bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the anticipated growth response of northern conifer populations to a warming climate
Authors: Pedlar John H. , McKenney Daniel W.
Published: March 2017

The growth response of trees to ongoing climate change has important implications for future forest dynamics, accurate carbon accounting, and sustainable forest management. We used data from black spruce (Picea mariana) and jack pine (Pinus banksiana) provenance trials, along with published data for three other northern conifers, to identify a consistent growth response to climate warming in which cold-origin populations are expected to benefit and warm-origin populations are expected to decline. Specifically, populations from across the geographic range of a species appear to grow well at temperatures characteristic of the southern portion of the range, indicating significant potential for a positive growth response to climate warming in cold-origin populations. Few studies have quantified and compared this pattern across multiple species using provenance data. We present a forest regeneration strategy that incorporates these anticipated growth responses to promote populations that are both local to the planting site and expected to grow well under climate change.
Cre/lox-Recombinase-Mediated Cassette Exchange for Reversible Site-Specific Genomic Targeting of the Disease Vector, Aedes aegypti
Authors: Häcker Irina , Harrell II Robert A. , Eichner Gerrit , Pilitt Kristina L. , O’Brochta David A. , Handler Alfred M. , Schetelig Marc F.
Published: March 2017

Site-specific genome modification (SSM) is an important tool for mosquito functional genomics and comparative gene expression studies, which contribute to a better understanding of mosquito biology and are thus a key to finding new strategies to eliminate vector-borne diseases. Moreover, it allows for the creation of advanced transgenic strains for vector control programs. SSM circumvents the drawbacks of transposon-mediated transgenesis, where random transgene integration into the host genome results in insertional mutagenesis and variable position effects. We applied the Cre/lox recombinase-mediated cassette exchange (RMCE) system to Aedes aegypti, the vector of dengue, chikungunya, and Zika viruses. In this context we created four target site lines for RMCE and evaluated their fitness costs. Cre-RMCE is functional in a two-step mechanism and with good efficiency in Ae. aegypti. The advantages of Cre-RMCE over existing site-specific modification systems for Ae. aegypti, phiC31-RMCE and CRISPR, originate in the preservation of the recombination sites, which 1) allows successive modifications and rapid expansion or adaptation of existing systems by repeated targeting of the same site; and 2) provides reversibility, thus allowing the excision of undesired sequences. Thereby, Cre-RMCE complements existing genomic modification tools, adding flexibility and versatility to vector genome targeting.
The Role of Lipid Droplets in Mortierella alpina Aging Revealed by Integrative Subcellular and Whole-Cell Proteome Analysis
Authors: Yu Yadong , Li Tao , Wu Na , Jiang Ling , Ji Xiaojun , Huang He
Published: March 2017

Lipid droplets (LDs) participate in many cellular processes in oleaginous microorganisms. However, the exact function of LDs in the Mortierella alpina aging process remains elusive. Herein, subcellular proteomics was employed to unveil the composition and dynamics of the LD proteome in the aging M. alpina for the first time. More than 400 proteins were detected in LDs and 62 of them changed expression significantly during aging. By combining the LD proteomic data with whole-cell data, we found that the carbohydrate metabolism and de novo lipid biosynthesis were all inhibited during aging of M. alpina mycelia. The up-regulation of fructose metabolism-related enzymes in LDs might imply that LDs facilitated the fructose metabolism, which in turn might cause pyruvate to accumulate and enter malate-pyruvate cycle, and ultimately, provide additional NADPH for the synthesis of arachidonic acid (ARA). Lysophospholipase and lecithinase were up-regulated in LDs during the aging process, suggesting that the phospholipids and lecithin were starting to be hydrolyzed, in order to release fatty acids for the cells. The impairment of the anti-oxidant system might lead to the accumulation of ROS and consequently cause the up-regulation of autophagy-related proteins in LDs, which further induces the M. alpina mycelia to activate the autophagy process.
Identifying the chiral d-wave superconductivity by Josephson φ0-states
Authors: Liu Jun-Feng , Xu Yong , Wang Jun
Published: March 2017

