bluuebunny/crossref_metadata_2025_split huggingface dataset:
NADH/NADPH bi-cofactor-utilizing and thermoactive ketol-acid reductoisomerase from Sulfolobus acidocaldarius
Authors: Chen Chin-Yu , Ko Tzu-Ping , Lin Kuan-Fu , Lin Bo-Lin , Huang Chun-Hsiang , Chiang Cheng-Hung , Horng Jia-Cherng 
Published: May 2018

AbstractKetol-acid reductoisomerase (KARI) is a bifunctional enzyme in the second step of branched-chain amino acids biosynthetic pathway. Most KARIs prefer NADPH as a cofactor. However, KARI with a preference for NADH is desirable in industrial applications including anaerobic fermentation for the production of branched-chain amino acids or biofuels. Here, we characterize a thermoacidophilic archaeal Sac-KARI from Sulfolobus acidocaldarius and present its crystal structure at a 1.75-Å resolution. By comparison with other holo-KARI structures, one sulphate ion is observed in each binding site for the 2′-phosphate of NADPH, implicating its NADPH preference. Sac-KARI has very high affinity for NADPH and NADH, with K
M
values of 0.4 μM for NADPH and 6.0 μM for NADH, suggesting that both are good cofactors at low concentrations although NADPH is favoured over NADH. Furthermore, Sac-KARI can catalyze 2(S)-acetolactate (2S-AL) with either cofactor from 25 to 60 °C, but the enzyme has higher activity by using NADPH. In addition, the catalytic activity of Sac-KARI increases significantly with elevated temperatures and reaches an optimum at 60 °C. Bi-cofactor utilization and the thermoactivity of Sac-KARI make it a potential candidate for use in metabolic engineering or industrial applications under anaerobic or harsh conditions.
Haplotypic polymorphisms and mutation rate estimates of 22 Y-chromosome STRs in the Northern Chinese Han father–son pairs
Authors: Yang Yaran , Wang Weini , Cheng Feng , Chen Man , Chen Tong , Zhao Jing , Chen Chong , Shi Yan , Li Chen , Chen Chuguang , Liu Yacheng , Yan Jiangwei 
Published: May 2018

AbstractY chromosome Short tandem repeats (Y-STRs) analysis has been widely used in forensic identification, kinship testing, and population evolution. An accurate understanding of haplotype and mutation rate will benefit these applications. In this work, we analyzed 1123 male samples from Northern Chinese Han population which including 578 DNA-confirmed father-son pairs at 22 Y-STRs loci. A total of 537 haplotypes were observed and the overall haplotype diversity was calculated as 1.0000 ± 0.0001. Except that only two haplotypes were observed twice, all the rest of the 535 were unique. Furthermore, totally 47 mutations were observed during 13,872 paternal meiosis. The mutation rate for each locus estimates ranged from 0.0 to 15.6 × 10−3 with an average mutation rate 3.4 × 10−3 (95% CI 2.5–4.5 × 10−3). Among the 22 loci, DYS449, DYS389 II and DYS458 are the most prone to mutations. This study adds to the growing data on Y-STR haplotype diversity and mutation rates and could be very useful for population and forensic genetics.
Infants’ dietary arsenic exposure during transition to solid food
Authors: Signes-Pastor Antonio J. , Cottingham Kathryn L. , Carey Manus , Sayarath Vicki , Palys Thomas , Meharg Andrew A. , Folt Carol L. , Karagas Margaret R. 
Published: May 2018

AbstractEarly-life exposure to inorganic arsenic (i-As) may cause long-lasting health effects, but as yet, little is known about exposure among weaning infants. We assessed exposure before and during weaning and investigated the association between solid food intake and infants’ urinary arsenic species concentrations. Following the recording of a comprehensive 3 day food diary, paired urine samples (pre- and post-weaning) were collected and analyzed for arsenic speciation from 15 infants participating in the New Hampshire Birth Cohort Study. Infants had higher urinary i-As (p-value = 0.04), monomethylarsonic acid (MMA) (p-value = 0.002), dimethylarsinic acid (DMA) (p-value = 0.01), and sum of arsenic species (i-As + MMA + DMA, p-value = 0.01) during weaning than while exclusively fed on a liquid diet (i.e., breast milk, formula, or a mixture of both). Among weaning infants, increased sum of urinary arsenic species was pairwise-associated with intake of rice cereal (Spearman’s ρ = 0.90, p-value = 0.03), fruit (ρ = 0.70, p-value = 0.03), and vegetables (ρ = 0.86, p-value = 0.01). Our observed increases in urinary arsenic concentrations likely indicate increased exposure to i-As during the transition to solid foods, suggests the need to minimize exposure during this critical period of development.
Different patterns of epileptiform-like activity are generated in the sclerotic hippocampus from patients with drug-resistant temporal lobe epilepsy
Authors: Reyes-Garcia Selvin Z. , Scorza Carla A. , Araújo Noemi S. , Ortiz-Villatoro Nancy N. , Jardim Anaclara Prada , Centeno Ricardo , Yacubian Elza Márcia Targas , Faber Jean , Cavalheiro Esper A. 
Published: May 2018

