bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilization of a combined EEG/NIRS system to predict driver drowsiness
Authors: Nguyen Thien , Ahn Sangtae , Jang Hyojung , Jun Sung Chan , Kim Jae Gwan 
Published: March 2017

AbstractThe large number of automobile accidents due to driver drowsiness is a critical concern of many countries. To solve this problem, numerous methods of countermeasure have been proposed. However, the results were unsatisfactory due to inadequate accuracy of drowsiness detection. In this study, we introduce a new approach, a combination of EEG and NIRS, to detect driver drowsiness. EEG, EOG, ECG and NIRS signals have been measured during a simulated driving task, in which subjects underwent both awake and drowsy states. The blinking rate, eye closure, heart rate, alpha and beta band power were used to identify subject’s condition. Statistical tests were performed on EEG and NIRS signals to find the most informative parameters. Fisher’s linear discriminant analysis method was employed to classify awake and drowsy states. Time series analysis was used to predict drowsiness. The oxy-hemoglobin concentration change and the beta band power in the frontal lobe were found to differ the most between the two states. In addition, these two parameters correspond well to an awake to drowsy state transition. A sharp increase of the oxy-hemoglobin concentration change, together with a dramatic decrease of the beta band power, happened several seconds before the first eye closure.
Anordrin Eliminates Tamoxifen Side Effects without Changing Its Antitumor Activity
Authors: Gu Wenwen , Xu Wenping , Sun Xiaoxi , Zeng Bubing , Wang Shuangjie , Dong Nian , Zhang Xu , Chen Chengshui , Yang Long , Chen Guowu , Xin Aijie , Ni Zhong , Wang Jian , Yang Jun 
Published: March 2017

AbstractTamoxifen is administered for estrogen receptor positive (ER+) breast cancers, but it can induce uterine endometrial cancer and non-alcoholic fatty liver disease (NAFLD). Importantly, ten years of tamoxifen treatment has greater protective effect against ER+ breast cancer than five years of such treatment. Tamoxifen was also approved by the FDA as a chemopreventive agent for those deemed at high risk for the development of breast cancer. The side effects are of substantial concern because of these extended methods of tamoxifen administration. In this study, we found that anordrin, marketed as an antifertility medicine in China, inhibited tamoxifen-induced endometrial epithelial cell mitosis and NAFLD in mouse uterus and liver as an anti-estrogenic and estrogenic agent, respectively. Additionally, compared with tamoxifen, anordiol, the active metabolite of anordrin, weakly bound to the ligand binding domain of ER-α. Anordrin did not regulate the classic estrogen nuclear pathway; thus, it did not affect the anti-tumor activity of tamoxifen in nude mice. Taken together, these data suggested that anordrin could eliminate the side effects of tamoxifen without affecting its anti-tumor activity.
Single-molecule studies reveal reciprocating of WRN helicase core along ssDNA during DNA unwinding
Authors: Wu Wen-Qiang , Hou Xi-Miao , Zhang Bo , Fossé Philippe , René Brigitte , Mauffret Olivier , Li Ming , Dou Shuo-Xing , Xi Xu-Guang 
Published: March 2017

AbstractWerner syndrome is caused by mutations in the WRN gene encoding WRN helicase. A knowledge of WRN helicase’s DNA unwinding mechanism in vitro is helpful for predicting its behaviors in vivo, and then understanding their biological functions. In the present study, for deeply understanding the DNA unwinding mechanism of WRN, we comprehensively characterized the DNA unwinding properties of chicken WRN helicase core in details, by taking advantages of single-molecule fluorescence resonance energy transfer (smFRET) method. We showed that WRN exhibits repetitive DNA unwinding and translocation behaviors on different DNA structures, including forked, overhanging and G-quadruplex-containing DNAs with an apparently limited unwinding processivity. It was further revealed that the repetitive behaviors were caused by reciprocating of WRN along the same ssDNA, rather than by complete dissociation from and rebinding to substrates or by strand switching. The present study sheds new light on the mechanism for WRN functioning.
Subglacial discharges create fluctuating foraging hotspots for sea birds in tidewater glacier bays
Authors: Urbanski Jacek Andrzej , Stempniewicz Lech , Węsławski Jan Marcin , Dragańska-Deja Katarzyna , Wochna Agnieszka , Goc Michał , Iliszko Lech 
Published: March 2017

