bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Cell Penetrating Peptide from SOCS-1 Prevents Ocular Damage in Experimental Autoimmune Uveitis
Authors: Ahmed Chulbul M. , Massengill Michael T. , Ildefonso Cristhian J. , Johnson Howard M. , Lewin Alfred S. 
Published: May 2018

AbstractWe describe an immunosuppressive peptide corresponding to the kinase inhibitory region (KIR) of the intracellular checkpoint protein suppressor of cytokine signaling 1 (SOCS-1) that binds to the phospho-tyrosine containing regions of the tyrosine kinases JAK2 and TYK2 and the adaptor protein MAL, and thereby inhibits signaling downstream from these signaling mediators. The peptide, SOCS1-KIR, is thus capable of downregulating overactive JAK/STAT or NF-kB signaling in somatic cells, including those in many compartments of the eye. Attachment of poly-arginine to this peptide (R9-SOCS1-KIR) allows it to penetrate the plasma membrane in aqueous media. R9-SOCS1-KIR was tested in ARPE-19 cells and was found to attenuate mediators of inflammation by blocking the inflammatory effects of IFNγ, TNFα, or IL-17A. R9-SOCS1-KIR also protected against TNFα or IL-17A mediated damage to the barrier properties of ARPE-19 cells, as evidenced by immunostaining with the tight junction protein, zona occludin 1 (ZO-1), and measurement of transepithelial electrical resistance (TEER). Experimental autoimmune uveitis (EAU) was generated in B10.RIII mice using a peptide of interphotoreceptor retinal binding protein (IRBP161-180) as immunogen. Topical administration of R9-SOCS1-KIR protected ocular structure and function as seen by fundoscopy, optical coherence tomography (OCT), and electroretinography (ERG). The ability R9-SOCS1-KIR to suppress ocular inflammation and preserve barrier properties of retinal pigment epithelium makes it a potential candidate for aqueous treatment of autoimmune uveitis.Highlightspeptide corresponding to the kinase inhibitory region of SOCS-1 linked to poly-arginine (R9-SOCS1-KIR) and its inactive control peptide were chemically synthesized.R9-SOCS1-KIR attenuated pro-inflammatory effects of IFNγ, TNFα, and IL-17 in ARPE-19 cells, thus showing a simultaneous inhibition Th1 and Th17 cell functions.Damage to barrier properties of ARPE-19 cells caused by TNFα or IL-17 was prevented in the presence of R9-SOCS1-KIR.Topical administration of R9-SOCS1-KIR prevented ocular damage in a mouse model of experimental autoimmune uveitis.
Improved localizers and anatomical images to enable phosphorus magnetic resonance spectroscopy of liver metastasis at 7T
Authors: Rivera Debra , Kalleveen Irene , Arteaga de Castro Catalina , van Laarhoven Hanneke , Klomp Dennis , van der Kemp Wybe , Stoker Jaap , Nederveen Aart 
Published: May 2018

ABSTRACTPhosphorus spectroscopy (31P) at 7T (300 MHz) enables clinically-relevant spatial resolutions and time scales with high potential for monitoring response to cancer treatment. However, at 7T collecting a radiological-grade anatomical image of the liver—which is required for performing localized 31P spectroscopy—presents a challenge. Unlike lower field-strength scanners, there is no body coil in the bore of the 7T and despite inadequate penetration depth (<10 cm), surface coils are the current state-of-the-art for acquiring anatomical (1H) images. Therefore, thus far, high field 31P spectroscopy has been limited to diffuse liver disease. However, the use of antennas enable improved penetration depths at 300 MHz, and when combined with parallel transmit, can enable body imaging at 7T. We have developed a protocol for imaging liver metastases of patients using parallel transmit and 31P spectroscopy at 7T. We used a custom-made liver coil consisting of eight 30-cm dipole antennas tuned to the proton (300 MHz) frequency, and two partially overlapping 20-cm-diameter loops tuned for 31P (120 MHz). The field of view afforded by the two antennas underneath the 31P loops is not sufficient to image the complete boundaries of the liver for chemical shift imaging (CSI) planning and region-of-interest-based B0 shimming. The liver and full axial slice of the abdomen was imaged with eight transmit/receive antennas using parallel transmit B1-shimming to overcome image voids. Through the use of antennas we overcome the challenges for multi-parametric body imaging, and can begin to explore the possibility of monitoring the response of patients with liver metastasis to cancer treatments.ABBREVIATIONS(PDE)Phosphodiester(GPE)Glycerophosphoethanolamine(GPC)Glycerophosphocholine(PME)Phosphomonoesther(PC)Phosphocholine(PE)Phosphoethanalomine(PI)Inorganic Phosphate(PCR)Phosphocreatine(PTC)Phophotidylcholine(CSI)Chemical Shift Imaging(GE)Gradient Echo(L)Left(R)Right(H)Head(F)Foot(A)Anterior(P)Posterior(TR)Repetition Time(TE)Echo Time
Inward tubulation of the plasma membrane expedites membrane exchange and receptor presentation
Authors: Yao Long-fang , Zhou Li , Zhang Ruilin , Cai Liang 
Published: May 2018

