bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knockdown of TFPI-Anchored Endothelial Cells Exacerbates Lipopolysaccharide-Induced Acute Lung Injury Via NF-κB Signaling Pathway
Authors: Wang Bao Q. , Shi Meng , Zhang Jian P. , Wu Xie , Chang Mei J. , Chen Zhi H. , Shen Hua H. , Song Yuan L. , Zhou Jian , Bai Chun X. 
Published: February 2018

ABSTRACT
As activation of the coagulation system is both a consequence and contributor to acute lung injury (ALI), pulmonary coagulopathy has become a potential target for therapeutic intervention in ALI patients. We investigated the effects and possible mechanisms of endothelial cell (EC)-anchored tissue factor pathway inhibitor (TFPI) on lipopolysaccharide (LPS)-induced ALI in mice. To assess the effect of EC-anchored TFPI deletion on ALI indices, TFPI knockout (cKO) mice were generated. Mice were instilled by direct intratracheal injection LPS for the preparation of an ALI model. Evans blue dye (EBD) was injected intravenously 2 h prior to animal sacrifice (48 h post-LPS). Lungs were fixed for histopathology and the prepared tissue was homogenized or used to extract bronchoalveolar lavage fluid (BALF) or detect EBD concentration. TFPI knockdown mice with ALI were compared to wild-type (WT) mice with ALI to assess the effect of TFPI on endothelial barrier function and inflammation. TFPI deletion markedly exacerbated LPS histopathological changes in lung, and the LPS changes in protein, EBD extravasation, proinflammatory cytokines TNF-α, IL-1β, and IL-6 in BALF in lung. The number and infiltration of white blood cells (WBCs) from BALF and lung tissue of TFPI cKO mice with LPS-challenged ALI was increased compared to WT mice with LPS-challenged ALI. We also found further increased toll-like receptor 4 and nuclear factor kappa-light-chain-enhancer of activated B cells activation and additional expression of vascular cell adhesion molecule 1 and reduction of angiotensin converting enzyme 2 expression in TFPI cKO+LPS mice compared with WT+LPS mice. Endothelial-specific TFPI deficiency promoted LPS-induced pulmonary inflammation and endothelial barrier permeability possibly via toll-like receptor 4-mediated nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway activation.
Toxins in pain
Authors: Cardoso Fernanda C. , Hasan Mahadhi , Zhao Tianjiao , Lewis Richard J. 
Published: February 2018

Purpose of reviewPain is a distressing protective sensory experience warning of actual or potential tissue damage. Natural toxins have evolved to exploit pain and related neuronal pathways to facilitate prey capture and for defence, often producing either numbness, paralysis or intense pain by selectively modulating ion channels and receptors in pain pathways. Understanding how toxins modulate pain pathways can enhance our understanding of the physiological and pathological basis of pain.Recent findingsToxins continue to provide a rich source of unique pharmacological tools and novel drug leads to treat severe neurological disorders, including chronic pain. Recently discovered toxins that selectively modulate Nav1.7 and Nav1.1 have helped unravel their involvement in pain signalling.SummaryToxins have evolved to induce or inhibit pain by targeting a broad range of ion channels and receptors, including NaV, CaV,KV, TRP, ASIC, P2X, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid,N-methyl-D-aspartate, NET and GPCRs. These toxins bind to specific sites to stimulate or inhibit the activity of these membrane proteins. Toxins continue to yield some of the most exciting leads for developing novel nonopioid analgesics.
Central and peripheral processes in headache
Authors: Varma Adithya , Jain Saurabh , Majid Arshad , De Felice Milena 
Published: February 2018

Purpose of reviewMigraine is an extremely incapacitating collection of neurological symptoms that usually includes a severe, throbbing, recurring pain on one side of the head. The World Health Organization ranks migraine as the third most prevalent disease and the seventh commonest primary pain condition in the world. Trigeminovascular-mediated central sensitization has been implicated in the development of migraine symptoms including pain following light touch. This review explores the activation and sensitization of the brain systems that have emerged from recent studies and that contribute to migraine.Recent findingsA number of pathophysiological mechanisms have been implicated in the development of migraine and other primary headache disorders. Neuroimaging techniques used to identify both structural and functional features of the brain in migraineurs have helped identify brain regions that are active during or in between migraine attacks, with particular emphasis on those areas relevant to pain pathways, including the hypothalamus and periaqueductal grey.SummarySeveral key studies have helped address the long-standing debate over whether migraine originates from vascular or neuronal dysfunction and now support that migraine is a neurological disorder. However, a complete understanding of the central nervous system dysfunction underlying this condition has yet to be elucidated.
Validity and Acceptance of Color Vision Testing on Smartphones
Authors: Ozgur Omar K. , Emborgo Trisha S. , Vieyra Mark B. , Huselid Rebecca F. , Banik Rudrani 
Published: February 2018

