bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiological Evidence for Isopotential Tunneling in the Electron Transport Chain of Methane-Producing Archaea
Authors: Duszenko Nikolas , Buan Nicole R. 
Published: July 2017

ABSTRACTMany, but not all, organisms use quinones to conserve energy in their electron transport chains. Fermentative bacteria and methane-producing archaea (methanogens) do not produce quinones but have devised other ways to generate ATP. Methanophenazine (MPh) is a unique membrane electron carrier found inMethanosarcinaspecies that plays the same role as quinones in the electron transport chain. To extend the analogy between quinones and MPh, we compared the MPh pool sizes between two well-studiedMethanosarcinaspecies,Methanosarcina acetivoransC2A andMethanosarcina barkeriFusaro, to the quinone pool size in the bacteriumEscherichia coli. We found the quantity of MPh per cell increases as cultures transition from exponential growth to stationary phase, and absolute quantities of MPh were 3-fold higher inM. acetivoransthan inM. barkeri. The concentration of MPh suggests the cell membrane ofM. acetivorans, but not ofM. barkeri, is electrically quantized as if it were a single conductive metal sheet and near optimal for rate of electron transport. Similarly, stationary (but not exponentially growing)E. colicells also have electrically quantized membranes on the basis of quinone content. Consistent with our hypothesis, we demonstrated that the exogenous addition of phenazine increases the growth rate ofM. barkerithree times that ofM. acetivorans. Our work suggests electron flux through MPh is naturally higher inM. acetivoransthan inM. barkeriand that hydrogen cycling is less efficient at conserving energy than scalar proton translocation using MPh.IMPORTANCECan we grow more from less? The ability to optimize and manipulate metabolic efficiency in cells is the difference between commercially viable and nonviable renewable technologies. Much can be learned from methane-producing archaea (methanogens) which evolved a successful metabolic lifestyle under extreme thermodynamic constraints. Methanogens use highly efficient electron transport systems and supramolecular complexes to optimize electron and carbon flow to control biomass synthesis and the production of methane. Worldwide, methanogens are used to generate renewable methane for heat, electricity, and transportation. Our observations suggestMethanosarcina acetivorans, but notMethanosarcina barkeri, has electrically quantized membranes.Escherichia coli, a model facultative anaerobe, has optimal electron transport at the stationary phase but not during exponential growth. This study also suggests the metabolic efficiency of bacteria and archaea can be improved using exogenously supplied lipophilic electron carriers. The enhancement of methanogen electron transport through methanophenazine has the potential to increase renewable methane production at an industrial scale.
Novel Alphacoronaviruses and Paramyxoviruses Cocirculate with Type 1 and Severe Acute Respiratory System (SARS)-Related Betacoronaviruses in Synanthropic Bats of Luxembourg
Authors: Pauly Maude , Pir Jacques B. , Loesch Catherine , Sausy Aurélie , Snoeck Chantal J. , Hübschen Judith M. , Muller Claude P. 
Published: July 2017

ABSTRACT

Several infectious disease outbreaks with high mortality in humans have been attributed to viruses that are thought to have evolved from bat viruses. In this study from Luxembourg, the genetic diversity and epidemiology of paramyxoviruses and coronaviruses shed by the bat species
Rhinolophus ferrumequinum
and
Myotis emarginatus
were evaluated. Feces collection (
n
= 624) was performed longitudinally in a mixed-species colony in 2015 and 2016. In addition, feces (
n
= 254) were collected cross-sectionally from six
Myotis emarginatus
colonies in 2016. By use of degenerate primers in a nested format, overall prevalences of 1.1% (10/878) and 4.9% (43/878) were determined for paramyxoviruses and coronaviruses. Sequences of the partial RNA-dependent RNA polymerase and spike glycoprotein genes of coronaviruses, as well as sequences of the partial L gene of paramyxoviruses, were obtained. Novel paramyxovirus and
Alphacoronavirus
strains were identified in different
Myotis emarginatus
colonies, and severe acute respiratory syndrome (SARS)-related
Betacoronavirus
strains were shed by
Rhinolophus ferrumequinum
. Logistic regression revealed that the level of
Alphacoronavirus
shedding was highest in July (odds ratio, 2.8;
P
< 0.01), probably due to periparturient stress. Phylogenetic analyses point to close virus-host coevolution, and the high genetic similarity of the study strains suggests that the
Myotis emarginatus
colonies in Luxembourg are socially connected. Most interestingly, we show that bats also host
Betacoronavirus
1
strains. The high similarity of the spike gene sequences of these viruses with mammalian
Betacoronavirus 1
strains may be of concern. Both the SARS-related and
Betacoronavirus 1
strains detected in bats in Luxembourg may cross the species barrier after a host adaptation process.

