bluuebunny/crossref_metadata_2025_split huggingface dataset:
The MarR-Type Regulator Rdh2R Regulates
rdh
Gene Transcription in Dehalococcoides mccartyi Strain CBDB1
Authors: Krasper Lydia , Lilie Hauke , Kublik Anja , Adrian Lorenz , Golbik Ralph , Lechner Ute 
Published: September 2016

ABSTRACT

Reductive dehalogenases are essential enzymes in organohalide respiration and consist of a catalytic subunit A and a membrane protein B, encoded by
rdhAB
genes. Thirty-two
rdhAB
genes exist in the genome of
Dehalococcoides mccartyi
strain CBDB1. To gain a first insight into the regulation of
rdh
operons, the control of gene expression of two
rdhAB
genes (cbdbA1453/cbdbA1452 and cbdbA1455/cbdbA1454) by the MarR-type regulator Rdh2R (cbdbA1456) encoded directly upstream was studied using heterologous expression and
in vitro
studies. Promoter-
lacZ
reporter fusions were generated and integrated into the genome of the
Escherichia coli
host. The
lacZ
reporter activities of both
rdhA
promoters decreased upon transformation of the cells with a plasmid carrying the
rdh2R
gene, suggesting that Rdh2R acts as repressor, whereas the
lacZ
reporter activity of the
rdh2R
promoter was not affected. The transcriptional start sites of both
rdhA
genes in strain CBDB1 and/or the heterologous host mapped to a conserved direct repeat with 11- to 13-bp half-sites. DNase I footprinting revealed binding of Rdh2R to a ∼30-bp sequence covering the complete direct repeat in both promoters, including the transcriptional start sites. Equilibrium sedimentation ultracentrifugation revealed that Rdh2R binds as tetramer to the direct-repeat motif of the
rdhA
(cbdbA1455) promoter. Using electrophoretic mobility shift assays, a similar binding affinity was found for both
rdhA
promoters. In the presence of only one half-site of the direct repeat, the interaction was strongly reduced, suggesting a positive cooperativity of binding, for which unusual short palindromes within the direct-repeat half-sites might play an important role.

IMPORTANCE
Dehalococcoides mccartyi
strains are obligate anaerobes that grow by organohalide respiration. They have an important bioremediation potential because they are capable of reducing a multitude of halogenated compounds to less toxic products. We are now beginning to understand how these organisms make use of this large catabolic potential, whereby
D. mccartyi
expresses dehalogenases in a compound-specific fashion. MarR-type regulators are often encoded in the vicinity of reductive dehalogenase genes. In this study, we made use of heterologous expression and
in vitro
studies to demonstrate that the MarR-type transcription factor Rdh2R acts as a negative regulator. We identify its binding site on the DNA, which suggests a mechanism by which it controls the expression of two adjacent reductive dehalogenase operons.
Corrected Genome Annotations Reveal Gene Loss and Antibiotic Resistance as Drivers in the Fitness Evolution of Salmonella enterica Serovar Typhimurium
Authors: Paul Sandip , Sokurenko Evgeni V. , Chattopadhyay Sujay 
Published: September 2016

ABSTRACT

Horizontal acquisition of novel chromosomal genes is considered to be a key process in the evolution of bacterial pathogens. However, the identification of gene presence or absence could be hindered by the inconsistencies in bacterial genome annotations. Here, we performed a cross-annotation of omnipresent core and mosaic accessory genes in the chromosome of
Salmonella enterica
serovar Typhimurium across a total of 20 fully assembled genomes deposited into GenBank. Cross-annotation resulted in a 32% increase in the number of core genes and a 3-fold decrease in the number of genes identified as mosaic genes (i.e., genes present in some strains only) by the original annotation. Of the remaining noncore genes, the vast majority were prophage genes, and 255 of the nonphage genes were actually of core origin but lost in some strains upon the emergence of the
S
. Typhimurium serovar, suggesting that the chromosomal portion of the
S
. Typhimurium genome acquired a very limited number of novel genes other than prophages. Only horizontally acquired nonphage genes related to bacterial fitness or virulence were found in four recently sequenced isolates, all located on three different genomic islands that harbor multidrug resistance determinants. Thus, the extensive use of antimicrobials could be the main selection force behind the new fitness gene acquisition and the emergence of novel
Salmonella
pathotypes.

