bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wnt/β-catenin signaling stimulates the expression and synaptic clustering of the autism-associated Neuroligin 3 gene
Authors: Medina Matías A. , Andrade Víctor M. , Caracci Mario O. , Avila Miguel E. , Verdugo Daniela A. , Vargas Macarena F. , Ugarte Giorgia D. , Reyes Ariel E. , Opazo Carlos , De Ferrari Giancarlo V. 
Published: February 2018

AbstractSynaptic abnormalities have been described in individuals with autism spectrum disorders (ASD). The cell-adhesion molecule Neuroligin-3 (Nlgn3) has an essential role in the function and maturation of synapses and NLGN3 ASD-associated mutations disrupt hippocampal and cortical function. Here we show that Wnt/β-catenin signaling increases Nlgn3 mRNA and protein levels in HT22 mouse hippocampal cells and primary cultures of rat hippocampal neurons. We characterized the activity of mouse and rat Nlgn3 promoter constructs containing conserved putative T-cell factor/lymphoid enhancing factor (TCF/LEF)-binding elements (TBE) and found that their activity is significantly augmented in Wnt/β-catenin cell reporter assays. Chromatin immunoprecipitation (ChIP) assays and site-directed mutagenesis experiments revealed that endogenous β-catenin binds to novel TBE consensus sequences in the Nlgn3 promoter. Moreover, activation of the signaling cascade increased Nlgn3 clustering and co- localization with the scaffold PSD-95 protein in dendritic processes of primary neurons. Our results directly link Wnt/β-catenin signaling to the transcription of the Nlgn3 gene and support a functional role for the signaling pathway in the dysregulation of excitatory/inhibitory neuronal activity, as is observed in animal models of ASD.
Genetic alterations driving metastatic colony formation are acquired outside of the primary tumour in melanoma
Authors: Werner-Klein Melanie , Scheitler Sebastian , Hoffmann Martin , Hodak Isabelle , Dietz Klaus , Lehnert Petra , Naimer Veronika , Polzer Bernhard , Treitschke Steffi , Werno Christian , Markiewicz Aleksandra , Weidele Kathrin , Czyz Zbigniew , Hohenleutner Ulrich , Hafner Christian , Haferkamp Sebastian , Berneburg Mark , Rümmele Petra , Ulmer Anja , Klein Christoph A. 
Published: February 2018

AbstractMouse models indicate that metastatic dissemination occurs extremely early; however, the timing in human cancers is unknown. We therefore determined the time point of metastatic seeding relative to tumour thickness and genomic alterations in melanoma. Here, we find that lymphatic dissemination occurs shortly after dermal invasion of the primary lesion at a median thickness of ~0.5 mm and that typical driver changes, includingBRAFmutation and gained or lost regions comprising genes likeMETorCDKNA2, are acquired within the lymph node at the time of colony formation. These changes define a colonisation signature that was linked to xenograft formation in immunodeficient mice and death from melanoma. Thus, melanoma cells leave primary tumours early and evolve at different sites in parallel. We propose a model of metastatic melanoma dormancy, evolution and colonisation that will inform direct monitoring of adjuvant therapy targets.
LARP7-like protein Pof8 regulates telomerase assembly and poly(A)+TERRA expression in fission yeast
Authors: Mennie Amanda K. , Moser Bettina A. , Nakamura Toru M. 
Published: February 2018

AbstractTelomerase is a reverse transcriptase complex that ensures stable maintenance of linear eukaryotic chromosome ends by overcoming the end replication problem, posed by the inability of replicative DNA polymerases to fully replicate linear DNA. The catalytic subunit TERT must be assembled properly with its telomerase RNA for telomerase to function, and studies in Tetrahymena have established that p65, a La-related protein 7 (LARP7) family protein, utilizes its C-terminal xRRM domain to promote assembly of the telomerase ribonucleoprotein (RNP) complex. However, LARP7-dependent telomerase complex assembly has been considered as unique to ciliates that utilize RNA polymerase III to transcribe telomerase RNA. Here we show evidence that fission yeast Schizosaccharomyces pombe utilizes the p65-related protein Pof8 and its xRRM domain to promote assembly of RNA polymerase II-encoded telomerase RNA with TERT. Furthermore, we show that Pof8 contributes to repression of the transcription of noncoding RNAs at telomeres.
Tridimensional visualization reveals direct communication between the embryo and glands critical for implantation
Authors: Yuan Jia , Deng Wenbo , Cha Jeeyeon , Sun Xiaofei , Borg Jean-Paul , Dey Sudhansu. K. 
Published: February 2018

