bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of novel choline acetyltransferase inhibitors using structure-based virtual screening
Authors: Kumar Rajnish , Kumar Amit , Långström Bengt , Darreh-Shori Taher 
Published: November 2017

AbstractAlzheimer disease and related dementias are major challenges, demanding urgent needs for earliest possible diagnosis to optimize the success rate in finding effective therapeutic interventions. Mounting solid scientific premises point at the core acetylcholine-biosynthesizing cholinergic enzyme, ChAT as a legitimate in vivo target for developing positron emission tomography biomarker for early diagnosis and/or monitoring therapeutic responses in the neurodegenerative dementias. Up-to-date, no PET tracer ligands for ChAT are available. Here we report for the first time a novel hierarchical virtual screening approach on a commercial library of ~300,000 compounds, followed by in vitro screening of the hits by a new High-Throughput ChAT assay. We report detailed pharmacodynamic data for three identified selective novel ChAT ligands with IC50 and K
i
values ranging from ~7 to 26 µM. In addition, several novel selective inhibitors of the acetylcholine-degrading enzymes, AChE and BuChE were identified, with one of the compounds showing an IC50-value of ~6 µM for AChE. In conclusion, this report provides an excellent starting platform for designing and optimizing potent and selective ChAT ligands, with high potential as PET-imaging probe for early diagnosis of AD, and related dementias, such as Down’s syndrome and Lewy body disorders.
Hall conductance for open two-band system beyond rotating-wave approximation
Authors: Zhang W. Q. , Shen H. Z. , Yi X. X. 
Published: November 2017

AbstractThe response of the open two-band system to external fields would in general be different from that of a strictly isolated one. In this paper, we systematically study the Hall conductance of a two-band model under the influence of its environment by treating the system and its environment on equal footing. In order to clarify some well-established conclusions about the Hall conductance, we do not use the rotating wave approximation (RWA) in obtaining an effective Hamiltonian. Specifically, we first derive the ground state of the whole system (the system plus the environment) beyond the RWA, then calculate an analytical expression for Hall conductance of this open system in the ground state. We apply the expression to two examples, including a magnetic semiconductor with Rashba-type spin-orbit coupling and an electron gas on a square two-dimensional lattice. The calculations show that the transition points of topological phase are robust against the environment. Our results suggest a way to the controlling of the whole system response, which has potential applications for condensed matter physics and quantum statistical mechanics.
Avian Influenza H5N6 Viruses Exhibit Differing Pathogenicities and Transmissibilities in Mammals
Authors: Zhao Zongzheng , Guo Zhendong , Zhang Chunmao , Liu Lina , Chen Ligong , Zhang Cheng , Wang Zhongyi , Fu Yingying , Li Jiaming , Shao Huabin , Luo Qingping , Qian Jun , Liu Linna 
Published: November 2017

AbstractSince 2013, highly pathogenic avian influenza H5N6 viruses have emerged in poultry and caused sporadic infections in humans, increasing global concerns regarding their potential as human pandemic threats. Here, we characterized the receptor-binding specificities, pathogenicities and transmissibilities of three H5N6 viruses isolated from poultry in China. The surface genes hemagglutinin (HA) and neuraminidase (NA) were closely related to the human-originating strain A/Changsha/1/2014 (H5N6). Phylogenetic analyses showed that the HA genes were clustered in the 2.3.4.4 clade, and the NA genes were derived from H6N6 viruses. These H5N6 viruses bound both α-2,3-linked and α-2,6-linked sialic acid receptors, but they exhibited different pathogenicities in mice. In addition, one virus was fully infective and transmissible by direct contact in guinea pigs. These results highlight the importance of monitoring the continual adaptation of H5N6 viruses in poultry due to their potential threat to human health.
Incidence and risk of respiratory tract infection associated with specific drug therapy in pulmonary arterial hypertension: a systematic review
Authors: Gu Zhichun , Zhang Chi , Wei Anhua , Cui Min , Pu Jun , Lin Houwen , Liu Xiaoyan 
Published: November 2017

