bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential transactivation of the upstream aggrecan enhancer regulated by PAX1/9 depends on SOX9-driven transactivation
Authors: Takimoto Aki , Kokubu Chikara , Watanabe Hitomi , Sakuma Tetsushi , Yamamoto Takashi , Kondoh Gen , Hiraki Yuji , Shukunami Chisa 
Published: March 2019

AbstractA previously identified enhancer 10 kb upstream of the Aggrecan (Acan) gene (UE) can drive cartilage specific reporter expression in vivo. Here, we report that the paralogous transcription factors PAX1 and PAX9 differentially drive UE, depending on the presence or absence of SOX9-driven transactivation. In the developing vertebral column, PAX1/9 expression was inversely correlated with Acan expression. Moreover, PAX1/9 was co-expressed with SOX9/5/6 in the intervertebral mesenchyme and the inner annulus fibrosus (AF), and with SOX9 in the outer AF. Significant Acan upregulation was observed during chondrification of Pax1-silenced AF cells, while, Acan was significantly downregulated by persistent expression of Pax1 in cartilage. Deletion of UE using CRISPR/Cas9 resulted in ~30% and ~40% reduction of Acan expression in cartilage and the AF, respectively. In the UE, PAX1/9 acts as weak transactivators through a PAX1/9-binding site partially overlapped with a SOX9-binding site. In the presence of SOX9, which otherwise drives robust Acan expression along with SOX5/6, PAX1/9 competes with SOX9 for occupancy of the binding site, resulting in reduced transactivation of Acan. Coimmunoprecipitation revealed the physical interaction of Pax1 with SOX9. Thus, transactivation of the UE is differentially regulated by concerted action of PAX1/9, SOX9, and SOX5/6 in a context-dependent manner.
The association analysis between HLA-A*26 and Behçet’s disease
Authors: Nakamura Jutaro , Meguro Akira , Ishii Genji , Mihara Takahiro , Takeuchi Masaki , Mizuki Yuki , Yuda Kentaro , Yamane Takahiro , Kawagoe Tatsukata , Ota Masao , Mizuki Nobuhisa 
Published: March 2019

AbstractThe strongest genetic risk factor of Behçet’s disease (BD) is HLA-B*51. Our group previously reported that HLA-A*26 is independently associated with the risk of the onset of BD apart from HLA-B*51. Here, we re-evaluated the association between HLA-A*26 and BD in the Japanese population. We also performed a comprehensive literature search and meta-analyzed the extracted published data concerning the relationship between HLA-A*26 and BD to estimate the odds ratio (OR) of HLA-A*26 to BD. In this study, we genotyped 611 Japanese BD patients and 2,955 unrelated ethnically matched healthy controls. Genotyping results showed that the phenotype frequency of HLA-A*26 was higher in BD patients than in controls (OR = 2.12, 95% CI: 1.75–2.56). Furthermore, within the HLA-B*51-negative populations, the phenotype frequency of HLA-A*26 was significantly higher in BD patients than in controls (OR = 3.10, 95% CI: 2.43–3.95). Results obtained from meta-analysis combined with our data showed that the modified OR of HLA-A*26 became 1.80 (95% CI:1.58–2.06), whereas within the HLA-B*51-negative population, the modified OR became 4.02 (95% CI: 2.29–7.05). A subgroup analysis arranged by the geographical regions showed HLA-A*26 is in fact associated with the onset of BD in Northeast Asia (OR = 2.11, 95% CI: 1.75–2.56), but not in the Middle East or in Europe.
Clathrin Adaptor Complex-interacting Protein Irc6 Functions through the Conserved C-Terminal Domain
Authors: Zhou Huajun , Costaguta Giancarlo , Payne Gregory S. 
Published: March 2019

