bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cystathionine γ-lyase protects vascular endothelium: a role for inhibition of histone deacetylase 6
Authors: Leucker Thorsten M. , Nomura Yohei , Kim Jae Hyung , Bhatta Anil , Wang Victor , Wecker Andrea , Jandu Sandeep , Santhanam Lakshmi , Berkowitz Dan , Romer Lewis , Pandey Deepesh 
Published: February 2017

Endothelial cystathionine γ-lyase (CSEγ) contributes to cardiovascular homeostasis, mainly through production of H2S. However, the molecular mechanisms that control CSEγ gene expression in the endothelium during cardiovascular diseases are unclear. The aim of the current study is to determine the role of specific histone deacetylases (HDACs) in the regulation of endothelial CSEγ. Reduced CSEγ mRNA expression and protein abundance were observed in human aortic endothelial cells (HAEC) exposed to oxidized LDL (OxLDL) and in aortas from atherogenic apolipoprotein E knockout (ApoE−/−) mice fed a high-fat diet compared with controls. Intact murine aortic rings exposed to OxLDL (50 μg/ml) for 24 h exhibited impaired endothelium-dependent vasorelaxation that was blocked by CSEγ overexpression or the H2S donor NaHS. CSEγ expression was upregulated by pan-HDAC inhibitors and by class II-specific HDAC inhibitors, but not by other class-specific inhibitors. The HDAC6 selective inhibitor tubacin and HDAC6-specific siRNA increased CSEγ expression and blocked OxLDL-mediated reductions in endothelial CSEγ expression and CSEγ promoter activity, indicating that HDAC6 is a specific regulator of CSEγ expression. Consistent with this finding, HDAC6 mRNA, protein expression, and activity were upregulated in OxLDL-exposed HAEC, but not in human aortic smooth muscle cells. HDAC6 protein levels in aortas from high-fat diet-fed ApoE−/− mice were comparable to those in controls, whereas HDAC6 activity was robustly upregulated. Together, our findings indicate that HDAC6 is upregulated by atherogenic stimuli via posttranslational modifications and is a critical regulator of CSEγ expression in vascular endothelium. Inhibition of HDAC6 activity may improve endothelial function and prevent or reverse the development of atherosclerosis. NEW & NOTEWORTHY Oxidative injury to endothelial cells by oxidized LDL reduced cystathionine γ-lyase (CSEγ) expression and H2S production, leading to endothelial dysfunction, which was prevented by histone deacetylase 6 (HDAC6) inhibition. Our data suggest HDAC6 as a novel therapeutic target to prevent the development of atherosclerosis.
Pancreatic Neuroendocrine Tumors and EMT Behavior Are Driven by the CSC Marker DCLK1
Authors: Ikezono Yu , Koga Hironori , Akiba Jun , Abe Mitsuhiko , Yoshida Takafumi , Wada Fumitaka , Nakamura Toru , Iwamoto Hideki , Masuda Atsutaka , Sakaue Takahiko , Yano Hirohisa , Tsuruta Osamu , Torimura Takuji 
Published: February 2017

