bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nedd4 ubiquitylates VDAC2/3 to suppress erastin-induced ferroptosis in melanoma
Authors: Yang Yongfei , Luo Meiying , Zhang Kexin , Zhang Jun , Gao Tongtong , Connell Douglas O’ , Yao Fengping , Mu Changwen , Cai Bingyu , Shang Yuxue , Chen Wei 
Published: January 2020

AbstractFerroptosis is a newly defined form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides. Erastin, the ferroptosis activator, binds to voltage-dependent anion channels VDAC2 and VDCA3, but treatment with erastin can result in the degradation of the channels. Here, the authors show that Nedd4 is induced following erastin treatment, which leads to the ubiquitination and subsequent degradation of the channels. Depletion of Nedd4 limits the protein degradation of VDAC2/3, which increases the sensitivity of cancer cells to erastin. By understanding the molecular mechanism of erastin-induced cellular resistance, we can discover how cells adapt to new molecules to maintain homeostasis. Furthermore, erastin-induced resistance mediated by FOXM1-Nedd4-VDAC2/3 negative feedback loop provides an initial framework for creating avenues to overcome the drug resistance of ferroptosis activators.
A meta-analysis of the efficacy of HAART on HIV transmission and its impact on sexual risk behaviours among men who have sex with men
Authors: Jiang Ying , Su Shu , Borné Yan 
Published: January 2020

AbstractEvidence showed preventive impacts of the highly active antiretroviral therapy (HAART) on the Human Immunodeficiency Virus (HIV) transmission amomg heterosexual population, however, that is of deficit among men who have sex with men (MSM). The aim was to systematically examine the efficacy of HAART on HIV transmission and the association between the HAART initiation and unprotected anal intercourse (UAI) in MSM population. Three electronic databases were fully searched for articles published in peer-reviewed journals between 1996 and 2017. Of 1616 identified articles, fifteen articles were eligible for meta-analyses. The summary incidence rate (IR) of HIV was 6.63/100 person-year (95%CI 2.06–11.20/100 person-year)(p = 0.004). The pooled per-contact rate (PCR) of HIV was 0.42% (95% CI 0.21–0.63%)(p < 0.05). The HAART initiation (vs non-HAART) was not associated with engaging in UAI, with odds ratio (OR) 1.09 (95% CI 0.90–1.34)(p > 0.05). In the stratified analysis, participants with no less than 6 months recall period was slightly more likely to engage in UAI (OR 1.32; 95% CI 1.01–1.74)(p < 0.05). It indicated that HAART has potential efficacy on reducing infectivity of HIV positive individuals in anal intercourses. The relationship between the HAART initiation and UAI was not significant and may be influenced by some social-demographic factors. Consistent condom use and education on safe sex among MSM are crucial.
Restoring Wnt6 signaling ameliorates behavioral deficits in MeCP2 T158A mouse model of Rett syndrome
Authors: Hsu Wei-Lun , Ma Yun-Li , Liu Yen-Chen , Tai Derek J. C. , Lee Eminy H. Y. 
Published: January 2020

AbstractThe methyl-CpG-binding protein 2 gene, MECP2, is an X chromosome-linked gene encoding the MeCP2 protein, and mutations of MECP2 cause Rett syndrome (RTT). Previous study has shown that re-expression of SUMO-modified MeCP2 in Mecp2-null neurons rescues synaptic and behavioral deficits in Mecp2 conditional knockout mice, whereas about 12-fold decrease in Wnt6 mRNA level was found in MeCP2K412R sumo-mutant mice. Here, we examined the role of Wnt6 in MeCP2 T158A mouse model of RTT. Results show that lentiviral delivery of Wnt6 to the amygdala ameliorates locomotor impairment and social behavioral deficits in these animals. MeCP2 T158A mice show decreased level of GSK-3β phosphorylation and increased level of β-catenin phosphorylation. They also show reduced level of MeCP2 SUMOylation. These alterations were also restored by lenti-Wnt6 transduction. Further, both BDNF and IGF-1 expressions are decreased in MeCP2 T158A mice. Overexpression of Wnt6 increases Bdnf and Igf-1 promoter activity in HEK293T cells in a dose-dependent manner. Lenti-Wnt6 transduction to the amygdala similarly increases the mRNA level and protein expression of BDNF and IGF-1 in MeCP2 T158A mice. Moreover, environmental enrichment (EE) similarly ameliorates the locomotor and social behavioral deficits in MeCP2 T158A mice. One of the mechanisms underlying EE is mediated through enhanced MeCP2 SUMOylation and increased Wnt6 expression in these animals by EE.
Gender-based pairings influence cooperative expectations and behaviours
Authors: Cigarini Anna , Vicens Julián , Perelló Josep 
Published: January 2020

