. Comparison ofA. linariaeandA. solanipopulations by principal component analysis revealed the first (83.8% of variation) and second (8.0% of variation) components containedA. linariaefrom tomato in NC andA. solanifrom potato in WI, respectively, providing evidence of population structure. Genetic differentiation (Hedrick’s G’ST) inA. linariaepopulations from Haywood, Macon, and Madison counties in NC were little or no differentiated (G’ST0.0 - 0.2). However,A. linariaepopulation from Swain county appeared to be highly differentiated (G’ST> 0.8). To measure the strength of the linkage disequilibrium (LD), we also calculated the allelic association between pairs of loci. Lewontin’sD(measures the fraction of allelic variations) and physical distances provided evidence of linkage throughout the entire genome, consistent with the hypothesis of non-random association of alleles among loci. Our findings provide new insights into the understanding of clonal populations on a genome-wide scale and microevolutionary factors that might play an important role in population structure. Although we found limited genetic diversity, the threeAlternariaspp. studied here are genetically distinct and each species is preferentially associated with one host.
Kinetic foundation of the zero-inflated negative binomial model for single-cell RNA sequencing data
Authors: Jia Chen 
Published: November 2019

AbstractSingle-cell RNA sequencing data have complex features such as dropout events, over-dispersion, and high-magnitude outliers, resulting in complicated probability distributions of mRNA abundances that are statistically characterized in terms of a zero-inflated negative binomial (ZINB) model. Here we provide a mesoscopic kinetic foundation of the widely used ZINB model based on the biochemical reaction kinetics underlying transcription. Using multiscale modeling and simplification techniques, we show that the ZINB distribution of mRNA abundance and the phenomenon of transcriptional bursting naturally emerge from a three-state stochastic transcription model. We further reveal a nontrivial quantitative relation between dropout events and transcriptional bursting, which provides novel insights into how and to what extent the burst size and burst frequency could reduce the dropout rate. Three different biophysical origins of over-dispersion are also clarified at the single-cell level.
Chromatin organization in early land plants reveals an ancestral association between H3K27me3, transposons, and constitutive heterochromatin
Authors: Montgomery Sean A. , Tanizawa Yasuhiro , Galik Bence , Wang Nan , Ito Tasuku , Mochizuki Takako , Akimcheva Svetlana , Bowman John , Cognat Valérie , Drouard Laurence , Ekker Heinz , Houng Syuan-Fei , Kohchi Takayuki , Lin Shih-Shun , Liu Li-Yu Daisy , Nakamura Yasukazu , Valeeva Lia R. , Shakirov Eugene V. , Shippen Dorothy E. , Wei Wei-Lun , Yagura Masaru , Yamaoka Shohei , Yamato Katsuyuki T. , Liu Chang , Berger Frédéric 
Published: November 2019

SummaryGenome packaging by nucleosomes is a hallmark of eukaryotes. Histones and the pathways that deposit, remove, and read histone modifications are deeply conserved. Yet, we lack information regarding chromatin landscapes in extant representatives of ancestors of the main groups of eukaryotes and our knowledge of the evolution of chromatin related processes is limited. We used the bryophyte Marchantia polymorpha, which diverged from vascular plants 400 Mya, to obtain a whole chromosome genome assembly and explore the chromatin landscape and three-dimensional organization of the genome of early land plants. Based on genomic profiles of ten chromatin marks, we conclude that the relationship between active marks and gene expression is conserved across land plants. In contrast, we observed distinctive features of transposons and repeats in Marchantia compared with flowering plants. Silenced transposons and repeats did not accumulate around centromeres, and a significant proportion of transposons were marked by H3K27me3, which is otherwise dedicated to the transcriptional repression of protein coding genes in flowering plants. Chromatin compartmentalization analyses of Hi-C data revealed that chromatin regions belonging to repressed heterochromatin were densely decorated with H3K27me3 but not H3K9 or DNA methylation as reported in flowering plants. We conclude that in early plants, H3K27me3 played an essential role in heterochromatin function, suggesting an ancestral role of this mark in transposon silencing.
IL-17A both initiates (via IFNγ suppression) and limits the pulmonary type-2 immune response to nematode infection
Authors: Ajendra Jesuthas , Chenery Alistair L. , Parkinson James E. , Chan Brian H. K. , Pearson Stella , Colombo Stefano A. P. , Boon Louis , Grencis Richard K. , Sutherland Tara E. , Allen Judith E. 
Published: November 2019

ABSTRACTNippostrongylus brasiliensisis a well-defined model of type-2 immunity but the early lung-migrating phase is dominated by innate IL-17A production and neutrophilia. UsingN. brasiliensisinfection we confirm previous observations thatIl17a-KO mice exhibit an impaired type-2 immune response. Neutrophil depletion and reconstitution studies demonstrated that neutrophils contribute to the subsequent eosinophilia but are not responsible for the ability of IL-17A to promote type-2 cytokine responses. Transcriptional profiling of the lung on day 2 ofN. brasiliensisinfection revealed an increasedIfnγsignature in theIl17a-KO mice confirmed by enhanced IFNγ protein production. Depletion of early IFNγ rescued type-2 immune responses in theIl17a-KO mice demonstrating that IL-17A-mediated suppression of IFNγ promotes type-2 immunity. Notably, when IL-17A was blocked later in infection, the type-2 response increased. IL-17A regulation of type-2 immunity was lung-specific and infection withTrichuris muris,revealed that IL-17A promotes a type-2 immune response in the lung even when a parasite lifecycle is restricted to the intestine. Together our data reveal IL-17A as a major regulator of pulmonary type-2 immunity which supports the development of a protective type-2 immune response but subsequently limits the magnitude of that response.