bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neonatal treatment with scopolamine butylbromide prevents metabolic dysfunction in male rats
Authors: Malta Ananda , Souza Aline Amenencia de , Ribeiro Tatiane Aparecida , Francisco Flávio Andrade , Pavanello Audrei , Prates Kelly Valério , Tófolo Laize Peron , Miranda Rosiane Aparecida , Oliveira Júlio Cezar de , Martins Isabela Peixoto , Previate Carina , Gomes Rodrigo Mello , Franco Claudinéia Conationi da Silva , Natali Maria Raquel Marçal , Palma-Rigo Kesia , Mathias Paulo Cezar de Freitas 
Published: August 2016

AbstractWe tested whether treatment with a cholinergic antagonist could reduce insulin levels in early postnatal life and attenuate metabolic dysfunctions induced by early overfeeding in adult male rats. Wistar rats raised in small litters (SLs, 3 pups/dam) and normal litters (NLs, 9 pups/dam) were used in models of early overfeeding and normal feeding, respectively. During the first 12 days of lactation, animals in the SL and NL groups received scopolamine butylbromide (B), while the controls received saline (S) injections. The drug treatment decreased insulin levels in pups from both groups, and as adults, these animals showed improvements in glucose tolerance, insulin sensitivity, vagus nerve activity, fat tissue accretion, insulinemia, leptinemia, body weight gain and food intake. Low glucose and cholinergic insulinotropic effects were observed in pancreatic islets from both groups. Low protein expression was observed for the muscarinic M3 acetylcholine receptor subtype (M3mAChR), although M2mAChR subtype expression was increased in SL-B islets. In addition, beta-cell density was reduced in drug-treated rats. These results indicate that early postnatal scopolamine butylbromide treatment inhibits early overfeeding-induced metabolic dysfunctions in adult rats, which might be caused by insulin decreases during lactation, associated with reduced parasympathetic activity and expression of M3mAChR in pancreatic islets.
Metadynamic metainference: Enhanced sampling of the metainference ensemble using metadynamics
Authors: Bonomi Massimiliano , Camilloni Carlo , Vendruscolo Michele 
Published: August 2016

AbstractAccurate and precise structural ensembles of proteins and macromolecular complexes can be obtained with metainference, a recently proposed Bayesian inference method that integrates experimental information with prior knowledge and deals with all sources of errors in the data as well as with sample heterogeneity. The study of complex macromolecular systems, however, requires an extensive conformational sampling, which represents a separate challenge. To address such challenge and to exhaustively and efficiently generate structural ensembles we combine metainference with metadynamics and illustrate its application to the calculation of the free energy landscape of the alanine dipeptide.
The Cytomegalovirus protein pUL37×1 targets mitochondria to mediate neuroprotection
Authors: Hong Chien Tai , Chau Kai-Yin , Schapira Anthony H. V. 
Published: August 2016

AbstractThere is substantial evidence that mitochondrial dysfunction plays a significant role in the pathogenesis of Parkinson disease (PD). This contribution probably encompasses defects of oxidative phosphorylation, mitochondrial turnover (mitophagy), mitochondrial derived oxidative stress and apoptotic signalling. Human cytomegalovirus immediate-early protein pUL37 × 1 induces Bax mitochondrial translocation and inactivation to prevent apoptosis. Over-expressing pUL37 × 1 in neuronal cells protects against staurosporin and 6-hydroxydopamine induced apoptosis and cell death. Protection is not enhanced by bax silencing in pUL37 × 1 over-expressing cells, suggesting a bax-dependent mechanism of action. pUL37 × 1 increases glycolysis and induces mitochondrial hyperpolarization, a bax independent anti-apoptotic action. pUL37 × 1 increases glycolysis through activation of phosphofructokinase by a calcium-dependent pathway. The dual anti-apoptotic mechanism of pUL37 × 1 may be considered a novel neuroprotective strategy in diseases where mitochondrial dysfunction and apoptotic pathways are involved.
A novel method to predict visual field progression more accurately, using intraocular pressure measurements in glaucoma patients
Authors:   The Japanese Archive of Multicentral Database in Glaucoma (JAMDIG) construction group, Asaoka Ryo , Fujino Yuri , Murata Hiroshi , Miki Atsuya , Tanito Masaki , Mizoue Shiro , Mori Kazuhiko , Suzuki Katsuyoshi , Yamashita Takehiro , Kashiwagi Kenji , Shoji Nobuyuki 
Published: August 2016