AbstractThe study explores the expectations and cooperative behaviours of men and women in a lab-in-the-field experiment by means of citizen science practices in the public space. It specifically examines the influence of gender-based pairings on the decisions to cooperate or defect in a framed and discrete Prisoner’s Dilemma game after visual contact. Overall, we found that when gender is considered behavioural differences emerge in expectations of cooperation, cooperative behaviours, and their decision time depending on whom the partner is. Men pairs are the ones with the lowest expectations and cooperation rates. After visual contact women infer men’s behaviour with the highest accuracy. Also, women take significantly more time to defect than to cooperate, compared to men. Finally, when the interacting partners have the opposite gender they expect significantly more cooperation and they achieve the best collective outcome. Together, the findings suggest that non verbal signals may influence men and women differently, offering novel interpretations to the context-dependence of gender differences in social decision tasks.
Linking Small-Scale Flight Manoeuvers and Density Profiles to the Vertical Movement of Insects in the Nocturnal Stable Boundary Layer
Authors: Wainwright Charlotte E. , Reynolds Don R. , Reynolds Andy M. 
Published: January 2020

AbstractHuge numbers of insects migrate over considerable distances in the stably-stratified night-time atmosphere with great consequences for ecological processes, biodiversity, ecosystem services and pest management. We used a combination of meteorological radar and lidar instrumentation at a site in Oklahoma, USA, to take a new look at the general assistance migrants receive from both vertical and horizontal airstreams during their long-distance flights. Movement in the nocturnal boundary layer (NBL) presents very different challenges for migrants compared to those prevailing in the daytime convective boundary layer, but we found that Lagrangian stochastic modelling is effective at predicting flight manoeuvers in both cases. A key feature for insect transport in the NBL is the frequent formation of a thin layer of fast-moving air – the low-level jet. Modelling suggests that insects can react rapidly to counteract vertical air movements and this mechanism explains how migrants are retained in the jet for long periods (e.g. overnight, and perhaps for several hours early in the morning). This results in movements over much longer distances than are likely in convective conditions, and is particularly significant for the reintroduction of pests to northern regions where they are seasonally absent due to low winter temperatures.
Structural, optical, thermal and conducting properties of V2−xLixO5−δ (0.15 ≤ x ≤ 0.30) systems
Authors: Khan Savidh , Singh K. 
Published: January 2020

AbstractLithium-doped vanadates (V2−xLixO5−δ (0.15 ≤ x ≤ 0.30)) are synthesized by melt-quench method. The physical, structural, optical, thermal and conducting properties of as-quenched samples are investigated using various experimental techniques to study their suitability for electrolyte in battery/solid oxide fuel cell application. X-ray diffraction (XRD) patterns confirm the formation of three different crystalline phases. FTIR and Raman spectra indicate that the doping of Li2O into V2O5 leads to a transition from VO5 into VO4 structural unit. The optical diffused reflectance spectra revealed that the optical band gap (Eg) decreases from 2.2 to 2.08 eV while Urbach energy (EU) increases (0.31–0.41 eV) with the addition of Li2O content in place of vanadium. The thermal stability is studied by thermogravimetric analyser (TGA). The DC conductivity of the present samples is increased from 0.08 to 0.12 Scm−1 at 450 °C with Li2O doping. These materials can be used as electrolyte for battery/solid oxide fuel cell due to their good conductivity (~0.12 Scm−1) at 450 °C.
Thermostabilization of VPR, a kinetically stable cold adapted subtilase, via multiple proline substitutions into surface loops
Authors: Óskarsson K. R. , Sævarsson A. F. , Kristjánsson M. M. 
Published: January 2020