AbstractAlthough the processes occurring at the front of an ice face in tidewater glacier bays still await thorough investigation, their importance to the rapidly changing polar environment is spurring a considerable research effort. Glacier melting, sediment delivery and the formation of seabird foraging hotspots are governed by subglacial discharges of meltwater. We have combined the results of tracking black-legged kittiwakes Rissa tridactyla equipped with GPS loggers, analyses of satellite images and in situ measurements of water temperature, salinity and turbidity in order to examine the magnitude and variability of such hotspots in the context of glacier bay hydrology. Small though these hotspots are in size, foraging in them appears to be highly intensive. They come into existence only if the subglacial discharge reaches the surface, if the entrainment velocity at a conduit is high and if there is sufficient macroplankton in the entrainment layer. The position and type of subglacial discharges may fluctuate in time and space, thereby influencing glacier bay hydrology and the occurrence of foraging hotspots.
The protective effect of the anti-Toll-like receptor 9 antibody against acute cytokine storm caused by immunostimulatory DNA
Authors: Murakami Yusuke , Fukui Ryutaro , Motoi Yuji , Shibata Takuma , Saitoh Shin-Ichiroh , Sato Ryota , Miyake Kensuke 
Published: March 2017

AbstractToll-like Receptor 9 (TLR9) is an innate immune receptor recognizing microbial DNA. TLR9 is also activated by self-derived DNA, such as mitochondrial DNA, in a variety of inflammatory diseases. We show here that TLR9 activation in vivo is controlled by an anti-TLR9 monoclonal Ab (mAb). A newly established mAb, named NaR9, clearly detects endogenous TLR9 expressed in primary immune cells. The mAb inhibited TLR9-dependent cytokine production in vitro by bone marrow-derived macrophages and conventional dendritic cells. Furthermore, NaR9 treatment rescued mice from fulminant hepatitis caused by administering the TLR9 ligand CpGB and D-(+)-galactosamine. The production of proinflammatory cytokines induced by CpGB and D-(+)-galactosamine was significantly impaired by the mAb. These results suggest that a mAb is a promising tool for therapeutic intervention in TLR9-dependent inflammatory diseases.
Information-theoretic equilibrium and observable thermalization
Authors: Anzà F. , Vedral V. 
Published: March 2017

AbstractA crucial point in statistical mechanics is the definition of the notion of thermal equilibrium, which can be given as the state that maximises the von Neumann entropy, under the validity of some constraints. Arguing that such a notion can never be experimentally probed, in this paper we propose a new notion of thermal equilibrium, focused on observables rather than on the full state of the quantum system. We characterise such notion of thermal equilibrium for an arbitrary observable via the maximisation of its Shannon entropy and we bring to light the thermal properties that it heralds. The relation with Gibbs ensembles is studied and understood. We apply such a notion of equilibrium to a closed quantum system and show that there is always a class of observables which exhibits thermal equilibrium properties and we give a recipe to explicitly construct them. Eventually, an intimate connection with the Eigenstate Thermalisation Hypothesis is brought to light.
Double-stranded RNA induces inflammation via the NF-κB pathway and inflammasome activation in the outer root sheath cells of hair follicles
Authors: Shin Jung-Min , Choi Dae-Kyoung , Sohn Kyung-Cheol , Kim Soo-Yeon , Min Ha Jeong , Ho Lee Young , Im Myung , Seo Young-Joon , Deok Kim Chang , Lee Jeung-Hoon , Lee Young 
Published: March 2017

