bluuebunny/crossref_metadata_2025_split huggingface dataset:
A convenient qualitative and quantitative method to investigate RHD‐RHCE hybrid genes
Authors: Fichou Yann , Le Maréchal Cédric , Bryckaert Laurence , Dupont Isabelle , Jamet Déborah , Chen Jian‐Min , Férec Claude 
Published: April 2013

BackgroundMolecular biology techniques, such as single specific‐primer polymerase chain reaction (PCR), denaturing‐high performance liquid chromatography, direct sequencing, next‐generation sequencing, and microarray platforms, contribute to the efficient genotyping of the human blood group RHD gene. However, some alleles remain undetermined in rare cases in DNA samples carrying two copies of the RHD gene, which challenge the identification of D‐CE hybrid genes.Study Design and MethodsWe set up, in a single‐tube format, a qualitative and quantitative assay based on multiplex PCR of short fluorescent fragments (QMPSF) to simultaneously amplify all 10 RHD exons on the one hand and all 10 RHCE exons on the other hand.ResultsThe test proved to be useful to rapidly identify hybrid genes in hemizygous RHD samples carrying a hybrid D‐CE gene and to resolve unknown genotypes by quantifying individual exons in compound heterozygous samples, but also unexpectedly helped to redefine the RHDΨ haplotype. While validating the test, two novel single‐point variants, c.648G>C (p.L216F) and c.1048G>C (p.D350H), were found.ConclusionFor the first time, a QMPSF‐based method is reliable to individually quantify the exons of both RH genes, including hybrid D‐CE genes in compound heterozygous samples and may help to investigate samples with unknown RHD and/or RHCE status.
Salmonella enterica Serovar Typhimurium Skills To Succeed in the Host: Virulence and Regulation
Authors: Fàbrega Anna , Vila Jordi 
Published: April 2013

SUMMARYSalmonella entericaserovar Typhimurium is a primary enteric pathogen infecting both humans and animals. Infection begins with the ingestion of contaminated food or water so that salmonellae reach the intestinal epithelium and trigger gastrointestinal disease. In some patients the infection spreads upon invasion of the intestinal epithelium, internalization within phagocytes, and subsequent dissemination. In that case, antimicrobial therapy, based on fluoroquinolones and expanded-spectrum cephalosporins as the current drugs of choice, is indicated. To accomplish the pathogenic process, theSalmonellachromosome comprises several virulence mechanisms. The most important virulence genes are those located within the so-calledSalmonellapathogenicity islands (SPIs). Thus far, five SPIs have been reported to have a major contribution to pathogenesis. Nonetheless, further virulence traits, such as the pSLT virulence plasmid, adhesins, flagella, and biofilm-related proteins, also contribute to success within the host. Several regulatory mechanisms which synchronize all these elements in order to guarantee bacterial survival have been described. These mechanisms govern the transitions from the different pathogenic stages and drive the pathogen to achieve maximal efficiency inside the host. This review focuses primarily on the virulence armamentarium of this pathogen and the extremely complicated regulatory network controlling its success.
Insights into the Origin, Emergence, and Current Spread of a Successful Russian Clone of Mycobacterium tuberculosis
Authors: Mokrousov Igor 
Published: April 2013

SUMMARY

Mycobacterium tuberculosis
variant Beijing B0/W148 is regarded as a successful clone of
M. tuberculosis
that is widespread in the former Soviet Union and respective immigrant communities. Understanding the pathobiology and phylogeography of this notorious strain may help to clarify its origin and evolutionary history and the driving forces behind its emergence and current dissemination. I present the first review and analysis of all available data on the subject. In spite of the common perception of the omnipresence of B0/W148 across post-Soviet countries, its geographic distribution shows a peculiar clinal gradient. Its frequency peaks in Siberian Russia and, to a lesser extent, in the European part of the former Soviet Union. In contrast, the frequency of B0/W148 is sharply decreased in the Asian part of the former Soviet Union, and it is absent in autochthonous populations elsewhere in the world. Placing the molecular, clinical, and epidemiological features in a broad historical, demographic, and ecological context, I put forward two interdependent hypotheses. First, B0/W148 likely originated in Siberia, and its primary dispersal was driven by a massive population outflow from Siberia to European Russia in the 1960s to 1980s. Second, a historically recent, phylogenetically demonstrated successful dissemination of the Beijing B0/W148 strain was triggered by the advent and wide use of modern antituberculosis (anti-TB) drugs and was due to the remarkable capacity of this strain to acquire drug resistance. In contrast, there is some indication, but not yet systematic proof, of an enhanced virulence of this strain.
Myeloid Differentiation Factor 88 Promotes Growth and Metastasis of Human Hepatocellular Carcinoma
Authors: Liang Beibei , Chen Rui , Wang Tao , Cao Lei , Liu Yingying , Yin Fan , Zhu Minhui , Fan Xiaoyu , Liang Yingchao , Zhang Lu , Guo Yajun , Zhao Jian 
Published: April 2013