AbstractSpecific drug therapy has been proven to improve functional capacity and slow disease progression in pulmonary arterial hypertension (PAH), regretfully with the data on the risk of respiratory tract infection (RTI) associated with specific drug therapy being limited. Databases of Medline, Embase, Cochrane Library and the ClinicalTrials.gov Website were searched for randomized controlled trials (RCTs) that reported the RTI data of PAH-specific drug therapy in patients. The primacy outcome was assessed by employing a fixed-effects model. Totally, 24 trials involving 6307 patients were included in the analysis. PAH-specific drug therapy was not significantly associated with the increased risk of both RTI (19.4% vs. 21.1% RR 1.02, 95%CI 0.92–1.14, P = 0.69) and serious RTI (4.3% vs. 5.0% RR 0.99, 95%CI 0.77–1.26, P = 0.93) compared to placebo. The results were consistent across the key subgroups. No heterogeneity between the studies (I2 = 35.8% for RTI, and I2 = 0.0% for serious RTI) and no publication bias was identified. In conclusion, no significant increase in RTI had been found in PAH-specific drug therapy when compared with placebo. Whereas, RTI in PAH patients is still worthy of clinical attention.
Alanine substitution in cellobiohydrolase provides new insights into substrate threading
Authors: Mitsuzawa Shigenobu , Fukuura Maiko , Shinkawa Satoru , Kimura Keiichi , Furuta Tadaomi 
Published: November 2017

AbstractThe glycoside hydrolase family 7 (GH7) member cellobiohydrolase (CBH) is a key enzyme that degrades crystalline cellulose, an important structural component of plant cell walls. As GH7 CBH is a major component in the enzyme mixture used to degrade biomass into fermentable glucose in biorefineries, enhancing its catalytic activity will significantly impact development in this field. GH7 CBH possesses a catalytic tunnel through which cellulose substrates are threaded and hydrolysed. Despite numerous studies dissecting this processive mechanism, the role of amino acid residues in the tunnel remains not fully understood. Herein, we examined the respective contributions of nine amino acid residues in the catalytic tunnel of GH7 CBH from Talaromyces cellulolyticus by substitution with alanine. As a result, N62A and K203A mutants were found to possess significantly higher cellulase activities than wild type. Molecular dynamics simulations showed that the N62 residue interacted strongly with the cellulose substrate, impeding threading, while the N62A mutant allowed cellulose to proceed more smoothly. Furthermore, the W63 residue was observed to facilitate twisting of the cellulose substrate in our simulations. This study helps elucidate cellulose threading and provides insight into biomass hydrolysis.
Simple eco-friendly synthesis of the surfactant free SnS nanocrystal toward the photoelectrochemical cell application
Authors: Huang Xiaoguang , Woo Heechul , Wu Peinian , Hong Hyo Jin , Jung Wan Gil , Kim Bong-Joong , Vanel Jean-Charles , Choi Jin Woo 
Published: November 2017

AbstractA simple, low cost, non-toxic and eco-friendly pathway for synthesizing efficient sunlight-driven tin sulfide photocatalyst was studied. SnS nanocrystals were prepared by using mechanical method. The bulk SnS was obtained by evaporation of SnS nanocrystal solution. The synthesized samples were characterized by using XRD, SEM, TEM, UV-vis, and Raman analyses. Well crystallized SnS nanocrystals were verified and the electrochemical characterization was also performed under visible light irradiation. The SnS nanocrystals have shown remarkable photocurrent density of 7.6 mA cm−2 under 100 mW cm−2 which is about 10 times larger than that of the bulk SnS under notably stable operation conditions. Furthermore, the SnS nanocrystals presented higher stability than the bulk form. The IPCE(Incident photon to current conversion efficiency) of 9.3% at 420 nm was obtained for SnS nanocrystal photoanode which is strikingly higher than that of bulk SnS, 0.78%. This work suggests that the enhancement of reacting area by using SnS nanocrystal absorbers could give rise to the improvement of photoelectrochemical cell efficiency.
Induction of Immune Surveillance of the Dysmorphogenic Lens
Authors: Logan Caitlin M. , Bowen Caitlin J. , Menko A. Sue 
Published: November 2017