IMPORTANCE
Bats are a natural reservoir of a number of zoonotic pathogens. Several severe outbreaks in humans (e.g., a Nipah virus outbreak in Malaysia in 1998, and the almost global spread of severe acute respiratory syndrome in 2003) have been caused by bat-borne viruses that were transmitted to humans mostly after virus adaptation (e.g., in intermediate animal hosts). Despite the indigenousness of bat species that host viruses with suspected zoonotic potential and despite the zoonotic transmission of European bat 1 lyssavirus in Luxembourg, knowledge about the diversity and epidemiology of bat viruses remains limited in this country. Moreover, in contrast to other European countries, bat viruses are currently not included in the national surveillance activities of this land-locked country. We suggest that this gap in disease surveillance should be addressed, since we show here that synanthropic bats host viruses that may be able to cross the species barrier.
Dissimilar Crystal Proteins Cry5Ca1 and Cry5Da1 Synergistically Act against Meloidogyne incognita and Delay Cry5Ba-Based Nematode Resistance
Authors: Geng Ce , Liu Yingying , Li Miaomiao , Tang Zhen , Muhammad Sajid , Zheng Jinshui , Wan Danfeng , Peng Donghai , Ruan Lifang , Sun Ming 
Published: July 2017

ABSTRACT

Cry proteins of
Bacillus thuringiensis
(Bt) have been successfully used as biopesticides and in transgenic crops throughout the world. However, resources against the most serious agricultural pathogens, plant root-knot nematodes, are limited. The genomes of several highly nematicidal virulent Bt strains from our laboratory have been sequenced, facilitating the identification of novel Cry proteins and other virulence factors. We identified two novel Cry proteins, Cry5Ca1 and Cry5Da1, that exhibit high toxicity against
Meloidogyne incognita
. Using the
Caenorhabditis elegans
model, the two Cry5 toxins were shown to negatively affect nematode life span, fertility, and survival. The 50% lethal concentrations (LC
50
s) of Cry5Ca1 and Cry5Da1 were 57.22 μg/ml and 36.69 μg/ml, respectively. Moreover, a synergistic effect (synergism factor, 1.61 to 2.04) was observed for nematicidal toxicity of Cry5Ca1 and Cry5Da1, which is accordant with the phylogenetic results suggesting that domain II of the two novel Cry5 toxins evolved into two independent clades. Through comparison of the depressed degree of toxicity in the β-methylgalactoside detoxification test, we found that the novel toxin Cry5D possesses a different galactose-binding epitope; meanwhile, the finding that Cry5D does not share a motif (GXXXE) in the corresponding loop of domain II with Cry5B could explain the different galactose binding performance. Additionally, low-level cross-resistance of
C. elegans bre
mutant strains was evident between Cry5B and Cry5D. These results suggest that Cry5D can be used as an alternative to delay the potential resistance of nematodes to Cry5B.

IMPORTANCE
Although proper gene resources for Bt crops against the most serious agricultural pathogens, plant root-knot nematodes, are limited, we have identified two novel nematicidal toxins, Cry5Ca1 and Cry5Da1, against
M. incognita
, which have supplied more gene candidates for Bt crops designed against nematodes. Moreover, the association of the dissimilarity between Cry5Da1 and Cry5Ba1 and their low cross-resistance can be attributed not only to a low sequence similarity of domain II but also to the structural difference of the key motif and receptor-binding epitope in the loops. This association facilitates the selection of a proper candidate for the prospective design of pyramided Bt crops that can delay potential resistance.
Liver cirrhosis in England—an observational study: are we measuring its burden occurrence correctly?
Authors: Ratib Sonia , West Joe , Fleming Kate M 
Published: July 2017