AbstractClathrin coats drive transport vesicle formation from the plasma membrane and in pathways between the trans-Golgi network (TGN) and endosomes. Clathrin adaptors play central roles orchestrating assembly of clathrin coats. The yeast clathrin adaptor-interacting protein Irc6 is an orthologue of human p34, which is mutated in the inherited skin disorder punctate palmoplantar keratoderma type I. Irc6 and p34 bind to clathrin adaptor complexes AP-1 and AP-2 and are members of a conserved family characterized by a two-domain architecture. Irc6 is required for AP-1-dependent transport between the TGN and endosomes in yeast. Here we present evidence that the C-terminal two amino acids of Irc6 are required for AP-1 binding and transport function. Additionally, like the C-terminal domain, the N-terminal domain when overexpressed partially restores AP-1-mediated transport in cells lacking full-length Irc6. These findings support a functional role for Irc6 binding to AP-1. Negative genetic interactions with irc6∆ are enriched for genes related to membrane traffic and nuclear processes, consistent with diverse cellular roles for Irc6.
Sensitization and synergistic anti-cancer effects of Furanodiene identified in zebrafish models
Authors: Zhu Xiao-Yu , Guo Dian-Wu , Lao Qiao-Cong , Xu Yi-Qiao , Meng Zhao-Ke , Xia Bo , Yang Hua , Li Chun-Qi , Li Ping 
Published: March 2019

AbstractFuranodiene is a natural terpenoid isolated from Rhizoma Curcumae, a well-known Chinese medicinal herb that presents anticancer effects in various types of cancer cell lines. In this study, we have successfully established zebrafish xenografts with 5 various human cancer cell lines; and validated these models with anti-cancer drugs used clinically for treating human cancer patients. We found that Furanodiene was therapeutically effective for human JF 305 pancreatic cancer cells and MCF-7 breast cancer cells xenotranplanted into zebrafish. Furanodiene showed a markedly synergistic anti-cancer effect when used in combination with 5-FU (5-Fluorouracil) for both human breast cancer MDA-MB-231 cells and human liver cancer BEL-7402 cells xenotransplanted into zebrafish. Unexpectedly, Furanodiene reversed multiple drug resistance in the zebrafish xenotransplanted with cis-Platinum-resistant human non-small cell lung cancer cells and Adriamycin-resistant human breast cancer cells. Furanodiene played its anti-cancer effects through anti-angiogenesis and inducing ROS production, DNA strand breaks and apoptosis. Furanodiene suppresseed efflux transporter Pgp (P-glycoprotein) function and reduced Pgp protein level, but no effect on Pgp related gene (MDR1) expression. These results suggest sensitizition and synergistic anti-cancer effects of Furanodiene that is worthy of a further investigation.
Simulating Anisotropic quantum Rabi model via frequency modulation
Authors: Wang Gangcheng , Xiao Ruoqi , Shen H. Z. , Sun Chunfang , Xue Kang 
Published: March 2019

AbstractAnisotropic quantum Rabi model is a generalization of quantum Rabi model, which allows its rotating and counter-rotating terms to have two different coupling constants. It provides us with a fundamental model to understand various physical features concerning quantum optics, solid-state physics, and mesoscopic physics. In this paper, we propose an experimental feasible scheme to implement anisotropic quantum Rabi model in a circuit quantum electrodynamics system via periodic frequency modulation. An effective Hamiltonian describing the tunable anisotropic quantum Rabi model can be derived from a qubit-resonator coupling system modulated by two periodic driving fields. All effective parameters of the simulated system can be adjusted by tuning the initial phases, the frequencies and the amplitudes of the driving fields. We show that the periodic driving is able to drive a coupled system in dispersive regime to ultrastrong coupling regime, and even deep-strong coupling regime. The derived effective Hamiltonian allows us to obtain pure rotating term and counter-rotating term. Numerical simulation shows that such effective Hamiltonian is valid in ultrastrong coupling regime, and stronger coupling regime. Moreover, our scheme can be generalized to the multi-qubit case. We also give some applications of the simulated system to the Schrödinger cat states and quantum gate generalization. The presented proposal will pave a way to further study the stronger anisotropic Rabi model whose coupling strength is far away from ultrastrong coupling and deep-strong coupling regimes in quantum optics.
Molecular dynamic simulations of oxidized skin lipid bilayer and permeability of reactive oxygen species
Authors: Yadav Dharmendra Kumar , Kumar Surendra , Choi Eun-Ha , Chaudhary Sandeep , Kim Mi-Hyun 
Published: March 2019