Abstract
Purpose: To investigate the expression of myeloid differentiation factor 88 (MyD88) in hepatocellular carcinoma (HCC) and its prognostic value in patients with HCC.
Experimental Design: Expression of MyD88 was detected by immunohistochemistry in surgical HCC specimens (n = 110). The correlation of MyD88 expression to clinicopathologic characteristics was analyzed. The involvement of MyD88 in tumor growth and invasion was investigated.
Results: The expression of MyD88 was significantly higher in HCC tumors than that in adjacent nontumor tissues. Particularly, high expression of MyD88 was found in HCCs with late tumor stage (P = 0.029). Patients with high MyD88 staining revealed a higher recurrence rate (65% vs. 40%; P = 0.008). Kaplan–Meier analysis showed that recurrence-free survival (RFS; P = 0.011) and overall survival (OS; P = 0.022) were significantly worse among patients with high MyD88 staining. Univariate and multivariate analyses revealed that MyD88 was an independent predictor for OS and RFS. Ectopic expression of MyD88 promoted HCC cell proliferation and invasion in vitro. Suppression of MyD88 expression with lentivirus encoding short hairpin RNA reduced tumor growth and invasion, as well as lung metastasis. Finally, silencing of MyD88 inhibited the activation of NF-κB and AKT in HCC cells, whereas forced expression of MyD88 was able to enhance the activation of NF-κB and p38/extracellular signal–regulated kinase without Toll-like receptor/interleukin-1 receptor (TLR/IL-1R) signaling.
Conclusion: Elevated expression of MyD88 may promote tumor growth and metastasis via both TLR/IL-1R–dependent and –independent signaling and may serve as a biomarker for prognosis of patients with HCC. Clin Cancer Res; 19(11); 2905–16. ©2013 AACR.
G Protein–Coupled Estrogen Receptor Is Apoptotic and Correlates with Increased Distant Disease-Free Survival of Estrogen Receptor–Positive Breast Cancer Patients
Authors: Broselid Stefan , Cheng Benxu , Sjöström Martin , Lövgren Kristina , Klug-De Santiago Heather L.P. , Belting Mattias , Jirström Karin , Malmström Per , Olde Björn , Bendahl Pär-Ola , Hartman Linda , Fernö Mårten , Leeb-Lundberg L.M. Fredrik 
Published: April 2013

AbstractPurpose: G protein–coupled estrogen receptor 1 (GPER1), previously named GPR30, is a membrane receptor reported to mediate nongenomic estrogen responses. We investigated if GPER1 expression correlates with any clinicopathologic variables and distant disease-free survival (DDFS) in patients with breast cancer, if any prognostic impact of the receptor is dependent on estrogen receptor-α (ER-α) status, and if the receptor impacts apoptotic signaling in ER-positive breast cancer cells.Experimental Design: GPER1 expression was analyzed by immunohistochemistry in breast tumors from 273 pre- and postmenopausal stage II patients, all treated with adjuvant tamoxifen for 2 years (cohort I) and from 208 premenopausal lymph node-negative patients, of which 87% were not subjected to any adjuvant systemic treatment (cohort II). GPER1-dependent proapoptotic signaling was analyzed in MCF7 cells with and without GPER1 knockdown, T47D cells, HEK293 cells (HEK), and HEK stably expressing GPER1 (HEK-R).Results: GPER1 positively correlates with ER and progesterone receptor expression. Multivariate analysis showed that GPER1 is an independent prognostic marker of increased 10-year DDFS in the ER-positive subgroup. HEK-R has higher basal proapoptotic signaling compared with HEK including increased cytochrome C release, caspase-3 cleavage, PARP cleavage, and decreased cell viability. Treating HEK-R with the proteasome inhibitor epoxomicin, to decrease GPER1 degradation, further increases receptor-dependent proapoptotic signaling. Also, GPER1 knockdown decreases basal and agonist-stimulated proapoptotic receptor signaling in MCF7 cells.Conclusions: GPER1 is a prognostic indicator for increased DDFS in ER-positive breast cancer, which may be associated with constitutive GPER1-dependent proapoptotic signaling in ER-positive breast cancer cells. Clin Cancer Res; 19(7); 1681–92. ©2013 AACR.
ASS1as a Novel Tumor Suppressor Gene in Myxofibrosarcomas: Aberrant Loss via Epigenetic DNA Methylation Confers Aggressive Phenotypes, Negative Prognostic Impact, and Therapeutic Relevance
Authors: Huang Hsuan-Ying , Wu Wen-Ren , Wang Yu-Hui , Wang Jun-Wen , Fang Fu-Min , Tsai Jen-Wei , Li Shau-Hsuan , Hung Hsiao-Chin , Yu Shih-Chen , Lan Jui , Shiue Yow-Ling , Hsing Chung-His , Chen Li-Tzong , Li Chien-Feng 
Published: April 2013

