bluuebunny/crossref_metadata_2025_split huggingface dataset:
Search for non-lactam inhibitors of mtb β-lactamase led to its open shape in apo state: new concept for antibiotic design
Authors: Sagar Amin , Haleem Nazia , Bashir Yaawar Mir , Ashish  
Published: July 2017

AbstractMtb β-lactamase (BlaC) is extremely efficient in hydrolyzing ß-lactam antibiotics which renders/leads to protection and/or resistance to this bug. There is a compelling need to develop new non-lactam inhibitors which can bind and inhibit BlaC, but cannot be hydrolyzed, thus neutralizing this survival mechanism of Mtb. Using the crystal structure of BlaC we screened 750000 purchasable compounds from ZINC Database for their theoretical affinity to the enzyme’s active site. 32 of the best hits of the compounds having tetra-, tri- and thiadi-azole moiety were tested in vitro, and 4 efficiently inhibited the enzymatic activity of recombinant BlaC. Characterization of the shape of BlaC−/+ inhibitors by small angle X-ray scattering (SAXS) brought forth that BlaC adopts: (1) an open shape (radius of gyration of 2.3 nm compared to 1.9 nm of crystal structures) in solution; (2) closed shape similar to observed crystal structure(s) in presence of effective inhibitor; and (3) a closed shape which opens up when a hydrolysable inhibitor is present in solution. New BlaC inhibitors were: 1-(4-(pyridin-3-yl)-thiazol-2-ylamino)-2-(7,8,9-triaza-bicyclo[4.3.0]nona-1(6),2,4,8-tetraen-7-yl)-ethanone; 8-butyl-3-((5-(pyridin-2-yl)-4H-1,2,4-triazol-3-ylamino)-formyl)-8-aza-bicyclo[4.3.0]nona-1(6),2,4-triene-7,9-dione; 1-(3-((5-(5-bromo-thiophen-2-yl)-1,3,4-oxadiazol-2-yl)-methoxy)-phenyl)-1H-1,2,3,4-tetraazole; and 1-(2,3-dimethyl-phenylamino)-2-(2-(1-(2-methoxy-5-methyl-phenyl)-1H-1,2,3,4-tetraazol-5-ylsulfanyl)-acetylamino)-ethanone. The open-close shape of BlaC questions the physiological significance of the closed shape known for BlaC−/+ inhibitors and paves new path for structure aided design of novel inhibitors.
Relation between Arterial Stiffness and Markers of Inflammation and Hemostasis – Data from the Population-based Gutenberg Health Study
Authors: Arnold Natalie , Gori Tommaso , Schnabel Renate B. , Schulz Andreas , Prochaska Jürgen H. , Zeller Tanja , Binder Harald , Pfeiffer Norbert , Beutel Manfred , Espinola-Klein Christine , Lackner Karl J. , Blankenberg Stefan , Münzel Thomas , Wild Philipp S. 
Published: July 2017

AbstractThe relation between inflammation, hemostasis and arterial stiffness is of pathophysiological relevance for the development of cardiovascular disease (CVD). Data investigating this interplay using stiffness index (SI) by digital photoplethysmography are not available yet. Therefore, sex-specific relation between SI and inflammatory and hemostatic biomarkers was investigated within 13,724 subjects from the population-based Gutenberg Health Study. C-reactive protein (CRP), white blood cell count (WBCC), neopterin, interleukin-18, interleukin-1 receptor antagonist (IL-1RA), fibrinogen and hematocrit were measured. Multivariable linear regression analysis with adjustment for cardiovascular risk factors, medication, and hormonal status (in females) revealed an independent association between SI and WBCC, IL-1RA and hematocrit in both sexes, and with fibrinogen in women. There was a joint effect of increasing tertiles of SI and biomarker concentrations for future CVD risk prediction. Subjects with both SI and biomarker concentration above the median had the worst overall survival and with both below the median the best survival during a follow-up period of 6.2 ± 1.7 years, except for hematocrit. The results support the relation between inflammation, hemostasis and arterial stiffness measured by digital photoplethysmography. Markers of inflammation and hemostasis modulate the ability of SI to identify subjects at risk for future CVD or higher mortality.
A modified formulation of Huanglian-Jie-Du-Tang reduces memory impairments and β-amyloid plaques in a triple transgenic mouse model of Alzheimer’s disease
Authors: Durairajan Siva Sundara Kumar , Iyaswamy Ashok , Shetty Sravan Gopalakrishna , Kammella Ananth Kumar , Malampati Sandeep , Shang Wenbin , Yang Chuanbin , Song Juxian , Chung Sookja , Huang Jiandong , Ilango Kaliappan , Han Quan-Bin , Li Min 
Published: July 2017