AbstractEmbryo implantation is central to pregnancy success. Our previous understanding is limited by studying this phenomenon primarily in two dimensions. Here we employ 3D visualization, revealing that epithelial evaginations that form implantation chambers (crypts) consistently arise with preexisting glands, suggesting direct access of glands to embryos within the chamber. While the lobular domains of the glands become more developed, the ductal regions continue to elongate and progressively stretch following implantation. Using diapausing mice and mice with deletion of the planar cell polarity gene Vangl2 in uterine epithelial cells, we show that dynamic changes in gland topography depend on implantation-competent blastocysts and planar cell polarity. By transferring blastocyst-size beads preloaded with HB-EGF in pseudopregnant mice, we found that HB-EGF is a trigger for the communication between embryos and glands. Glands directly connecting the crypt encasing the embryo during implantation are therefore fundamental to pregnancy success.
Galectin-1 is required for the regulatory function of B cells
Authors: Alhabbab R. , Blair P. , Smyth L. A. , Ratnasothy K. , Peng Q. , Moreau A. , Lechler R. , Elgueta R. , Lombardi G. 
Published: February 2018

AbstractGalectin-1 (Gal-1) is required for the development of B cells in the bone marrow (BM), however very little is known about the contribution of Gal-1 to the development of B cell regulatory function. Here, we report an important role for Gal-1 in the induction of B cells regulatory function. Mice deficient of Gal-1 (Gal-1−/−) showed significant loss of Transitional-2 (T2) B cells, previously reported to include IL-10+regulatory B cells. Gal-1−/−B cells stimulatedin vitrovia CD40 molecules have impaired IL-10 and Tim-1 expression, the latter reported to be required for IL-10 production in regulatory B cells, and increased TNF-α expression compared to wild type (WT) B cells. Unlike their WT counterparts, T2 and T1 Gal-1−/−B cells did not suppress TNF-α expression by CD4+T cells activatedin vitrowith allogenic DCs (allo-DCs), nor were they suppressivein vivo, being unable to delay MHC-class I mismatched skin allograft rejection following adoptive transfer. Moreover, T cells stimulated with allo-DCs show an increase in their survival when co-cultured with Gal-1−/−T2 and MZ B cells compared to WT T2 and MZ B cells. Collectively, these data suggest that Gal-1 contributes to the induction of B cells regulatory function.
Early life exposure to ethinylestradiol enhances subsequent responses to environmental estrogens measured in a novel transgenic zebrafish
Authors: Green Jon M. , Lange Anke , Scott Aaron , Trznadel Maciej , Wai Htoo Aung , Takesono Aya , Brown A. Ross , Owen Stewart F. , Kudoh Tetsuhiro , Tyler Charles R. 
Published: February 2018

AbstractEstrogen plays fundamental roles in a range of developmental processes and exposure to estrogen mimicking chemicals has been associated with various adverse health effects in both wildlife and human populations. Estrogenic chemicals are found commonly as mixtures in the environment and can have additive effects, however risk analysis is typically conducted for single-chemicals with little, or no, consideration given for an animal’s exposure history. Here we developed a transgenic zebrafish with a photoconvertable fluorophore (Kaede, green to red on UV light exposure) in a skin pigment-free mutant element (ERE)-Kaede-Casper model and applied it to quantify tissue-specific fluorescence biosensor responses for combinations of estrogen exposures during early life using fluorescence microscopy and image analysis. We identify windows of tissue-specific sensitivity to ethinylestradiol (EE2) for exposure during early-life (0–5 dpf) and illustrate that exposure to estrogen (EE2) during 0–48 hpf enhances responsiveness (sensitivity) to different environmental estrogens (EE2, genistein and bisphenol A) for subsequent exposures during development. Our findings illustrate the importance of an organism’s stage of development and estrogen exposure history for assessments on, and possible health risks associated with, estrogen exposure.
Next generation high throughput DNA damage detection platform for genotoxic compound screening
Authors: Sykora Peter , Witt Kristine L. , Revanna Pooja , Smith-Roe Stephanie L. , Dismukes Jonathan , Lloyd Donald G. , Engelward Bevin P. , Sobol Robert W. 
Published: February 2018