AbstractProtein stability is a widely studied topic, there are still aspects however that need addressing. In this paper we examined the effects of multiple proline substitutions into loop regions of the kinetically stable proteinase K-like serine protease VPR, using the thermostable structural homologue AQUI as a template. Four locations for proline substitutions were chosen to imitate the structure of AQUI. Variants were produced and characterized using differential scanning calorimetry (DSC), circular dichroism (CD), steady state fluorescence, acrylamide fluorescence quenching and thermal inactivation experiments. The final product VPRΔC_N3P/I5P/N238P/T265P was greatly stabilized which was achieved without any noticeable detrimental effects to the catalytic efficiency of the enzyme. This stabilization seems to be derived from the conformation restrictive properties of the proline residue in its ability to act as an anchor point and strengthen pre-existing interactions within the protein and allowing for these interactions to prevail when thermal energy is applied to the system. In addition, the results underline the importance of the synergy between distant local protein motions needed to result in stabilizing effects and thus giving an insight into the nature of the stability of VPR, its unfolding landscape and how proline residues can infer kinetic stability onto protein structures.
A facile and efficient method for the synthesis of crystalline tetrahydro-β-carbolines via the Pictet-Spengler reaction in water
Authors: Byeon Hong-Ju , Jung Kyung-Hwan , Moon Gi-Seong , Moon Sung-Kwon , Lee Hyang-Yeol 
Published: January 2020

AbstractA facile and efficient synthesis of tetrahydro-β-carbolines (tryptolines) in one step from tryptamine and aldehydes, in an environmentally friendly water solvent, has been investigated. This convenient and clean synthesis of various tryptolines was facilitated by l-tartaric acid, a natural compound, to obtain the desired products as clear crystals. Among the four crystalline products, the most substituted tryptoline 2 showed the best inhibitory activity against EJ cells and the least cytotoxicity, with an LC50 value of 1.49 mg/mL, against brine shrimp larvae.
Centre of Rotation of the Human Subtalar Joint Using Weight-Bearing Clinical Computed Tomography
Authors: Peña Fernández Marta , Hoxha Dorela , Chan Oliver , Mordecai Simon , Blunn Gordon W. , Tozzi Gianluca , Goldberg Andy 
Published: January 2020

AbstractAccurate in vivo quantification of subtalar joint kinematics can provide important information for the clinical evaluation of subtalar joint function; the analysis of outcome of surgical procedures of the hindfoot; and the design of a replacement subtalar joint prosthesis. The objective of the current study was to explore the potential of full weight-bearing clinical computed tomography (CT) to evaluate the helical axis and centre of rotation of the subtalar joint during inversion and eversion motion. A subject specific methodology was proposed for the definition of the subtalar joint motion combining three-dimensional (3D) weight-bearing imaging at different joint positions with digital volume correlation (DVC). The computed subtalar joint helical axis parameters showed consistency across all healthy subjects and in line with previous data under simulated loads. A sphere fitting approach was introduced for the computation of subtalar joint centre of rotation, which allows to demonstrate that this centre of rotation is located in the middle facet of the subtalar joint. Some translation along the helical axis was also observed, reflecting the elasticity of the soft-tissue restraints. This study showed a novel technique for non-invasive quantitative analysis of bone-to-bone motion under full weight-bearing of the hindfoot. Identifying different joint kinematics in patients with ligamentous laxity and instability, or in the presence of stiffness and arthritis, could help clinicians to define optimal patient-specific treatments.
Novel genes exhibiting DNA methylation alterations in Korean patients with chronic lymphocytic leukaemia: a methyl-CpG-binding domain sequencing study
Authors: Kim Miyoung , Lee Eunyup , Zang Dae Young , Kim Hyo Jung , Kim Ho Young , Han Boram , Kim Han-Sung , Kang Hee Jung , Hwang Seungwoo , Lee Young Kyung 
Published: January 2020

AbstractChronic lymphocytic leukaemia (CLL) exhibits differences between Asians and Caucasians in terms of incidence rate, age at onset, immunophenotype, and genetic profile. We performed genome-wide methylation profiling of CLL in an Asian cohort for the first time. Eight Korean patients without somatic immunoglobulin heavy chain gene hypermutations underwent methyl-CpG-binding domain sequencing (MBD-seq), as did five control subjects. Gene Ontology, pathway analysis, and network-based prioritization of differentially methylated genes were also performed. More regions were hypomethylated (2,062 windows) than were hypermethylated (777 windows). Promoters contained the highest proportion of differentially methylated regions (0.08%), while distal intergenic and intron regions contained the largest number of differentially methylated regions. Protein-coding genes were the most abundant, followed by long noncoding and short noncoding genes. The most significantly over-represented signalling pathways in the differentially methylated gene list included immune/cancer-related pathways and B-cell receptor signalling. Among the top 10 hub genes identified via network-based prioritization, four (UBC, GRB2, CREBBP, and GAB2) had no known relevance to CLL, while the other six (STAT3, PTPN6, SYK, STAT5B, XPO1, and ABL1) have previously been linked to CLL in Caucasians. As such, our analysis identified four novel candidate genes of potential significance to Asian patients with CLL.
Neuropeptide receptor genes GHSR and NMUR1 are candidate epigenetic biomarkers and predictors for surgically treated patients with oropharyngeal cancer
Authors: Misawa Kiyoshi , Mima Masato , Satoshi Yamada , Misawa Yuki , Imai Atsushi , Mochizuki Daiki , Nakagawa Takuya , Kurokawa Tomoya , Oguro Miki , Ishikawa Ryuji , Yamaguchi Yuki , Endo Shiori , Kawasaki Hideya , Kanazawa Takeharu , Mineta Hiroyuki 
Published: January 2020