AbstractHuman hippocampal slice preparations from patients with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) are excellent material for the characterization of epileptiform-like activity. However, it is still unknown if hippocampal regions ascornu Ammonis(CA) 1, CA3 and CA4, generate population epileptiform-like activity. Here, we investigated epileptiform activities of the subiculum, CA1, CA2, CA3, CA4 (induced by elevation of extracellular potassium concentration) and the dentate gyrus (induced with hilar stimulation and elevation of potassium concentration) from sclerotic hippocampi of patients with drug-resistant TLE. Five types of epileptiform-like activity were observed: interictal-like events; periodic ictal spiking; seizure-like events; spreading depression-like events; tonic seizure-like events and no activity. Different susceptibilities to generate epileptiform activity among hippocampal regions were observed; the dentate gyrus was the most susceptible region followed by the subiculum, CA4, CA1, CA2 and CA3. The incidence of epileptiform activity pattern was associated with specific regions of the hippocampal formation. Moreover, it was observed that each region of the hippocampal formation exhibits frequency-specific ranges in each subfield of the sclerotic human tissue. In conclusion, this study demonstrates that epileptiform-like activity may be induced in different regions of the hippocampal formation, including regions that are severely affected by neuronal loss.
Ameliorative potential of desalted Salicornia europaea L. extract in multifaceted Alzheimer’s-like scopolamine-induced amnesic mice model
Authors: Karthivashan Govindarajan , Park Shin-Young , Kweon Mee-Hyang , Kim Joonsoo , Haque Md. Ezazul , Cho Duk-Yeon , Kim In-Su , Cho Eun-Ah , Ganesan Palanivel , Choi Dong-Kug 
Published: May 2018

AbstractThe Salicornia europaea L. (SE) plant is a halophyte that has been widely consumed as a seasoned vegetable, and it has been recently reported to counteract chronic diseases related to oxidative and inflammatory stress. In this study, we performed an initial phytochemical analysis with in vitro biochemical tests and chromatographic profiling of desalted and enzyme-digested SE ethanol extract (SE-EE). Subsequently, we evaluated the anti-neuroinflammatory and ameliorative potential of SE-EE in LPS-inflicted BV-2 microglial cells and scopolamine-induced amnesic C57/BL6N mice, respectively. SE-EE possess considerable polyphenols and flavonoids that are supposedly responsible to improve its bio-efficacy. SE-EE dose-dependently attenuated LPS-induced inflammation in BV-2 cells, significantly repressed behavioural/cognitive impairment, dose-dependently regulated the cholinergic function, suppressed oxidative stress markers, regulated inflammatory cytokines/associated proteins expression and effectively ameliorated p-CREB/BDNF levels, neurogenesis (DCX stain), neuron proliferation (Ki67 stain) in scopolamine-administered mice. Thus, SE-EE extract shows promising multifactorial disease modifying activities and can be further developed as an effective functional food, drug candidate, or supplemental therapy to treat neuroinflammatory mediated disorders.
Observation of Magnetic Radial Vortex Nucleation in a Multilayer Stack with Tunable Anisotropy
Authors: Karakas Vedat , Gokce Aisha , Habiboglu Ali Taha , Arpaci Sevdenur , Ozbozduman Kaan , Cinar Ibrahim , Yanik Cenk , Tomasello Riccardo , Tacchi Silvia , Siracusano Giulio , Carpentieri Mario , Finocchio Giovanni , Hauet Thomas , Ozatay Ozhan 
Published: May 2018