We propose the Josephson junctions linked by a normal metal between a d + id superconductor and another d + id superconductor, a d-wave superconductor, or a s-wave superconductor for identifying the chiral d + id superconductivity. The time-reversal breaking in the chiral d-wave superconducting state is shown to result in a Josephson φ0-junction state where the current-phase relation is shifted by a phase φ0 from the sinusoidal relation, other than 0 and π. The ground-state phase difference φ0 and the critical current can be used to definitely confirm and read the information about the d + id superconductivity. A smooth evolution from conventional 0-π transitions to tunable φ0-states can be observed by changing the relative magnitude of two types of d-wave components in the d + id pairing. On the other hand, the Josephson junction involving the d + id superconductor is also the simplest model to realize a φ0- junction, which is useful in superconducting electronics and superconducting quantum computation.
A peptide vaccine targeting angiotensin II attenuates the cardiac dysfunction induced by myocardial infarction
Authors: Watanabe Ryo , Suzuki Jun-ichi , Wakayama Kouji , Maejima Yasuhiro , Shimamura Munehisa , Koriyama Hiroshi , Nakagami Hironori , Kumagai Hidetoshi , Ikeda Yuichi , Akazawa Hiroshi , Morishita Ryuichi , Komuro Issei , Isobe Mitsuaki
Published: March 2017

A peptide vaccine targeting angiotensin II (Ang II) was recently developed as a novel treatment for hypertension to resolve the problem of noncompliance with pharmacotherapy. Ang II plays a crucial role in the pathogenesis of cardiac remodeling after myocardial infarction (MI), which causes heart failure. In the present study, we examined whether the Ang II vaccine is effective in preventing heart failure. The injection of the Ang II vaccine in a rat model of MI attenuated cardiac dysfunction in association with an elevation in the serum anti-Ang II antibody titer. Furthermore, any detrimental effects of the Ang II vaccine were not observed in the rats that underwent sham operations. Treatment with immunized serum from Ang II vaccine-injected rats significantly suppressed post-MI cardiac dysfunction in MI rats and Ang II-induced remodeling-associated signaling in cardiac fibroblasts. Thus, our present study demonstrates that the Ang II vaccine may provide a promising novel therapeutic strategy for preventing heart failure.
Notch1 Signaling Contributes to Hypoxia-induced High Expression of Integrin β1 in Keratinocyte Migration
Authors: Tang Di , Yan Tiantian , Zhang Junhui , Jiang Xupin , Zhang Dongxia , Huang Yuesheng
Published: March 2017

Oxygen tension is an important micro-environmental factor that affects epidermal development and function. After injury, high oxygen consumption and vascular injury result in partial hypoxia. However, whether hypoxia benefits or hurts wound healing remains controversial. In this study, a tissue oxygen tension monitor was used to detect the spatial and temporal distribution of oxygen in burn wounds. In vitro, we demonstrate that hypoxia promoted the expression of integrin β1 and the migration of keratinocytes. Furthermore, hypoxia-induced migration was slowed by Notch1 ligands and a siRNA against ITGB1 (integrin β1). Our findings suggest that integrin β1 may be an oxygen-sensitive molecule that promotes keratinocyte migration during wound healing and that Notch1 signaling is involved in this process.
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

The 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

Tamoxifen 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

Werner 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

Although 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

Toll-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

A 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

Alopecia 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

T 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

Depression 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.
The phase and interfacial properties of azeotropic refrigerants: the prediction of aneotropes from molecular theory
Authors: Fouad Wael A. , Vega Lourdes F.
Published: March 2017

Predicting the azeotropic (bulk) and aneotropic (interface) behavior of refrigerant mixtures using polar PC-SAFT coupled with DGT.
Direct experimental probing and theoretical analysis of the reaction between the simplest Criegee intermediate CH2OO and isoprene
Authors: Decker Z. C. J. , Au K. , Vereecken L. , Sheps L.
Published: March 2017

The reaction of CH2OO with isoprene, the highest-emitted unsaturated compound on Earth, is similar to reactions with small singly-unsaturated alkenes.
Betti's base for crystallization-induced deracemization of substituted aldehydes: synthesis of enantiopure amorolfine and fenpropimorph
Authors: Carella Andrea , Ramos Ferronatto Gabriel , Marotta Emanuela , Mazzanti Andrea , Righi Paolo , Paolucci Claudio
Published: March 2017

Betti's base was used to deracemize substituted aldehydes via a CIDT process.
Confined polydiacetylene polymerization reactions for programmed length control
Authors: Verstraete Lander , Hirsch Brandon E. , Greenwood John , De Feyter Steven
Published: March 2017

In situ nanocorrals on graphite yield oriented precursor self-assembly for controlled polymerization reactions.
Generalization of the Tolman electronic parameter: the metal–ligand electronic parameter and the intrinsic strength of the metal–ligand bond
Authors: Cremer Dieter , Kraka Elfi
Published: March 2017

The MLEP is a new, generally applicable measure of the metal–ligand bond strength based on vibrational spectroscopy, replacing the TEP.
Tuneable reversible redox of cobalt(iii) carbazole complexes
Authors: Bennington Michael S. , Feltham Humphrey L. C. , Buxton Zoë J. , White Nicholas G. , Brooker Sally
Published: March 2017

