bluuebunny/crossref_metadata_2025_split huggingface dataset:
High resolution X-ray and NMR structural study of human T-cell immunoglobulin and mucin domain containing protein-3
Authors: Gandhi Amit K. , Kim Walter M. , Sun Zhen-Yu J. , Huang Yu-Hwa , Bonsor Daniel A. , Sundberg Eric J. , Kondo Yasuyuki , Wagner Gerhard , Kuchroo Vijay K. , Petsko Gregory , Blumberg Richard S. 
Published: November 2018

AbstractT-cell immunoglobulin and mucin domain containing protein-3 (TIM-3) is an important immune regulator. Here, we describe a novel high resolution (1.7 Å) crystal structure of the human (h)TIM-3 N-terminal variable immunoglobulin (IgV) domain with bound calcium (Ca++) that was confirmed by nuclear magnetic resonance (NMR) spectroscopy. Significant conformational differences were observed in the B-C, C′-C″ and C′-D loops of hTIM-3 compared to mouse (m)TIM-3, hTIM-1 and hTIM-4. Further, the conformation of the C-C′ loop of hTIM-3 was notably different from hTIM-4. Consistent with the known metal ion-dependent binding of phosphatidylserine (PtdSer) to mTIM-3 and mTIM-4, the NMR spectral analysis and crystal structure of Ca++-bound hTIM-3 revealed that residues in the hTIM-3 F-G loop coordinate binding to Ca++. In addition, we established a novel biochemical assay to define hTIM-3 functionality as determined by binding to human carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1). These studies provide new insights useful for understanding and targeting hTIM-3.
Discrimination of contagious and environmental strains of Streptococcus uberis in dairy herds by means of mass spectrometry and machine-learning
Authors: Esener Necati , Green Martin J. , Emes Richard D. , Jowett Benjamin , Davies Peers L. , Bradley Andrew J. , Dottorini Tania 
Published: November 2018

AbstractStreptococcus uberis is one of the most common pathogens of clinical mastitis in the dairy industry. Knowledge of pathogen transmission route is essential for the selection of the most suitable intervention. Here we show that spectral profiles acquired from clinical isolates using matrix-assisted laser desorption ionization/time of flight (MALDI-TOF) can be used to implement diagnostic classifiers based on machine learning for the successful discrimination of environmental and contagious S. uberis strains. Classifiers dedicated to individual farms achieved up to 97.81% accuracy at cross-validation when using a genetic algorithm, with Cohen’s kappa coefficient of 0.94. This indicates the potential of the proposed methodology to successfully support screening at the herd level. A global classifier developed on merged data from 19 farms achieved 95.88% accuracy at cross-validation (kappa 0.93) and 70.67% accuracy at external validation (kappa 0.34), using data from another 10 farms left as holdout. This indicates that more work is needed to develop a screening solution successful at the population level. Significant MALDI-TOF spectral peaks were extracted from the trained classifiers. The peaks were found to correspond to bacteriocin and ribosomal proteins, suggesting that immunity, growth and competition over nutrients may be correlated to the different transmission routes.
Selection and Validation of Novel RT-qPCR Reference Genes under Hormonal Stimuli and in Different Tissues of Santalum album
Authors: Yan Haifeng , Zhang Yueya , Xiong Yuping , Chen Qingwei , Liang Hanzhi , Niu Meiyun , Guo Beiyi , Li Mingzhi , Zhang Xinhua , Li Yuan , Teixeira da Silva Jaime A. , Ma Guohua 
Published: November 2018

AbstractReverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) is a widely used technique to investigate gene expression levels due to its high throughput, specificity, and sensitivity. An appropriate reference gene is essential for RT-qPCR analysis to obtain accurate and reliable results. To date, no reliable reference gene has been validated for the economically tropical tree, sandalwood (Santalum albumL.). In this study, 13 candidate reference genes, including 12 novel putative reference genes selected from a large set ofS.albumtranscriptome data, as well as the currently used β-actin gene (ACT), were validated in different tissues (stem, leaf, root and callus), as well as callus tissue under salicylic acid (SA), jasmonic acid methyl ester (MeJA), and gibberellin (GA) treatments using geNorm, NormFinder, BestKeeper, Delta Ct and comprehensive RefFinder algorithms. Several novel candidate reference genes were much more stable than the currently used traditional geneACT.ODDpaired withFbp1for SA treatment,CSAandFbp3for MeJA treatment,PP2CandFbp2for GA treatment, as well asFbp1combined withFbp2for the total of three hormone treatments were the most accurate reference genes, respectively.FAB1A, when combined withPP2C, was identified as the most suitable reference gene combination for the four tissues tested, while the combination ofHLMt,PPRandFAB1Awere the most optimal reference genes for all of the experimental samples. In addition, to verify our results, the relative expression level of theSaSSygene was evaluated by the validated reference genes and their combinations in the threeS.albumtissues and under MeJA treatment. The evaluated reference genes in this study will improve the accuracy of RT-qPCR analysis and will benefitS.albumfunctional genomics studies in different tissues and under hormone stimuli in the future.
Sensitization of renal carcinoma cells to TRAIL-induced apoptosis by rocaglamide and analogs
Authors: Nalli Ancy D. , Brown Lauren E. , Thomas Cheryl L. , Sayers Thomas J. , Porco John A. , Henrich Curtis J. 
Published: November 2018

