bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lmx1b is required for the glutamatergic fates of a subset of spinal cord neurons
Authors: Hilinski William C. , Bostrom Jonathan R. , England Samantha J. , Juárez-Morales José L. , de Jager Sarah , Armant Olivier , Legradi Jessica , Strähle Uwe , Link Brian A. , Lewis Katharine E. 
Published: August 2016

Abstract

Background
Alterations in neurotransmitter phenotypes of specific neurons can cause imbalances in excitation and inhibition in the central nervous system (CNS), leading to diseases. Therefore, the correct specification and maintenance of neurotransmitter phenotypes is vital. As with other neuronal properties, neurotransmitter phenotypes are often specified and maintained by particular transcription factors. However, the specific molecular mechanisms and transcription factors that regulate neurotransmitter phenotypes remain largely unknown.

Methods
In this paper we use single mutant, double mutant and transgenic zebrafish embryos to elucidate the functions of Lmx1ba and Lmx1bb in the regulation of spinal cord interneuron neurotransmitter phenotypes.

Results
We demonstrate that lmx1ba and lmx1bb are both expressed in zebrafish spinal cord and that lmx1bb is expressed by both V0v cells and dI5 cells. Our functional analyses demonstrate that these transcription factors are not required for neurotransmitter fate specification at early stages of development, but that in embryos with at least two lmx1ba and/or lmx1bb mutant alleles there is a reduced number of excitatory (glutamatergic) spinal interneurons at later stages of development. In contrast, there is no change in the numbers of V0v or dI5 cells. These data suggest that lmx1b-expressing spinal neurons still form normally, but at least a subset of them lose, or do not form, their normal excitatory fates. As the reduction in glutamatergic cells is only seen at later stages of development, Lmx1b is probably required either for the maintenance of glutamatergic fates or to specify glutamatergic phenotypes of a subset of later forming neurons. Using double labeling experiments, we also show that at least some of the cells that lose their normal glutamatergic phenotype are V0v cells. Finally, we also establish that Evx1 and Evx2, two transcription factors that are required for V0v cells to acquire their excitatory neurotransmitter phenotype, are also required for lmx1ba and lmx1bb expression in these cells, suggesting that Lmx1ba and Lmx1bb act downstream of Evx1 and Evx2 in V0v cells.

Conclusions
Lmx1ba and Lmx1bb function at least partially redundantly in the spinal cord and three functional lmx1b alleles are required in zebrafish for correct numbers of excitatory spinal interneurons at later developmental stages. Taken together, our data significantly enhance our understanding of how spinal cord neurotransmitter fates are regulated.
Employment chances of immigrants and their children in Germany: does sense of personal control matter?
Authors: Thum-Thysen Anna 
Published: August 2016

AbstractLabour market integration is a social process suggesting that personality traits are relevant. This paper explores whether immigrants with a higher belief in their ability to control outcomes tend to be more likely to be employed. This trait is known in psychology as the locus of control (LOC). I employ a model framework that allows LOC to depend on a set of observable determining variables. Results indicate that sense of personal control is correlated with employment probability and that there is a risk that immigrants and their children tend to have a more externalized LOC. Mother’s education is a key factor correlated with the sense of personal control.
Eosinophils, probiotics, and the microbiome
Authors: Rosenberg Helene F , Masterson Joanne C , Furuta Glenn T 
Published: August 2016

Abstract
There is currently substantial interest in the therapeutic properties of probiotic microorganisms as recent research suggests that oral administration of specific bacterial strains may reduce inflammation and alter the nature of endogenous microflora in the gastrointestinal tract. Eosinophils are multifunctional tissue leukocytes, prominent among the resident cells of the gastrointestinal mucosa that promote local immunity. Recent studies with genetically altered mice indicate that eosinophils not only participate in maintaining gut homeostasis, but that the absence of eosinophils may have significant impact on the nature of the endogenous gut microflora and responses to gut pathogens, notably Clostridium difficile. Furthermore, in human subjects, there is an intriguing relationship between eosinophils, allergic inflammation, and the nature of the lung microflora, notably a distinct association between eosinophil infiltration and detection of bacteria of the phylum Actinobacteria. Among topics for future research, it will be important to determine whether homeostatic mechanisms involve direct interactions between eosinophils and bacteria or whether they involve primarily eosinophil-mediated responses to cytokine signaling in the local microenvironment. Likewise, although is it clear that eosinophils can and do interact with bacteria in vivo, their ability to discern between pathogenic and probiotic species in various settings remains to be explored.
Genome-Wide DNA Methylation Analysis Reveals Epigenetic Dysregulation of MicroRNA-34A in TP53-Associated Cancer Susceptibility
Authors: Samuel Nardin , Wilson Gavin , Lemire Mathieu , Id Said Badr , Lou Youliang , Li Weili , Merino Diana , Novokmet Ana , Tran James , Nichols Kim E. , Finlay Jonathan L. , Choufani Sanaa , Remke Marc , Ramaswamy Vijay , Cavalli Florence M.G. , Elser Christine , Meister Lynn , Taylor Michael D. , Tabori Uri , Irwin Meredith , Weksberg Rosanna , Wasserman Jonathan D. , Paterson Andrew D. , Hansford Jordan R. , Achatz Maria Isabel W. , Hudson Thomas J. , Malkin David 
Published: August 2016