Four structurally characterised [CoIIILR/R′2]BF4 complexes, of four acyclic bis(triazolyl)carbazole ligands LR/R′, all show a pair of reversible one-electron redox processes which can be tuned by variation of the carbazole substituents R.
Large, weakly basic bis(carboranyl)phosphines: an experimental and computational study
Authors: Riley Laura E. , Krämer Tobias , McMullin Claire L. , Ellis David , Rosair Georgina M. , Sivaev Igor B. , Welch Alan J.
Published: March 2017

Bis(carboranyl)phosphines and their {AuCl} and {Se} derivatives have been the subject of experimental and computational studies.
The Ca2+-ATPase pump facilitates bidirectional proton transport across the sarco/endoplasmic reticulum
Authors: Espinoza-Fonseca L. Michel
Published: March 2017

We propose that the Ca2+-ATPase pump forms pores that facilitate bidirectional proton transport across the sarco/endoplasmic reticulum.
Well-defined hyperstar copolymers based on a thiol–yne hyperbranched core and a poly(2-oxazoline) shell for biomedical applications
Authors: Hartlieb Matthias , Floyd Thomas , Cook Alexander B. , Sanchez-Cano Carlos , Catrouillet Sylvain , Burns James A. , Perrier Sébastien
Published: March 2017

Well defined ‘hyperstar’ copolymers were synthesized by combining hyperbranched polymers produced by thiol–yne chemistry with poly(oxazoline)s.
Enhancement of fluorescent resonant energy transfer and the antenna effect in DNA structures with multiple fluorescent dyes
Authors: Oh Taeseok , Kim Sejung , Choi Jae-Young , Chang Haeun , Heller Michael J.
Published: March 2017

This study examines the use of surfactants and metal cations to enhance the long range fluorescent resonant energy transfer (FRET) and the antenna effect from three TAMRA donor dyes to one Texas Red acceptor dye conjugated in dsDNA structure.
Characterization of the catalytic properties of the membrane-anchored metalloproteinase ADAM9 in cell-based assays
Authors: Maretzky Thorsten , Swendeman Steven , Mogollon Elin , Weskamp Gisela , Sahin Umut , Reiss Karina , Blobel Carl P.
Published: March 2017

ADAM9 (A Disintegrin And Metalloprotease 9) is a membrane-anchored metalloproteinase that has been implicated in pathological retinal neovascularization and in tumor progression. ADAM9 has constitutive catalytic activity in both biochemical and cell-based assays and can cleave several membrane proteins, including epidermal growth factor and Ephrin receptor B4; yet little is currently known about the catalytic properties of ADAM9 and its post-translational regulation and inhibitor profile in cell-based assays. To address this question, we monitored processing of the membrane-anchored Ephrin receptor B4 (EphB4) by co-expressing ADAM9, with the catalytically inactive ADAM9 E > A mutant serving as a negative control. We found that ADAM9-dependent shedding of EphB4 was not stimulated by three commonly employed activators of ADAM-dependent ectodomain shedding: phorbol esters, pervanadate or calcium ionophores. With respect to the inhibitor profile, we found that ADAM9 was inhibited by the hydroxamate-based metalloprotease inhibitors marimastat, TAPI-2, BB94, GM6001 and GW280264X, and by 10 nM of the tissue inhibitor of metalloproteinases (TIMP)-3, but not by up to 20 nM of TIMP-1 or -2. Additionally, we screened a non-hydroxamate small-molecule library for novel ADAM9 inhibitors and identified four compounds that selectively inhibited ADAM9-dependent proteolysis over ADAM10- or ADAM17-dependent processing. Taken together, the present study provides new information about the molecular fingerprint of ADAM9 in cell-based assays by showing that it is not stimulated by strong activators of ectodomain shedding and by defining a characteristic inhibitor profile. The identification of novel non-hydroxamate inhibitors of ADAM9 could provide the basis for designing more selective compounds that block the contribution of ADAM9 to pathological neovascularization and cancer.
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

Glutaric 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

We 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

Researchers 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

The 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.
Interfacial and topological effects on the glass transition in free-standing polystyrene films
Authors: Lyulin Alexey V. , Balabaev Nikolay K. , Baljon Arlette R. C. , Mendoza Gerardo , Frank Curtis W. , Yoon Do Y.
Published: March 2017