AbstractAlopecia areata (AA), a chronic, relapsing, hair-loss disorder, is considered to be a T cell-mediated autoimmune disease. It affects approximately 1.7% of the population, but its precise pathogenesis remains to be elucidated. Despite the recent attention focused on the roles of inflammasomes in the pathogenesis of autoinflammatory diseases, little is known about inflammasome activation in AA. Thus, in this study, we investigated the pattern of NLRP3 inflammasome activation in the outer root sheath (ORS) cells of hair follicles. We found that interleukin (IL)-1β and caspase-1 expression was increased in hair follicle remnants and inflammatory cells of AA tissue specimens. After stimulation of ORS cells with the double-stranded (ds)RNA mimic polyinosinic:polycytidylic acid (poly[I:C]), the activation of caspase-1 and secretion of IL-1β were enhanced. Moreover, NLRP3 knockdown decreased this poly(I:C)-induced IL-1β production. Finally, we found that high-mobility group box 1 (HMGB1) translocated from the nucleus to the cytosol and was secreted into the extracellular space by inflammasome activation. Taken together, these findings suggest that ORS cells are important immunocompetent cells that induce NLRP3 inflammasomes. In addition, dsRNA-induced IL-1β and HMGB1 secretion from ORS cells may contribute to clarifying the pathogenesis and therapeutic targets of AA.
A missense mutation in zbtb17 blocks the earliest steps of T cell differentiation in zebrafish
Authors: Lawir Divine-Fondzenyuy , Iwanami Norimasa , Schorpp Michael , Boehm Thomas 
Published: March 2017

AbstractT cells are an evolutionarily conserved feature of the adaptive immune systems of vertebrates. Comparative studies using evolutionarily distant species hold great promise for unraveling the genetic landscape underlying this process. To this end, we used ENU mutagenesis to generate mutant zebrafish with specific aberrations in early T cell development. Here, we describe the identification of a recessive missense mutation in the transcriptional regulator zbtb17 (Q562K), which affects the ninth zinc finger module of the protein. Homozygous mutant fish exhibit an early block of intrathymic T cell development, as a result of impaired thymus colonization owing to reduced expression of the gene encoding the homing receptor ccr9a, and inefficient T cell differentiation owing to reduced expression of socs1a. Our results reveal the zbtb17-socs1 axis as an evolutionarily conserved central regulatory module of early T cell development of vertebrates.
VEGF-related polymorphisms identified by GWAS and risk for major depression
Authors: Xie T , Stathopoulou M G , de Andrés F , Siest G , Murray H , Martin M , Cobaleda J , Delgado A , Lamont J , Peñas-LIedó E , LLerena A , Visvikis-Siest S 
Published: March 2017

AbstractDepression is a common, severe, disabling mental disease that affects millions of people of all ages worldwide. Various studies have shown that neurotrophic/growth factors have a key role in depression and, more specifically, vascular endothelial growth factor (VEGF) is implicated in the pathogenesis of depression. The purpose of this study was to investigate the potential links between four VEGF-related single-nucleotide polymorphisms (SNPs), previously identified through a genome-wide association study (GWAS) and depression. The direct effects and epistatic interactions of the four VEGF-related SNPs (rs10738760, rs6921438, rs6993770 and rs4416670) on depression were investigated through a case–control study including 437 individuals diagnosed with depression and 477 healthy volunteers as controls. Gender, age and body mass index influence was additionally analyzed. The SNP rs4416670 was associated with increased risk for depression (OR: 1.60, P: 0.010). This result demonstrates the existence of relationships between VEGF genetic determinants and depression. This novel association reveals new molecular mechanisms suggesting the potential role of VEGF in depression development that could help to promote a personalized prediction for this severe common disease.
Preclinical models in the study of sex differences
Authors: Buoncervello Maria , Marconi Matteo , Carè Alessandra , Piscopo Paola , Malorni Walter , Matarrese Paola 
Published: March 2017

The biology of sex differences deals with the study of the disparities between females and males and the related biological mechanisms. Gender medicine focuses on the impact of gender and sex on human physiology, pathophysiology and clinical features of diseases that are common to women and men. The term gender refers to a complex interrelation and integration of sex–as a biological and functional determinant–and psychological and cultural behaviours (due to ethnical, social or religious background). The attention to the impact of gender differences on the pathophysiology and, therefore, on the clinical management of the most common diseases, such as cardiovascular diseases (CVD), neurodegenerative disorders, immune and autoimmune diseases as well as several tumours, is in fact often neglected. Hence, studies covering different fields of investigation and including sex differences in the pathogenesis, in diagnostic and prognostic criteria as well as in response to therapy appear mandatory. However, prerequisites for this development are preclinical studies, including in vitro and in vivo approaches. They represent the first step in the development of a drug or in the comprehension of the pathogenetic mechanisms of diseases, in turn a necessary step for the development of new or more appropriate therapeutic strategies. However, sex differences are still poorly considered and the great majority of preclinical studies do not take into account the relevance of such disparities. In this review, we describe the state of the art of these studies and provide some paradigmatic examples of key fields of investigation, such as oncology, neurology and CVD, where preclinical models should be improved.
Genetic Screening of Selected Disease-Causing Mutations in Glutaryl-CoA Dehydrogenase Gene among Indian Patients with Glutaric Aciduria Type I
Authors: Muntaj Shaik , Devaraju K. , Kamate M. , Vedamurthy A. , TP Kruthika-Vinod 
Published: March 2017