Abstract
Doublecortin-like kinase 1 (DCLK1), a marker for intestinal and pancreatic cancer stem cells, is highly expressed in neuroblastomas. This study was conducted to assess DCLK1 expression levels in pancreatic neuroendocrine tumor (PNET) tissues and to explore the roles of this molecule in clinical tissue from multiple PNET patients, cells (BON1, QGP1, and CM) and tumor xenografts. Immunohistochemically, all PNET tissues highly and diffusely expressed DCLK1 as a full-length isoform, identical to that detected in primary liver NETs. A DCLK1-overexpressing PNET cell line (QGP1-DCLK1) exhibited epithelial–mesenchymal transition (EMT)-related gene signatures, and robust upregulation of Slug (SNAI2), N-Cadherin (CDH2), and Vimentin (VIM) was validated by real-time PCR and immunoblotting. QGP1-DCLK1 cells had increased cell migration in a wound-healing assay and formed significantly larger xenograft tumors in nude mice. The factors involved in the formation of the fast-growing tumors included p-FAK (on Tyr925), p-ERK1/2, p-AKT, Paxillin, and Cyclin D1, which upon knockdown or pharmacologic inhibition of DCLK1 abolished the expression of these molecules. In conclusion, robust and ubiquitous expression of DCLK1 was first demonstrated here in human PNET tissue specimens and cells. DCLK1 characterized the PNET cell behavior, inducing p-FAK/SLUG-mediated EMT. These findings suggest the possibility of developing novel therapeutic strategies against PNETs by targeting DCLK1.
Implications: Evidence here reveals that human PNETs diffusely and robustly express the cancer stem cell marker DCLK1, which drives SLUG-mediated EMT, and suggests that NETs share biological features for druggable targets with other tumors, including neuroblastoma that also highly expresses DCLK1. Mol Cancer Res; 15(6); 744–52. ©2017 AACR.
Phosphatidylserine Sensing by TAM Receptors Regulates AKT-Dependent Chemoresistance and PD-L1 Expression
Authors: Kasikara Canan , Kumar Sushil , Kimani Stanley , Tsou Wen-I , Geng Ke , Davra Viralkumar , Sriram Ganapathy , Devoe Connor , Nguyen Khanh-Quynh N. , Antes Anita , Krantz Allen , Rymarczyk Grzegorz , Wilczynski Andrzej , Empig Cyril , Freimark Bruce , Gray Michael , Schlunegger Kyle , Hutchins Jeff , Kotenko Sergei V. , Birge Raymond B. 
Published: February 2017

Abstract
Tyro3, Axl, and Mertk (collectively TAM receptors) are three homologous receptor tyrosine kinases that bind vitamin K–dependent endogenous ligands, Protein S (ProS), and growth arrest–specific factor 6 (Gas6), and act as bridging molecules to promote phosphatidylserine (PS)-mediated clearance of apoptotic cells (efferocytosis). TAM receptors are overexpressed in a vast array of tumor types, whereby the level of expression correlates with the tumor grade and the emergence of chemo- and radioresistance to targeted therapeutics, but also have been implicated as inhibitory receptors on infiltrating myeloid-derived cells in the tumor microenvironment that can suppress host antitumor immunity. In the present study, we utilized TAM-IFNγR1 reporter lines and expressed TAM receptors in a variety of epithelial cell model systems to show that each TAM receptor has a unique pattern of activation by Gas6 or ProS, as well as unique dependency for PS on apoptotic cells and PS liposomes for activity. In addition, we leveraged this system to engineer epithelial cells that express wild-type TAM receptors and show that although each receptor can promote PS-mediated efferocytosis, AKT-mediated chemoresistance, as well as upregulate the immune checkpoint molecule PD-L1 on tumor cells, Mertk is most dominant in the aforementioned pathways. Functionally, TAM receptor–mediated efferocytosis could be partially blocked by PS-targeting antibody 11.31 and Annexin V, demonstrating the existence of a PS/PS receptor (i.e., TAM receptor)/PD-L1 axis that operates in epithelial cells to foster immune escape. These data provide a rationale that PS-targeting, anti–TAM receptor, and anti–PD-L1-based therapeutics will have merit as combinatorial checkpoint inhibitors.
Implications: Many tumor cells are known to upregulate the immune checkpoint inhibitor PD-L1. This study demonstrates a role for PS and TAM receptors in the regulation of PD-L1 on cancer cells. Mol Cancer Res; 15(6); 753–64. ©2017 AACR.
Chromosome 20q Amplification Defines a Subtype of Microsatellite Stable, Left-Sided Colon Cancers with Wild-type RAS/RAF and Better Overall Survival
Authors: Ptashkin Ryan N. , Pagan Carlos , Yaeger Rona , Middha Sumit , Shia Jinru , O'Rourke Kevin P. , Berger Michael F. , Wang Lu , Cimera Robert , Wang Jiajing , Klimstra David S. , Saltz Leonard , Ladanyi Marc , Zehir Ahmet , Hechtman Jaclyn F. 
Published: February 2017