AbstractVisual field (VF) data were retrospectively obtained from 491 eyes in 317 patients with open angle glaucoma who had undergone ten VF tests (Humphrey Field Analyzer, 24-2, SITA standard). First, mean of total deviation values (mTD) in the tenth VF was predicted using standard linear regression of the first five VFs (VF1-5) through to using all nine preceding VFs (VF1-9). Then an ‘intraocular pressure (IOP)-integrated VF trend analysis’ was carried out by simply using time multiplied by IOP as the independent term in the linear regression model. Prediction errors (absolute prediction error or root mean squared error: RMSE) for predicting mTD and also point wise TD values of the tenth VF were obtained from both approaches. The mTD absolute prediction errors associated with the IOP-integrated VF trend analysis were significantly smaller than those from the standard trend analysis when VF1-6 through to VF1-8 were used (p < 0.05). The point wise RMSEs from the IOP-integrated trend analysis were significantly smaller than those from the standard trend analysis when VF1-5 through to VF1-9 were used (p < 0.05). This was especially the case when IOP was measured more frequently. Thus a significantly more accurate prediction of VF progression is possible using a simple trend analysis that incorporates IOP measurements.
Complete De Novo Assembly of Monoclonal Antibody Sequences
Authors: Tran Ngoc Hieu , Rahman M. Ziaur , He Lin , Xin Lei , Shan Baozhen , Li Ming 
Published: August 2016

AbstractDe novo protein sequencing is one of the key problems in mass spectrometry-based proteomics, especially for novel proteins such as monoclonal antibodies for which genome information is often limited or not available. However, due to limitations in peptides fragmentation and coverage, as well as ambiguities in spectra interpretation, complete de novo assembly of unknown protein sequences still remains challenging. To address this problem, we propose an integrated system, ALPS, which for the first time can automatically assemble full-length monoclonal antibody sequences. Our system integrates de novo sequencing peptides, their quality scores and error-correction information from databases into a weighted de Bruijn graph to assemble protein sequences. We evaluated ALPS performance on two antibody data sets, each including a heavy chain and a light chain. The results show that ALPS was able to assemble three complete monoclonal antibody sequences of length 216–441 AA, at 100% coverage and 96.64–100% accuracy.
Eye fixation during multiple object attention is based on a representation of discrete spatial foci
Authors: Fluharty Meg , Jentzsch Ines , Spitschan Manuel , Vishwanath Dhanraj 
Published: August 2016

AbstractWe often look at and attend to several objects at once. How the brain determines where to point our eyes when we do this is poorly understood. Here we devised a novel paradigm to discriminate between different models of spatial selection guiding fixation. In contrast to standard static attentional tasks where the eye remains fixed at a predefined location, observers selected their own preferred fixation position while they tracked static targets that were arranged in specific geometric configurations and which changed identity over time. Fixations were best predicted by a representation of discrete spatial foci, not a polygonal grouping, simple 2-foci division of attention or a circular spotlight. Moreover, attentional performance was incompatible with serial selection. Together with previous studies, our findings are compatible with a view that attentional selection and fixation rely on shared spatial representations and suggest a more nuanced definition of overt vs. covert attention.
FFPred 3: feature-based function prediction for all Gene Ontology domains
Authors: Cozzetto Domenico , Minneci Federico , Currant Hannah , Jones David T. 
Published: August 2016

AbstractPredicting protein function has been a major goal of bioinformatics for several decades, and it has gained fresh momentum thanks to recent community-wide blind tests aimed at benchmarking available tools on a genomic scale. Sequence-based predictors, especially those performing homology-based transfers, remain the most popular but increasing understanding of their limitations has stimulated the development of complementary approaches, which mostly exploit machine learning. Here we present FFPred 3, which is intended for assigning Gene Ontology terms to human protein chains, when homology with characterized proteins can provide little aid. Predictions are made by scanning the input sequences against an array of Support Vector Machines (SVMs), each examining the relationship between protein function and biophysical attributes describing secondary structure, transmembrane helices, intrinsically disordered regions, signal peptides and other motifs. This update features a larger SVM library that extends its coverage to the cellular component sub-ontology for the first time, prompted by the establishment of a dedicated evaluation category within the Critical Assessment of Functional Annotation. The effectiveness of this approach is demonstrated through benchmarking experiments, and its usefulness is illustrated by analysing the potential functional consequences of alternative splicing in human and their relationship to patterns of biological features.
Dual-Band Dual-Mode Substrate Integrated Waveguide Filters with Independently Reconfigurable TE101 Resonant Mode
Authors: Wu Yongle , Chen Yuqing , Jiao Lingxiao , Liu Yuanan , Ghassemlooy Zabih 
Published: August 2016