Purpose Although the link between mutant TP53 and human cancer is unequivocal, a significant knowledge gap exists in clinically actionable molecular targets in Li-Fraumeni syndrome (LFS), a highly penetrant cancer predisposition syndrome associated with germline mutations in TP53. This study surveyed the epigenome to identify functionally and clinically relevant novel genes implicated in LFS. Patients and Methods We performed genome-wide methylation analyses of peripheral blood leukocyte DNA in germline TP53 mutation carriers (n = 72) and individuals with TP53 wild type in whom histologically comparable malignancies developed (n = 111). Targeted bisulfite pyrosequencing was performed on a validation cohort of 30 TP53 mutation carriers and 46 patients with TP53 wild type, and candidate sites were evaluated in primary tumors from patients with LFS across multiple histologic tumor types. Results In 183 patients, distinct DNA methylation signatures were associated with deleterious TP53 mutations in peripheral blood leukocytes. TP53-associated DNA methylation marks occurred in genomic regions that harbored p53 binding sites and in genes encoding p53 pathway proteins. Moreover, loss-of-function TP53 mutations were significantly associated with differential methylation at the locus encoding microRNA miR-34A, a key component of the p53 regulatory network (adjusted P < .001), and validated in an independent patient cohort (n = 76, P < .001). Targeted bisulfite pyrosequencing demonstrated that miR-34A was inactivated by hypermethylation across many histologic types of primary tumors from patients with LFS. Moreover, miR-34A tumor hypermethylation was associated with decreased overall survival in a cohort of 29 patients with choroid plexus carcinomas, a characteristic LFS tumor (P < .05). Conclusion Epigenetic dysregulation of miR-34A may comprise an important path in TP53-associated cancer predisposition and represents a therapeutically actionable target with potential clinical relevance.
Cost-Effectiveness Analysis of Elective Neck Dissection in Patients With Clinically Node-Negative Oral Cavity Cancer
Authors: Acevedo Joseph R. , Fero Katherine E. , Wilson Bayard , Sacco Assuntina G. , Mell Loren K. , Coffey Charles S. , Murphy James D. 
Published: August 2016

Purpose Recently, a large randomized trial found a survival advantage among patients who received elective neck dissection in conjunction with primary surgery for clinically node-negative oral cavity cancer compared with those receiving primary surgery alone. However, elective neck dissection comes with greater upfront cost and patient morbidity. We present a cost-effectiveness analysis of elective neck dissection for the initial surgical management of early-stage oral cavity cancer. Methods We constructed a Markov model to simulate primary, adjuvant, and salvage therapy; disease recurrence; and survival in patients with T1/T2 clinically node-negative oral cavity squamous cell carcinoma. Transition probabilities were derived from clinical trial data; costs (in 2015 US dollars) and health utilities were estimated from the literature. Incremental cost-effectiveness ratios, expressed as dollar per quality-adjusted life-year (QALY), were calculated with incremental cost-effectiveness ratios less than $100,000/QALY considered cost effective. We conducted one-way and probabilistic sensitivity analyses to examine model uncertainty. Results Our base-case model found that over a lifetime the addition of elective neck dissection to primary surgery reduced overall costs by $6,000 and improved effectiveness by 0.42 QALYs compared with primary surgery alone. The decrease in overall cost despite the added neck dissection was a result of less use of salvage therapy. On one-way sensitivity analysis, the model was most sensitive to assumptions about disease recurrence, survival, and the health utility reduction from a neck dissection. Probabilistic sensitivity analysis found that treatment with elective neck dissection was cost effective 76% of the time at a willingness-to-pay threshold of $100,000/QALY. Conclusion Our study found that the addition of elective neck dissection reduces costs and improves health outcomes, making this a cost-effective treatment strategy for patients with early-stage oral cavity cancer.
Vitamin D Receptor Down-Regulation Is Associated With Severity of Albuminuria in Type 2 Diabetes Patients
Authors: Yi Bin , Huang Jing , Zhang Wei , Li Ai Mei , Yang Shi Kun , Sun Jian , Wang Jian Wen , Li Yan Chun , Zhang Hao 
Published: August 2016