AbstractRocaglamide has been reported to sensitize several cell types to TRAIL-induced apoptosis. In recent years, advances in synthetic techniques have led to generation of novel rocaglamide analogs. However, these have not been extensively analyzed as TRAIL sensitizers, particularly in TRAIL-resistant renal cell carcinoma cells. Evaluation of rocaglamide and analogs identified 29 compounds that are able to sensitize TRAIL-resistant ACHN cells to TRAIL-induced, caspase-dependent apoptosis with sub-µM potency which correlated with their potency as protein synthesis inhibitors and with loss of cFLIP protein in the same cells. Rocaglamide alone induced cell cycle arrest, but not apoptosis. Rocaglates averaged 4–5-fold higher potency as TRAIL sensitizers than as protein synthesis inhibitors suggesting a potential window for maximizing TRAIL sensitization while minimizing effects of general protein synthesis inhibition. A wide range of other rocaglate effects (e.g. on JNK or RAF-MEK-ERK signaling, death receptor levels, ROS, ER stress, eIF4E phosphorylation) were assessed, but did not contribute to TRAIL sensitization. Other than a rapid loss of MCL-1, rocaglates had minimal effects on mitochondrial apoptotic pathway proteins. The identification of structurally diverse/mechanistically similar TRAIL sensitizing rocaglates provides insights into both rocaglate structure and function and potential further development for use in RCC-directed combination therapy.
Mechanisms of fitness cost reduction for rifampicin-resistant strains with deletion or duplication mutations in rpoB
Authors: Brandis Gerrit , Hughes Diarmaid 
Published: November 2018

AbstractRifampicin resistance (RifR) is caused by mutations in rpoB, encoding the β-subunit of RNA polymerase. RifR mutations generally incur a fitness cost and in resistant isolates are frequently accompanied by compensatory mutations in rpoA, rpoB or rpoC. Previous studies of fitness compensation focused on RifR caused by amino acid substitutions within rpoB. RifR is also caused by deletion and duplication mutations in rpoB but it is not known whether or how such mutants can ameliorate their fitness costs. Using experimental evolution of Salmonella carrying RifR deletion or duplication mutations we identified compensatory amino acid substitution mutations within rpoA, rpoB or rpoC in 16 of 21 evolved lineages. Additionally, we found one lineage where a large deletion was compensated by duplication of adjacent amino acids (possibly to fill the gap within the protein structure), two lineages where mutations occurred outside of rpoABC, and two lineages where a duplication mutant reverted to the wild-type sequence. All but the two revertant mutants maintained the RifR phenotype. These data suggest that amino acid substitution mutations are the major compensatory mechanism regardless of the nature of the primary RifR mutation.
Immediate and persistent antidepressant-like effects of Chaihu-jia-Longgu-Muli-tang are associated with instantly up-regulated BDNF in the hippocampus of mice
Authors: Wang Xing , Chen Jie , Zhang Hailou , Huang Zhiheng , Zou Zhilu , Chen Yin , Sheng Lei , Xue Wenda , Tang Juanjuan , Wu Haoxin , Liu Hongquan , Chen Gang 
Published: November 2018