IMPORTANCE
Significant discrepancies in the annotations of bacterial genomes could mislead the conclusions about evolutionary origin of chromosomal genes, as we demonstrate here via a cross-annotation-based analysis of
Salmonella
Typhimurium genomes from GenBank. We conclude that despite being able to infect a broad range of vertebrate hosts, the genomic diversity of
S
. Typhimurium strains is almost exclusively limited to gene loss and the transfer of prophage DNA. Only nonphage chromosomal genes acquired after the emergence of the serovar are linked to the genomic islands harboring multidrug resistance factors. Since the fitness factors could lead to increased virulence, this poses an important research question: could overuse or misuse of antimicrobials act as selection forces for the emergence of more pathogenic strains of
Salmonella
?
Boron isotopic discrimination for subduction-related serpentinites
Authors: Martin Céline , Flores Kennet E. , Harlow George E. 
Published: September 2016

Abstract
The Guatemala Suture Zone (GSZ), Guatemala, is a region that contains two distinct suture-related serpentinite mélanges straddling the Motagua fault and an ophiolitic complex paired with the northern mélange. The serpentinite matrix of the mélanges formed by subduction-fluid hydration of peridotite from the deep mantle wedge. The occurrence of serpentinite from both exhumed subduction channel mélange and ophiolite is not uncommon in paleo–suture zones, but distinguishing them and their tectonic origin can be difficult. A new method of discrimination, based on boron isotopes in serpentine from both mélanges and ophiolite, as well as on mica and pyroxene from the metamorphic and vein-rock blocks embedded within the mélanges, has been developed. The metamorphic and vein samples have mainly negative δ11B, ranging from –15.3‰ to +4.3‰, in the same range as the serpentine from the mélanges (–14.4‰ to +9.7‰). In addition to being the most negative δ11B values ever measured in serpentinite, comparable values from vein minerals indicate that the same fluid serpentinized the overlying mantle. In contrast, serpentine samples from the ophiolite have positive δ11B, in the range 0‰ to +18.0‰, consistent with hydration by seawater-derived fluids. As the GSZ displays two mélanges whose serpentinite originated from two different deep subductions and mantle hydration, we hypothesize that the negative signature of exhumed mélange serpentine is the norm and that the B isotopic signature can be a useful tool to discriminate the tectonic origin of serpentinization in paleo–suture zones.
How did a Housing First intervention improve health and social outcomes among homeless adults with mental illness in Toronto? Two-year outcomes from a randomised trial
Authors: O'Campo Patricia , Stergiopoulos Vicky , Nir Pam , Levy Matthew , Misir Vachan , Chum Antony , Arbach Bouchra , Nisenbaum Rosane , To Matthew J , Hwang Stephen W 
Published: September 2016

ObjectivesWe studied the impact of a Housing First (HF) intervention on housing, contact with the justice system, healthcare usage and health outcomes among At Home/Chez Soi randomised trial participants in Toronto, a city with an extensive service network for social and health services for individuals who are experiencing homelessness and mental illness.MethodsParticipants identified as high needs were randomised to receive either the intervention which provided them with housing and supports by an assertive community treatment team (HF+ACT) or treatment as usual (TAU). Participants (N=197) had in-person interviews every 3 months for 2 years.ResultsThe HF+ACT group spent more time stably housed compared to the TAU group with the mean difference between the groups of 45.8% (95% CI 37.1% to 54.4%, p<0.0001). Accounting for baseline differences, HF+ACT group showed significant improvements over TAU group for community functioning, selected quality-of-life subscales and arrests at some time points during follow-up. No differences between HF+ACT and TAU groups over the follow-up were observed for health service usage, community integration and substance use.ConclusionsHF for individuals with high levels of need increased housing stability and selected health and justice outcomes over 2 years in a city with many social and health services.Trial registration numberISRCTN42520374.
Improving care for victims: a study protocol of the evaluation of a centre for sexual and family violence
Authors: Zijlstra E , LoFoWong S , Hutschemaekers G , Lagro-Janssen A 
Published: September 2016