United-atom molecular-dynamics computer simulations of atactic polystyrene (PS) were performed for the bulk and free-standing films of 2 nm–20 nm thickness, for both linear and cyclic polymers comprised of 80 monomers. Simulated volumetric glass-transition temperatures (Tg) show a strong dependence on the film thickness below 10 nm. The glass-transition temperature of linear PS is 13% lower than that of the bulk for 2.5 nm-thick films, as compared to less than 1% lower for 20 nm films. Our studies reveal that the fraction of the chain-end groups is larger in the interfacial layer with its outermost region approximately 1 nm below the surface than it is in the bulk. The enhanced population of the end groups is expected to result in a more mobile interfacial layer and the consequent dependence of Tg on the film thickness. In addition, the simulations show an enrichment of backbone aliphatic carbons and concomitant deficit of phenyl aromatic carbons in the interfacial film layer. This deficit would weaken the strong phenyl-phenyl aromatic (π−π) interactions and, hence, lead to a lower film-averaged Tg in thin films, as compared to the bulk sample. To investigate the relative importance of the two possible mechanisms (increased chain ends at the surface or weakened π−π interactions in the interfacial region), the data for linear PS are compared with those for cyclic PS. For the cyclic PS, the reduction of the glass-transition temperature is also significant in thin films, albeit not as much as for linear PS. Moreover, the deficit of phenyl carbons in the film interface is comparable to that observed for linear PS. Therefore, chain-end effects alone cannot explain the observed pronounced Tg dependence on the thickness of thin PS films; the weakened phenyl-phenyl interactions in the interfacial region seems to be an important cause as well.
Plasma block acceleration via double targets driven by an ultraintense circularly polarized laser pulse
Authors: Xu Yanxia , Wang Jiaxiang , Qi Xin , Li Meng , Xing Yifan , Yang Lei , Zhu Wenjun
Published: March 2017

By using two-dimensional particle-in-cell simulations, plasma block acceleration via radiation pressure from an ultraintense circularly polarized laser pulse with intensity I≈1022W/cm2 is investigated based on a double-target scheme, in which the targets are composed of a pre-target with a relatively low plasma density and a main target with a high plasma density. It has been demonstrated that an appropriately selected pre-target can help to greatly enhance the charge separation field in the main target, which then leads to generation of a strongly accelerated and well directed plasma block with proton energy in GeV magnitude. This result can have potential applications in the plasma block ignition of proton-born fusion.
Conformal invariance and new exact solutions of the elastostatics equations
Authors: Chirkunov Yu. A.
Published: March 2017

We fulfilled a group foliation of the system of n-dimensional (n ≥ 2) Lame equations of the classical static theory of elasticity with respect to the infinite subgroup contained in normal subgroup of main group of this system. It permitted us to move from the Lame equations to the equivalent unification of two first-order systems: automorphic and resolving. We obtained a general solution of the automorphic system. This solution is an n-dimensional analogue of the Kolosov-Muskhelishvili formula. We found the main Lie group of transformations of the resolving system of this group foliation. It turned out that in the two-dimensional and three-dimensional cases, which have a physical meaning, this system is conformally invariant, while the Lame equations admit only a group of similarities of the Euclidean space. This is a big success, since in the method of group foliation, resolving equations usually inherit Lie symmetries subgroup of the full symmetry group that was not used for the foliation. In the three-dimensional case for the solutions of the resolving system, we found the general form of the transformations similar to the Kelvin transformation. These transformations are the consequence of the conformal invariance of the resolving system. In the three-dimensional case with a help of the complex dependent and independent variables, the resolving system is written as a simple complex system. This allowed us to find non-trivial exact solutions of the Lame equations, which direct for the Lame equations practically impossible to obtain. For this complex system, all the essentially distinct invariant solutions of the maximal rank we have found in explicit form, or we reduced the finding of those solutions to the solving of the classical one-dimensional equations of the mathematical physics: the heat equation, the telegraph equation, the Tricomi equation, the generalized Darboux equation, and other equations. For the resolving system, we obtained double wave of a special type and double waves of the shear deformations in an elastic medium. By the obtained formulas for generating new solutions, these solutions give an infinite set of exact solutions of this complex system. By the three-dimensional analog of the Kolosov-Muskhelishvili formula, the found solutions produce an infinite-dimensional vector space of exact solutions of the Lame equations.
Effective suppression of pulse shortening in a relativistic backward wave oscillator
Authors: Cao Yibing , Song Zhimin , Wu Ping , Fan Zhiqiang , Zhang Yuchuan , Teng Yan , Sun Jun
Published: March 2017