AbstractThe lens has been considered to be an immune privileged site not susceptible to the immune processes normally associated with tissue injury and wound repair. However, as greater insight into the immune surveillance process is gained, we have reevaluated the concept of immune privilege. Our studies using an N-cadherin lens-specific conditional knockout mouse, N-cadΔlens, show that loss of this cell-cell junctional protein leads to lens degeneration, necrosis and fibrotic change, postnatally. The degeneration of this tissue induces an immune response resulting in immune cells populating the lens that contribute to the development of fibrosis. Additionally, we demonstrate that the lens is connected to the lymphatic system, with LYVE(+) labeling reaching the lens along the suspensory ligaments that connect the lens to the ciliary body, providing a potential mechanism for the immune circulation. Importantly, we observe that degeneration of the lens activates an immune response throughout the eye, including cornea, vitreous humor, and retina, suggesting a coordinated protective response in the visual system to defects of a component tissue. These studies demonstrate that lens degeneration induces an immune response that can contribute to the fibrosis that often accompanies lens dysgenesis, a consideration for understanding organ system response to injury.
A comparison of micro-CT and histomorphometry for evaluation of osseointegration of PEO-coated titanium implants in a rat model
Authors: He Tao , Cao Cong , Xu Zhiguo , Li Gen , Cao Huiliang , Liu Xuanyong , Zhang Chao , Dong Yuqi 
Published: November 2017

AbstractThe aim of the present study was to determine the correlation between bone volume density (BV/TV) around a titanium implant determined by micro-computed tomography (micro-CT) and bone area density (BA/TA) measurements obtained using histomorphometry. An intramedullary rat femur implant model was evaluated to compare raw titanium implants with plasma electrolytic oxidation (PEO)-coated titanium implants. Titanium and PEO-treated titanium pins were inserted into rat femurs under general anesthesia. The animals were sacrificed and femurs harvested at 0, 2, 4 and 6 weeks, and subsequently, histomorphometry and micro-CT were performed. BV/TV and BA/TA values were strongly and positively correlated at all time points and locations (with all correlation coefficients being >0.8 and with P < 0.001). BV/TV and BA/TA were significantly higher proximal to the growth plate than distal to the growth plate, with estimated differences of 14.10% (P < 0.001) and 11.95% (P < 0.001), respectively. BV/TV and BA/TA were significantly higher on the PEO-coated surface than on the raw titanium surface, with estimated differences of 3.20% (P = 0.044) and 4.10% (P = 0.018), respectively. Therefore, quantitative micro-CT analysis of BV/TV is correlated with BA/TA determined by histomorphometry when artifacts around titanium implants are minimized by a region of interest modification.
A micro-Raman study of exfoliated few-layered n-type Bi2 Te2.7Se0.3
Authors: Liu Fengjiao , Hu Longyu , Karakaya Mehmet , Puneet Pooja , Rao Rahul , Podila Ramakrishna , Bhattacharya Sriparna , Rao Apparao M. 
Published: November 2017

AbstractPreviously we showed that the thermoelectric (TE) performance of bulk n-type Bi2Te2.7Se0.3 can be enhanced by subjecting it to a combined process of chemical or mechanical exfoliation (C/ME) followed by a rapid densification and restacking of the exfoliated layers via the spark-plasma-sintering technique (SPS). Here, we present a systematic micro-Raman study of two-dimensional flakes of n-type Bi2Te2.7Se0.3 produced by the C/ME process, as a function of the flake thickness. We found Raman evidence for flakes with: (i) integer number of quintuples which exhibited a strong electron-phonon coupling, and (ii) non-integer number of quintuples, or sub-quintuples which exhibited the forbidden IR active mode due to symmetry lowering. Detailed atomic force microscopy was used to confirm the number of quintuples in all flakes examined in this study. The restacking and densification of these flakes by SPS promoted the formation of charged grain boundaries, which led to the enhanced TE properties via the energy filtering process.
New Early Cretaceous palaeomagnetic and geochronological results from the far western Lhasa terrane: Contributions to the Lhasa-Qiangtang collision
Authors: Bian Weiwei , Yang Tianshui , Ma Yiming , Jin Jingjie , Gao Feng , Zhang Shihong , Wu Huaichun , Li Haiyan 
Published: November 2017

AbstractTo better constrain the Lhasa-Qiangtang collision, a combined palaeomagnetic and geochronological study of the far western Lhasa terrane was conducted on the Duoai Formation lava flows (~113–116 Ma), as well as on the Early Cretaceous Jiega Formation limestone. Following detailed rock magnetic, petrographical, and palaeomagnetic experiments, characteristic remanent magnetisation directions were successfully isolated from most samples using principal component analysis. The tilt-corrected direction groups yielded a palaeopole at 69.1°N, 319.8°E with A95 = 4.8° (N = 19). A primary origin for the magnetisation is consistent with positive fold tests. Our results from the Early Cretaceous units, combined with published palaeomagnetic data obtained from Cretaceous strata from the Lhasa and western Qiangtang terranes, show that these two terranes had already collided by the Early Cretaceous, the Lhasa terrane had a relatively east-west alignment, and it remained at a relatively stable palaeolatitude during the entire Cretaceous. Comparing the Cretaceous palaeolatitude calculated for the western Lhasa terrane with those from Eurasia and Mongolia suggests a latitudinal convergence of ~1400 ± 290 km and ~1800 ± 300 km, respectively, since the Early Cretaceous.
Stiffness-dependent motility and proliferation uncoupled by deletion of CD44
Authors: Razinia Ziba , Castagnino Paola , Xu Tina , Vázquez-Salgado Alexandra , Puré Ellen , Assoian Richard K. 
Published: November 2017