IntroductionWorldwide, sexual and family violence are highly prevalent problems. Victims of sexual and family violence often do not seek formal help in the acute phase. When they do seek help, they encounter a system of scattered care. For this reason, a centre for sexual and family violence was launched in Nijmegen, the Netherlands. The centre provides multidisciplinary care for victims of acute sexual and/or family violence. With the study described in this study protocol, we want to evaluate the implementation process and the reach of the Center for Sexual and Family Violence Nijmegen (CSFVN).Methods and analysisWe will conduct a mixed-methods study including quantitative and qualitative methods of data collection and analysis. Data about the implementation process will be obtained via semistructured interviews and focus group discussions. Content analysis will be done in software program Atlas.ti. Analysis of file data will be undertaken to assess the reach of the CSFVN (patient characteristics and characteristics of the care they received). The data will be analysed in SPSS.Ethics and disseminationThe Medical Ethics Committee of the Radboud University Nijmegen Medical Center approved the study protocol under file number 2012–1218. Dissemination will be done by submitting scientific articles to academic peer-reviewed journals. We will present the results at relevant international, national and local conferences and meetings. We will send press releases to relevant media. We will share the results with the network of assault centres in the Netherlands.
Evaluation of use and cost of medical care of common lumbar disorders in Korea: cross-sectional study of Korean Health Insurance Review and Assessment Service National Patient Sample data
Authors: Ahn Yong-Jun , Shin Joon-Shik , Lee Jinho , Lee Yoon Jae , Kim Me-Riong , Park Ki Byung , Lee Jun-Hwan , Shin Kyung-Min , Ha In-Hyuk 
Published: September 2016

ObjectivesTo assess medical care and costs of the 3 highest prevalence lumbar disorders—non-specific low back pain (nLBP), intervertebral disc disorder (IDD) and spinal stenosis (SS)—from national billing data to provide basic information for standards of appropriate management.DesignRetrospective analysis of National Health Insurance National Patient Sample data provided by the Korean Health Insurance Review and Assessment Service (HIRA).Setting2011 claims data from all medical institutions which filed billing statements to HIRA.ParticipantsA total of 135 561 patients with lumbar disorder who received medical services during 2011.Outcome measuresPatient characteristics, medical procedures, medication, cost, injection and surgery.ResultsIn the nLBP and IDD groups, the 50–59 age range had the highest prevalence, whereas prevalence increased with age in SS. All 3 groups showed a higher percentage in women. The average treatment cost was 196 552 KRW in the nLBP and 362 050 KRW in the IDD group, and highest in the SS group at 439 025 KRW. While in the nLBP group women spent more on medical expenses, in the other 2 groups men showed higher expenditure. Expenditure grew with age in the nLBP and SS groups, whereas that of the IDD group peaked in their 40s. Analgesics were used in 73.43% of patients with nLBP, 82.64% of patients with IDD and 86.46% of patients with SS, and opioids in 4.12% of patients with IDD and 5.36% of patients with SS. Surgery rates were highest in the SS group at 4.85%, with 0.9% for nLBP and 4.59% for IDD. The most frequent injection code was lumbar/caudal epidural nerve block. Expenditure and surgery rates were higher in the injection than in the non-injection subgroup in all 3 groups.ConclusionsPatterns of medical care of most frequent lumbar disorders from HIRA data showed significant difference between groups and provide a basic standard for future usual care guidelines linked with health policy and budget appropriation.
Solitons, Bäcklund transformation and Lax pair for a (2+1)-dimensional B-type Kadomtsev–Petviashvili equation in the fluid/plasma mechanics
Authors: Lan Zhong-Zhou , Gao Yi-Tian , Yang Jin-Wei , Su Chuan-Qi , Wang Qi-Min 
Published: September 2016

Under investigation in this paper is a (2[Formula: see text]+[Formula: see text]1)-dimensional B-type Kadomtsev–Petviashvili equation for the shallow water wave in a fluid or electrostatic wave potential in a plasma. Bilinear form, Bäcklund transformation and Lax pair are derived based on the binary Bell polynomials. Multi-soliton solutions are constructed via the Hirota’s method. Propagation and interaction of the solitons are illustrated graphically: (i) Through the asymptotic analysis, elastic and inelastic interactions between the two solitons are discussed analytically and graphically, respectively. The elastic interaction, amplitudes, velocities and shapes of the two solitons remain unchanged except for a phase shift. However, in the area of the inelastic interaction, amplitudes of the two solitons have a linear superposition. (ii) Elastic interactions among the three solitons indicate that the properties of the elastic interactions among the three solitons are similar to those between the two solitons. Moreover, oblique and overtaking interactions between the two solitons are displayed. Oblique interactions among the three solitons and interactions among the two parallel solitons and a single one are presented as well. (iii) Inelastic–elastic interactions imply that the interaction between the inelastic region and another one is elastic.
Ccl22 Diverts T Regulatory Cells and Controls the Growth of Melanoma
Authors: Klarquist Jared , Tobin Kristen , Farhangi Oskuei Peyman , Henning Steven W. , Fernandez Manuel F. , Dellacecca Emilia R. , Navarro Flor C. , Eby Jonathan M. , Chatterjee Shilpak , Mehrotra Shikhar , Clark Joseph I. , Le Poole I. Caroline 
Published: September 2016