Abstract
Here, comprehensive analysis was performed on the molecular and clinical features of colorectal carcinoma harboring chromosome 20q amplification. Tumor and normal DNA from patients with advanced colorectal carcinoma underwent next-generation sequencing via MSK-IMPACT, and a subset of case samples was subjected to high-resolution microarray (Oncoscan). Relationships between genomic copy number and transcript expression were assessed with The Cancer Genome Atlas (TCGA) colorectal carcinoma data. Of the colorectal carcinoma patients sequenced (n = 401) with MSK-IMPACT, 148 (37%) had 20q gain, and 30 (7%) had 20q amplification. In both the MSK-IMPACT and TCGA datasets, BCL2L1 was the most frequently amplified 20q oncogene. However, SRC was the only recognized 20q oncogene with a significant inverse relationship between mRNA upregulation and RAS/RAF mutation (OR, −0.4 ± 0.2, P = 0.02). In comparison with 20q diploid colorectal carcinoma, 20q gain/amplification was associated with wild-type KRAS (P &lt; 0.001) and BRAF (P = 0.01), microsatellite stability (P &lt; 0.001), distal primary tumors (P &lt; 0.001), and mutant TP53 (P &lt; 0.001), but not stage. On multivariate analysis, longer overall survival from the date of metastasis was observed with chromosome 20q gain (P = 0.02) or amplification (P = 0.04) compared with diploid 20q.
Implications: 20q amplification defines a subset of colorectal cancer patients with better overall survival from the date of metastasis, and further studies are warranted to assess whether the inhibition of 20q oncogenes, such as SRC, may benefit this subset of patients. Mol Cancer Res; 15(6); 708–13. ©2017 AACR.
Incidence rates and case fatality rates of portal vein thrombosis and Budd-Chiari Syndrome
Authors: Dentali Francesco , Pomero Fulvio , Fenoglio Luigi , Squizzato Alessandro , Pagani Giovanni , Re Roberta , Bonzini Matteo , Ageno Walter 
Published: February 2017

SummaryLittle information is available on the incidence of splanchnic vein thrombosis and on mortality rates during the acute phase of the disease. We performed a large epidemiologic study on hospital admissions for portal vein thrombosis (PVT) and the Budd-Chiari syndrome (BCS) between 2002 and 2012 in Northwestern Italy. Primary and secondary discharge diagnoses of PVT and BCS were identified using the 9th edition International Classification of Diseases codes 453.0, 572.1 and 452. Hospitalisations for recurrent events were not included. Information was collected on age and gender, vital status at discharge, duration of hospitalisation, and up to five secondary discharge diagnoses. Comorbidity was evaluated using the Charlson comorbidity index (CCI). A total of 3535 patients with PVT and 287 with BCS were hospitalized. The overall gender-specific incidence rates for PVT were 3.78 per 100,000 inhabitants in males and 1.73 per 100,000 inhabitants in females; for BCS 2.0 and 2.2 per million inhabitants, respectively. In-hospital case fatality was 7.3 % in patients with PVT and 4.9 % in patients with BCS. Age, non-abdominal solid cancer, and CCI were independently associated with in-hospital mortality in both PVT and BCS after stepwise regression analysis, male gender and haematologic cancer were associated with mortality in BCS patients only. In this large study we confirmed the low incidence of BCS and we found an incidence of PVT higher than previously reported. This incidence was stable during the period of observation. In-hospital mortality is not negligible, in particular in PVT patients.
Modifiable Risk Factors Versus Age on Developing High Predicted Cardiovascular Disease Risk in Blacks
Authors: Bress Adam P. , Colantonio Lisandro D. , Booth John N. , Spruill Tanya M. , Ravenell Joseph , Butler Mark , Shallcross Amanda J. , Seals Samantha R. , Reynolds Kristi , Ogedegbe Gbenga , Shimbo Daichi , Muntner Paul 
Published: February 2017

Background

Clinical guidelines recommend using predicted atherosclerotic cardiovascular disease (
ASCVD
) risk to inform treatment decisions. The objective was to compare the contribution of changes in modifiable risk factors versus aging to the development of high 10‐year predicted
ASCVD
risk.