AbstractGlutaric aciduria type I (GA-I) is an organic aciduria caused by glutaryl-CoA dehydrogenase (GCDH) deficiency. There are limited studies on GA-I from India. A total of 48 Indian GA-I patients were screened for selected disease-causing mutations such as R402W, A421V, A293T, R227P, and V400M using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Among these patients, 9 (18.8%) had R402W mutation, and none had A421V, A293T, R227P, or V400M mutation. One low excretor mutation (P286S) and several novel mutations (I152M, Q144P, and E414X) were also found in this study. We conclude that among selected mutations, R402W is the most common mutation found among Indian GA-I patients.
Effect of a Bicyclic Pyrimidine Derivative (KRP-103), a Novel Selective Tachykinin NK1 Receptor Antagonist, on Bladder Function in Guinea Pigs
Authors: Tanioka Asao , Deguchi Takashi 
Published: March 2017

AbstractWe evaluated the pharmacological characteristics of KRP-103, chemically named as ((2-(4-acetylpiperazin-1-yl)-6-[3,5-bis(trifluorometheyl)-phenylmethyl]-4- (2-methylphenyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,5]oxazocin-5-one), and its effects on lower urinary tract function in guinea pigs. In radioligand binding assay, KRP-103 showed higher selectivity for human NK1 receptor (hNK1R) than for human NK2 receptor (hNK2R) and human NK3 receptor (hNK3R) (Ki for hNK1R, hNK2R and hNK3R=0.126 nM, > 10 000 nM and > 10 000 nM). In distention-induced rhythmic bladder contractions (RBCs) in urethane-anesthetized guinea pigs, intravenous administration of KRP-103 dose-dependently increased the shutdown time of RBCs and slightly decreased the amplitude of RBCs (only about 20%). In acutely spinalized guinea pig cystometory, intraduodenal administration of KRP-103 dose-dependently increased the effective bladder capacity with a minimum effective dose of 1 mg/kg. Furthermore, to clarify the site of action of KRP-103, we evaluated the inhibitory effects of KRP-103 on bladder contractions induced by electrical stimulation (ES) of the central or peripheral cut end of the pelvic nerve (PN). KRP-103 inhibited the bladder contractions induced by ES of the central cut end of PN but not those induced by ES of the peripheral cut end of PN. These results indicate that KRP-103 enhances bladder storage function by inhibiting sensory transmission from the bladder at the level of spinal cord without affecting bladder efferent function, suggesting that KRP-103 may be a suitable therapeutic drug for treatment of overactive bladder.
Role of Chemically Modified Tetracyclines in the Management of Periodontal Diseases: A Review
Authors: Ghangurde Archit , Ganji Kiran , Bhongade Manohar , Sehdev Bhumika 
Published: March 2017

AbstractResearchers have found that Chemically Modified Tetracyclines (CMTs) act through multiple mechanisms, affecting several parameters of osteoclast function and consequently inhibit bone resorption by altering intracellular calcium concentration and interacting with the putative calcium receptor; decreasing ruffled border area; diminishing acid production; diminishing the secretion of lysosomal cysteine proteinases (cathepsins); inducing cell retraction by affecting podosomes; inhibiting osteoclast gelatinase activity; selectively inhibiting osteoclast ontogeny or development; and inducing apoptosis or programmed cell death of osteoclasts. Thus TCs/CMTs, as anti-resorptive drugs, may act similarly to bisphosphonates and primarily affect osteoclast function. Researchers have evaluated the influence of various chemically modified tetracyclines from CMT-1 to CMT-10 on collagenases and gelatinases through in vitro or animal studies and concluded that all the CMTs except CMT-5 inhibited periodontal breakdown through MMP inhibition in the following order of efficacy: CMT-8>CMT-1>CMT-3>CMT-4>CMT-7. Thus the non-antimicrobial actions of the chemically modified analogues of tetracyclines have shown remarkably better mechanisms to those of agents with established anti-inflammatory/antioxidant potential. These findings clarify the multi-faceted actions of tetracyclines which are unique amongst antimicrobials, with therapeutic applications in periodontal and metabolic diseases. Hence, the present review describes the role of chemically modified tetracyclines in the management of periodontal diseases.
Limitations of time resources in human relationships determine social structures
Authors: Takano Masanori , Fukuda Ichiro 
Published: March 2017