AbstractMethods for quantifying DNA damage, as well as repair of that damage, in a high-throughput format are lacking. Single cell gel electrophoresis (SCGE; comet assay) is a widely-used method due to its technical simplicity and sensitivity, but the standard comet assay has limitations in reproducibility and throughput. We have advanced the SCGE assay by creating a 96-well hardware platform coupled with dedicated data processing software (CometChip Platform). Based on the original cometchip approach, the CometChip Platform increases capacity ~200 times over the traditional slide-based SCGE protocol, with excellent reproducibility. We tested this platform in several applications, demonstrating a broad range of potential uses including the routine identification of DNA damaging agents, using a 74-compound library provided by the National Toxicology Program. Additionally, we demonstrated how this tool can be used to evaluate human populations by analysis of peripheral blood mononuclear cells to characterize susceptibility to genotoxic exposures, with implications for epidemiological studies. In summary, we demonstrated a high level of reproducibility and quantitative capacity for the CometChip Platform, making it suitable for high-throughput screening to identify and characterize genotoxic agents in large compound libraries, as well as for human epidemiological studies of genetic diversity relating to DNA damage and repair.
Caffeine Caused a Widespread Increase of Resting Brain Entropy
Authors: Chang Da , Song Donghui , Zhang Jian , Shang Yuanqi , Ge Qiu , Wang Ze 
Published: February 2018

AbstractEntropy is an important trait of brain function and high entropy indicates high information processing capacity. We recently demonstrated that brain entropy (BEN) is stable across time and differs between controls and patients with various brain disorders. The purpose of this study was to examine whether BEN is sensitive to pharmaceutical modulations with caffeine. Both cerebral blood flow (CBF) and resting fMRI were collected from sixty caffeine-naïve healthy subjects before and after taking a 200 mg caffeine pill. Our data showed that caffeine reduced CBF in the whole brain but increased BEN across the cerebral cortex with the highest increase in lateral prefrontal cortex, the default mode network (DMN), visual cortex, and motor network, consistent with the beneficial effects of caffeine (such as vigilance and attention) on these areas. BEN increase was correlated to CBF reduction only in several regions (−0.5 < r < −0.4), indicating a neuronal nature for most of the observed BEN alterations. In summary, we showed the first evidence of BEN alterations due to caffeine ingestion, suggesting BEN as a biomarker sensitive to pharmaceutical brain function modulations.
Hypoxia induces pulmonary fibroblast proliferation through NFAT signaling
Authors: Senavirathna Lakmini Kumari , Huang Chaoqun , Yang Xiaoyun , Munteanu Maria Cristina , Sathiaseelan Roshini , Xu Dao , Henke Craig A. , Liu Lin 
Published: February 2018

AbstractIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive and typically fatal lung disease with a very low survival rate. Excess accumulation of fibroblasts, myofibroblasts and extracellular matrix creates hypoxic conditions within the lungs, causing asphyxiation. Hypoxia is, therefore, one of the prominent features of IPF. However, there have been few studies concerning the effects of hypoxia on pulmonary fibroblasts. In this study, we investigated the molecular mechanisms of hypoxia-induced lung fibroblast proliferation. Hypoxia increased the proliferation of normal human pulmonary fibroblasts and IPF fibroblasts after exposure for 3–6 days. Cell cycle analysis demonstrated that hypoxia promoted the G1/S phase transition. Hypoxia downregulated cyclin D1 and A2 levels, while it upregulated cyclin E1 protein levels. However, hypoxia had no effect on the protein expression levels of cyclin-dependent kinase 2, 4, and 6. Chemical inhibition of hypoxia-inducible factor (HIF)-2 reduced hypoxia-induced fibroblast proliferation. Moreover, silencing of Nuclear Factor Activated T cell (NFAT) c2 attenuated the hypoxia-mediated fibroblasts proliferation. Hypoxia also induced the nuclear translocation of NFATc2, as determined by immunofluorescence staining. NFAT reporter assays showed that hypoxia-induced NFAT signaling activation is dependent on HIF-2, but not HIF-1. Furthermore, the inhibition or silencing of HIF-2, but not HIF-1, reduced the hypoxia-mediated NFATc2 nuclear translocation. Our studies suggest that hypoxia induces the proliferation of human pulmonary fibroblasts through NFAT signaling and HIF-2.
A lumenal interrupted helix in human sperm tail microtubules
Authors: Zabeo Davide , Heumann John M. , Schwartz Cindi L. , Suzuki-Shinjo Azusa , Morgan Garry , Widlund Per O. , Höög Johanna L. 
Published: February 2018