Methods and Results

A prospective follow‐up was done of the Jackson Heart Study, an exclusively black cohort at visit 1 (2000–2004) and visit 3 (2009–2012). Analyses included 1115 black participants without high 10‐year predicted
ASCVD
risk (<7.5%), hypertension, diabetes mellitus, or
ASCVD
at visit 1. We used the Pooled Cohort equations to calculate the incidence of high (≥7.5%) 10‐year predicted
ASCVD
risk at visit 3. We recalculated the percentage with high 10‐year predicted
ASCVD
risk at visit 3 assuming each risk factor (age, systolic blood pressure, antihypertensive medication use, diabetes mellitus, smoking, total and high‐density lipoprotein cholesterol), one at a time, did not change from visit 1. The mean age at visit 1 was 45.2±9.5 years. Overall, 30.9% (95%
CI
28.3–33.4%) of participants developed high 10‐year predicted
ASCVD
risk. Aging accounted for 59.7% (95%
CI
54.2–65.1%) of the development of high 10‐year predicted
ASCVD
risk compared with 32.8% (95%
CI
27.0–38.2%) for increases in systolic blood pressure or antihypertensive medication initiation and 12.8% (95%
CI
9.6–16.5%) for incident diabetes mellitus. Among participants <50 years, the contribution of increases in systolic blood pressure or antihypertensive medication initiation was similar to aging.

Conclusions

Increases in systolic blood pressure and antihypertensive medication initiation are major contributors to the development of high 10‐year predicted
ASCVD
risk in blacks, particularly among younger adults.
Sipunculans from the coast of northern Cyprus (eastern Mediterranean Sea)
Authors: AÇIK S. , MURINA G. V. , ÇINAR M. E. , ERGEN Z. 
Published: February 2017

The present study deals with the species of Sipuncula collected from northern Cyprus in 1997 and 1998 by RV K. Piri Reis at depths ranging from 0 to 600 m. Faunistic analysis of the material yielded a total of 6 species and 5 subspecies belonging to four families Golfingiidae, Phascolionidae, Phascolosomatidae, and Aspidosiphonidae, of which four species (Nephasoma (Nephasoma) constrictum, Phascolosoma (Phascolosoma) scolops, P. (P.) agassizii agassizii and P. (P.) stephensoni) are reported for the first time from the eastern Mediterranean. Among the habitats sampled, Posidonia oceanica and mud were represented by the highest number of species (6 species), followed by rocks (5 species) and Cystoseira crinita (5 species). Quantitative analysis of shallow-water benthic habitats indicated that sipunculan density in the area ranged from 25 individuals m-2 to 350 individuals m-2. According to the MDS analysis, there are two major species assemblages in the area, mainly structured by the types of habitats and depth.
Description of a new species of weasel shark, Hemigaleus australiensis n. sp. (Carcharhiniformes: Hemigaleidae) from Australian waters
Authors: WHITE WILLIAM T. , LAST PETER R. , COMPAGNO LEONARD J.V. 
Published: February 2017

A new species of weasel shark from the genus Hemigaleus Bleeker, 1852 (Carcharhiniformes: Hemigaleidae) is described from northern Australia. Hemigaleus australiensis n. sp. is known from the insular and continental shelves of northern Australia from inshore bays to depths of 170 m. The new species differs from the only other member of this genus, Hemigaleus microstoma, in having substantially lower vertebral counts, much higher tooth counts in lower jaw, and a black-tipped second dorsal fin. Hemigaleus australiensis and H. microstoma are also readily separated by differences in morphometrics and sizes at birth and maturity.
Description of two leaf-miner larvae (Coleoptera: Chrysomelidae: Cassidinae) from the Brazilian Atlantic forest
Authors: CASARI SÔNIA A. , QUEIROZ JARBAS M. 
Published: February 2017