AbstractPurpose: The principal goals were to identify and validate targetable metabolic drivers relevant to myxofibrosarcoma pathogenesis using a published transcriptome.Experimental Design: As the most significantly downregulated gene regulating amino acid metabolism, argininosuccinate synthetase (ASS1) was selected for further analysis by methylation-specific PCR, pyrosequencing, and immunohistochemistry of myxofibrosarcoma samples. The roles of ASS1 in tumorigenesis and the therapeutic relevance of the arginine-depriving agent pegylated arginine deiminase (ADI-PEG20) were elucidated in ASS1-deficient myxofibrosarcoma cell lines and xenografts with and without stable ASS1 reexpression.Results: ASS1 promoter hypermethylation was detected in myxofibrosarcoma samples and cell lines and was strongly linked to ASS1 protein deficiency. The latter correlated with increased tumor grade and stage and independently predicted a worse survival. ASS1-deficient cell lines were auxotrophic for arginine and susceptible to ADI-PEG20 treatment, with dose-dependent reductions in cell viability and tumor growth attributable to cell-cycle arrest in the S-phase. ASS1 expression was restored in 2 of 3 ASS1-deficient myxofibrosarcoma cell lines by 5-aza-2′-deoxycytidine, abrogating the inhibitory effect of ADI-PEG20. Conditioned media following ASS1 reexpression attenuated HUVEC tube-forming capability, which was associated with suppression of MMP-9 and an antiangiogenic effect in corresponding myxofibrosarcoma xenografts. In addition to delayed wound closure and fewer invading cells in a Matrigel assay, ASS1 reexpression reduced tumor cell proliferation, induced G1-phase arrest, and downregulated cyclin E with corresponding growth inhibition in soft agar and xenograft assays.Conclusions: Our findings highlight ASS1 as a novel tumor suppressor in myxofibrosarcomas, with loss of expression linked to promoter methylation, clinical aggressiveness, and sensitivity to ADI-PEG20. Clin Cancer Res; 19(11); 2861–72. ©2013 AACR.
Abstract A18: p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2
Authors: Kim Taewan , Lee Tae Jin , Jeon Young-Jun , Pineau Pascal , Dejean Anne , Croce Carlo Maria 
Published: April 2013

Abstract
p53 suppresses tumor progression and metastasis. Epithelial-mesenchymal transition (EMT) is a key process in tumor progression and metastasis. The transcription factors ZEB1 and ZEB2 promote EMT. Here we show that p53 suppresses EMT by repressing expression of ZEB1 and ZEB2. By profiling 92 primary hepatocellular carcinomas (HCCs) and 9 HCC cell lines, we found that p53 upregulates microRNAs including miR-200 and miR-192 family members. The miR-200 family members transactivated by p53 then repress ZEB1/2 expression. p53-regulated miR-192 family members also repress ZEB2 expression. Inhibition or over-expression of the microRNAs affects p53-regulated EMT by altering ZEB1 and ZEB2 expression. Our findings indicate that p53 can regulate EMT, and that p53-regulated microRNAs are critical mediators of p53-regulated EMT.
Citation Format: Taewan Kim, Tae Jin Lee, Young-Jun Jeon, Pascal Pineau, Anne Dejean, Carlo Maria Croce. p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2 [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr A18.
Controllable Factors in Aviation Safety
Authors: McLean Donald 
Published: April 2013