AbstractRecently discovered exotic magnetic configurations, namely magnetic solitons appearing in the presence of bulk or interfacial Dzyaloshinskii-Moriya Interaction (i-DMI), have excited scientists to explore their potential applications in emerging spintronic technologies such as race-track magnetic memory, spin logic, radio frequency nano-oscillators and sensors. Such studies are motivated by their foreseeable advantages over conventional micro-magnetic structures due to their small size, topological stability and easy spin-torque driven manipulation with much lower threshold current densities giving way to improved storage capacity, and faster operation with efficient use of energy. In this work, we show that in the presence of i-DMI in Pt/CoFeB/Ti multilayers by tuning the magnetic anisotropy (both in-plane and perpendicular-to-plane) via interface engineering and postproduction treatments, we can stabilize a variety of magnetic configurations such as Néel skyrmions, horseshoes and most importantly, the recently predicted isolated radial vortices at room temperature and under zero bias field. Especially, the radial vortex state with its absolute convergence to or divergence from a single point can potentially offer exciting new applications such as particle trapping/detrapping in addition to magnetoresistive memories with efficient switching, where the radial vortex state can act as a source of spin-polarized current with radial polarization.
Impact of technological innovation and regulation development on e-waste toxicity: a case study of waste mobile phones
Authors: Chen Yu , Chen Mengjun , Li Yungui , Wang Bin , Chen Shu , Xu Zhonghui 
Published: May 2018

AbstractTechnology innovation has accelerated progress in Information and Communications Technology (ICT), especially in the mobile phones sector. Concurrently, local, national, and international governments are enforcing stricter regulations to protect natural resources and human health. The paper attempts to address the question: Have technological innovations and regulation development had a positive impact on ecosystems and public health? We identified 36 waste mobile phones (WMPs) manufactured between 2002 and 2013, assessed their metals concentration, leachability, and potential impact on environment and human health using digestion, Toxicity Characteristic Leaching Procedure (TCLP), and USEtox model, respectively. The results highlight that regulations did not have significant impact on total metal content, except some heavy metals, while technology innovation recorded stronger impact. WMPs should be classified as hazardous due to excessive lead content. Copper posed the most significant ecotoxicity risk, and chromium showed the most significant risk for both cancerous and non-cancerous diseases. Additionally, we demonstrated that WMPs toxicity increased with technology innovation.
Fishing and temperature effects on the size structure of exploited fish stocks
Authors: Tu Chen-Yi , Chen Kuan-Ting , Hsieh Chih-hao 
Published: May 2018

AbstractSize structure of fish stock plays an important role in maintaining sustainability of the population. Size distribution of an exploited stock is predicted to shift toward small individuals caused by size-selective fishing and/or warming; however, their relative contribution remains relatively unexplored. In addition, existing analyses on size structure have focused on univariate size-based indicators (SBIs), such as mean length, evenness of size classes, or the upper 95-percentile of the length frequency distribution; these approaches may not capture full information of size structure. To bridge the gap, we used the variation partitioning approach to examine how the size structure (composition of size classes) responded to fishing, warming and the interaction. We analyzed 28 exploited stocks in the West US, Alaska and North Sea. Our result shows fishing has the most prominent effect on the size structure of the exploited stocks. In addition, the fish stocks experienced higher variability in fishing is more responsive to the temperature effect in their size structure, suggesting that fishing may elevate the sensitivity of exploited stocks in responding to environmental effects. The variation partitioning approach provides complementary information to univariate SBIs in analyzing size structure.
Lack of genetic support for shared aetiology of Coronary Artery Disease and Late-onset Alzheimer’s disease
Authors: Grace Christopher , Clarke Robert , Goel Anuj , Farrall Martin , Watkins Hugh , Hopewell Jemma C. 
Published: May 2018