Larvae of the leaf-miners Sceloenopla pretiosa (Baly, 1858) (Cassidinae, Sceloenoplini) and Octuroplata walkeri (Baly, 1865) (Cassidinae, Chalepini) are described and illustrated. This larval description of O. walkeri is the first for the genus Octuroplata. The larvae were collected in atlantic rain forest and reared in the laboratory. The studied larvae shown the morphological adaptations common to the highly specialized leaf-miners and the larvae pupate inside the mine. Larvae of Octuroplata walkeri is similar to Sceloenopla pretiosa and the differing characteristics are described.
A new species of Plectromerus Haldeman (Coleoptera: Cerambycidae) from Dominican amber with notes on the fossil Plectromerus tertiarius Vitali
Authors: NEARNS EUGENIO H. , BRANHAM MARC A. 
Published: February 2017

A new species, Plectromerus grimaldii (Coleoptera: Cerambycidae: Cerambycinae: Curiini), from Dominican amber (Oligo-Miocene) is described. Features distinguishing the new species from its congeners are presented. A discussion of the comparison of this new species to another Plectromerus fossil, P. tertiarius Vitali, is also presented.
A 20-Year Climatology of Nocturnal Convection Initiation over the Central and Southern Great Plains during the Warm Season
Authors: Reif Dylan W. , Bluestein Howard B. 
Published: February 2017

Abstract
A nocturnal maximum in rainfall and thunderstorm activity over the central Great Plains has been widely documented, but the mechanisms for the development of thunderstorms over that region at night are still not well understood. Elevated convection above a surface frontal boundary is one explanation, but this study shows that many thunderstorms form at night without the presence of an elevated frontal inversion or nearby surface boundary.
This study documents convection initiation (CI) events at night over the central Great Plains from 1996 to 2015 during the months of April–July. Storm characteristics such as storm type, linear system orientation, initiation time and location, and others were documented. Once all of the cases were documented, surface data were examined to locate any nearby surface boundaries. The event’s initiation location relative to these boundaries (if a boundary existed) was documented. Two main initiation locations relative to a surface boundary were identified: on a surface boundary and on the cold side of a surface boundary; CI events also occur without any nearby surface boundary. There are many differences among the different nocturnal CI modes. For example, there appear to be two main peaks of initiation time at night: one early at night and one later at night. The later peak is likely due to the events that form without a nearby surface boundary. Finally, a case study of three nocturnal CI events that occurred during the Plains Elevated Convection At Night (PECAN) field project when there was no nearby surface boundary is discussed.
Acute Health Effects After the Elk River Chemical Spill, West Virginia, January 2014
Authors: Thomasson Erica D. , Scharman Elizabeth , Fechter-Leggett Ethan , Bixler Danae , Ibrahim Sheri’f , Duncan Mary Anne , Hsu Joy , Scott Melissa , Wilson Suzanne , Haddy Loretta , Pizon Anthony , L. Burrer Sherry , Wolkin Amy , Lewis Lauren 
Published: February 2017

Objectives: On January 9, 2014, approximately 10 000 gallons of a mixture of 4-methylcyclohexanemethanol and propylene glycol phenyl ether spilled into West Virginia’s Elk River, contaminating the potable water supply of about 300 000 West Virginia residents. This study sought to describe acute health effects after the chemical spill. Methods: We conducted a descriptive analysis using 3 complementary data sources: (1) medical records of patients who visited an emergency department during January 9-23, 2014, with illness potentially related to the spill; (2) West Virginia Poison Center caller records coded as “contaminated water” during January 9-23, 2014; and (3) answers to household surveys about health effects from a Community Assessment for Public Health Emergency Response (CASPER) questionnaire administered 3 months after the spill. Results: In the 2 weeks after the spill, 2000 people called the poison center reporting exposure to contaminated water, and 369 people visited emergency departments in the affected area with reports of exposure and symptoms potentially related to the spill. According to CASPER weighted cluster analyses, an estimated 25 623 households (21.7%; 95% confidence interval [CI], 14.4%-28.9%) had ≥1 person with symptoms who felt that they were related to the spill in the 3 months after it. Reported health effects across all 3 data sources included mild skin, respiratory, and gastrointestinal symptoms that resolved with no or minimal treatment. Conclusions: Medical records, poison center data, and CASPER household surveys were inexact but useful data sources to describe overall community health effects after a large-scale chemical spill. Analyzing multiple data sources could inform epidemiologic investigations of similar events.
Employment structures, employee attitudes and workplace resistance in neoliberal Poland
Authors: Żuk Piotr 
Published: February 2017