AbstractThe number of social relationships that a single human being can possibly be involved in is limited because individuals face time constraints (that is, time costs) in constructing and maintaining social relationships; furthermore, the distribution of the strength of such relationships (as measured by frequency of social interaction) looks significantly skewed (a power law distribution), that is, a few strong relationships and many weak relationships. This skewedness suggests that the costs and benefits of bonding with others depend on the strength of the social relationships: if it involves uniform costs and benefits, the distribution would not be skewed. The bonding is known as social grooming; that is, humans strategically construct their social relationships, and thus, complex human societies should also be strategically constructed. Therefore, it is important to know their strategies for understanding human societies. Previous studies provide evidence of social grooming strategies by examining the evolution and the difference between the various social grooming methods. However, quantitative laws that are important for theoretically understanding human societies are still open to investigation. Social big data is a particularly powerful tool for finding such laws. Therefore, we analyse data from six communication systems (Twitter, a social networking site providing two types of interactions, an avatar chat, a mobile phone and a short message service). We find a simple quantitative law by which social relationships are constrained Nma (a>1); here, N is the number of social relationships and m is a mean of the strength of those relationships. The fact that deep social relationships require higher costs per relationship than shallow relationships is suggested by a>1 (if the both is equal then a will be 1), because the effect of m on the constraint increases with m. For exploring why a is greater than 1, we conduct an individual-based simulation where social grooming costs are assumed to increase linearly with the strength of social relationships. Our results indicate that this model fits all data sets; that is, it displays an explanation capacity for the phenomenon. In addition, an analysis of this simulation proves our assumption about the social grooming cost increasing with the strength of social relationships as being true. Moreover, it suggests that its gradient increases the width and shallowness of these relationships. The law and its causes suggest that mankind’s evolution of social grooming has enabled changing social structures, and the phenomenon is because of the constraints of the social network generation. These findings will contribute towards an explanation of the evolution of the various social grooming methods of humans and their significantly large social group.
Clinical concentrations of chemically diverse general anesthetics minimally affect lipid bilayer properties
Authors: Herold Karl F. , Sanford R. Lea , Lee William , Andersen Olaf S. , Hemmings Hugh C. 
Published: March 2017

Significance
General anesthetics are essential to modern medicine, yet their molecular mechanisms remain poorly understood. Whether general anesthetics primarily act by altering lipid bilayer properties or by interacting directly with specific membrane proteins is a longstanding controversy. We now show that diverse classes of general anesthetics do not alter bilayer properties at concentrations that induce clinical anesthesia. Although anesthetics can have bilayer-perturbing effects at supratherapeutic (toxic) concentrations, this has little pharmacological relevance. Our findings exclude indirect ion channel effects due to perturbations of lipid bilayer properties, supporting the notion that general anesthetics interact directly with therapeutically relevant membrane protein targets.
Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in
S. cerevisiae
Authors: Ostrow A. Zachary , Kalhor Reza , Gan Yan , Villwock Sandra K. , Linke Christian , Barberis Matteo , Chen Lin , Aparicio Oscar M. 
Published: March 2017

Significance
The spatial organization of chromatin within the nucleus regulates genomic functions including DNA repair, transcription, and replication. For example, replication origins cluster prior to initiating replication, likely to aggregate the many necessary factors, but the mechanism is poorly understood. We recently discovered yeast “Forkhead Box” (Fox) DNA binding proteins, Forkhead 1 (Fkh1) and Forkhead 2 (Fkh2), as required for this origin clustering and regulation of initiation timing. This study reveals that Fkh1 and Fkh2 share a structural motif that allows dimerization to bring distal DNA binding sites into close proximity. Mutation that disrupts dimerization ablates origin clustering and deregulates origin activation, suggesting causality between origin clustering and initiation control. We propose that Fkh1 and Fkh2 and related Fox proteins in metazoans establish chromatin architecture.