ObjectivesMortality due to liver disease (of which cirrhosis is the end stage) is increasing more than any other chronic condition in the UK. This study aims to demonstrate that (1) exclusive reliance on mortality rates may not reveal the true burden of liver cirrhosis, and (2) diverse use of diagnostic coding may produce misleading estimates.DesignObservational study.SettingThe Office for National Statistics death registry was interrogated to investigate liver cirrhosis mortality trends in England and Wales from 1968 to 2011.Main outcomeStandardised mortality trends according to three different definitions of liver cirrhosis based on the specificity of diagnostic codes were calculated: 1 (chronic liver diseases), 2 (alcoholic and unspecified cirrhosis only) and 3 (cirrhosis as end-stage liver disease). The mortality trends were compared with incidence rates established in a previous population-based study (based on definition 3), from 1998 to 2009, to investigate discrepancies between these two measures.ResultsOver the study period, the overall standardised liver cirrhosis mortality rates were 8.8, 5,1 and 5.4 per 100 000 person-years for definitions 1, 2 and 3, respectively. The mortality rates for definition 3 in 1998 and 2009 were 6.2 and 5.9 per 100 000 person-years, respectively; while the equivalent incidence rates were at least threefold and sixfold higher: 23.4 and 35.9 per 100 000 person-years, respectively. This discrepancy between incidence and mortality rates was also at least threefold in men and women separately and across age groups.ConclusionMortality rates underestimated the incidence of liver cirrhosis by at least threefold between 1998 and 2009 and varied with differing definitions of disease. Mortality data should not be used exclusively as an indicator for the occurrence of liver cirrhosis in the population. Routinely collected healthcare data are available to measure occurrence of this disease. Careful consideration should be taken when selecting diagnostic codes for cirrhosis.
Impact of a patient-tailored complementary/integrative medicine programme on disturbed sleep quality among patients undergoing chemotherapy
Authors: Kerner Hilit , Samuels Noah , Ben Moshe Shlomi , Sharabi Ilanit Shalom , Ben-Arye Eran 
Published: July 2017

ObjectivesThe present study examined the impact of a patient-tailored complementary/integrative medicine (CIM) programme on sleep quality in patients undergoing chemotherapy for breast and gynaecological cancer.MethodsStudy participants received standard supportive care, with or without weekly CIM treatments. Disturbed sleep quality was defined as a score of ≥4 on the Edmonton Symptom Assessment Scale (ESAS) or a score of ≥3 on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Adherence to integrative care was defined as attending ≥4 CIM treatments, with ≤30 days between each session.ResultsOf 388 eligible patients, 264 (68%) reported disturbed sleep quality. Baseline-to-follow up assessment (at 6 weeks) was optimal for 104 patients in the treatment group and for 76 controls, with 75 of treated patients found to be adherent to the CIM intervention. Sleep-related ESAS scores improved more significantly in treated patients (p=0.008), as did sleep-related concerns on EORTC (treatment group, p=0.026).ConclusionsA patient-tailored CIM programme may improve sleep quality and related concerns among patients with breast and gynaecological cancer undergoing chemotherapy. Further research is needed to better understand the impact of CIM on sleep quality in this patient population.Trial registration numberNCT01860365.
Regional deprivation is associated with the distribution of vulnerable asylum seekers: a nationwide small area analysis in Germany
Authors: Bozorgmehr Kayvan , Razum Oliver , Szecsenyi Joachim , Maier Werner , Stock Christian 
Published: July 2017

BackgroundNewly arriving asylum seekers in many European Union countries are assigned a place of residence based on administrative quota. This may have important consequences for the exposure to contextual health risks. We assessed the association between regional deprivation and the distribution of asylum seekers in Germany considered as vulnerable (women, children <7 years, persons >64 years) because of their increased health needs.MethodsUsing nationally representative data, we analysed the rates of observed to expected numbers of asylum seekers and vulnerable subgroups in Bayesian spatial models. Regional deprivation was measured by the German Index of Multiple Deprivation. The analyses were performed at the district level (N=402) and adjusted for district population size, effects of federal states as well as spatial effects.ResultsOf the 224 993 asylum seekers, 38.7% were women, 13.8% children aged <7 years and 19.8% aged >64 years. The adjusted number of asylum seekers (totals and vulnerable subgroups) was higher in more deprived districts (Q3, Q4 and Q5) relative to districts in the lowest deprivation quintile (Q1). The adjusted rate ratios for districts with highest relative to those with lowest deprivation were 1.26 (1.03–1.53) for women, 1.28 (1.04–1.58) for children aged <7 years and 1.50 (1.08–2.08) for older asylum seekers.ConclusionThe adjusted number of vulnerable asylum seekers was higher in districts with medium and highest deprivation compared with districts with lowest deprivation. The disproportionate distribution was highest for older asylum seekers and children <7 years. Vulnerable subgroups tend to be exposed to more deprived places of residence, which may further increase health risks and healthcare needs.
Geological evolution of Central Asian Basins and the western Tien Shan Range
Authors: Brunet Marie-Françoise , Sobel Edward R. , McCann Tom 
Published: July 2017