Background:
Ishihara color plates (ICP) are the most commonly used color vision test (CVT) worldwide. With the advent of new technologies, attempts have been made to streamline the process of CVT. As hardware and software evolve, smartphone-based testing modalities may aid ophthalmologists in performing more efficient ophthalmic examinations. We assess the validity of smartphone color vision testing (CVT) by comparing results using the Eye Handbook (EHB) CVT application with standard Ishihara color plates (ICP).

Methods:
Prospective case–control study of subjects 18 years and older with visual acuity of 20/100 or better at 14 inches. The study group included patients with any ocular pathology. The color vision deficient (CVD) group was patients who failed more than 2 plates. The control group had no known ocular pathology. CVT was performed with both ICP and EHB under standardized background illuminance. Eleven plates were tested with each modality. Validity of EHB CVT and acceptance of EHB CVT were analyzed. Statistical analyses were performed using Bland–Altman plot with limits of agreement (LOA) at the 95th percentile of differences in score, independent samples t tests with 95% confidence interval (CI), and Pearson χ
2 tests.

Results:
The Bland–Altman plot showed agreement between correct number of plates in EHB and ICP for the study subjects (bias, −0.25; LOA, −1.92 to 1.42). Agreement was also observed between the correct number of plates in EHB and ICP for the controls (bias, −0.01; LOA, −0.61 to 0.59) and CVD (bias, −0.50; LOA, −4.64 to 3.64) subjects. The sensitivity of EHB was 0.92 (95% CI 0.76–1.07) and the specificity of EHB was 1.00 (95% CI 1.00–1.00). Fifty-nine percent preferred EHB, 12% preferred ICP, and 29% had no preference.

Conclusions:
In healthy controls and patients with ocular pathology, there was an agreement of CVT results comparing EHB with ICP. Overall, the majority preferred EHB to ICP. These findings demonstrate that further testing is required to understand and improve the validity of smartphone CVT in subjects with ocular pathology.
EEG Factors After Pediatric Cardiac Arrest
Authors: Abend Nicholas S. , Wiebe Douglas J. , Xiao Rui , Massey Shavonne L. , Fitzgerald Mark , Fung France , Topjian Alexis A. 
Published: February 2018

Purpose:
We aimed to determine whether conventional standardized EEG features could be consolidated into a more limited number of factors and whether the derived factor scores changed during the acute period after pediatric cardiac arrest.

Methods:
Children resuscitated after cardiac arrest underwent conventional continuous EEG monitoring. The EEG was scored in 12-hour epochs for up to 72-hours after return of circulation by an electroencephalographer using standardized critical care EEG terminology. We performed a polychoric factor analysis to determine whether numerous observed EEG features could be represented by a smaller number of derived factors. Linear mixed-effects regression models and heat maps evaluated whether the factor scores remained stable across epochs.

Results:
We performed EEG monitoring in 89 consecutive children, which yielded 453 EEG segments. We identified two factors, which were not correlated. The background features were factor loaded with the features continuity, voltage, and frequency. The intermittent features were factor loaded with the features of seizures, periodic patterns, and interictal discharges. Factor scores were calculated for each EEG segment. Linear, mixed-effect, regression results indicated that the factor scores did not change over time for the background features factor (coefficient, 0.18; 95% confidence interval, 0.04–0.07; P = 0.52) or the intermittent features factor (coefficient, −0.003; 95% confidence interval, −0.02 to 0.01; P = 0.70). However, heat maps showed that some individual subjects did experience factor score changes over time, particularly if they had medium initial factor scores.