AbstractAlzheimer’s disease (AD) is a degenerative disorder typified by progressive deterioration of memory and the appearance of β-amyloid peptide (Aβ)-rich senile plaques. Recently we have identified a novel function of a patented formulation of modified Huanglian-Jie-Tu-Tang (HLJDT-M), a Chinese herbal medicine, in treating AD in in vitro studies (US patent No. 9,375,457). HLJDT-M is a formulation composed of Rhizoma Coptitis, Cortex Phellodendri and Fructus Gardeniae without Radix Scutellariae. Here, we assessed the efficacy of HLJDT-M on a triple transgenic mouse model of AD (3XTg-AD). Oral administration of HLJDT-M ameliorated the cognitive dysfunction of 3XTg-AD mice and lessened the plaque burden. In addition, biochemical assays revealed a significant decrease in levels of detergent-soluble and acid-soluble Aβ via decreasing the levels of full length amyloid-β precursor protein (FL-APP) and C-terminal fragments of APP (CTFs) in brain lysates of HLJDT-M-treated mice. HLJDT-M treatment also significantly reduced the levels of FL-APP and CTFs in N2a/SweAPP cells. In contrast, treatment using the classical formula HLJDT did not reduce the memory impairment of 3XTg-AD mice and, rather, increased the Aβ/Fl-APP/CTFs in both animal and cell culture studies. Altogether, our study indicates that HLJDT-M is a promising herbal formulation to prevent and/or cure AD.
Elucidating the mechanisms underlying the beneficial health effects of dietary pollen on honey bees (Apis mellifera) infested by Varroa mite ectoparasites
Authors: Annoscia Desiderato , Zanni Virginia , Galbraith David , Quirici Anna , Grozinger Christina , Bortolomeazzi Renzo , Nazzi Francesco 
Published: July 2017

AbstractParasites and pathogens of the honey bee (Apis mellifera) are key factors underlying colony losses, which are threatening the beekeeping industry and agriculture as a whole. To control the spread and development of pathogen infections within the colony, honey bees use plant resins with antibiotic activity, but little is known about the properties of other substances, that are mainly used as a foodstuff, for controlling possible diseases both at the individual and colony level. In this study, we tested the hypothesis that pollen is beneficial for honey bees challenged with the parasitic mite Varroa destructor associated to the Deformed Wing Virus. First, we studied the effects of pollen on the survival of infested bees, under laboratory and field conditions, and observed that a pollen rich diet can compensate the deleterious effects of mite parasitization. Subsequently, we characterized the pollen compounds responsible for the observed positive effects. Finally, based on the results of a transcriptomic analysis of parasitized bees fed with pollen or not, we developed a comprehensive framework for interpreting the observed effects of pollen on honey bee health, which incorporates the possible effects on cuticle integrity, energetic metabolism and immune response.
Partial Correlation between Spatial and Temporal Regularities of Human Mobility
Authors: Geng Wei , Yang Guang 
Published: July 2017