AbstractEpidemiological studies suggest a positive association between coronary artery disease (CAD) and late-onset Alzheimer’s disease (LOAD). This large-scale genetic study brings together ‘big data’ resources to examine the causal impact of genetic determinants of CAD on risk of LOAD. A two-sample Mendelian randomization approach was adopted to estimate the causal effect of CAD on risk of LOAD using summary data from 60,801 CAD cases from CARDIoGRAMplusC4D and 17,008 LOAD cases from the IGAP Consortium. Additional analyses assessed the independent relevance of genetic associations at the APOE locus for both CAD and LOAD. Higher genetically determined risk of CAD was associated with a slightly higher risk of LOAD (Odds Ratio (OR) per log-odds unit of CAD [95% CI]: 1.07 [1.01–1.15]; p = 0.027). However, after exclusion of the APOE locus, the estimate of the causal effect of CAD for LOAD was attenuated and no longer significant (OR 0.94 [0.88–1.01]; p = 0.072). This Mendelian randomization study indicates that the APOE locus is the chief determinant of shared genetic architecture between CAD and LOAD, and suggests a lack of causal relevance of CAD for risk of LOAD after exclusion of APOE.
Mammary fibroblasts reduce apoptosis and speed estrogen-induced hyperplasia in an organotypic MCF7-derived duct model
Authors: Morgan Molly M. , Livingston Megan K. , Warrick Jay W. , Stanek Eli M. , Alarid Elaine T. , Beebe David J. , Johnson Brian P. 
Published: May 2018

AbstractThe estrogen receptor (ER) regulates the survival and growth of breast cancer cells, but it is less clear how components of the tissue microenvironment affect ER-mediated responses. We set out to test how human mammary fibroblasts (HMFs) modulate ER signaling and downstream cellular responses. We exposed an organotypic mammary model consisting of a collagen-embedded duct structure lined with MCF7 cells to 17-β estradiol (E2), with and without HMFs in the surrounding matrix. MCF7 cells grown as ductal structures were polarized and proliferated at rates comparable to in vivo breast tissue. In both culture platforms, exposure to E2 increased ER transactivation, increased proliferation, and induced ductal hyperplasia. When the surrounding matrix contained HMFs, the onset and severity of E2-induced ductal hyperplasia was increased due to decreased apoptosis. The reduced apoptosis may be due to fibroblasts modulating ER signaling in MCF7 cells, as suggested by the increased ER transactivation and reduced ER protein in MCF7 cells grown in co-culture. These findings demonstrate the utility of organotypic platforms when studying stromal:epithelial interactions, and add to existing literature that implicate the mammary microenvironment in ER + breast cancer progression.
Patient-derived mutations within the N-terminal domains of p85α impact PTEN or Rab5 binding and regulation
Authors: Mellor Paul , Marshall Jeremy D. S. , Ruan Xuan , Whitecross Dielle E. , Ross Rebecca L. , Knowles Margaret A. , Moore Stanley A. , Anderson Deborah H. 
Published: May 2018

AbstractThe p85α protein regulates flux through the PI3K/PTEN signaling pathway, and also controls receptor trafficking via regulation of Rab-family GTPases. In this report, we determined the impact of several cancer patient-derived p85α mutations located within the N-terminal domains of p85α previously shown to bind PTEN and Rab5, and regulate their respective functions. One p85α mutation, L30F, significantly reduced the steady state binding to PTEN, yet enhanced the stimulation of PTEN lipid phosphatase activity. Three other p85α mutations (E137K, K288Q, E297K) also altered the regulation of PTEN catalytic activity. In contrast, many p85α mutations reduced the binding to Rab5 (L30F, I69L, I82F, I177N, E217K), and several impacted the GAP activity of p85α towards Rab5 (E137K, I177N, E217K, E297K). We determined the crystal structure of several of these p85α BH domain mutants (E137K, E217K, R262T E297K) for bovine p85α BH and found that the mutations did not alter the overall domain structure. Thus, several p85α mutations found in human cancers may deregulate PTEN and/or Rab5 regulated pathways to contribute to oncogenesis. We also engineered several experimental mutations within the p85α BH domain and identified L191 and V263 as important for both binding and regulation of Rab5 activity.
On the design of random metasurface based devices
Authors: Dupré Matthieu , Hsu Liyi , Kanté Boubacar 
Published: May 2018

AbstractMetasurfaces are generally designed by placing scatterers in periodic or pseudo-periodic grids. We propose and discuss design rules for functional metasurfaces with randomly placed anisotropic elements that randomly sample a well-defined phase function. By analyzing the focusing performance of random metasurface lenses as a function of their density and the density of the phase-maps used to design them, we find that the performance of 1D metasurfaces is mostly governed by their density while 2D metasurfaces strongly depend on both the density and the near-field coupling configuration of the surface. The proposed approach is used to design all-polarization random metalenses at near infrared frequencies. Challenges, as well as opportunities of random metasurfaces compared to periodic ones are discussed. Our results pave the way to new approaches in the design of nanophotonic structures and devices from lenses to solar energy concentrators.
Locus specific engineering of tandem DNA repeats in the genome of Saccharomyces cerevisiae using CRISPR/Cas9 and overlapping oligonucleotides
Authors: Lancrey Astrid , Joubert Alexandra , Boulé Jean-Baptiste 
Published: May 2018