Context:Inflammation plays an important role in albuminuria in type 2 diabetes mellitus (T2DM). The vitamin D receptor (VDR) has potent anti-inflammatory activities.Objective:To investigate the correlation between VDR expression and albuminuria in T2DM.Design/Setting/Patients:Renal biopsies from T2DM patients with albuminuria (n = 8) and nondiabetic subjects (n = 4) were compared for VDR expression by immunohistochemistry. Recruited T2DM patients (n = 242; estimated glomerular filtration rate &gt; 60 mL/min/1.73 m2) were divided into three groups based on urinary albumin-to-creatinine ratio (uACR): normal albuminuria (uACR &lt; 30 mg/g; n = 85), microalbuminuria (30 mg/g ≤ uACR &lt; 300 mg/g; n = 84), and macroalbuminuria (uACR ≥ 300 mg/g; n = 73), with healthy individuals (n = 72) as controls. Peripheral blood mononuclear cells (PBMCs) from these subjects were analyzed for VDR mRNA (n = 314), TNF-α mRNA (n = 314), microRNA (miR)-346 (n = 120; 30 for each group), and VDR protein (n = 80; 20 for each group). PBMCs from randomly selected subjects (n = 6 for each group) were cultured ex vivo to evaluate the effect of TNF-α on miR-346 and VDR, and miR-346-mediated VDR suppression was further explored in HK2 cells.Results:VDR expression was down-regulated in PBMCs and renal tubular epithelial cells from T2DM patients with albuminuria. VDR mRNA and protein levels were both negatively correlated with uACR, and VDR mRNA was inversely correlated with TNF-α and miR-346 in PBMCs from T2DM patients. TNF-α reduced VDR while inducing miR-346 in cultured PBMCs. TNF-α suppressed VDR by up-regulating miR-346 in HK2 cells.Conclusions:VDR down-regulation in PBMCs is independently associated with the severity of albuminuria in T2DM. TNF-α suppression of VDR in PBMCs and HK2 cells is mediated by miR-346.
Salivary Testosterone Levels and Health Status in Men and Women in the British General Population: Findings from the Third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)
Authors: Clifton S. , Macdowall W. , Copas A. J. , Tanton C. , Keevil B. G. , Lee D. M. , Mitchell K. R. , Field N. , Sonnenberg P. , Bancroft J. , Mercer C. H. , Wallace A. M. , Johnson A. M. , Wellings K. , Wu F. C. W. 
Published: August 2016

Context:
Salivary T (Sal-T) measurement by liquid chromatography–tandem mass spectroscopy resents the opportunity to examine health correlates of Sal-T in a large-scale population survey.

Objective:
This study sought to examine associations between Sal-T and health-related factors in men and women age 18–74 years.

Design and Setting:
Morning saliva samples were obtained from participants in a cross-sectional probability-sample survey of the general British population (Natsal-3). Self-reported health and lifestyle questions were administered as part of a wider sexual health interview.

Participants:
Study participants included 1599 men and 2123 women.

Methods:
Sal-T was measured using liquid chromatography–tandem mass spectroscopy. Linear regression was used to examine associations between health factors and mean Sal-T.

Results:
In men, mean Sal-T was associated with a range of health factors after age adjustment, and showed a strong independent negative association with body mass index (BMI) in multivariable analysis. Men reporting cardiovascular disease or currently taking medication for depression had lower age-adjusted Sal-T, although there was no association with cardiovascular disease after adjustment for BMI. The decline in Sal-T with increasing age remained after adjustment for health-related factors. In women, Sal-T declined with increasing age; however, there were no age-independent associations with health-related factors or specific heath conditions with the exception of higher Sal-T in smokers.