Conclusions:
Subsequent studies assessing whether EEG is informative for neurobehavioral outcomes after pediatric cardiac arrest could combine numerous EEG features into two factors, each reflecting multiple background and intermittent features. Furthermore, the factor scores would be expected to remain stable during the acute period for most subjects.
Cultural transmission in an ever-changing world: trial-and-error copying may be more robust than precise imitation
Authors: Truskanov Noa , Prat Yosef 
Published: February 2018

Cultural transmission facilitates the spread of behaviours within social groups and may lead to the establishment of stable traditions in both human and non-human animals. The fidelity of transmission is frequently emphasized as a core component of cultural evolution and as a prerequisite for cumulative culture. Fidelity is often considered a synonym of precise copying of observed behaviours. However, while precise copying guarantees reliable transmission in an ideal static world, it may be vulnerable to realistic variability in the actual environment. Here, we argue that fidelity may be more naturally achieved when the social learning mechanisms incorporate trial-and-error; and that the robustness of social transmission is thereby increased. We employed a simple model to demonstrate how culture that is produced through exact copying is fragile in an (even slightly) noisy world. When incorporating a certain degree of trial-and-error, however, cultures are more readily formed in a stochastic environment and are less vulnerable to rare ecological changes. We suggest that considering trial-and-error learning as a stabilizing component of social transmission may provide insights into cultural evolution in a realistic, variable, world.
This article is part of the theme issue ‘Bridging cultural gaps: interdisciplinary studies in human cultural evolution’.
Tetracyclines Modify Translation By Targeting Key Human rRNA Substructures
Authors: Mortison Jonathan D. , Schenone Monica , Myers Jacob A. , Zhang Ziyang , Chen Linfeng , Ciarlo Christie , Comer Eamon , Natchiar S. Kundhavai , Carr Steven A. , Klaholz Bruno P. , Myers Andrew G. 
Published: February 2018

SUMMARYApart from their antimicrobial properties, tetracyclines demonstrate clinically validated effects in the amelioration of pathological inflammation and human cancer. Delineation of the target(s) and mechanism(s) responsible for these effects, however, has remained elusive. Here, employing quantitative mass spectrometry-based proteomics, we identified human 80S ribosomes as targets of the tetracyclines Col-3 and doxycycline. We then developed in cell click selective crosslinking with RNA sequence profiling (icCL-Seq) to map binding sites for these tetracyclines on key human rRNA substructures at nucleotide resolution. Importantly, we found that structurally and phenotypically variant tetracycline analogs could chemically discriminate these rRNA binding sites. We also found that tetracyclines both subtly modify human ribosomal translation and selectively activate the cellular integrated stress response (ISR). Together, the data reveal that targeting of specific rRNA substructures, activation of the ISR, and inhibition of translation are correlated with the anti-proliferative properties of tetracyclines in human cancer cell lines.
The maternal effect geneWdscontrolsWolbachiatiter inNasonia
Authors: Funkhouser-Jones Lisa J. , van Opstal Edward J. , Sharma Ananya , Bordenstein Seth R. 
Published: February 2018

SUMMARYMaternal transmission of intracellular microbes is pivotal in establishing long-term, intimate symbioses. For germline microbes that exert negative reproductive effects on their hosts, selection can theoretically favor the spread of host genes that counteract the microbe’s harmful effects. Here, we leverage a major difference in bacterial (Wolbachia pipientis) titers between closely-related wasp species with forward genetic, transcriptomic, and cytological approaches to map two quantitative trait loci that suppress bacterial titers via a maternal effect. Fine mapping and knockdown experiments identify the geneWolbachia density suppressor(Wds), which dominantly suppresses bacterial transmission from mother to embryo.Wdsevolved by lineage-specific non-synonymous changes driven by positive selection. Collectively, our findings demonstrate that a genetically simple change arose by Darwinian selection in less than a million years to regulate maternally transmitted bacteria via a dominant, maternal effect gene.
Rare variants in the genetic background modulate the expressivity of neurodevelopmental disorders
Authors: Pizzo Lucilla , Jensen Matthew , Polyak Andrew , Rosenfeld Jill A. , Mannik Katrin , Krishnan Arjun , McCready Elizabeth , Pichon Olivier , Le Caignec Cedric , Van Dijck Anke , Pope Kate , Voorhoeve Els , Yoon Jieun , Stankiewicz Paweł , Cheung Sau Wai , Pazuchanics Damian , Huber Emily , Kumar Vijay , Kember Rachel , Mari Francesca , Curró Aurora , Castiglia Lucia , Galesi Ornella , Avola Emanuela , Mattina Teresa , Fichera Marco , Mandarà Luana , Vincent Marie , Nizon Mathilde , Mercier Sandra , Bénéteau Claire , Blesson Sophie , Martin-Coignard Dominique , Mosca-Boidron Anne-Laure , Caberg Jean-Hubert , Bucan Maja , Zeesman Susan , Nowaczyk Małgorzata J.M. , Lefebvre Mathilde , Faivre Laurence , Callier Patrick , Skinner Cindy , Keren Boris , Perrine Charles , Prontera Paolo , Marle Nathalie , Renieri Alessandra , Reymond Alexandre , Kooy R Frank , Isidor Bertrand , Schwartz Charles , Romano Corrado , Sistermans Erik , Amor David J. , Andrieux Joris , Girirajan Santhosh 
Published: February 2018