AbstractT regulatory cells (Treg) avert autoimmunity, but their increased levels in melanoma confer a poor prognosis. To explore the basis for Treg accumulation in melanoma, we evaluated chemokine expression in patients. A 5-fold increase was documented in the Treg chemoattractants CCL22 and CCL1 in melanoma-affected skin versus unaffected skin, as accompanied by infiltrating FoxP3+ T cells. In parallel, there was an approximately two-fold enhancement in expression of CCR4 in circulating Treg but not T effector cells. We hypothesized that redirecting Treg away from tumors might suppress autoimmune side effects caused by immune checkpoint therapeutics now used widely in the clinic. In assessing this hypothesis, we observed a marked increase in skin Treg in mice vaccinated with Ccl22, with repetitive vaccination sufficient to limit Treg accumulation and melanoma growth in the lungs of animals challenged by tumor cell injection, whether using a prevention or treatment protocol design. The observed change in Treg accumulation in this setting could not be explained by Treg conversion. Overall, our findings offered a preclinical proof of concept for the potential use of CCL22 delivered by local injection as a strategy to enhance the efficacious response to immune checkpoint therapy while suppressing its autoimmune side effects. Cancer Res; 76(21); 6230–40. ©2016 AACR.
Characterization of Biomarkers of Tumorigenic and Chemoresistant Cancer Stem Cells in Human Gastric Carcinoma
Authors: Nguyen Phu Hung , Giraud Julie , Chambonnier Lucie , Dubus Pierre , Wittkop Linda , Belleannée Geneviève , Collet Denis , Soubeyran Isabelle , Evrard Serge , Rousseau Benoit , Senant-Dugot Nathalie , Mégraud Francis , Mazurier Frédéric , Varon Christine 
Published: September 2016

Abstract
Purpose: Gastric carcinomas are heterogeneous, and the current therapy remains essentially based on surgery with conventional chemotherapy and radiotherapy. This study aimed to characterize biomarkers allowing the detection of cancer stem cells (CSC) in human gastric carcinoma of different histologic types.
Experimental Design: The primary tumors from 37 patients with intestinal- or diffuse-type noncardia gastric carcinoma were studied, and patient-derived tumor xenograft (PDX) models in immunodeficient mice were developed. The expressions of 10 putative cell surface markers of CSCs, as well as aldehyde dehydrogenase (ALDH) activity, were studied, and the tumorigenic properties of cells were evaluated by in vitro tumorsphere assays and in vivo xenografts by limiting dilution assays.
Results: We found that a subpopulation of gastric carcinoma cells expressing EPCAM, CD133, CD166, CD44, and a high ALDH activity presented the properties to generate new heterogeneous tumorspheres in vitro and tumors in vivo. CD44 and CD166 were coexpressed, representing 6.1% to 37.5% of the cells; ALDH activity was detected in 1.6% to 15.4% of the cells; and the ALDH+ cells represented a core within the CD44+/CD166+ subpopulation that contained the highest frequency of tumorigenic CSCs in vivo. The ALDH+ cells possessed drug efflux properties and were more resistant to standard chemotherapy than the ALDH− cells, a process that was partially reversed by verapamil treatment.
Conclusions: CD44 and ALDH are the most specific biomarkers to detect and isolate tumorigenic and chemoresistant gastric CSCs in noncardia gastric carcinomas independently of the histologic classification of the tumor. Clin Cancer Res; 23(6); 1586–97. ©2016 AACR.
Multilayer OMIC Data in Medullary Thyroid Carcinoma Identifies the STAT3 Pathway as a Potential Therapeutic Target in RETM918T Tumors
Authors: Mancikova Veronika , Montero-Conde Cristina , Perales-Paton Javier , Fernandez Agustin , Santacana María , Jodkowska Karolina , Inglada-Pérez Lucia , Castelblanco Esmeralda , Borrego Salud , Encinas Mario , Matias-Guiu Xavier , Fraga Mario , Robledo Mercedes 
Published: September 2016