AbstractThe regularity of human mobility has been extensively studied because of its prominent applications in a considerable number of important areas. Entropy, in addition to many other measures, has long been used to quantify the regularity of human mobility. We adopt the commonly used spatial entropy and develop an analogical temporal entropy to separately investigate the spatial and temporal regularities of human mobility. The underlying data are from an automated transit fare collection system operated by a metropolitan public transit authority in China. The distributions of both spatial and temporal entropies and their dependences on several widely used statistics are examined. The spatial and temporal entropies present a statistically significant correlation, which has not previously been reported to the best of our knowledge.
Alantolactone induces apoptosis, promotes STAT3 glutathionylation and enhances chemosensitivity of A549 lung adenocarcinoma cells to doxorubicin via oxidative stress
Authors: Maryam Amara , Mehmood Tahir , Zhang He , Li Yongming , Khan Muhammad , Ma Tonghui 
Published: July 2017

AbstractAlantolactone (ALT), a sesquiterpene lactone component of Inula helenium, has been reported to exert anticancer activity in various cancers. However, the cellular targets and underlying mechanism of anticancer activity of ALT in various cancers including lung cancer has not been fully defined. In the present study, we found that ALT effectively inhibits proliferation and triggers oxidative stress mediated-apoptosis in A549 lung adenocarcinoma cells by inducing ER stress and mitochondrial dysfunction. This ALT-mediated apoptosis was inhibited by NAC while diamide potentiated it. Moreover, ALT effectively suppressed both constitutive and inducible STAT3 activation, inhibited its translocation into nucleus and decreased its DNA binding activity. Further mechanistic study revealed that ALT abrogated STAT3 activation by promoting STAT3 glutathionylation. ROS scavenger NAC reverted ALT-mediated STAT3 glutathionylation and inhibition of STAT3 phosphorylation. Finally, ALT enhanced chemosensitivity of A549 cells to doxorubicin and reversed doxorubicin resistance in A549/DR cells by inhibiting STAT3 activation and P-glycoprotein expression and increasing intracellular accumulation of doxorubicin. Suppression of STAT3 activation by targeting ROS metabolism with ALT thus discloses a previously unrecognized mechanism underlying the biological activity of ALT. Taken together; ALT induces oxidative stress-dependent apoptosis, inhibits STAT3 activation and augments doxorubicin toxicity in A549 lung cancer cells. These findings provide an in-depth insight into the molecular mechanism of ALT in the treatment of lung cancer.
Overexpression of DNMT3b target genes during Enteric Nervous System development contribute to the onset of Hirschsprung disease
Authors: Villalba-Benito Leticia , Torroglosa Ana , Fernández Raquel María , Ruíz-Ferrer Macarena , Moya-Jiménez María José , Antiñolo Guillermo , Borrego Salud 
Published: July 2017

AbstractHirschsprung disease (HSCR) is attributed to a failure of neural crest cells (NCCs) to migrate, proliferate, differentiate and/or survive in the bowel wall during embryonic Enteric Nervous System (ENS) development. ENS formation is the result from a specific gene expression pattern regulated by epigenetic events, such DNA methylation by the DNA methyltransferases (DNMTs), among other mechanisms. Specifically, DNMT3b de novo methyltransferase is associated with NCCs development and has been shown to be implicated in ENS formation and in HSCR. Aiming to elucidate the specific mechanism underlying the DNMT3b role in such processes, we have performed a chromatin immunoprecipitation coupled with massively parallel sequencing analysis to identify the DNMT3B target genes in enteric precursor cells (EPCs) from mice. Moreover, the expression patterns of those target genes have been analyzed in human EPCs from HSCR patients in comparison with controls. Additionally, we have carried out a search of rare variants in those genes in a HSCR series. Through this approach we found 9 genes showing a significantly different expression level in both groups. Therefore, those genes may have a role in the proper human ENS formation and a failure in their expression pattern might contribute to this pathology.
Freeze-drying of mammalian cells using trehalose: preservation of DNA integrity
Authors: Zhang Miao , Oldenhof Harriëtte , Sydykov Bulat , Bigalk Judith , Sieme Harald , Wolkers Willem F. 
Published: July 2017