AbstractEukaryotic flagella are complex cellular extensions involved in many human diseases gathered under the term ciliopathies. Currently, detailed insights on flagellar structure come mostly from studies on protists. Here, cryo-electron tomography (cryo-ET) was performed on intact human spermatozoon tails and showed a variable number of microtubules in the singlet region (inside the end-piece). Inside the microtubule plus end, a novel left-handed interrupted helix which extends several micrometers was discovered. This structure was named Tail Axoneme Intra-Lumenal Spiral (TAILS) and binds directly to 11 protofilaments on the internal microtubule wall, in a coaxial fashion with the surrounding microtubule lattice. It leaves a gap over the microtubule seam, which was directly visualized in both singlet and doublet microtubules. We speculate that TAILS may stabilize microtubules, enable rapid swimming or play a role in controlling the swimming direction of spermatozoa.
Why are there (almost) no randomised controlled trial-based evaluations of business support programmes?
Authors: Dalziel Margaret 
Published: February 2018

AbstractBased on the achievements of randomised controlled trials (RCTs) in medicine, and the need for effective government interventions in support of business, some have advocated for the use of RCTs in the evaluation of business support programmes (BSPs). Notwithstanding these recommendations, the use of RCTs in the evaluation of BSPs has been resisted by (almost) all. Policy makers and managers are correct in their reluctance to undertake RCT-based evaluations for four reasons. First, while RCTs require the random allocation of support, judicious programmes select firms on the basis of potential and amenability to support. Second, while RCTs require treatments that exhibit low variability, the most effective BSPs draw upon substantive knowledge to provide support that is customised. Third, BSPs aim to produce outliers—firms whose performance is exceptional. When outliers are present, very large samples will be required to produce reliable results. Finally, an RCT may not yield a meaningful contribution to knowledge. The strength of an RCT is its ability to estimate the magnitude of the treatment effect under controlled conditions. But where much depends on the nature of participants and circumstances, we seek evidence of what works, for whom, in which circumstances, and why.
Lipid bilayer composition modulates the unfolding free energy of a knotted α-helical membrane protein
Authors: Sanders M. R. , Findlay H. E. , Booth P. J. 
Published: February 2018

Significance
Cells in our bodies sense and communicate with the outside world via proteins embedded in membranes that surround the cells. As with all proteins, a fundamental parameter governing their biological function is the inherent, thermodynamic stability of the folded state. Surprisingly, there is no measure of this thermodynamic stability in a lipid membrane for the ubiquitous class of membrane proteins with structures based on α-helices. We remedy this through the study of a protein related to the physiologically important membrane proteins that are partly responsible for transmitting signals in the nervous system. We identify key properties of the surrounding lipid membrane that regulate the thermodynamic stability of the protein.
Functional comparision between truncated MTT1 and truncated MTT2 from Tetrahyemna thermophila
Authors: Zhou Huanxin , Xu Jing , Wang Wei 
Published: February 2018

Abstract
Metallothioneins (MTs) are low-molecular-weight proteins with high Cys content and high metal-chelating ability. CdMT and CuMT subfamilies present different characteristics in Tetrahymena. To explore the effect of the cysteine arrangement and sequence length of MTs for binding different metal ions, MTT1, truncated MTT1 (TM1), MTT2, and truncated MTT2 (TM2) were expressed in E. coli. The half-maximal inhibiting concentrations (IC50) of Cd2+ and Cu+ for the recombinant strains were different. Furthermore, E. coli cells expressing MTT1 and TM1 exhibited higher accumulating ability for Cd2+ than cells expressing MTT2 and TM2. However, the opposite is true for Cu+. The binding ability of the different recombinant proteins to Cd2+ and Cu+ were also different. MTT1 and truncated mutant TM1 were the preference for Cd2+, whereas MTT2 and truncated mutant TM2 were the preference for Cu+ coordination. These results showed that metal ion tolerance and accumulation ability not only depended on cysteine arrangement pattern but also on sequence length of MT in Tetrahymena.
Repeated‐sprint training in hypoxia induced by voluntary hypoventilation improves running repeated‐sprint ability in rugby players
Authors: Fornasier‐Santos Charly , Millet Grégoire P. , Woorons Xavier 
Published: February 2018