This paper discusses pulse shortening present in a C-band relativistic backward wave oscillator (RBWO). Effects of the collector plasma are believed to be the main cause. This viewpoint is first verified in numerical simulation. The simulation results show that light charged particles such as hydrogen ions in the collector plasma would axially enter into the beam-microwave interaction region and suppress high-power microwave (HPM) generation. Simultaneously, heavy charged particles such as oxygen or ferric ions in the collector plasma would radially expand out and change the end reflection of the RBWO. All these effects can result in pulse shortening. Simulations also demonstrate that a coaxial collector can effectively suppress plasma effects by retarding their axial and radial expansions. Furthermore, a HPM experiment has confirmed the validity of the coaxial collector. Using this structure, the output power of the RBWO has been increased from 2.5 GW to 3 GW. No pulse shortening has been observed in the HPM experiment.
Evolution of target condition in reactive HiPIMS as a function of duty cycle: An opportunity for refractive index grading
Authors: Ganesan Rajesh , Akhavan Behnam , Partridge James G. , McCulloch Dougal G. , McKenzie David R. , Bilek Marcela M. M.
Published: March 2017

Competition between target erosion and compound layer formation during pulse cycles in reactive HiPIMS opens up the possibility of tuning discharge conditions and the properties of deposited films by varying the duty cycle in situ without altering the reactive gas mixture. Three different reactive systems, hafnium in oxygen, tungsten in oxygen, and tungsten in oxygen/nitrogen, are studied in which amorphous films of hafnium oxide (HfO2), tungsten oxide (WO3), and tungsten oxynitride (WOxNy) are deposited. We show that the cyclic evolution of the target surface composition depends on the properties of the target including its affinity for the reactive gas mix and the compound layer melting point and volatility. We find that pulse length variations modulate the target compound layer and hence the discharge chemistry and properties of the films deposited. The refractive indices of HfO2 and WO3 were progressively reduced with the duty cycle, whereas that of WOxNy increased. These variations were found to be due to changes in the chemical composition and/or densification. We present and validate a phenomenological model that explains these findings in terms of a compound layer on the target surface that undergoes evolution during each pulse resulting in a cyclic equilibrium. The end points of the composition of the target surface depend on the duty cycle. Tuning the pulse characteristics holds great promise for the fabrication of multilayer films with through thickness graded properties.
Focusing hard x rays beyond the critical angle of total reflection by adiabatically focusing lenses
Authors: Patommel Jens , Klare Susanne , Hoppe Robert , Ritter Stephan , Samberg Dirk , Wittwer Felix , Jahn Andreas , Richter Karola , Wenzel Christian , Bartha Johann W. , Scholz Maria , Seiboth Frank , Boesenberg Ulrike , Falkenberg Gerald , Schroer Christian G.
Published: March 2017

In response to the conjecture that the numerical aperture of x-ray optics is fundamentally limited by the critical angle of total reflection [Bergemann et al., Phys. Rev. Lett. 91, 204801 (2003)], the concept of adiabatically focusing refractive lenses was proposed to overcome this limit [Schroer and Lengeler, Phys. Rev. Lett. 94, 054802 (2005)]. We present an experimental realization of these optics made of silicon and demonstrate that they indeed focus 20 keV x rays to a 18.4 nm focus with a numerical aperture of 1.73(9) × 10−3 that clearly exceeds the critical angle of total reflection of 1.55 mrad.
Nonlinear excitations for the positron acoustic shock waves in dissipative nonextensive electron-positron-ion plasmas
Authors: Saha Asit
Published: March 2017

Positron acoustic shock waves (PASHWs) in unmagnetized electron-positron-ion (e-p-i) plasmas consisting of mobile cold positrons, immobile positive ions, q-nonextensive distributed electrons, and hot positrons are studied. The cold positron kinematic viscosity is considered and the reductive perturbation technique is used to derive the Burgers equation. Applying traveling wave transformation, the Burgers equation is transformed to a one dimensional dynamical system. All possible vector fields corresponding to the dynamical system are presented. We have analyzed the dynamical system with the help of potential energy, which helps to identify the stability and instability of the equilibrium points. It is found that the viscous force acting on cold mobile positron fluid is a source of dissipation and is responsible for the formation of the PASHWs. Furthermore, fully nonlinear arbitrary amplitude positron acoustic waves are also studied applying the theory of planar dynamical systems. It is also observed that the fundamental features of the small amplitude and arbitrary amplitude PASHWs are significantly affected by the effect of the physical parameters qe, qh, μe, μh, σ, η, and U. This work can be useful to understand the qualitative changes in the dynamics of nonlinear small amplitude and fully nonlinear arbitrary amplitude PASHWs in solar wind, ionosphere, lower part of magnetosphere, and auroral acceleration regions.
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.