AbstractPathological staging and histological grading systems are useful, but imperfect, predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). Aberrant promoter methylation is the main type of epigenetic modification that plays a role in the inactivation of tumor suppressor genes. To identify new potential prognostic markers, we investigated the promoter methylation status of five neuropeptide receptor genes. The methylation status of the target genes was compared with clinical characteristics in 278 cases; 72 hypopharyngeal cancers, 54 laryngeal cancers, 75 oropharyngeal cancers, and 77 oral cavity cancers were studied. We found that the NTSR1, NTSR2, GHSR, MLNR, and NMUR1 promoters were methylated in 47.8%, 46.8%, 54.3%, 39.2%, and 43.5% of the samples, respectively. GHSR and NMUR1 promoter methylation independently predicted recurrence in HNSCC. In patients with oropharyngeal cancer (n = 75), GHSR and NMUR1 promoter methylation significantly correlates with survival in surgically treated patients. We classified our patients as having a low, intermediate, or high-risk of death based on three factors: HPV status, and GHSR and NMUR1 promoter methylation. The disease-free survival (DFS) rates were 87.1%, 42.7%, and 17.0%, respectively. Combined data analysis of the methylation status of ten-eleven translocation (TET) family genes indicated a trend toward greater methylation indices as the number of TET methylation events increased. In the current study, we presented the relationship between the methylation status of the GHSR and NMUR1 genes and recurrence in HNSCC, specifically in risk classification of oropharyngeal carcinomas cases with HPV status.
Transcriptional regulation of the IL-13Rα2 gene in human lung fibroblasts
Authors: Penke Loka R. , Ouchi Hideyasu , Speth Jennifer M. , Lugogo Njira , Huang Yvonne J. , Huang Steven K. , Peters-Golden Marc 
Published: January 2020

AbstractInterleukin (IL)−13 is a type 2 cytokine with important roles in allergic diseases, asthma, and tissue fibrosis. Its receptor (R) α1 is primarily responsible for the biological actions of this cytokine, while Rα2 possesses a decoy function which can block IL-13 signaling. Although the expression of Rα2 is known to be subject to modulation, information about its transcriptional regulation is limited. In this study, we sought to expand the understanding of transcriptional control of Rα2 in lung fibroblasts. We confirmed previous reports that IL-13 elicited modest induction of Rα2 in normal adult human lung fibroblasts, but found that prostaglandin E2(PGE2) and fibroblast growth factor 2 (FGF-2) –mediators known to influence fibroblast activation in tissue fibrosis but not previously investigated in this regard – led to a much greater magnitude of Rα2 induction. Although both PGE2(via protein kinase A) and FGF-2 (via protein kinase B, also known as AKT) depended on activation of cAMP-responsive element-binding protein (CREB) for induction of Rα2 expression, they nevertheless demonstrated synergy in doing so, likely attributable to their differential utilization of distinct transcriptional start sites on the Rα2 promoter. Our data identify CREB activation via PGE2and FGF-2 as a previously unrecognized molecular controller of Rα2 gene induction and provide potential new insights into strategies for therapeutic manipulation of this endogenous brake on IL-13 signaling.
Hepatic ILC2 activity is regulated by liver inflammation-induced cytokines and effector CD4+ T cells
Authors: Steinmann Silja , Schoedsack Marek , Heinrich Fabian , Breda Philippe C. , Ochel Aaron , Tiegs Gisa , Neumann Katrin 
Published: January 2020