AbstractLipid peroxidation by reactive oxygen species (ROS) during oxidative stress is non-enzymatic damage that affects the integrity of biological membrane, and alters the fluidity and permeability. We conducted molecular dynamic simulation studies to evaluate the structural properties of the bilayer after lipid peroxidation and to measure the permeability of distinct ROS. The oxidized membrane contains free fatty acid, ceramide, cholesterol, and 5α-hydroperoxycholesterol (5α-CH). The result of unconstrained molecular dynamic simulations revealed that lipid peroxidation causes area-per-lipid of the bilayer to increase and bilayer thickness to decrease. The simulations also revealed that the oxidized group of 5α-CH (-OOH) moves towards the aqueous layer and its backbone tilts causing lateral expansion of the bilayer membrane. These changes are detrimental to structural and functional properties of the membrane. The measured free energy profile for different ROS (H2O2, HO2, HO, and O2) across the peroxidized lipid bilayer showed that the increase in lipid peroxidation resulted in breaching barrier decrease for all species, allowing easy traversal of the membrane. Thus, lipid peroxidation perturbs the membrane barrier and imposes oxidative stress resulting into apoptosis. The collective insights increase the understanding of oxidation stress at the atomic level.
Transgenerational response to early spring warming in Daphnia
Authors: Toyota Kenji , Cambronero Cuenca Maria , Dhandapani Vignesh , Suppa Antonio , Rossi Valeria , Colbourne John K. , Orsini Luisa 
Published: March 2019

AbstractTemperature and photoperiod regulate key fitness traits in plants and animals. However, with temperature increase due to global warming, temperature cue thresholds are experienced at shorter photoperiods, disrupting the optimal seasonal timing of physiological, developmental and reproductive events in many species. Understanding the mechanisms of adaptation to the asynchrony between temperature and photoperiod is key to inform our understanding of how species will respond to global warming. Here, we studied the transgenerational mechanisms of responses of the cyclical parthenogenDaphnia magnato different photoperiod lengths co-occurring with warm temperature thereby assessing the impact of earlier spring warming on its fitness.Daphniauses temperature and photoperiod cues to time dormancy, and to switch between sexual and asexual reproduction.Daphnialife cycle offers the opportunity to measure the relative contribution of plastic and genetic responses to environmental change across generations and over evolutionary time. We use transgenerational common garden experiments on three populations ‘resurrected’ from a biological archive experiencing temperature increase over five decades. Our results suggest that response to early spring warming evolved underpinned by a complex interaction between plastic and genetic mechanisms while a positive maternal contribution at matching environments between parental and offspring generation was also observed.
Electrically tunable valley polarization in Weyl semimetals with tilted energy dispersion
Authors: Yesilyurt Can , Siu Zhuo Bin , Tan Seng Ghee , Liang Gengchiau , Yang Shengyuan A. , Jalil Mansoor B. A. 
Published: March 2019

AbstractTunneling transport across electrical potential barriers in Weyl semimetals with tilted energy dispersion is investigated. We report that the electrons around different valleys experience opposite direction refractions at the barrier interface when the energy dispersion is tilted along one of the transverse directions. Chirality dependent refractions at the barrier interface polarize the Weyl fermions in angle-space according to their valley index. A real magnetic barrier configuration is used to select allowed transmission angles, which results in electrically controllable and switchable valley polarization. Our findings may pave the way for experimental investigation of valley polarization, as well as valleytronic and electron optic applications in Weyl semimetals.
The rsmS (ybaM) mutation causes bypass suppression of the RsmAB post-transcriptional virulence regulation system in enterobacterial phytopathogens
Authors: Monson Rita E. , Apagyi Katinka , Bowden Steven D. , Simpson Natalie , Williamson Neil R , Cubitt Marion F. , Harris Steve , Toth Ian K. , Salmond George P. C. 
Published: March 2019

AbstractPlant cell wall degrading enzymes (PCWDEs) are the primary virulence determinants of soft rotting bacteria such as the potato pathogen, Pectobacterium atrosepticum. The regulation of secondary metabolite (Rsm) system controls production of PCWDEs in response to changing nutrient conditions. This work identified a new suppressor of an rsmB mutation – ECA1172 or rsmS (rsmBsuppressor). Mutants defective in rsmB (encoding a small regulatory RNA), show reduced elaboration of the quorum sensing molecule (N-3-oxohexanoyl-homoserine lactone; OHHL) and PCWDEs. However, OHHL and PCWDE production were partially restored in an rsmB, rsmS double mutant. Single rsmS mutants, overproduced PCWDEs and OHHL relative to wild type P. atrosepticum and exhibited hypervirulence in potato. RsmS overproduction also resulted in increased PCWDEs and OHHL. Homology searches revealed rsmS conservation across pathogens such as Escherichia coli (ybaM), Dickeya solani, Klebsiella pneumoniae and Shigella flexneri. An rsmS mutant of Pectobacterium carotovorum ATCC39048 showed bypass of rsmB-dependent repression of PCWDEs and OHHL production. P. carotovorum ATCC39048 produces the β-lactam antibiotic, 1-carbapen-2-em-3-carboxylic acid (a carbapenem). Production of the antibiotic was repressed in an rsmB mutant but partially restored in an rsmB, rsmS double mutant. This work highlights the importance of RsmS, as a conserved pleiotropic regulator of virulence and antibiotic biosynthesis.
High-throughput epitope profiling of antibodies in the plasma of Alzheimer’s disease patients using random peptide microarrays
Authors: Sim Kyu-Young , Park Sang-Heon , Choi Kyu Yeong , Park Jung Eun , Lee Jung Sup , Kim Byeong C. , Gwak Jeonghwan , Song Woo Keun , Lee Kun Ho , Park Sung-Gyoo 
Published: March 2019