AbstractInformation in the microenvironment guides complex cellular decisions such as whether or not to proliferate and migrate. The effects of soluble extracellular signals on these cellular functions are fairly well understood, but relatively little is known about how the extracellular matrix (ECM), and particularly the mechanical information in the ECM, guides these cellular decisions. Here, we show that CD44, a major receptor for the glycosaminoglycan ECM component hyaluronan, coordinates the motility and proliferative responses to ECM stiffening. We analyzed these cellular responses on fibronectin-coated polyacrylamide hydrogels prepared at a physiologic range of ECM stiffness and found that stiffening of the ECM leads to both cell cycling and cell motility in serum-stimulated primary mouse dermal fibroblasts. Remarkably, deletion of CD44 impaired stiffness-stimulated motility of the primary cells without affecting other hallmark cellular responses to ECM stiffening including cell spread area, stress fiber formation, focal adhesion maturation, and intracellular stiffening. Even stiffness-mediated cell proliferation was unaffected by deletion of CD44. Our results reveal a novel effect of CD44, which is imposed downstream of ECM-mechanosensing and determines if cells couple or uncouple their proliferative and motility responses to ECM stiffness.
Inhalation Exposure to PM2.5 Counteracts Hepatic Steatosis in Mice Fed High-fat Diet by Stimulating Hepatic Autophagy
Authors: Qiu Yining , Zheng Ze , Kim Hyunbae , Yang Zhao , Zhang Gary , Shi Xiangyang , Sun Fei , Peng Changya , Ding Yuchuan , Wang Aixia , Chen Lung-Chi , Rajagopalan Sanjay , Sun Qinghua , Zhang Kezhong 
Published: November 2017

AbstractAir pollution is associated with the increased risk of metabolic syndrome. In this study, we performed inhalation exposure of mice fed normal chow or a high-fat diet to airborne fine particulate matters (PM2.5), and then investigated the complex effects and mechanisms of inhalation exposure to PM2.5 on hepatic steatosis, a precursor or manifestation of metabolic syndrome. Our studies demonstrated that inhalation exposure of mice fed normal chow to concentrated ambient PM2.5 repressed hepatic transcriptional regulators involved in fatty acid oxidation and lipolysis, and thus promoted hepatic steatosis. However, PM2.5 exposure relieved hepatic steatosis in high-fat diet-induced obese mice. Further investigation revealed that inhalation exposure to PM2.5 induced hepatic autophagy in mouse livers in a manner depending on the MyD88-mediated inflammatory pathway. The counteractive effect of PM2.5 exposure on high-fat diet-induced hepatic steatosis was mediated through PM2.5-induced hepatic autophagy. The findings from this study not only defined the effects and mechanisms of PM2.5 exposure in metabolic disorders, but also revealed the pleotrophic acts of an environmental stressor in a complex stress system relevant to public health.
Dependence of the sliding distance of a one-dimensional atom chain on initial velocity
Authors: Li Jian-Wen , Wang Tong-Biao , Liu Nian-Hua , Yu Tianbao 
Published: November 2017

AbstractIn our daily lives, a body with a high initial velocity sliding freely on a rough surface moves a longer distance than that with a low initial velocity. However, such a phenomenon may not occur in the microscopic world. The dynamical behavior of a one-dimensional atom chain (1DAC) sliding on a substrate is investigated in this study by using a modified Frenkel–Kontorova model, in which the vibration of atoms on the substrate is considered. The dependence of sliding distance on initial velocity is examined. Result shows that although sliding distance is proportional to the initial value for most velocities, such a linear relation does not exist in some special velocities. This phenomenon is explained by a theoretical analysis of phonon excitation. The physical process is divided into three stages. The first stage is a superlubric sliding process with small amplitude of the vibrication of the atoms. The single-mode phonon is excited in the second stage. In the third stage, the system exhibits instability because of multiple-mode phonon excitations. In addition, the dependence of the coupling strength between 1DAC and the substrate is investigated. The findings are helpful in understanding the energy dissipation mechanism of friction.
propr: An R-package for Identifying Proportionally Abundant Features Using Compositional Data Analysis
Authors: Quinn Thomas P. , Richardson Mark F. , Lovell David , Crowley Tamsyn M. 
Published: November 2017