AbstractA novel perturbation approach using additional metalized via-holes for implementation of the dual-band or wide-band dual-mode substrate integrated waveguide (SIW) filters is proposed in this paper. The independent perturbation on the first resonant mode TE101 can be constructed by applying the proposed perturbation approach, whereas the second resonant mode TE102 is not affected. Thus, new kinds of dual-band or wide-band dual-mode SIW filters with a fixed or an independently reconfigurable low-frequency band have been directly achieved. In order to experimentally verify the proposed design method, four two-cavity dual-band SIW filters, which have different numbers of perturbation via-holes in each cavity and a two-cavity dual-band SIW filter, which includes four via-holes and eight reconfigurable states in each cavity, are designed and experimentally assessed. The measured results indicate that the available frequency-ratio range from 1 to 1.3 can be realized by using four two-cavity dual-band SIW filters. The center frequency of the first band can be tuned from 4.61 GHz to 5.24 GHz, whereas the center frequency of the second one is fixed at around 6.18 GHz for the two-cavity dual-band SIW filter with four reconfigurable states via-holes. All the simulated and measured results show an acceptable agreement with the predicted data.
Pubertal Expression of α4βδ GABAA Receptors Reduces Seizure-Like Discharges in CA1 Hippocampus
Authors: Yang Lie , Shen Hui , Merlin Lisa R. , Smith Sheryl S. 
Published: August 2016

AbstractMore than half of children with epilepsy outgrow their seizures, yet the underlying mechanism is unknown. GABAergic inhibition increases at puberty in female mice due to expression of extrasynaptic α4βδ GABAA receptors (GABARs). Therefore, we tested the role of these receptors in regulating seizure-like discharges in CA1 hippocampus using a high K+ (8.5 mM) seizure model. Spontaneous field potentials were recorded from hippocampus of pre-pubertal (~28–32 PND) and pubertal (~35–44 PND) female wild-type or α4−/− mice. The coastline length, a measure of burst intensity, was assessed. 8.5 mM K+ induced seizure-like discharges in over 60% of pre-pubertal slices, but only in 7% of pubertal slices, where the coastline length was reduced by 70% (P = 0.04). However, the pubertal decrease in seizure-like discharges was not seen in the α4−/−, implicating α4βδ GABARs as the cause of the decreased seizure-like activity during puberty. Administration of THIP or DS2, to selectively increase α4βδ current, reduced activity in 8.5 mM K+ at puberty, while blockade of α5-GABARs had no effect. GABAergic current was depolarizing but inhibitory in 8.5 mM K+, suggesting a mechanism for the effects of α4βδ and α5-GABARs, which exhibit different polarity-dependent desensitization. These data suggest that α4βδ GABARs are anti-convulsant during adolescence.
Activation of Nrf2 by the dengue virus causes an increase in CLEC5A, which enhances TNF-α production by mononuclear phagocytes
Authors: Cheng Yi-Lin , Lin Yee-Shin , Chen Chia-Ling , Tsai Tsung-Ting , Tsai Cheng-Chieh , Wu Yan-Wei , Ou Yi-Dan , Chu Yu-Yi , Wang Ju-Ming , Yu Chia-Yi , Lin Chiou-Feng 
Published: August 2016