Abstract
Purpose: Medullary thyroid carcinoma (MTC) is a rare disease with few genetic drivers, and the etiology specific to each known susceptibility mutation remains unknown. Exploiting multilayer genomic data, we focused our interest on the role of aberrant DNA methylation in MTC development.
Experimental Design: We performed genome-wide DNA methylation profiling assessing more than 27,000 CpGs in the largest MTC series reported to date, comprising 48 molecularly characterized tumors. mRNA and miRNA expression data were available for 33 and 31 tumors, respectively. Two human MTC cell lines and 101 paraffin-embedded MTCs were used for validation.
Results: The most distinctive methylome was observed for RETM918T-related tumors. Integration of methylation data with mRNA and miRNA expression data identified genes negatively regulated by promoter methylation. These in silico findings were confirmed in vitro for PLCB2, DKK4, MMP20, and miR-10a, -30a, and -200c. The mutation-specific aberrant methylation of PLCB2, DKK4, and MMP20 was validated in 25 independent MTCs by bisulfite pyrosequencing. The methylome and transcriptome data underscored JAK/Stat pathway involvement in RETM918T MTCs. Immunostaining [immunohistochemistry (IHC)] for the active form of signaling effector STAT3 was performed in a series of 101 MTCs. As expected, positive IHC was associated with RETM918T-bearing tumors (P &lt; 0.02). Pharmacologic inhibition of STAT3 activity increased the sensitivity to vandetanib of the RETM918T-positive MTC cell line, MZ-CRC-1.
Conclusions: Multilayer OMIC data analysis uncovered methylation hallmarks in genetically defined MTCs and revealed JAK/Stat signaling effector STAT3 as a potential therapeutic target for the treatment of RETM918T MTCs. Clin Cancer Res; 23(5); 1334–45. ©2016 AACR.
Genomic Amplification of CD274 (PD-L1) in Small-Cell Lung Cancer
Authors: George Julie , Saito Motonobu , Tsuta Koji , Iwakawa Reika , Shiraishi Kouya , Scheel Andreas H. , Uchida Shinsuke , Watanabe Shun-ichi , Nishikawa Ryo , Noguchi Masayuki , Peifer Martin , Jang Se Jin , Petersen Iver , Büttner Reinhard , Harris Curtis C. , Yokota Jun , Thomas Roman K. , Kohno Takashi 
Published: September 2016

Abstract
Purpose: Programmed death ligand-1 (PD-L1), encoded by the CD274 gene, is a target for immune checkpoint blockade; however, little is known about genomic CD274 alterations. A subset of small-cell lung cancer (SCLC) exhibits increased copy number of chromosome 9p24, on which CD274 resides; however, most SCLCs show low expression of PD-L1. We therefore examined whether CD274 is a target of recurrent genomic alterations.
Experimental Design: We examined somatic copy number alterations in two patient cohorts by quantitative real-time PCR in 72 human SCLC cases (cohort 1) and SNP array analysis in 138 human SCLC cases (cohort 2). Whole-genome sequencing revealed the detailed genomic structure underlying focal amplification. PD-L1 expression in amplified cases from cohorts 1 and 2 was further examined by transcriptome sequencing and immunohistochemical (IHC) staining.
Results: By examining somatic copy number alterations in two cohorts of primary human SCLC specimens, we observed 9p24 copy number gains (where CD274 resides) and focal, high-level amplification of CD274. We found evidence for genomic targeting of CD274, suggesting selection during oncogenic transformation. CD274 amplification was caused by genomic rearrangements not affecting the open reading frame, thus leading to massively increased CD274 transcripts and high level expression of PD-L1.
Conclusions: A subset (4/210, 1.9%) of human SCLC patient cases exhibits massive expression of PD-L1 caused by focal amplification of CD274. Such tumors may be particularly susceptible to immune checkpoint blockade. Clin Cancer Res; 23(5); 1220–6. ©2016 AACR.