AbstractIn the life sciences, many assays measure only the relative abundances of components in each sample. Such data, called compositional data, require special treatment to avoid misleading conclusions. Awareness of the need for caution in analyzing compositional data is growing, including the understanding that correlation is not appropriate for relative data. Recently, researchers have proposed proportionality as a valid alternative to correlation for calculating pairwise association in relative data. Although the question of how to best measure proportionality remains open, we present here a computationally efficient R package that implements three measures of proportionality. In an effort to advance the understanding and application of proportionality analysis, we review the mathematics behind proportionality, demonstrate its application to genomic data, and discuss some ongoing challenges in the analysis of relative abundance data.
Baculovirus-Mediated miR-214 Knockdown Shifts Osteoporotic ASCs Differentiation and Improves Osteoporotic Bone Defects Repair
Authors: Li Kuei-Chang , Chang Yu-Han , Hsu Mu-Nung , Lo Shih-Chun , Li Wan-Hua , Hu Yu-Chen 
Published: November 2017

AbstractOsteoporotic patients often suffer from bone fracture but its healing is compromised due to impaired osteogenesis potential of bone marrow-derived mesenchymal stem cells (BMSCs). Here we aimed to exploit adipose-derived stem cells from ovariectomized rats (OVX-ASCs) for bone healing. We unraveled that OVX-ASCs highly expressed miR-214 and identified 2 miR-214 targets: CTNNB1 (β-catenin) and TAB2. We demonstrated that miR-214 targeting of these two genes blocked the Wnt pathway, led to preferable adipogenesis and hindered osteogenesis. As a result, OVX-ASCs implantation into OVX rats failed to heal critical-size metaphyseal bone defects. We further engineered the OVX-ASCs with a novel Cre/loxP-based hybrid baculovirus vector that conferred prolonged expression of miR-214 sponge. Gene delivery for miR-214 sponge expression successfully downregulated miR-214 levels, activated the Wnt pathway, upregulated osteogenic factors β-catenin/Runx2, downregulated adipogenic factors PPAR-γ and C/EBP-α, shifted the differentiation propensity towards osteogenic lineage, enhanced the osteogenesis of co-cultured OVX-BMSCs, elevated BMP7/osteoprotegerin secretion and hindered exosomal miR-214/osteopontin release. Consequently, implanting the miR-214 sponge-expressing OVX-ASCs tremendously improved bone healing in OVX rats. Co-expression of miR-214 sponge and BMP2 further synergized the OVX-ASCs-mediated bone regeneration in OVX rats. This study implicates the potential of suppressing miR-214 by baculovirus-mediated gene delivery in osteoporotic ASCs for regenerative medicine.
Prognostic value of thyroid hormones in acute ischemic stroke – a meta analysis
Authors: Jiang Xingjun , Xing Hongyi , Wu Jing , Du Ruofei , Liu Houfu , Chen Jixiang , Wang Ji , Wang Chen , Wu Yan 
Published: November 2017

AbstractPrevious studies on the association between thyroid hormones and prognosis of acute ischemic stroke (AIS) reported conflicting results. We conducted a meta-analysis to assess the prognostic value of thyroid hormones in AIS. The PubMed, EMBASE, and Cochrane library databases were searched through May 12, 2017 to identify eligible studies on this subject. Out of 2,181 studies retrieved, 11 studies were finally included with a total number of 3,936 acute stroke patients for analysis. Odds ratio (OR) for predicting poor outcome or standardized mean difference (SMD) of thyroid hormone levels with 95% confidence intervals (95% CI) obtained from the studies were pooled using Review Manager 5.3. From the results, in AIS, patients with a poor outcome had lower levels of triiodothyronine (T3) and higher thyroxine (T4). Pooled OR confirmed the same association. Our study provides statistical evidence supporting the utility of thyroid hormone levels in prognosis of acute stroke.