Conclusions:
Sal-T levels were associated, independently of age, with a range of self-reported health markers, particularly BMI, in men but not women. The findings support the view that there is an age-related decline in Sal-T in men and women, which cannot be explained by an increase in ill health. Our results demonstrate the potential of Sal-T as a convenient measure of tissue androgen exposure for population research.
ARHGEF10 directs the localization of Rab8 to Rab6-positive executive vesicles
Authors: Shibata Satoshi , Kawanai Tsubasa , Hara Takayuki , Yamamoto Asuka , Chaya Taro , Tokuhara Yasunori , Tsuji Chinami , Sakai Manabu , Tachibana Taro , Inagaki Shinobu 
Published: August 2016

ABSTRACT
The function of ARHGEF10, a known guanine nucleotide exchange factor (GEF) for RhoA with proposed roles in various diseases, is poorly understood. To understand the precise function of this protein, we raised a monoclonal antibody against ARHGEF10 and determined its localization in HeLa cells. ARHGEF10 was found to localize to vesicles containing Rab6 (of which there are three isoforms, Rab6a, Rab6b and Rab6c), Rab8 (of which there are two isoforms, Rab8a and Rab8b), and/or the secretion marker neuropeptide Y (NPY)–Venus in a Rab6-dependent manner. These vesicles were known to originate from the Golgi and contain secreted or membrane proteins. Ectopic expression of an N-terminal-truncated ARHGEF10 mutant led to the generation of large vesicle-like structures containing both Rab6 and Rab8. Additionally, small interfering (si)RNA-mediated knockdown of ARHGEF10 impaired the localization of Rab8 to these exocytotic vesicles. Furthermore, the invasiveness of MDA-MB231 cells was markedly decreased by knockdown of ARHGEF10, as well as of Rab8. From these results, we propose that ARHGEF10 acts in exocytosis and tumor invasion in a Rab8-dependent manner.
PrP-containing aggresomes are cytosolic components of an ER quality control mechanism
Authors: Dubnikov Tatyana , Ben-Gedalya Tziona , Reiner Robert , Hoepfner Dominic , Cabral Wayne A. , Marini Joan C. , Cohen Ehud 
Published: August 2016

ABSTRACT
Limited detoxification capacity often directs aggregation-prone, potentially hazardous, misfolded proteins to be deposited in designated cytosolic compartments known as ‘aggresomes’. The roles of aggresomes as cellular quality control centers, and the cellular origin of the deposits contained within these structures, remain to be characterized. Here, we utilized the observation that the prion protein (PrP, also known as PRNP) accumulates in aggresomes following the inhibition of folding chaperones, members of the cyclophilin family, to address these questions. We found that misfolded PrP molecules must pass through the endoplasmic reticulum (ER) in order to be deposited in aggresomes, that the Golgi plays no role in this process and that cytosolic PrP species are not deposited in pre-existing aggresomes. Prior to their deposition in the aggresome, PrP molecules lose the ER localization signal and have to acquire a GPI anchor. Our discoveries indicate that PrP aggresomes are cytosolic overflow deposition centers for the ER quality control mechanisms and highlight the importance of these structures for the maintenance of protein homeostasis within the ER.
The microtubule-binding and coiled-coil domains of Kid are required to turn off the polar ejection force at anaphase
Authors: Soeda Shou , Yamada-Nomoto Kaori , Ohsugi Miho 
Published: August 2016

ABSTRACT
Mitotic chromosomes move dynamically along the spindle microtubules using the forces generated by motor proteins such as chromokinesin Kid (also known as KIF22). Kid generates a polar ejection force and contributes to alignment of the chromosome arms during prometaphase and metaphase, whereas during anaphase, Kid contributes to chromosome compaction. How Kid is regulated and how this regulation is important for chromosome dynamics remains unclear. Here, we address these questions by expressing mutant forms of Kid in Kid-deficient cells. We demonstrate that Cdk1-mediated phosphorylation of Thr463 is required to generate the polar ejection force on Kid-binding chromosomes, whereas dephosphorylation of Thr463 prevents generation of the ejection force on such chromosomes. In addition to activation of the second microtubule-binding domain through dephosphorylation of Thr463, the coiled-coil domain is essential in suspending generation of the polar ejection force, preventing separated chromosomes from becoming recongressed during anaphase. We propose that phosphorylation of Thr463 switches the mitotic chromosome movement from an anti-poleward direction to a poleward direction by converting the Kid functional mode from polar-ejection-force-ON to -OFF during the metaphase–anaphase transition, and that both the second microtubule-binding domain and the coiled-coil domain are involved in this switching process.
Bilateral adrenalectomy: a review of 10 years’ experience
Authors: Maccora D , Walls GV , Sadler GP , Mihai R 
Published: August 2016