AbstractPurpose: The goal of this study was to determine the effects of repeated‐sprint training in hypoxia induced by voluntary hypoventilation at low lung volume (VHL) on running repeated‐sprint ability (RSA) in team‐sport players.Methods: Twenty‐one highly trained rugby players performed, over a 4‐week period, seven sessions of repeated 40‐m sprints either with VHL (RSH‐VHL, n = 11) or with normal breathing (RSN, n = 10). Before (Pre‐) and after training (Post‐), performance was assessed with an RSA test (40‐m all‐out sprints with a departure every 30 s) until task failure (85% of the reference velocity assessed in an isolated sprint).Results: The number of sprints completed during the RSA test was significantly increased after the training period in RSH‐VHL (9.1 ± 2.8 vs. 14.9 ± 5.3; +64%; p < .01) but not in RSN (9.8 ± 2.8 vs. 10.4 ± 4.7; +6%; p = .74). Maximal velocity was not different between Pre‐ and Post‐ in both groups whereas the mean velocity decreased in RSN and remained unchanged in RSH‐VHL. The mean SpO2 recorded over an entire training session was lower in RSH‐VHL than in RSN (90.1 ± 1.4 vs. 95.5 ± 0.5%, p < .01).Conclusion: RSH‐VHL appears to be an effective strategy to produce a hypoxic stress and to improve running RSA in team‐sport players.
Does perceived inclusion matter in the workplace?
Authors: Chen Chiyin , Tang Ningyu 
Published: February 2018

PurposePerceived inclusion refers to employees’ perception of their inclusion status in the workplace. This concept offers a new perspective to understand employees’ experiences within today’s complex working environment. However, research on how perceived inclusion influences employee behavior is lacking. The purpose of this paper is to explore the mechanism of perceived inclusion through the lens of the social exchange perspective and role identity theory.Design/methodology/approachSurvey data were collected from 257 employees and 60 supervisors in a manufacturing company. Multi-level structural equation modeling and the Monte Carlo method were applied to test the mediation effect.FindingsThe results indicated that employees’ perceived inclusion was positively associated with job role and innovator role performance through the mediation of organizational commitment. Perceived inclusion was also directly associated with team role performance.Originality/valueThis is the first study to empirically examine perceived inclusion in the workplace from the social exchange and role identity perspective. It revealed that perceived inclusion fosters employees’ commitment toward the organization, which in turn influences their work-role behaviors. Theoretical contributions and practical implications are discussed.
Building successful franchise partnerships: the importance of communication and trust
Authors: Fernández-Monroy Margarita , Martín-Santana Josefa D. , Galván-Sánchez Inmaculada 
Published: February 2018

PurposeThe purpose of this paper is to propose a conceptual model for building successful franchise partnerships. The model examines the influence of communication and trust on satisfaction and performance in franchise partnerships, considering that franchises are based on franchisor-franchisee and franchisor-supplier relationships.Design/methodology/approachThe unit of analysis refers to the relationships that the franchisor maintains with the franchisees and the main supplier, from the franchisor’s perspective. A mail survey of 592 franchises was conducted by means of a structured, self-administered questionnaire for data collection. A total of 98 valid questionnaires were received and analyzed using structural equation modeling.FindingsResults indicate that communication between franchise partners is related to satisfaction through trust. In fact, communication is a major precursor of trust. Findings also show the direct influence of trust on satisfaction in both relationships. Finally, results evidence that developing satisfactory relationships between partners improves strategic and operational franchise outcomes.Research limitations/implicationsThe use of the questionnaire limits the approach to information gathering. In addition, the study focused on the franchisor’s perspective of the relationships and it would be interesting to include other partners’ opinions. Further, research should broaden the study scope to include other factors of franchise partnerships.Practical implicationsThis study provides franchisors with guidelines to develop satisfactory relationships. It recommends that franchisors design adequate programs to create, maintain, and enhance franchise partnerships, and also to improve a trust-based culture.Originality/valueThe analysis is conducted taking into consideration the franchisor-franchisee relationship and the franchisor-supplier relationship. Measurement scales are developed and validated for both relationships.