AbstractThe plasma membrane is a crucial barrier between the cell and its external environment, and it also enables efficient passage of materials and information. Membrane vesicle trafficking allows precise delivery of materials but is rather inefficient. The mechanism for efficient membrane exchange remains elusive. Here we describe inward tubulation of the plasma membrane (PM tubes) that extends deep into the cytoplasm. These widespread PM tubes elongate along microtubules and are stabilized by actin filaments and cholesterol. PM tubes are preferred sites for connection between the endoplasmic reticulum and the plasma membrane. PM tubes facilitate receptor presentation at the surface of cells, possibly also shortening the distance for transported cargo to reach the external environment.In BriefA new type of tubular membrane structures was discovered in cells, revealing a shortcut that cells employ to expedite material exchange with their external environment.HighlightsInward tubulation of the plasma membrane (PM tubes), transiently interacts with the Golgi apparatusMicrotubule side-binding proteins pull PM tubes, while actin filaments and cholesterol stabilize PM tubesPM tubes are preferred sites where ER-PM contacts form in response to increased cytoplasmic calcium concentrationPM tubes are preferred sites for the surface presentation of GLUT1 upon glucose deprivation
Detecting differential transcription factor activity from ATAC-seq data
Authors: Tripodi Ignacio J. , Allen Mary A. , Dowell Robin D. 
Published: May 2018

AbstractTranscription factors are managers of the cellular factory, and key components to many diseases. Many non-coding single nucleotide polymorphisms affect transcription factors, either by directly altering the protein or its functional activity at individual binding sites. Here we first briefly summarize high throughput approaches to studying transcription factor activity. We then demonstrate, using published chromatin accessibility data (specifically ATAC-seq), that the genome wide profile of TF recognition motifs relative to regions of open chromatin can determine the key transcription factor altered by a perturbation. Our method of determining which TF are altered by a perturbation is simple, quick to implement and can be used when biological samples are limited. In the future, we envision this method could be applied to determining which TFs show altered activity in response to a wide variety of drugs and diseases.
Observed Antibody Space: a resource for data mining next generation sequencing of antibody repertoires
Authors: Kovaltsuk Aleksandr , Leem Jinwoo , Kelm Sebastian , Snowden James , Deane Charlotte M. , Krawczyk Konrad 
Published: May 2018

AbstractAntibodies are immune system proteins that recognize noxious molecules for elimination. Their sequence diversity and binding versatility have made antibodies the primary class of biopharmaceuticals. Recently it has become possible to query their immense natural diversity using next-generation sequencing of immunoglobulin gene repertoires (Ig-seq). However, Ig-seq outputs are currently fragmented across repositories and tend to be presented as raw nucleotide reads, which means nontrivial effort is required to reuse the data for analysis. To address this issue, we have collected Ig-seq outputs from 53 studies, covering more than half a billion antibody sequences across diverse immune states, organisms and individuals. We have sorted, cleaned, annotated, translated and numbered these sequences and make the data available via our Observed Antibody Space (OAS) resource at antibodymap.org. The data within OAS will be regularly updated with newly released Ig-seq datasets. We believe OAS will facilitate data mining of immune repertoires for improved understanding of the immune system and development of better biotherapeutics.
High-resolution analysis of the peptidoglycan composition inStreptomyces coelicolor
Authors: van der Aart Lizah T. , Spijksma Gerwin K. , Harms Amy , Vollmer Waldemar , Hankemeier Thomas , van Wezel Gilles P. 
Published: May 2018