AbstractThe aim of this study was to investigate preservation of biomolecular structures, particularly DNA, in freeze-dried fibroblasts, after loading with trehalose via freezing-induced uptake. Cells were freeze-dried with trehalose alone or in a mixture of albumin and trehalose. Albumin was added to increase the glass transition temperature and storage stability. No viable cells were recovered after freeze-drying and rehydration. FTIR studies showed that membrane phase behavior of freeze-dried cells resembles that of fresh cells. However, one day after rehydration membrane phase separation was observed, irrespective of the presence or absence of trehalose during freeze-drying. Freeze-drying did not affect the overall protein secondary structure. Analysis of DNA damage via single cell gel electrophoresis (‘comet assay’) showed that DNA damage progressively increased with storage duration and temperature. DNA damage was prevented during storage at 4 °C. It is shown that trehalose reduces DNA damage during storage, whereas addition of albumin did not seem to have an additional protective effect on storage stability (i.e. DNA integrity) despite the fact that albumin increased the glass transition temperature. Taken together, DNA in freeze-dried somatic cells can be preserved using trehalose as protectant and storage at or below 4 °C.
Phylodynamics of major CRF01_AE epidemic clusters circulating in mainland of China
Authors: Wang Xiaolin , He Xiang , Zhong Ping , Liu Yongjian , Gui Tao , Jia Dijing , Li Hanping , Wu Jianjun , Yan Jin , Kang Dianmin , Han Yang , Li Taisheng , Yang Rongge , Han Xiaoxu , Chen Lin , Zhao Jin , Xing Hui , Liang Shu , He Jianmei , Yan Yansheng , Xue Yile , Zhang Jiafeng , Zhuang Xun , Liang Shujia , Bao Zuoyi , Li Tianyi , Zhuang Daomin , Liu Siyang , Han Jingwan , Jia Lei , Li Jingyun , Li Lin 
Published: July 2017

AbstractAs the most dominant HIV-1 strain in China, CRF01_AE needs to have its evolutionary and demographic history documented. In this study, we provide phylogenetic analysis of all CRF01_AE pol sequences identified in mainland China. CRF01_AE sequences were collected from the Los Alamos HIV Sequence Database and the local Chinese provincial centers of disease control and prevention. Phylogenetic trees were constructed to identify major epidemic clusters. Bayesian coalescent-based method was used to reconstruct the time scale and demographic history. There were 2965 CRF01_AE sequences from 24 Chinese provinces that were collected, and 5 major epidemic clusters containing 85% of the total CRF01_AE sequences were identified. Every cluster contains sequences from more than 10 provinces with 1 or 2 dominant transmission routes. One cluster arose in the 1990s and 4 clusters arose in the 2000s. Cluster I is in the decline stage, while the other clusters are in the stable stage. Obvious lineage can be observed among sequences from the same transmission route but not the same area. Two large clusters in high-level prevalence were found in MSM (Men who have sex with men), which highlighted that more emphasis should be placed on MSM for HIV control in mainland China.
Validation of asynchronous quantitative bone densitometry of the spine: Accuracy, short-term reproducibility, and a comparison with conventional quantitative computed tomography
Authors: Wang Ling , Su Yongbin , Wang Qianqian , Duanmu Yangyang , Yang Minghui , Yi Chen , Cheng Xiaoguang 
Published: July 2017

AbstractAsynchronous calibration quantitative computed tomography (QCT) is a new tool that allows the quantification of bone mineral density (BMD) without the use of a calibration phantom during scanning; however, this tool is not fully validated for clinical use. We used the European spine phantom (ESP) with repositioning during scanning and assessed the accuracy and short-term reproducibility of asynchronous QCT. Intra-scanner and intra-observer precision were each calculated as the root mean square of the standard deviation (RMSSD) and the coefficient of variation (CV-RMSSD). We also compared asynchronous and conventional QCT results in 50 clinical subjects. The accuracy of asynchronous QCT for three ESP vertebrae ranged from 1.4–6.7%, whereas intra-scanner precision for these vertebrae ranged from 0.53–0.91 mg/cc. Asynchronous QCT was most precise for a trabecular BMD of 100 mg/cc (CV-RMSSD = 0.2%). For intra-observer variability, overall precision error was smaller than 3%. In clinical subjects there was excellent agreement between the two calibration methods with correlation coefficients ranging from 0.96–0.99. A Bland–Altman analysis demonstrated that methodological differences depended on the magnitude of the BMD variable. Our findings indicate that the asynchronous QCT has good accuracy and precision for assessing trabecular BMD in the spine.
Universality of maximum-work efficiency of a cyclic heat engine based on a finite system of ultracold atoms
Authors: Ye Zhuolin , Hu Yingying , He Jizhou , Wang Jianhui 
Published: July 2017