AbstractInfection by the dengue virus (DENV) threatens global public health due to its high prevalence and the lack of effective treatments. Host factors may contribute to the pathogenesis of DENV; herein, we investigated the role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which is activated by DENV in mononuclear phagocytes. DENV infection selectively activates Nrf2 following nuclear translocation. Following endoplasmic reticular (ER) stress, protein kinase R-like ER kinase (PERK) facilitated Nrf2-mediated transcriptional activation of C-type lectin domain family 5, member A (CLEC5A) to increase CLEC5A expression. Signaling downstream of the Nrf2-CLEC5A interaction enhances Toll-like receptor 3 (TLR3)-independent tumor necrosis factor (TNF)-α production following DENV infection. Forced expression of the NS2B3 viral protein induces Nrf2 nuclear translocation/activation and CLEC5A expression which increases DENV-induced TNF-α production. Animal studies confirmed Nrf2-induced CLEC5A and TNF-α in brains of DENV-infected mice. These results demonstrate that DENV infection causes Nrf2-regulated TNF-α production by increasing levels of CLEC5A.
Non-invasive MRI Assessments of Tissue Microstructures and Macromolecules in the Eye upon Biomechanical or Biochemical Modulation
Authors: Ho Leon C. , Sigal Ian A. , Jan Ning-Jiun , Yang Xiaoling , van der Merwe Yolandi , Yu Yu , Chau Ying , Leung Christopher K. , Conner Ian P. , Jin Tao , Wu Ed X. , Kim Seong-Gi , Wollstein Gadi , Schuman Joel S. , Chan Kevin C. 
Published: August 2016

AbstractThe microstructural organization and composition of the corneoscleral shell (CSS) determine the biomechanical behavior of the eye, and are important in diseases such as glaucoma and myopia. However, limited techniques can assess these properties globally, non-invasively and quantitatively. In this study, we hypothesized that multi-modal magnetic resonance imaging (MRI) can reveal the effects of biomechanical or biochemical modulation on CSS. Upon intraocular pressure (IOP) elevation, CSS appeared hyperintense in both freshly prepared ovine eyes and living rat eyes using T2-weighted MRI. Quantitatively, transverse relaxation time (T2) of CSS increased non-linearly with IOP at 0–40 mmHg and remained longer than unloaded tissues after being unpressurized. IOP loading also increased fractional anisotropy of CSS in diffusion tensor MRI without apparent change in magnetization transfer MRI, suggestive of straightening of microstructural fibers without modification of macromolecular contents. Lastly, treatments with increasing glyceraldehyde (mimicking crosslinking conditions) and chondroitinase-ABC concentrations (mimicking glycosaminoglycan depletion) decreased diffusivities and increased magnetization transfer in cornea, whereas glyceraldehyde also increased magnetization transfer in sclera. In summary, we demonstrated the changing profiles of MRI contrast mechanisms resulting from biomechanical or biochemical modulation of the eye non-invasively. Multi-modal MRI may help evaluate the pathophysiological mechanisms in CSS and the efficacy of corneoscleral treatments.
Discovery of a Carbazole-Derived Lead Drug for Human African Trypanosomiasis
Authors: Thomas Sarah M. , Purmal Andrei , Pollastri Michael , Mensa-Wilmot Kojo 
Published: August 2016

AbstractThe protozoan parasite Trypanosoma brucei causes the fatal illness human African trypanosomiasis (HAT). Standard of care medications currently used to treat HAT have severe limitations, and there is a need to find new chemical entities that are active against infections of T. brucei. Following a “drug repurposing” approach, we tested anti-trypanosomal effects of carbazole-derived compounds called “Curaxins”. In vitro screening of 26 compounds revealed 22 with nanomolar potency against axenically cultured bloodstream trypanosomes. In a murine model of HAT, oral administration of compound 1 cured the disease. These studies established 1 as a lead for development of drugs against HAT. Pharmacological time-course studies revealed the primary effect of 1 to be concurrent inhibition of mitosis coupled with aberrant licensing of S-phase entry. Consequently, polyploid trypanosomes containing 8C equivalent of DNA per nucleus and three or four kinetoplasts were produced. These effects of 1 on the trypanosome are reminiscent of “mitotic slippage” or endoreplication observed in some other eukaryotes.
Cell non-autonomous regulation of hepatic IGF-1 and neonatal growth by Kinase Suppressor of Ras 2 (KSR2)
Authors: Guo Lili , Costanzo-Garvey Diane L. , Smith Deandra R. , Zavorka Megan E. , Venable-Kang Megan , MacDonald Richard G. , Lewis Robert E. 
Published: August 2016