AbstractDNA repeats constitute a large part of genomes of multicellular eucaryotes. For a longtime considered as junk DNA, their role in genome organization and tuning of gene expression is being increasingly documented. Synthetic biology has so far largely ignored DNA repeats as regulatory elements to manipulate functions in engineered genomes. The yeastSaccharomyces cerevisiaehas been a workhorse of synthetic biology, owing to its genetic tractability. Here we demonstrate the ability to synthetize, in a simple manner, tandem DNA repeats of various size by Cas9-assisted oligonucleotidein vivoassembly in this organism. We show that long tandem DNA repeats of several kilobases can be assembled in one step for different monomer size and G/C content. The combinatorial nature of the approach allows exploring a wide variety of design for building synthetic tandem repeated DNA directly at a given locus in theSaccharomyces cerevisiaegenome. This approach provides a simple way to incorporate tandem DNA repeat in synthetic genome designs to implement regulatory functions.
Higher risk of hepatocellular carcinoma in Hispanic patients with hepatitis C cirrhosis and metabolic risk factors
Authors: Wong Alina , Le An , Lee Mei-Hsuan , Lin Yu-Ju , Nguyen Pauline , Trinh Sam , Dang Hansen , Nguyen Mindie H. 
Published: May 2018

AbstractThe effect of metabolic syndrome on chronic liver diseases other than non-alcoholic fatty liver disease has not been fully elucidated. Our goal was to evaluate if metabolic syndrome increased the risk of liver-related complications, specifically hepatocellular carcinoma (HCC) and decompensation, in cirrhotic chronic hepatitis C (CHC) patients. We conducted a retrospective cohort study of 3503 consecutive cirrhotic CHC patients seen at Stanford University from 1997–2015. HCC developed in 238 patients (8-year incidence 21%) and hepatic decompensation in 448 patients (8-year incidence 61%). The incidence of HCC and decompensation increased with Hispanic ethnicity, diabetes, and number of metabolic risk factors. Multivariate Cox regression analysis demonstrated that, independent of HCV therapy and cure and other background risks, Hispanic ethnicity with ≥2 metabolic risk factors significantly increased the risk of HCC and hepatic decompensation. There was no interaction between Hispanic ethnicity and metabolic risk factors. All in all, metabolic risk factors significantly increase the risk of liver-related complications in cirrhotic CHC patients, especially HCC among Hispanics. As the prevalence of metabolic syndrome increases globally, targeted health interventions are needed to help curb the effects of metabolic syndrome in CHC patients.
VIPER regulates naive T cell activation and effector responses: Implication in TLR4 associated acute stage T cell responses
Authors: Sahoo Subhransu Sekhar , Pratheek Belluru M. , Meena Vikram S. , Nayak Tapas Kumar , Kumar P. Sanjai , Bandyopadhyay Saumya , Maiti Prasanta Kumar , Chattopadhyay Subhasis 
Published: May 2018

AbstractNaive T cells are known to express the modest level of TLR4 while it is known to go down during TCR activation. However, information towards the requirement of TLR4 signaling during TCR or mitogenic activation of naive wild-type T cells remains scanty. Here we have investigated the endogenous functional expression of TLR4 in naive mice T cells during TCR and mitogenic stimulation in presence of VIPER peptide (VP), an established inhibitor of TLR4 signaling. As expected we found that TLR4 expression goes down during TCR and mitogenic activation. Interestingly, we observed that VP treatment restores TLR4 expression on those activated T cells. Moreover, VP was found to regulate such activation of naive T cell as evident by reduction of CD25, CD69 expression, effector cytokines (IL-2, IFN-γ, TNF) production, T cell proliferation and down-regulation of T cell activation-dependent Fas (CD95), FasL (CD95L) expression. Together, our current observation highlights a possible requirement of TLR4 responses in T cells, which might have possible implication towards the pathogenic acute phase activation of naive T cells.