Abstract
Conventional antidepressants have a disadvantage in delayed onset of efficacy. Here, we aimed to evaluate the immediate and persistent antidepressant-like action of a classic herbal medicine Chaihu-jia-Longgu-Muli decoction (CLM) as well as the action of CLM on hippocampal brain-derived neurotrophic factor (BDNF) over time. CLM consists of Xiaochaihu decoction (XchD), Longgu-Muli (LM) and several other herbs. The contribution of constituent herbal formula XchD and other parts of CLM was also assessed. Following a single dose of CLM, tail suspension test (TST), forced swim test (FST), and novelty-suppressed feeding test (NSF) were performed. The antidepressant activity of XchD, its interaction with LM or remaining parts of CLM was also examined after a single administration. BDNF expression in the hippocampus was examined at 30 min and 24 hr post a single CLM. A single administration of half of clinical dose of CLM elicited antidepressant effects at TST 30 min post administration, and lasted for 72 hr. Furthermore, CLM also reduced the latency to eat in NSF test. A single proportional dose of XchD induced antidepressant effects at 30 min and lasted for 48 hr, whereas the effect lasted for 72 hr when combined with either LM or the remaining parts of CLM. BDNF expression increased at 30 min and persisted at least for 24 hr after a single dose of CLM. The results support that Chaihu-jia-Longgu-Muli decoction was capable to immediately and enduringly elicit antidepressant activity via enhancement of hippocampal BDNF expression, in which the constituent Xiaochaihu decoction played the primary role.
Bewegungsförderung in Deutschland: Akteure, Strukturen und Netzwerkentwicklung
Authors: Wäsche Hagen , Peters Stefan , Appelles Luisa , Woll Alexander 
Published: November 2018

ZusammenfassungBewegung unterstützt in vielfältiger Weise die Gesundheit von Menschen jeden Lebensalters. Dennoch ist die Prävalenz körperlicher Inaktivität in Deutschland hoch und die meisten Menschen erreichen den von der Weltgesundheitsorganisation empfohlenen Bewegungsumfang nicht. Um gezielte Maßnahmen zur Bewegungsförderung zu unterstützen, ist die Kenntnis der relevanten Akteure, Berufsgruppen und Multiplikatoren sowie deren struktureller Zusammenhang notwendig. Im Rahmen einer explorativen Untersuchung wurden 2 Ziele verfolgt: (1) die Identifikation relevanter Akteure, Berufsgruppen und Multiplikatoren der Bewegungsförderung in Deutschland und (2) die Analyse der strukturellen Vernetzung dieser Akteure sowie die Formulierung von Empfehlungen zur nachhaltigen Entwicklung eines nationalen Netzwerks der Bewegungsförderung. Hierzu wurden qualitative Experteninterviews, eine anschließende Netzwerkvisualisierung und eine Analyse zur Netzwerkentwicklung durchgeführt. Es zeigte sich, dass das Feld der Akteure im Bereich der Bewegungsförderung ausgesprochen heterogen und umfangreich hinsichtlich verschiedener Akteursformen, Gesellschaftsbereiche und Bezugsräume ist. Insgesamt konnten 128 Akteure identifiziert werden. Davon werden 22 Akteure in Schlüsselpositionen gesehen. Bei den Multiplikatoren wurden 19 aktuelle und 17 weitere potenzielle identifiziert. Die strukturelle Vernetzung der Akteure ist nur schwach ausgeprägt. Für eine zukünftige Netzwerkentwicklung konnten verschiedene Voraussetzungen, Vorteile und Barrieren herausgearbeitet werden. Daran anschließend werden Empfehlungen formuliert, welche zur Bildung und effektiven Steuerung eines nationalen Netzwerks der Bewegungsförderung beitragen. Die Studie ermöglicht eine erste differenzierte Betrachtung der Akteursstrukturen der Bewegungsförderung in Deutschland.
Supportive Infusions in Integrative Breast and Gynecological Oncology – Report on Patientsʼ Satisfaction and Self-reported Effects and Side Effects
Authors: Hack Carolin , Antoniadis Sophia , Beckmann Matthias , Brandl Anna , Fasching Peter , Hackl Janina , Langemann Hanna , Katja Stock , Weber Natalie , Theuser Anna-Katharin 
Published: November 2018