ABSTRACTThe bacterial cell wall maintains cell shape and protects against bursting by the turgor. A major constituent of the cell wall is peptidoglycan (PG), which is continuously modified to allow cell growth and differentiation through the concerted activity of biosynthetic and hydrolytic enzymes. Streptomycetes are Gram-positive bacteria with a complex multicellular life style alternating between mycelial growth and the formation of reproductive spores. This involves cell-wall remodeling at apical sites of the hyphae during cell elongation and autolytic degradation of the vegetative mycelium during the onset of development and antibiotic production. Here, we show that there are distinct differences in the cross-linking and maturation of the PG between exponentially growing vegetative hyphae and the aerial hyphae that undergo sporulation. LC-MS/MS analysis identified over 80 different muropeptides, revealing that major PG hydrolysis takes place over the course of mycelial growth. Half of the dimers lack one of the disaccharide units in transition-phase cells, most likely due to autolytic activity. De-acetylation of MurNAc to MurN was particularly pronounced in spores, suggesting that MurN plays a role in spore development. Taken together, our work highlights dynamic and growth phase-dependent construction and remodeling of PG inStreptomyces.IMPORTANCEStreptomycetes are bacteria with a complex lifestyle, which are model organisms for bacterial multicellularity. From a single spore a large multigenomic, multicellular mycelium is formed, which differentiates to form spores. Programmed cell death is an important event during the onset of morphological differentiation. In this work we provide new insights into the changes in the peptidoglycan architecture over time, highlighting changes over the course of development and between growing mycelia and spores. This revealed dynamic changes in the peptidoglycan when the mycelia age, showing extensive PG hydrolysis and in particular an increase in the proportion of 3-3-cross-links. Additionally, we identified a muropeptide that is highly abundant specifically in spores, which may relate to dormancy and germination.
Price and perceived product quality: a comparison of denim jeans in three price categories
Authors: Ghaani Farashahi Behnoosh , Easter Elizabeth , Annett-Hitchcock Kate 
Published: May 2018

Purpose
The purpose of this paper is to compare a set of product specifications to evaluate appearance and performance characteristics of denim jeans at three price categories, and identify any relationships between price and product quality.

Design/methodology/approach
This research is as a quasi-experimental laboratory study. The product specifications of jeans are identified. Next, the appearance and performance characteristics of jeans are examined initially and after one and five repeated laundering cycles. The data are analyzed within and between each price category to identify any possible relationship between price and product quality.

Findings
The price category of jeans does not necessarily reflect different dimensions of product quality. Although higher priced jeans had superior product specifications and visual appearance, they did not show superior performance with respect to all elements of fit, durability, and color performance when these three factors were measured through laboratory testing.

Research limitations/implications
The limitations of this study from a research perspective include a small sample size, gender-focused sample selection. and the focus on only three retail categories. These limitations impact the generalizability of the results but could serve as a basis for similar studies. The evaluated product quality attributes were limited to intrinsic/measurable characteristics. Future studies should consider the extrinsic attributes of quality, especially as they are related to consumer’s purchasing decision.

Practical implications
Retailers in moderate and budget price categories can benefit from educating consumers about the quality attributes of jeans that would ultimately influence their post-purchase experience and are not necessarily related to the product’s price category. Educators can use this information to assist in teaching students about the multiple dimensions of materials and assembly choices, and how this will impact their final products as they are learning the apparel product development process.