AbstractWe study the performance of a cyclic heat engine which uses a small system with a finite number of ultracold atoms as its working substance and works between two heat reservoirs at constant temperatures T
h
and T
c
(<T
h
). Starting from the expression of heat capacity which includes finite-size effects, the work output is optimized with respect to the temperature of the working substance at a special instant along the cycle. The maximum-work efficiency η
mw at small relative temperature difference can be expanded in terms of the Carnot value $${{\boldsymbol{\eta }}}_{{\boldsymbol{C}}}={\bf{1}}-{{\boldsymbol{T}}}_{{\boldsymbol{c}}}/{{\boldsymbol{T}}}_{{\boldsymbol{h}}}$$

η

C

=
1
−

T

c

/

T

h

, $${{\boldsymbol{\eta }}}^{{\boldsymbol{m}}{\bf{w}}}={{\boldsymbol{\eta }}}_{{\boldsymbol{C}}}/{\bf{2}}+{{\boldsymbol{\eta }}}_{{\boldsymbol{C}}}^{{\bf{2}}}({\bf{1}}/{\bf{8}}+{{\boldsymbol{a}}}_{{\bf{0}}})+{\boldsymbol{\ldots }}$$

η

m
w

=

η

C

/
2

+

η

C

2

(

1
/
8

+

a

0

)
+
…
, where a0 is a function depending on the particle number N and becomes vanishing in the symmetric case. Moreover, we prove using the relationship between the temperatures of the working substance and heat reservoirs that the maximum-work efficiency, when accurate to the first order of η
C
, reads $${{\boldsymbol{\eta }}}^{{\boldsymbol{m}}{\bf{w}}}={{\boldsymbol{\eta }}}_{{\boldsymbol{CA}}}+{\bf{O}}$$

η

m
w

=

η

CA

+
O
(ΔT2). Within the framework of linear irreversible thermodynamics, the maximum-power efficiency is obtained as $${{\boldsymbol{\eta }}}^{{\boldsymbol{mp}}}={{\boldsymbol{\eta }}}_{{\boldsymbol{CA}}}+{\bf{O}}$$

η

mp

=

η

CA

+
O
(ΔT2) through appropriate identification of thermodynamic fluxes and forces, thereby showing that this kind of cyclic heat engines satisfy the tight-coupling condition.
Green tide development associated with submarine groundwater discharge in a coastal harbor, Jeju, Korea
Authors: Kwon Hyeong Kyu , Kang Hyekyung , Oh Yong Hwa , Park Sang Rul , Kim Guebuem 
Published: July 2017

AbstractWe measured the magnitude of submarine fresh groundwater discharge (SFGD) and associated nutrient inputs to Jocheon harbor, on Jeju Island, Korea, during four sampling periods, in order to determine the link between SFGD and Ulva sp. green tide development. Good correlations among salinity, 222Rn, and dissolved inorganic nitrogen (DIN) in harbor seawater suggest that SFGD is the major source of DIN and fresh water since there are no surface runoffs. Using a 222Rn mass balance model, SFGD to the harbor was estimated to be 5.8 ± 2.3 × 104 m3 d−1. The DIN inputs through SFGD enhanced DIN concentrations in harbor seawater approximately 10-fold of those in the open-ocean (outer harbor) seawater. Results from mesocosm experiments showed that the growth rate of U. pertusa increased by 160% on average due to the enhanced DIN concentrations (from 1 to 24 µM) through SFGD in this harbor. Thus, we conclude that DIN inputs through SFGD cause the green tide development in Jocheon harbor and perhaps in other green tide regions where river inputs are absent.
p38 MAPK signaling and phosphorylations in the BRCT1 domain regulate XRCC1 recruitment to sites of DNA damage
Authors: de Sousa Mirta Mittelstedt Leal , Bjørås Karine Øian , Hanssen-Bauer Audun , Solvang-Garten Karin , Otterlei Marit 
Published: July 2017