AbstractIn immune-mediated hepatitis, type 2 innate lymphoid cells (ILC2) as well as effector CD4+ T cells have been shown to drive disease pathology. However, less is known about mechanisms involved in the regulation of ILC2 function during liver inflammation. We showed that in homeostasis, hepatic ILC2 constituted a very small population with a naive, inactive phenotype. During immune-mediated hepatitis, the cytokines IL-33 and IFNγ were expressed in liver tissue. IL-33 induced strong activation and expression of type 2 cytokines as well as IL-6 by hepatic ILC2 while IFNγ suppressed cytokine production. Interestingly, this inhibitory effect was overcome by IL-33. The phenotype of activated hepatic ILC2 were stable since they did not show functional plasticity in response to liver inflammation-induced cytokines. Moreover, hepatic ILC2 induced a Th2 phenotype in activated CD4+ T cells, which increased ILC2-derived cytokine expression via IL-2. In contrast, Th1 cells inhibited survival of ILC2 by production of IFNγ. Thus, hepatic ILC2 function is regulated by IL-33, IL-2, and IFNγ. While IL-33 and IL-2 support hepatic ILC2 activation, their inflammatory activity in immune-mediated hepatitis might be limited by infiltrating IFNγ-expressing Th1 cells.
Semiochemicals for intraspecific communication of the fig weevil Aclees sp. cf. foveatus (Coleoptera: Curculionidae): a first survey
Authors: Iovinella Immacolata , Pierattini Erika Carla , Bedini Stefano , Dani Francesca Romana , Guarino Salvatore , Lucchi Andrea , Giannotti Paolo , Cuzzupoli Giorgio , Girardi Jessica , Conti Barbara 
Published: January 2020

AbstractThe fig tree weevilAcleessp. cf.foveatus(Coleoptera: Curculionidae), introduced in Italy in 2005, is currently causing significant economic and environmental losses to fig tree nurseries and orchards in Central Italy. Fig damages are due to the adults feeding on leaves and fruits, and to the galleries dug by the xylophagous larvae in the trunk, which lead the plants to death. To date, no chemical or biological control methods resulted to be effective against this invasive pest. In order to gain information about possible semiochemicals involved in mate recognition and choice, both the volatile organic compounds (VOCs) and the epicuticular lipids of male and female specimens were analysed. VOCs emissions of specimens were characterized essentially by monoterpenes, while epicuticular lipids contained long chained 2-ketones, alkanes, alkenes, including some methyl alkenes, and several fatty acid propyl esters. The attractiveness of reconstituted VOCs blends of the two sexes was tested in electrophysiological and behavioural assays in laboratory conditions. Both the male and the female reconstituted VOCs drove a significant response towards individuals of the opposite sex, thus demonstrating features of sexual attractants. Our results suggest a possible application of VOCs blends as pheromonic attractants in field monitoring and mass trapping ofAcleessp. cf.foveatus.
Germline-restricted chromosome (GRC) in the sand martin and the pale martin (Hirundinidae, Aves): synapsis, recombination and copy number variation
Authors: Malinovskaya Lyubov P. , Zadesenets Kira S. , Karamysheva Tatyana V. , Akberdina Ekaterina A. , Kizilova Elena A. , Romanenko Margarita V. , Shnaider Elena P. , Scherbakova Mariya M. , Korobitsyn Igor G. , Rubtsov Nikolai B. , Borodin Pavel M. , Torgasheva Anna A. 
Published: January 2020

AbstractAll songbirds studied to date have an additional Germline Restricted Chromosome (GRC), which is not present in somatic cells. GRCs show a wide variation in genetic content and little homology between species. To check how this divergence affected the meiotic behavior of the GRC, we examined synapsis, recombination and copy number variation for GRCs in the closely related sand and pale martins (Riparia riparia and R. diluta) in comparison with distantly related estrildid finches. Using immunolocalization of meiotic proteins and FISH with GRC-specific DNA probes, we found a striking similarity in the meiotic behavior of GRCs between martins and estrildid finches despite the millions of years of independent evolution. GRCs are usually present in two copies in female and in one copy in male pachytene cells. However, we detected polymorphism in female and mosaicism in male martins for the number of GRCs. In martin and zebra finch females, two GRCs synapse along their whole length, but recombine predominately at their ends. We suggest that the shared features of the meiotic behavior of GRCs have been supported by natural selection in favor of a preferential segregation of GRCs to the eggs.