Originality/value
The focus of this study on the quantification of intrinsic product attributes is unique and provides measurable data for product evaluation by consumer researchers and industry. The results of this research identify the strengths and weaknesses in the appearance and performance characteristics of jeans in different price categories, and how those may affect consumers’ purchase intention.
Taking the technical microbiome into the next decade
Authors: De Vrieze Jo , Boon Nico , Verstraete Willy 
Published: May 2018

SummaryThe ‘microbiome’ has become a buzzword. Multiple new technologies allow to gather information about microbial communities as they evolve under stable and variable environmental conditions. The challenge of the next decade will be to develop strategies to compose and manage microbiomes. Here, key aspects are considered that will be of crucial importance for future microbial technological developments. First, the need to deal not only with genotypes but also particularly with phenotypes is addressed. Microbial technologies are often highly dependent on specific core organisms to obtain the desired process outcome. Hence, it is essential to combine omics data with phenotypic information to invoke and control specific phenotypes in the microbiome. Second, the development and application of synthetic microbiomes is evaluated. The central importance of the core species is a no‐brainer, but the implementation of proper satellite species is an important route to explore. Overall, for the next decade, microbiome research should no longer almost exclusively focus on its capacity to degrade and dissipate but rather on its remarkable capability to capture disordered components and upgrade them into high‐value microbial products. These products can become valuable commodities in the cyclic economy, as reflected in the case of ‘reversed sanitation’, which is introduced here.
HTRA1, an age‐related macular degeneration protease, processes extracellular matrix proteins EFEMP1 and TSP1
Authors: Lin Michael K. , Yang Jin , Hsu Chun Wei , Gore Anuradha , Bassuk Alexander G. , Brown Lewis M. , Colligan Ryan , Sengillo Jesse D. , Mahajan Vinit B. , Tsang Stephen H. 
Published: May 2018

SummaryHigh‐temperature requirement protein A1 (HTRA1) is a serine protease secreted by a number of tissues including retinal pigment epithelium (RPE). A promoter variant of the gene encoding HTRA1 is part of a mutant allele that causes increased HTRA1 expression and contributed to age‐related macular degeneration (AMD) in genomewide association studies. AMD is characterized by pathological development of drusen, extracellular deposits of proteins and lipids on the basal side of RPE. The molecular pathogenesis of AMD is not well understood, and understanding dysregulation of the extracellular matrix may be key. We assess the high‐risk genotype at 10q26 by proteomic comparison of protein levels of RPE cells with and without the mutation. We show HTRA1 protein level is increased in high‐risk RPE cells along with several extracellular matrix proteins, including known HTRA1 cleavage targets LTBP‐1 and clusterin. In addition, two novel targets of HTRA1 have been identified: EFEMP1, an extracellular matrix protein mutated in Doyne honeycomb retinal dystrophy, a genetic eye disease similar to AMD, and thrombospondin 1 (TSP1), an inhibitor of angiogenesis. Our data support the role of RPE extracellular deposition with potential effects in compromised barrier to neovascularization in exudative AMD.
Imaging resilience and recovery in alcohol dependence
Authors: Charlet Katrin , Rosenthal Annika , Lohoff Falk W. , Heinz Andreas , Beck Anne 
Published: May 2018

AbstractBackground and aimsResilience and recovery are of increasing importance in the field of alcohol dependence (AD). This paper describes how imaging studies in man can be used to assess the neurobiological correlates of resilience and, if longitudinal, of disease trajectories, progression rates and markers for recovery to inform treatment and prevention options.MethodsOriginal papers on recovery and resilience in alcohol addiction and its neurobiological correlates were identified from PubMed and have been analyzed and condensed within a systematic literature review.ResultsFindings deriving from functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) studies have identified links between increased resilience and less task‐elicited neural activation within the basal ganglia, and benefits of heightened neural pre‐frontal cortex (PFC) engagement regarding resilience in a broader sense; namely, resilience against relapse in early abstinence of AD. Furthermore, findings consistently propose at least partial recovery of brain glucose metabolism and executive and general cognitive functioning, as well as structural plasticity effects throughout the brain of alcohol‐dependent patients during the course of short‐, medium‐ and long‐term abstinence, even when patients only lowered their alcohol consumption to a moderate level. Additionally, specific factors were found that appear to influence these observed brain recovery processes in AD, e.g. genotype‐dependent neuronal (re)growth, gender‐specific neural recovery effects, critical interfering effects of psychiatric comorbidities, additional smoking or marijuana influences or adolescent alcohol abuse.ConclusionsNeuroimaging research has uncovered neurobiological markers that appear to be linked to resilience and improved recovery capacities that are furthermore influenced by various factors such as gender or genetics. Consequently, future system‐oriented approaches may help to establish a broad neuroscience‐based research framework for alcohol dependence.
What is the effect of physical activity on duration and mode of delivery? Secondary analysis from the Norwegian Fit for Delivery trial
Authors: Sanda Birgitte , Vistad Ingvild , Sagedal Linda R. , Haakstad Lene A.H. , Lohne‐Seiler Hilde , Torstveit Monica K. 
Published: May 2018