Abstract
The geological evolution of Central Asia commenced with the evolution of a complex Precambrian–Palaeozoic orogen. Cimmerian blocks were then accreted to the southern margin during the Mesozoic, leading to tectonic reactivation of older structures and discrete episodes of basin formation. The Indian and Arabian blocks collided with Asia during the Cenozoic, leading to renewed structural reactivation, intracontinental deformation and basin development. This complex evolution resulted in the present-day setting of an elongated Tien Shan range flanked by large Mesozoic–Cenozoic sedimentary basins with smaller intramontane basins distributed within the range. The aim of this volume is to present multidisciplinary results and reviews from research groups in Europe and Central Asia that focus on the western part of the Tien Shan and some of the large sedimentary basins in that area. These works elucidate the Late Palaeozoic–Cenozoic tectono-sedimentary evolution of the area. Emphasis is placed on the collision of terranes and/or continents and the ensuing fault reactivation; the impact of changes in climate on the sedimentation is also examined.
Aspirin Inhibits Cancer Metastasis and Angiogenesis via Targeting Heparanase
Authors: Dai Xiaoyang , Yan Juan , Fu Xuhong , Pan Qiuming , Sun Danni , Xu Yuan , Wang Jiang , Nie Litong , Tong Linjiang , Shen Aijun , Zheng Mingyue , Huang Min , Tan Minjia , Liu Hong , Huang Xun , Ding Jian , Geng Meiyu 
Published: July 2017

Abstract
Purpose: Recent epidemiological and clinical studies have suggested the benefit of aspirin for patients with cancer, which inspired increasing efforts to demonstrate the anticancer ability of aspirin and reveal the molecular mechanisms behind. Nevertheless, the anticancer activity and related mechanisms of aspirin remain largely unknown. This study aimed to confirm this observation, and more importantly, to investigate the potential target contributed to the anticancer of aspirin.
Experimental Design: A homogeneous time-resolved fluorescence (HTRF) assay was used to examine the impact of aspirin on heparanase. Streptavidin pull-down, surface plasmon resonance (SPR) assay, and molecular docking were performed to identify heparanase as an aspirin-binding protein. Transwell, rat aortic rings, and chicken chorioallantoic membrane model were used to evaluate the antimetastasis and anti-angiogenesis effects of aspirin, and these phenotypes were tested in a B16F10 metastatic model, MDA-MB-231 metastatic model, and MDA-MB-435 xenograft model.
Results: This study identified heparanase, an oncogenic extracellular matrix enzyme involved in cancer metastasis and angiogenesis, as a potential target of aspirin. We had discovered that aspirin directly binds to Glu225 region of heparanase and inhibits the enzymatic activity. Aspirin impeded tumor metastasis, angiogenesis, and growth in heparanase-dependent manner.
Conclusions: In summary, this study has illustrated heparanase as a target of aspirin for the first time. It provides insights for a better understanding of the mechanisms of aspirin in anticancer effects, and offers a direction for the development of small-molecule inhibitors of heparanase. Clin Cancer Res; 23(20); 6267–78. ©2017 AACR.
Shallow Whole Genome Sequencing on Circulating Cell-Free DNA Allows Reliable Noninvasive Copy-Number Profiling in Neuroblastoma Patients
Authors: Van Roy Nadine , Van Der Linden Malaïka , Menten Björn , Dheedene Annelies , Vandeputte Charlotte , Van Dorpe Jo , Laureys Geneviève , Renard Marleen , Sante Tom , Lammens Tim , De Wilde Bram , Speleman Frank , De Preter Katleen 
Published: July 2017

Abstract
Purpose: Neuroblastoma (NB) is a heterogeneous disease characterized by distinct clinical features and by the presence of typical copy-number alterations (CNAs). Given the strong association of these CNA profiles with prognosis, analysis of the CNA profile at diagnosis is mandatory. Therefore, we tested whether the analysis of circulating cell-free DNA (cfDNA) present in plasma samples of patients with NB could offer a valuable alternative to primary tumor DNA for CNA profiling.
Experimental Design: In 37 patients with NB, cfDNA analysis using shallow whole genome sequencing (sWGS) was compared with arrayCGH analysis of primary tumor tissue.
Results: Comparison of CNA profiles on cfDNA showed highly concordant patterns, particularly in high-stage patients. Numerical chromosome imbalances as well as large and focal structural aberrations including MYCN and LIN28B amplification and ATRX deletion could be readily detected with sWGS using a low input of cfDNA.
Conclusions: In conclusion, sWGS analysis on cfDNA offers a cost-effective, noninvasive, rapid, robust and sensitive alternative for tumor DNA copy-number profiling in most patients with NB. Clin Cancer Res; 23(20); 6305–14. ©2017 AACR.
Sarcomatoid Renal Cell Carcinoma Has a Distinct Molecular Pathogenesis, Driver Mutation Profile, and Transcriptional Landscape
Authors: Wang Zixing , Kim Tae Beom , Peng Bo , Karam Jose , Creighton Chad , Joon Aron , Kawakami Fumi , Trevisan Patricia , Jonasch Eric , Chow Chi-Wan , Canales Jaime Rodriguez , Tamboli Pheroze , Tannir Nizar , Wood Christopher , Monzon Federico , Baggerly Keith , Varella-Garcia Marileila , Czerniak Bogdan , Wistuba Ignacio , Mills Gordon , Shaw Kenna , Chen Ken , Sircar Kanishka 
Published: July 2017