AbstractThe symptoms of Alzheimer’s disease (AD), a major cause of dementia in older adults, are linked directly with neuronal cell death, which is thought to be due to aberrant neuronal inflammation. Autoantibodies formed during neuronal inflammation show excellent stability in blood; therefore, they may be convenient blood-based diagnostic markers of AD. Here, we performed microarray analysis of 29,240 unbiased random peptides to be used for comprehensive screening of AD-specific IgG and IgM antibodies in the blood. The results showed that (1) sequence-specific and isotype-specific antibodies are regulated differentially in AD, and combinations of these antibodies showing high area under the receiver operating characteristic curve values (0.862–0.961) can be used to classify AD, (2) AD-specific IgG antibodies arise from IgM antibody-secreting cells that existed before disease onset and (3) target protein profiling of the antibodies identified some AD-related proteins, some of which are involved in AD-related signalling pathways. Therefore, we propose that these epitopes may facilitate the development of biomarkers for AD diagnosis and form the basis for a mechanistic study related to AD progression.
Extreme temperature impairs growth and productivity in a common tropical marine copepod
Authors: Doan Nam X. , Vu Minh T. T. , Pham Hung Q. , Wisz Mary S. , Nielsen Torkel Gissel , Dinh Khuong V. 
Published: March 2019

AbstractShallow, tropical marine ecosystems provide essential ecosystem goods and services, but it is unknown how these ecosystems will respond to the increased exposure to the temperature extremes that are likely to become more common as climate change progresses. To address this issue, we tracked the fitness and productivity of a key zooplankton species, the copepodPseudodiaptomus annandalei, acclimated at two temperatures (30 and 34 °C) over three generations. 30 °C is the mean temperature in the shallow water of the coastal regions in Southeast Asia, while 34 °C simulated a temperature extreme that occurs frequently during the summer period. For each generation, we measured the size at maturity and reproductive success of individuals. In all three generations, we found strong negative effects of warming on all measured fitness-related parameters, including prolonged development time, reduced size at maturity, smaller clutch sizes, lower hatching success, and reduced naupliar production. Our results suggest thatP.annandaleiare already exposed to temperatures that exceed their upper thermal optimum. Increased exposure to extreme temperatures may reduce the abundance of these tropical marine copepods, and thus reduce the availability of resources to higher trophic levels.
Scattering Assisted Imaging
Authors: Leonetti Marco , Grimaldi Alfonso , Ghirga Silvia , Ruocco Giancarlo , Antonacci Giuseppe 
Published: March 2019

AbstractStandard imaging systems provide a spatial resolution that is ultimately dictated by the numerical aperture (NA) of the illumination and collection optics. In biological tissues, the resolution is strongly affected by scattering, which limits the penetration depth to a few tenths of microns. Here, we exploit the properties of speckle patterns embedded into a strongly scattering matrix to illuminate the sample at high spatial frequency content. Combining adaptive optics with a custom deconvolution algorithm, we obtain an increase in the transverse spatial resolution by a factor of 2.5 with respect to the natural diffraction limit. Our Scattering Assisted Imaging (SAI) provides an effective solution to increase the resolution when long working distance optics are needed, potentially paving the way to bulk imaging in turbid tissues.
Systematic evaluation of gene variants linked to hearing loss based on allele frequency threshold and filtering allele frequency
Authors: Rim John Hoon , Lee Joon Suk , Jung Jinsei , Lee Ji Hyun , Lee Seung-Tae , Choi Jong Rak , Choi Jae Young , Lee Min Goo , Gee Heon Yung 
Published: March 2019