Abstract
Background During cancer therapy, many patients suffer from malnutrition or vitamin deficiency. Treatment for nutrition-related deficiencies should therefore include nutritional therapy and possibly oral or intravenous substitution of micronutrients. Little information exists on multinutrient infusion therapies. The aim of this study was to develop standardized infusion protocols for integrative medicine infusions with micronutrients (IMed infusions) and to report on side effects of the treatment and patientsʼ satisfaction with it.
Methods For the IMed consultancy service, four special formulas for intravenous use were developed in cooperation with the pharmacy at Erlangen University Hospital. A retrospective cross-sectional study was conducted between October 2015 and January 2018 in which 45 patients with gynecological or breast cancer (BC) and IMed infusion therapy were included. Follow-up data were obtained from 20 patients using a standardized questionnaire on IMed infusions.
Results A total of 280 IMed infusions were administered in the study period. The majority of the patients received an IMed regeneration infusion (78%). The majority of the patients had BC and were receiving chemotherapy. Most patients reported a high or very high level of satisfaction with the organization (60%), general treatment (65%) and counseling (85%). Subjective improvement in their disease-related and therapy-induced symptoms, such as fatigue, polyneuropathy and physical efficiency, was reported by 70% of the patients, while 75% reported a subjective increase in quality of life. Side effects were rare and minor.
Conclusions Therapy with IMed infusions in women with BC or gynecological cancer requires the same standards set for drug therapy. Although vitamins represent dietary supplements, appropriate assessment of the patientʼs medical history is needed and patients must receive appropriate information. For this purpose, standardized processes, as in the context of an IMed consultancy service, are helpful.
A Review of Plants Used in South African Traditional Medicine for the Management and Treatment of Hypertension
Authors: Balogun Fatai , Ashafa Anofi 
Published: November 2018

AbstractSouth Africa contains 9% of the worldʼs higher plants, and despite its rich biodiversity, it has one of the highest prevalence of hypertension in Africa. This review provides information on medicinal plants embraced in South Africa for hypertension management, with the aim of reporting pharmacological information on the indigenous use of these plants as antihypertensives. This review not only focuses on the activity of antihypertensive medicinal plants but also reports some of its phytochemical constituents and other ethnopharmacological and therapeutic properties. Information obtained from scientific and or unpublished databases such as Science Direct, PubMed, SciFinder, JSTOR, Google Scholar, Web of Science, and various books revealed 117 documented antihypertensive plant species from 50 families. Interestingly, Asteraceae topped the list with 16 species, followed by Fabaceae with 8 species; however, only 25% of all plant species have demonstrated antihypertensive effects originating from both in vitro and in vivo studies, lending credence to their folkloric use. Only 11 plant species reportedly possess antihypertensive properties in animal models, with very few species subjected to analytical processes to reveal the identity of their bioactive antihypertensive compounds. In this review, we hope to encourage researchers and global research institutions (universities, agricultural research councils, and medical research councils), particularly those showing an interest in natural products, for the need for concerted efforts to undertake more studies aimed at revealing the untapped potential of these plants. These studies are very important for the development of new pharmaceuticals of natural origin useful for the management of hypertension.
Does Time of Wound Complication after Cesarean Delivery Differ by Type of Skin Closure?
Authors: Cooper Shontreal M. , Blanchard Christina T. , Szychowski Jeffery M. , Tita Alan T. N. 
Published: November 2018

Objective A high proportion of postcesarean wound complications occur after patients have been discharged from the hospital, increasing personal and health care costs. We undertook this study to evaluate the association between skin closure methods (suture vs. staple) following a cesarean delivery and the frequency of wound complications occurring after hospital discharge.
Study Design This is a secondary analysis of data from a randomized trial in which women undergoing cesarean delivery at ≥24 weeks' gestation were randomized to receive metallic staples or subcuticular suture for skin closure after surgery. Staples were removed at the time of hospital discharge on postoperative days 3 to 4 for Pfannenstiel incisions or days 7 to 10 for vertical. The primary outcome for this analysis was any wound complication occurring after hospital discharge. Wound complications were infections or any wound disruption without infection (including seromas and hematomas). Associations were examined using chi-square and Fisher's exact tests, as appropriate, and multivariable logistic regression.
Results A total of 350 patients with follow-up through 4 to 6 weeks postpartum were included in the analysis: n = 171 received suture closure and n = 179 received staples. In the primary trial, wound complications occurred in 14.5% (n = 26) of individuals with staples and 5.9% (n = 10) with sutures (p = 0.008). Twenty-one (58.3%) of the 36 wound complications occurred after hospital discharge. The incidence of wound complications occurring after hospital discharge was 6.7% (n = 12) of patients receiving staples and 5.3% (n = 9) of those receiving sutures; p = 0.57; relative risk [95% confidence interval]: 1.27 [0.55–2.95]). After multivariable adjustment, type of skin closure method was not associated with wound complication after discharge from the hospital (odds ratio: 1.29; 0.52–3.17).
Conclusion Although suture closure compared with staples was associated with fewer wound complications after cesarean delivery, we found no significant differences between closure types in the frequency of wound complications occurring after hospital discharge.
Association between the Degree of Twin Birthweight Discordance and Perinatal Outcomes
Authors: Kim Lena H. , Caughey Aaron B. , Yee Lynn M. , Cheng Yvonne W. 
Published: November 2018