Abstract
Purpose: Sarcomatoid renal cell carcinoma (SRCC) ranks among the most aggressive clinicopathologic phenotypes of RCC. However, the paucity of high-quality, genome-wide molecular examinations of SRCC has hindered our understanding of this entity.
Experimental Design: We interrogated the mutational, copy number, and transcriptional characteristics of SRCC and compared these data with those of nonsarcomatoid RCC (RCC). We evaluated whole-exome sequencing, single-nucleotide polymorphism, and RNA sequencing data from patients with SRCC (n = 65) and RCC (n = 598) across different parent RCC subtypes, including clear-cell RCC, papillary RCC, and chromophobe RCC subtypes.
Results: SRCC was molecularly discrete from RCC and clustered according to its parent RCC subtype, though with upregulation of TGFβ signaling across all subtypes. The epithelioid (E-) and spindled (S-) histologic components of SRCC did not show differences in mutational load among cancer-related genes despite a higher mutational burden in S-. Notably, sarcomatoid clear-cell RCC (SccRCC) showed significantly fewer deletions at 3p21-25, a lower rate of two-hit loss for VHL and PBRM1, and more mutations in PTEN, TP53, and RELN compared with ccRCC. A two-hit loss involving VHL predicted for ccRCC and a better prognosis, whereas mutations in PTEN, TP53, or RELN predicted for SccRCC and worse prognosis.
Conclusions: SRCC segregates by parent subtype, and SccRCC has a fundamentally different early molecular pathogenesis, usually lacking the classic 3p21-25 deletion and showing distinctive mutational and transcriptional profiles. These features prompt a more precise molecular classification of RCC, with diagnostic, prognostic, and therapeutic implications. Clin Cancer Res; 23(21); 6686–96. ©2017 AACR.
See related commentary by Bergerot et al., p. 6381
Ex Vivo PD-L1/PD-1 Pathway Blockade Reverses Dysfunction of Circulating CEA-Specific T Cells in Pancreatic Cancer Patients
Authors: Chen Yuan , Xue Shao-An , Behboudi Shahriar , Mohammad Goran H. , Pereira Stephen P. , Morris Emma C. 
Published: July 2017

Abstract
Purpose: Carcinoembryonic antigen (CEA) is a candidate target for cellular immunotherapy of pancreatic cancer. In this study, we have characterized the antigen-specific function of autologous cytotoxic T lymphocytes (CTL) specific for the HLA-A2–restricted peptide, pCEA691-699, isolated from the peripheral T-cell repertoire of pancreatic cancer patients and sought to determine if ex vivo PD-L1 and TIM-3 blockade could enhance CTL function.
Experimental Design: CD8+ T-cell lines were generated from peripheral blood mononuclear cells of 18 HLA-A2+ patients with pancreatic cancer and from 15 healthy controls. In vitro peptide-specific responses were evaluated by flow cytometry after staining for intracellular cytokine production and carboxy fluorescein succinimydyl ester cytotoxicity assays using pancreatic cancer cell lines as targets.
Results: Cytokine-secreting functional CEA691-specific CTL lines were successfully generated from 10 of 18 pancreatic cancer patients, with two CTL lines able to recognize and kill both CEA691 peptide–loaded T2 cells and CEA+ HLA-A2+ pancreatic cancer cell lines. In the presence of ex vivo PD-L1 blockade, functional CEA691-specific CD8+ T-cell responses, including IFNγ secretion and proliferation, were enhanced, and this effect was more pronounced on Ag-specific T cells isolated from tumor draining lymph nodes.
Conclusions: These data demonstrate that CEA691-specific CTL can be readily expanded from the self-restricted T-cell repertoire of pancreatic cancer patients and that their function can be enhanced by PD-L1 blockade. Clin Cancer Res; 23(20); 6178–89. ©2017 AACR.