AbstractXRCC1 is a scaffold protein involved in base excision repair and single strand break repair. It is a phosphoprotein that contains more than 45 phosphorylation sites, however only a few of these have been characterized and connected to specific kinases and functions. Mitogen activated protein kinases (MAPK) are mediators of cellular stress responses, and here we demonstrate that p38 MAPK signaling is involved in phosphorylation of XRCC1 and regulation of recruitment to oxidative stress. Inhibition of p38 MAPK caused a marked pI shift of XRCC1 towards a less phosphorylated state. Inhibition of p38 also increased the immediate accumulation of XRCC1 at site of DNA damage in a poly(ADP)-ribose (PAR) dependent manner. These results suggest a link between PARylation, p38 signaling and XRCC1 recruitment to DNA damage. Additionally, we characterized two phosphorylation sites, T358 and T367, located within, or close to, the phosphate-binding pocket of XRCC1, which is important for interaction with PAR. Mutation of these sites impairs recruitment of XRCC1 to DNA damage and binding to PARP1/PAR. Collectively, our data suggest that phosphorylation of T358 and T367 and p38 signaling are important for proper regulation of XRCC1 recruitment to DNA damage and thereby avoidance of potential toxic and mutagenic BER-intermediates.
Environment Changes Genetic Effects on Respiratory Conditions and Allergic Phenotypes
Authors: Song Yong , Schwager Michelle J. , Backer Vibeke , Guo Jing , Porsbjerg Celeste , Khoo Siew-Kim , Laing Ingrid A. , Moses Eric K. , LeSouëf Peter , Zhang Guicheng 
Published: July 2017

AbstractThe prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically separated population. We evaluated 18 single nucleotide polymorphisms (SNPs) corresponding to 8 genes (ADAM33, ALOX5, LT-α, LTC4S, NOS1, ORMDL3, TBXA2R and TNF-α), the lung function and five respiratory/allergic conditions (ever asthma, bronchitis, rhinitis, dermatitis and atopy) in two populations of Inuit residing either in the westernized environment of Denmark or in the rural area of Greenland. Our results showed that lung function was associated with genetic variants in ORMDL3, with polymorphisms having a significant interaction with place of residence. LT-α SNP rs909253 and rs1041981 were significantly associated with bronchitis risk. LT-α SNP rs2844484 was related to dermatitis susceptibility and was significantly influenced by the place of residence. The observed gene-phenotype relationships were exclusively present in one population and absent in the other population. We conclude that the genotype-phenotype associations relating to bronchitis and allergy susceptibility are dependent on the environment and that environmental factors/lifestyles modify genetic predisposition and change the genetic effects on diseases.
Broadband dual‐circularly polarised SIW cavity antenna using a stacked structure
Authors: Kumar A. , Raghavan S. 
Published: July 2017

A wideband dual‐circularly polarised (CP) substrate integrated waveguide (SIW) cavity‐backed patch antenna is designed by using two‐layer structure. The realised dual‐CP, a cavity‐backed square patch lies on the top substrate is excited by two pins, which are symmetrically located at an offset to the diagonal axis of the patch. These pins induce strong loading effect in the cavity and generate additional resonances in the vicinity of the patch resonant that help to achieve a wideband response by adjusting their locations. Thus, generation of dual‐CP and wide impedance bandwidth is accomplished by using this new feeding topology. Moreover, the antenna is fabricated and tested for dual‐CP. The experimental results show an impedance bandwidth of nearly 28.4% (8.59–11.43 GHz) and an axial‐ratio bandwidth of 3.4% under the criterion <3‐dB.