Background Twin birthweight discordance is associated with adverse outcomes.
Objective To determine what degree of twin birthweight discordance is associated with adverse outcomes.
Study Design This is a retrospective cohort study of twins with vertex twin A delivered vaginally at 36 to 40 weeks (U.S. Vital Statistics Natality birth certificate registry data 2012–2014). The primary outcome was a composite of neonatal morbidity: 5-minute Apgar < 7, neonatal intensive care unit admission, neonatal mechanical ventilation > 6 hours, neonatal seizure, and/or neonatal transport to a higher level of care. Effect estimates were expressed as incidence rate and adjusted odds ratio (aOR) controlling for confounding using multivariate clustered analysis for between-pair effects, and multilevel random effect generalized estimating equation regressions to account for within-pair effects. We adjusted for sex discordance, breech delivery of the second twin, maternal race/ethnicity, nulliparity, age, marital status, obesity, and socioeconomic status.
Results In comparison to birthweight discordance of ≤20%, aORs with 95% confidence intervals (CIs) by weight discordance of the primary outcome among 27,276 twin deliveries were as follows: 20.01 to 25% (aOR: 1.46 [95% CI: 1.29–1.65]); 25.01 to 30% (aOR: 1.96 [95% CI: 1.68–2.29]); and 30.01 to 60% (aOR: 2.97 [95% CI: 2.52–3.50]).
Conclusion Twin birthweight discordance >20% was associated with increased odds of adverse neonatal outcome.
Clicks as discourse markers in Peninsular Spanish
Authors: Pinto Derrin , Vigil Donny 
Published: November 2018

Abstract
The research on clicks in Spanish has been surprisingly scarce. Using a data corpus of 764 clicks produced by 20 speakers from
Spain, we approach clicks as discourse markers that execute up to five different functions. Since clicks themselves do not possess
any core semantic meaning, their contribution to the discourse depends solely on their placement and the contextual features with
which they occur. In addition to an analysis of their functions, we report on several elements present in the contiguous pre- and
post-click environment, including pauses, fillers and prolonged syllables. The results indicate significant findings regarding how
click functions relate to certain elements in the click environment.
Structure elucidation of ostreocin-A and ostreocin-E1, novel palytoxin analogs produced by the dinoflagellate Ostreopsis siamensis, using LC/Q-TOF MS
Authors: Terajima Takehito , Uchida Hideaki , Abe Naoki , Yasumoto Takeshi 
Published: November 2018

ABSTRACT
Palytoxin analogs are marine toxins with large complex polyol structures. A benthic dinoflagellate Ostreopsis siamensis produces more than ten palytoxins (ostreocins, OSTs). The limited sample availability of minor OSTs restricts the definition of their chemical structures. The present investigation characterizes structures of two minor OSTs, i.e., ostreocin-A (OSTA) and ostreocin-E1 (OSTE1), using ostreocin-D (OSTD) as a reference compound, by liquid chromatography/quadrupole-time-of-flight mass spectrometry. The molecular formulas of OSTA and OSTE1 were C127H219N3O54 and C127H217N3O52, respectively. Compared to OSTD, OSTA has an extra oxygen atom whereas OSTE1 lacks one oxygen atom and two hydrogen atoms. The MS/MS experiments (precursor ions: [M + H]+ and [M-H]−) suggested a hydroxyl substitution at C82 in OSTA and alteration(s) between C53 and C100 in OSTE1. Further analysis of structural details in OSTE1 was performed through a pseudo-MS3 experiment (precursor ion: m/z 1432.748). Accordingly, the planar structures of OSTA and OSTE1 were assigned to 42,82-dihydroxy-3,26-didemethyl-19,44-dideoxypalytoxin and 42-hydroxy-3,26-didemethyl-19,44,73-trideoxypalytoxin-72-ene, respectively.
Abbreviations:CID: collision induced dissociation; HR-LC/MS/MS: high-resolution liquid chromatography/tandem mass spectrometry; LC/ESI/Q-TOF MS: liquid chromatography/quadrupole time-of-flight mass spectrometry equipped with an electrospray ionization source; NMR: nuclear magnetic resonance; OSTs: ostreocins; OSTA: ostreocin-A; OSTB: ostreocin-B; OSTD: ostreocin-D; OSTE1: ostreocin-E1; OVTX-a: ovatoxin-a; OVTXs: ovatoxins; PLTX: palytoxin