AbstractIndividuals with poor postnatal growth are at risk for cardiovascular and metabolic problems as adults. Here we show that disruption of the molecular scaffold Kinase Suppressor of Ras 2 (KSR2) causes selective inhibition of hepatic GH signaling in neonatal mice with impaired expression of IGF-1 and IGFBP3. ksr2−/− mice are normal size at birth but show a marked increase in FGF21 accompanied by reduced body mass, shortened body length, and reduced bone mineral density (BMD) and content (BMC) first evident during postnatal development. However, disrupting FGF21 in ksr2−/− mice does not normalize mass, length, or bone density and content in fgf21−/−ksr2−/− mice. Body length, BMC and BMD, but not body mass, are rescued by infection of two-day-old ksr2−/− mice with a recombinant adenovirus encoding human IGF-1. Relative to wild-type mice, GH injections reveal a significant reduction in JAK2 and STAT5 phosphorylation in liver, but not in skeletal muscle, of ksr2−/− mice. However, primary hepatocytes isolated from ksr2−/− mice show no reduction in GH-stimulated STAT5 phosphorylation. These data indicate that KSR2 functions in a cell non-autonomous fashion to regulate GH-stimulated IGF-1 expression in the liver of neonatal mice, which plays a key role in the development of body length.
Butyrate and bioactive proteolytic form of Wnt-5a regulate colonic epithelial proliferation and spatial development
Authors: Uchiyama Kazuhiko , Sakiyama Toshio , Hasebe Takumu , Musch Mark W. , Miyoshi Hiroyuki , Nakagawa Yasushi , He Tong-Chuan , Lichtenstein Lev , Naito Yuji , Itoh Yoshito , Yoshikawa Toshikazu , Jabri Bana , Stappenbeck Thaddeus , Chang Eugene B. 
Published: August 2016

AbstractProliferation and spatial development of colonic epithelial cells are highly regulated along the crypt vertical axis, which, when perturbed, can result in aberrant growth and carcinogenesis. In this study, two key factors were identified that have important and counterbalancing roles regulating these processes: pericrypt myofibroblast-derived Wnt-5a and the microbial metabolite butyrate. Cultured YAMC cell proliferation and heat shock protein induction were analzyed after butryate, conditioned medium with Wnt5a activity, and FrzB containing conditioned medium. In vivo studies to modulate Hsp25 employed intra-colonic wall Hsp25 encoding lentivirus. To silence Wnt-5a in vivo, intra-colonic wall Wnt-5a silencing RNA was used. Wnt-5a, secreted by stromal myofibroblasts of the lower crypt, promotes proliferation through canonical β-catenin activation. Essential to this are two key requirements: (1) proteolytic conversion of the highly insoluble ~40 kD Wnt-5a protein to a soluble 36 mer amino acid peptide that activates epithelial β-catenin and cellular proliferation, and (2) the simultaneous inhibition of butyrate-induced Hsp25 by Wnt-5a which is necessary to arrest the proliferative process in the upper colonic crypt. The interplay and spatial gradients of these factors insures that crypt epithelial cell proliferation and development proceed in an orderly fashion, but with sufficient plasticity to adapt to physiological perturbations including inflammation.
Neuroprotective levels of IGF-1 exacerbate epileptogenesis after brain injury
Authors: Song Yu , Pimentel Corrin , Walters Katherine , Boller Lauren , Ghiasvand Shabnam , Liu Jing , Staley Kevin J. , Berdichevsky Yevgeny 
Published: August 2016

AbstractExogenous Insulin-Like Growth Factor-1 (IGF-1) is neuroprotective in animal models of brain injury, and has been considered as a potential therapeutic. Akt-mTOR and MAPK are downstream targets of IGF-1 signaling that are activated after brain injury. However, both brain injury and mTOR are linked to epilepsy, raising the possibility that IGF-1 may be epileptogenic. Here, we considered the role of IGF-1 in development of epilepsy after brain injury, using the organotypic hippocampal culture model of post-traumatic epileptogenesis. We found that IGF-1 was neuroprotective within a few days of injury but that long-term IGF-1 treatment was pro-epileptic. Pro-epileptic effects of IGF-1 were mediated by Akt-mTOR signaling. We also found that IGF-1 – mediated increase in epileptic activity led to neurotoxicity. The dualistic nature of effects of IGF-1 treatment demonstrates that anabolic enhancement through IGF-1 activation of mTOR cascade can be beneficial or harmful depending on the stage of the disease. Our findings suggest that epilepsy risk may need to be considered in the design of neuroprotective treatments for brain injury.