AbstractPurposeTo assess the contribution of rare variants in the genetic background towards variability of neurodevelopmental phenotypes in individuals with rare copy-number variants (CNVs) and gene-disruptive mutations.MethodsWe analyzed quantitative clinical information, exome-sequencing, and microarray data from 757 probands and 233 parents and siblings who carry disease-associated mutations.ResultsThe number of rare secondary mutations in functionally intolerant genes (second-hits) correlated with the expressivity of neurodevelopmental phenotypes in probands with 16p12.1 deletion (n=23, p=0.004) and in probands with autism carrying gene-disruptive mutations (n=184, p=0.03) compared to their carrier family members. Probands with 16p12.1 deletion and a strong family history presented more severe clinical features (p=0.04) and higher burden of second-hits compared to those with mild/no family history (p=0.001). The number of secondary variants also correlated with the severity of cognitive impairment in probands carrying pathogenic rare CNVs (n=53) or de novo mutations in disease genes (n=290), and negatively correlated with head size among 80 probands with 16p11.2 deletion. These second-hits involved known disease-associated genes such as SETD5, AUTS2, and NRXN1, and were enriched for genes affecting cellular and developmental processes.ConclusionAccurate genetic diagnosis of complex disorders will require complete evaluation of the genetic background even after a candidate gene mutation is identified.
Habitat loss is information loss: Species distribution models are compromised in anthropogenic landscapes
Authors: Dinnage Russell , Cardillo Marcel 
Published: February 2018

AbstractSpecies distribution models (SDMs) are valuable tools to estimate species’ distributions, but are vulnerable to biases in the probability of a species being observed. One such bias is habitat loss, which has affected a substantial and increasing proportion of the Earth. In regions of severe habitat loss, data on a species’ occurrence may represent a small, non-random subset of sites it once occupied. This could cause distorted reconstructions of species distributions, and misleading inferences of evolutionary and ecological processes. We present a statistical approach for quantifying the influence on SDMs of habitat loss, and generating distribution predictions that are robust to these biases. We explored some of the effects of accounting for habitat loss on inferences from common downstream biogeographic and ecological analysis methods.We used herbarium record data to model the distribution of 325 plant species in the genera Banksia and Hakea across Australia, using point process models. We accounted for biases in the models by including a proxy variable representing habitat loss, and compared the fit of models without this variable to those with it. We explored the influence of habitat loss by mapping biodiversity patterns predicted with and without accounting for it.Generally, accounting for habitat loss in SDMs led to increases in the mean area of modelled species distributions of ~10% for Banksia and ~12% for Hakea across Australia (in some cases, up to several 100,000 km2 increases in predicted range), with somewhat greater average increases (11% and 15%) for species in the southwest Australian biodiversity hotspot. Accounting for habitat loss leads to an increase in predicted species richness (Alpha and Gamma diversity), but a decrease in compositional turnover (Beta diversity), across most of Australia. Accounting for habitat loss in SDMs had minimal influence on a downstream macroevolutionary analysis (Age-Range Correlation) that utilizes species distributions, seemingly because exposure to habitat loss did not show a phylogenetic pattern in this taxonomic group.The influence of habitat loss on species distributions estimated with SDM is likely to be context-dependent and difficult to generalize, but will tend to cause underestimates of range sizes. This may have consequences for mapping spatial patterns of diversity and for some downstream analyses of biogeographic, evolutionary, or ecological processes, based on species distributions, as well as conservation measures that rely on accurate species mapping.
DeepHINT: Understanding HIV-1 integration via deep learning with attention
Authors: Hu Hailin , Xiao An , Zhang Sai , Li Yangyang , Shi Xuanling , Jiang Tao , Zhang Linqi , Zhang Lei , Zeng Jianyang 
Published: February 2018