INTRODUCTION The 2012 British Association of Endocrine and Thyroid Surgeons audit report showed that only 86 of 1359 patients who underwent adrenalectomy had a bilateral operation; thus the experience with this procedure remains limited. METHODS Retrospective review of patients undergoing bilateral adrenalectomy in a tertiary referral centre. RESULTS Between November 2005 and January 2016, bilateral adrenalectomy was performed in 23 patients (6 male, 17 female, age 43 ± 4 years) diagnosed with Cushing’s disease (n = 13), hereditary phaeochromocytomas (n = 6), adrenocortical cancer (n = 2), colorectal metastatic disease (n = 1) and adrenocortical adenomas (n = 1). A laparoscopic transperitoneal approach was used in 17 patients, with one conversion to open. Three patients had open adrenalectomies for adrenocortical cancer and for simultaneous phaeochromocytomas and pancreatic neuroendocrine tumours in a patient with Von Hippel-Lindau syndrome. Three patients with Cushing’s had a bilateral retroperitoneoscopic operation. The mean operating time was 195 ± 16 minutes for laparoscopic operations (n = 16), 243 ± 44 minutes for open adrenalectomies (n = 4) and 151 ± 12 minutes for retroperitoneal operations. It was significantly shorter for Cushing’s disease than for phaeochromocytomas (162 ± 8 vs. 257 ± 39 minutes, P < 0.01). Median length of hospital stay was 5 days. Postoperative complications (Clavien-Dindo classification) included one chest infection (level 2), one postoperative haemorrhage and two chest drains for pneumothorax (level 3), two postoperative cardiac arrests (level 4) and one late cancer death from complications related to uncontrolled hypercortisolism (level 5). DISCUSSION Synchronous bilateral adrenalectomy remains an infrequent operation. The laparoscopic approach is feasible in the majority of patients. It is likely that the retroperitoneoscopic adrenalectomy will become the standard approach for bilateral operations.
Close genetic connectivity of soft coral Sarcophyton trocheliophorum in Indonesia and its implication for marine protected area
Authors: Kusuma Aradea Bujana , Bengen Dietrich Geoffrey , Madduppa Hawis , Subhan Beginer , Arafat Dondy , Negara Bertoka Fajar S.P. 
Published: August 2016

The genetic connectivity of soft coral is influenced by current and distance between islands. The complexity of islands and geographical region in Indonesia might influence the distribution of soft corals. The information of genetic connectivity can be used to design marine protected areas and to avoid destruction and possible extinction. The objective of the present study was to analyze genetic connectivity of one species of soft coral, Sarcophyton trocheliophorum, in three populations spanning Java, Nusa Tenggara, and Sulawesi’s waters, and to describe its implication for marine protected area. The mitochondrial protein-coding gene (750 bp of ND2) was used to analyze genetic population structure and genetic connectivity. Genetic connectivity was found in all populations with Fst value of 0.227 to 0.558, indicating populations had the close genetic relationship. The local and Indonesian currents were expected to distribute the larva to islands as a stepping stone, they moved slowly to spread them self far away. Tanakeke island (Sulawesi population) might be a center connectivity of S. trocheliophorum populations. This island connected with islands in west and east Indonesia, therefore that area need to protect
‘The Water, The Onion, The Slow March of the Stars’: Roberto Bolaño and the secret story
Authors: Glass Rodge 
Published: August 2016

Abstract
To talk of the transnational is to accept that borders – the skipping over them in life and on the page – is a messy business. It’s understandable that writers such as Roberto Bolaño, usually labelled ‘a Chilean exiled to Mexico’, shouldn’t be included in discussions of contemporary European short fiction. Understandable, but not inevitable. Bolaño left Chile at 15, only returning briefly post-Pinochet before ‘co-founding a Surrealist-influenced, anti-status-quo school’ of writers in Mexico. It wasn’t until Bolaño got clean, got married and settled down in Europe (he moved there in 1977) that he produced the prose which is now his legacy. This article argues that aside from the European novellas (Antwerp, Monsieur Pain), there are five key collections which deserve to be included in European literary discussions, having been composed in Europe and having gone on to make Bolaño’s name. They have also served to move the form forward in the continent he made his home: Bolaño was responding largely to a European tradition. He wouldn’t limit himself to one continent – as Kerr puts it, Bolaño had ‘a deep scepticism about national feeling, and it has been said that his work starts to point the way to a kind of post-national fiction’ – but there’s no doubt that for 25 years, Bolaño was essentially a European with a transnational outlook. For these reasons and others, I argue for Bolaño’s inclusion in European short fiction discourse.