AbstractIntroductionThe beneficial effects of physical activity during pregnancy for the mother and offspring have been reported by several studies but there are conflicting results concerning the possible effect of physical activity on the course of labor and risk of cesarean delivery. This study presents secondary analyses from the Norwegian Fit for Delivery randomized controlled trial, aiming at studying the effect of a lifestyle intervention including group exercise classes, as well as the possible influence of physical activity level in late pregnancy, on labor outcomes.Material and methodsHealthy nulliparous women with singleton pregnancy were randomized to an intervention group, n = 303 (dietary counseling and twice‐weekly exercise classes) or a control group, n = 303 (standard care). The participants were analyzed both by randomization and as a cohort comparing women with lowest (quartile 1, 0 metabolic equivalent of task‐hours moderate‐to‐vigorous physical activity/week) (n = 140) vs. highest (quartile 4, ≥16 metabolic equivalent of task‐hours moderate‐to‐vigorous physical activity/week) (n = 131) physical activity level in late pregnancy, assessed with the International Physical Activity Questionnaire.ResultThe intervention group had a longer first stage of labor compared with the control group (293 ± 202 min vs. 257 ± 181 min, p = 0.030). No differences between the randomization groups were seen for time spent in second stage of labor, prolonged labor or mode of delivery. In the total sample, women with the highest physical activity level had lower odds ratio (OR) of acute cesarean delivery (OR 0.33, 95% CI 0.11–0.97, p = 0.044) than did those with the lowest physical activity‐level.ConclusionA significantly longer first stage of labor was observed in the intervention group than in the control group. A high physical activity level in late pregnancy was associated with lower odds of acute cesarean delivery compared with a low physical activity level.
Hospital readmissions, mortality and potentially inappropriate prescribing: a retrospective study of older adults discharged from hospital
Authors: Counter David , Millar James W. T. , McLay James S. 
Published: May 2018

AimsApplying version 2 of the STOPP/START criteria to discharge prescriptions of older adults discharged from a general medical unit, the aim of this study is to assess potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) and their association with hospital readmission and mortality.MethodsDischarge medications, co‐morbidities and patient demographics were recorded over an 8‐month period for consecutive emergency admissions of patients aged ≥65 years. PIMs and PPOs were identified using version 2 of the STOPP/START criteria. Multivariate analysis for association of PIMs and PPOs with re‐admissions and mortality during the follow‐up period were assessed using binary logistic regression.ResultsData for 259 patients with a mean age of 77 (65–99, 51% female) were analysed. At discharge, the mean number of co‐morbidities and medications per patient were 5.4 (SD: 2.1 range: 0–14) and 9.3 (SD: 4.0 range: 1–31) respectively. During the follow‐up period (mean 41.5 months, SD: 2.0 range: 38–46 months), 50.2% of patients had died and the median number of readmissions was two (IQR: 1–4 range: 0–33). Prescription of more than five medications was significantly associated with PIMs and PPOs (OR: 2.75, 95% CI: 1.34–5.62 and OR 3.20, 95% CI: 1.57–6.54 respectively). Presence of a PIM was associated with three or more readmissions (OR: 2.43 95% CI: 1.19–4.98) and PPOs with mortality (OR: 1.88, 95% CI: 1.09–3.27).ConclusionsUsing version 2 of the STOPP/START criteria, the presence of PIMs and/or PPOs in older adults discharged from hospital is significantly associated with repeated hospital admissions and mortality respectively.