AbstractMotivationHuman immunodeficiency virus type 1 (HIV-1) genome integration is closely related to clinical latency and viral rebound. In addition to human DNA sequences that directly interact with the integration machinery, the selection of HIV integration sites has also been shown to depend on the heterogeneous genomic context around a large region, which greatly hinders the prediction and mechanistic studies of HIV integration.ResultsWe have developed an attention-based deep learning framework, named DeepHINT, to simultaneously provide accurate prediction of HIV integration sites and mechanistic explanations of the detected sites. Extensive tests on a high-density HIV integration site dataset showed that DeepHINT can outperform conventional modeling strategies by automatically learning the genomic context of HIV integration solely from primary DNA sequence information. Systematic analyses on diverse known factors of HIV integration further validated the biological relevance of the prediction result. More importantly, in-depth analyses of the attention values output by DeepHINT revealed intriguing mechanistic implications in the selection of HIV integration sites, including potential roles of several basic helix-loop-helix (bHLH) transcription factors and zinc-finger proteins. These results established DeepHINT as an effective and explainable deep learning framework for the prediction and mechanistic study of HIV integration.AvailabilityDeepHINT is available as an open-source software and can be downloaded fromhttps://github.com/nonnerdling/DeepHINTContactlzhang20@mail.tsinghua.edu.cnandzengjy321@tsinghua.edu.cn
Peroxiredoxin-mediated HMGB1 oxidation and secretion in response to inflammatory stimuli
Authors: Sup Kwak Man , Sue Kim Hee , Lkhamsuren Khulan , Hun Kim Young , Gil Hahn Myung , Min Shin Jae , Ho Park In , Kyung Lee Se , Goo Rhee Sue , Shin Jeon-Soo 
Published: February 2018

AbstractThe nuclear protein HMGB1 (high mobility group box 1) is secreted by monocytesmacrophages in response to inflammatory stimuli and serves as a danger-associated molecular pattern. Acetylation and phosphorylation of HMGB1 are implicated in the regulation of its nucleocytoplasmic translocation for secretion, although inflammatory stimuli are also known to induce H2O2production. Here we show that H2O2-induced oxidation of HMGB1 that results in formation of an intramolecular disulphide bond between Cys23and Cys45is necessary and sufficient for its nucleocytoplasmic translocation and secretion. The oxidation is catalysed by peroxiredoxin I (PrxI) and PrxII, which are first oxidized by H2O2and then transfer their disulphide oxidation state to HMGB1. The disulphide form of HMGB1 showed a higher affinity for the nuclear exportin CRM1 compared with the reduced form. Lipopolysaccharide (LPS)–induced HMGB1 secretion was greatly attenuated in macrophages derived from PrxI or PrxII knockout mice, as was the LPS-induced increase in serum HMGB1 levels in these mice.
Robustness of Transposable Element regulation but no genomic shock observed in interspecificArabidopsishybrids
Authors: Göbel Ulrike , Arce Agustin , He Fei , Rico Alain , Schmitz Gregor , Meaux Juliette de 
Published: February 2018

AbstractThe merging of two divergent genomes in a hybrid is believed to trigger a “genomic shock”, disrupting gene regulation and transposable element (TE) silencing. Here, we tested this expectation by comparing the pattern of expression of transposable elements in their native and hybrid genomic context. For this, we sequenced the transcriptome of theArabidopsis thalianagenotype Col-0, theA. lyratagenotype MN47 and their F1 hybrid. Contrary to expectations, we observe that the level of TE expression in the hybrid is strongly correlated to levels in the parental species. We detect that at most 1.1% of expressed transposable elements belonging to two specific subfamilies change their expression level upon hybridization. Most of these changes, however, are of small magnitude. We observe that the few hybrid-specific modifications in TE expression are more likely to occur when TE insertions are close to genes. In addition, changes in epigenetic histone marks H3K9me2 and H3K27me3 following hybridization do not coincide with TEs with changed expression. Finally, we further examined TE expression in parents and hybrids exposed to severe dehydration stress. Despite the major reorganization of gene and TE expression by stress, we observe that hybridization does not lead to increased disorganization of TE expression in the hybrid. We conclude that TE expression is globally robust to hybridization and that the term “genomic shock” is no longerappropriate to describe the anticipated consequences of merging divergent genomes in a hybrid.