AbstractDuring the past quarter century of neoliberal social, economic and political upheaval in Poland, the structure of workplaces has changed, and so have changes in worker attitudes to workplace and social solidarity. This article explores the links between changes to organisational and employment structures and shifts in worker attitudes, focusing on the implications of attitudinal shifts for the capacity for organised workplace resistance. It documents a loss of collective identity and a growth of individualism and social distrust. The analysis is based on publicly available economic and social statistics and the author’s own qualitative and quantitative research, drawn in part from computer-aided interviews in de-industrialising Lower Silesia. Evidence is provided that the extent and intensity of attitudinal shifts have varied according to changed workplace structures, based on privatisation and organisational size, and especially on the accompanying changes in workplace culture and climate. Increased individualism, based on formal decollectivisation, has been accompanied by attitudinal individualism and distrust of other people and social institutions. As a result, declining capacity for workplace resistance and an increased sense of powerlessness have increased workers’ susceptibility to right-wing propaganda.
Inhibition of Rho kinase protects from ischaemia–reperfusion injury via regulation of arginase activity and nitric oxide synthase in type 1 diabetes
Authors: Tratsiakovich Yahor , Kiss Attila , Gonon Adrian T , Yang Jiangning , Sjöquist Per-Ove , Pernow John 
Published: February 2017

Aim: RhoA/Rho-associated kinase and arginase are implicated in vascular complications in diabetes. This study investigated whether RhoA/Rho-associated kinase and arginase inhibition protect from myocardial ischaemia–reperfusion injury in type 1 diabetes and the mechanisms behind these effects. Methods: Rats with streptozotocin-induced type 1 diabetes and non-diabetic rats were subjected to 30 min myocardial ischaemia and 2 h reperfusion after being randomized to treatment with (1) saline, (2) RhoA/Rho-associated kinase inhibitor hydroxyfasudil, (3) nitric oxide synthase inhibitor NG-monomethyl-l-arginine monoacetate followed by hydroxyfasudil, (4) arginase inhibitor N-omega-hydroxy-nor-l-arginine, (5) NG-monomethyl-l-arginine monoacetate followed by N-omega-hydroxy-nor-l-arginine or (6) NG-monomethyl-l-arginine monoacetate given intravenous before ischaemia. Results: Myocardial arginase activity, arginase 2 expression and RhoA/Rho-associated kinase activity were increased in type 1 diabetes ( p < 0.05). RhoA/Rho-associated kinase inhibition and arginase inhibition significantly reduced infarct size in diabetic and non-diabetic rats ( p < 0.001). The cardioprotective effects of hydroxyfasudil and N-omega-hydroxy-nor-l-arginine in diabetes were abolished by nitric oxide synthase inhibition. RhoA/Rho-associated kinase inhibition attenuated myocardial arginase activity in diabetic rats via a nitric oxide synthase–dependent mechanism. Conclusion: Inhibition of either RhoA/Rho-associated kinase or arginase protects from ischaemia–reperfusion injury in rats with type 1 diabetes via a nitric oxide synthase–dependent pathway. These results suggest that inhibition of RhoA/Rho-associated kinase and arginase constitutes a potential therapeutic strategy to protect the diabetic heart against ischaemia–reperfusion injury.