AbstractAs the number of genes identified for linkage to hearing loss has been increasing and more public databases have become available, we aimed to systematically evaluate all variants reported for nonsyndromic hearing loss (NSHL) based on their allele frequencies (AFs) in the general population. Among the 3,549 variants in 97 NSHL genes reported as pathogenic/likely pathogenic in ClinVar and HGMD, 1,618 were found in public databases (gnomAD, ExAC, EVS, and 1000G). To evaluate the pathogenicity of these variants, we employed AF thresholds and NSHL-optimized ACMG guidelines. AF thresholds were determined using a high-resolution variant frequency framework and Hardy-Weinberg equilibrium calculation: 0.6% and 0.1% for recessive and dominant genes, respectively. Filtering AFs of variants linked to NSHL were obtained based on AFs reported in gnomAD and ExAC. We found that 48 variants in 23 genes had filtering AFs above the suggested thresholds and assumed that these variants might be benign based on their filtering AFs. 47 variants, except for one notorious high-frequency GJB2 mutation (c.109G > A; p.Val37Ile), were confirmed to be benign/likely benign by the NSHL-optimized ACMG guidelines. The proposed systematic approach will aid in precise evaluation of NSHL variant pathogenicity in the context of filtering AFs, AF thresholds, and NSHL-specific ACMG guidelines, thus improving NSHL diagnostics.
The reduced bactericidal activity of neutrophils as an incisive indicator of water-immersion restraint stress and impaired exercise performance in mice
Authors: Kinoshita Manabu , Nakashima Hiroyuki , Nakashima Masahiro , Koga Minori , Toda Hiroyuki , Koiwai Kazuki , Morimoto Yuji , Miyazaki Hiromi , Saitoh Daizoh , Suzuki Hiroaki , Seki Shuhji 
Published: March 2019

AbstractThe incisive evaluation of psychological stress may be required to determine the exercise performance of stressed hosts. We investigated objective markers of psychological stress that reflect exercise performance, focusing on the neutrophil function. We used murine water-immersion restraint (WIR) stress for our assessments. After receiving WIR for 1 or 2 h, mice were exercised on an airtight treadmill that monitors their respiratory exchange ratio. The neutrophil function was analyzed after WIR stress. Although the control mice (without WIR) showed good combustion of both carbohydrates and lipids as energy sources during treadmill exercise, mice that underwent 2-h WIR did not combust carbohydrates or lipids effectively, drastically reducing their performance. In contrast, the 1-h WIR mice showed carbohydrate combustion (albeit a slow response) but did not use lipids for energy, thereby running longer than the 2-h WIR mice but shorter than the control mice. The bactericidal activity of neutrophils, but not their superoxide production or microsphere-phagocytic activity, was significantly reduced by 1-h WIR and further reduced by 2-h WIR, indicating a significant association between WIR stress and exercise performance. The neutrophil bactericidal activity may be a good indicator of psychological stress and a useful tool for precisely assessing exercise performance.
Ultra-fast and automated immunohistofluorescent multistaining using a microfluidic tissue processor
Authors: Cappi Giulia , Dupouy Diego Gabriel , Comino Marta Aurelia , Ciftlik Ata Tuna 
Published: March 2019

AbstractMultistaining of a tissue section targeting multiple markers allows to reveal complex interplays in a tumor environment. However, the resource-intensive and impractically long nature of iterative multiplexed immunostainings prohibits its practical implementation in daily routine, even when using work-flow automation systems. Here, we report a fully automated and ultra-fast multistaining using a microfluidic tissue processor (MTP) in as short as 20 minutes per marker, by immunofluorescent staining employing commercially available tyramide signal amplification polymer precipitation by horse-radish peroxidase (HRP) activation. The reported duration includes (i) 15 minutes for the entire fluidic exchange and reagent incubation necessary for the immunostaining and (ii) 5 minutes for the heat-induced removal of the applied antibodies. Using the automated MTP, we demonstrated a 4-plex automated multistaining with clinically relevant biomarkers within 84 minutes, showing perfect agreement with the state-of-the-art microwave treatment antibody removal. The presented HRP-based method is in principle extendable to multistaining by both tyramides accommodating higher number of fluorescent channels and multi-color chromogenic staining. We anticipate that our automated multi-staining with a turn-around time shorter than existing monoplex immunohistochemistry methods has the potential to enable multistaining in routine without disturbing the current laboratory workflow, opening perspectives for implementation of -omics approaches in tissue diagnostics.