In 1999 there were 72 accidents involving scheduled airliners; 31 resulted in the total destruction of the hill of the aeroplane; and 33 caused major damage. The costs incurred in such accidents are recovered from insurance companies and, as a result, premiums are increased. Such increases affect the direct operating costs and evenntally the profits of the airlines. With passenger and cargo traffic growing worldwide at 6% per annum, it has been estimated that in the year 2005 twice as many passengers as are flying today and twice as much cargo will be handled, with an attendant increase in aircraft accidents. This paper briefly discusses a few of the factors involved in aircraft accidents and outlines some current programmes designed to enhance aviation safety. It also describes two avionic systems whose introduction into operational use is intended to lead to a reduction of the most common type of accident.
Safety Implications of ICAO Air Victim Support Rules
Authors: McLean Don 
Published: April 2013

With the continuous increase in world air travel which has been observed since 1995 being maintained, although at a somewhat lower rate after the terrorism enacted at the World Trade Centre in New York last year, it has been estimated that the number of aircraft hull loss accidents will double by 2012. Such serious accidents often involve fatalities. To ensure that there is in place an acceptable level of support for victims and their families, wherever the accident may have occurred, a Resolution A32–7 was adopted at the 32nd General Assembly of the International Civil Aviation Organisation (ICAO), a body of the United Nations. (Every nation which is a member of the UN is entitled to be a member of ICAO: once a member, the state and its airlines must provide air services to the standard required by the ICAO.) The Resolution is based implicitly on the rules which have been put in place by the National Transportation Safety Board (NTSB) of the USA. This short paper briefly explains what the rules entail, the likely impact that such rules will have on an airline affected by an air accident, and what are some of the other implications of implementing the Resolution.
Tunable Diode Laser (TDL) Systems for Trace Gas Analysis
Authors: Stockwell Paul 
Published: April 2013

A relatively new technique using a Tunable Diode Laser (TDL) systemto monitor water vapour, carbon dioxide and hydrogen sulphide isproviding higher on-line accuracy, lower maintenance, than traditionaltechniques and is significantly better at coping with contamination. It is the first technique to monitor the gas itself, rather than monitoringa reaction or a change on the surface of a sensor. It combines a highdegree of accuracy with an extremely good speed of response. Tunable Diode Laser Absorption Spectroscopy (TDLAS) works very wellacross the entire spectrum of gas concentration, and an area where it particularlyexcels is accurate moisture measurements in dry gases. Currentlymany hours are spent waiting for sensors using traditional techniquesto dry down: for example, when installing a new or re-calibrated watervapour sensor in a process where moisture levels are around 1 part permillion (ppmv), users normally wait 6 to 8 hours before the system settles;a TDL takes a few seconds and remains very responsive at that level. This paper will illustrate the progress made with this non-contactmethod in applications with natural gas, and gives details of why moisturemeasurement is important. The results of field trials are also presentedshowing how the technology compares with other techniques.
Energise or De-Energise to Trip?
Authors: Foord A G , Howard C R 
Published: April 2013

“De-energise to trip” is a long established principle because of the danger of common cause failures. Although there is little published on this topic, it is covered in the section “Protection systems (trips and interlocks)” in the HSE Technical Measure Document for COMAH sites, but the quality of UPS, diagnostics etc. is now very different from the last century. As well as the obvious effects of architecture, failure modes and frequency on the number of spurious trips and failures to dangers, we have also studied the relationships between design policies, (for example, overrides and diagnostic coverage), testing policies, repair policies, operating policies and their effects on common cause failures. The effects of different policies on spurious trips and failures to danger would be illustrated with practical examples from the energy industry: oil and gas production and power stations.
The Application of Safety Related Devices to Hazardous Areas Equipment
Authors: El-Sayed H 
Published: April 2013

As demand for electronic instrumentation devices used in applications which require equipment explosion protection to operate increases, it is the responsibility of companies and their design engineers to integrate protection and safety measures with minimum cost and less impact on the circuit operation. Compliance with potentially explosive standards can sometimes be difficult to meet due to non-harmonisation of standards in some countries, hence product approval may require combinations of different techniques or different levels of protection to provide the safety measures with respect to explosion risks and to meet a specific classification or category.
Container Type and Bactericidal Activity of Human Milk during Refrigerated Storage
Authors: Takci Sahin , Gulmez Dolunay , Yigit Sule , Dogan Ozlem , Hascelik Gulsen 
Published: April 2013

Background: Refrigeration of human milk has been recommended for its short-term storage. It has been shown that some nutritional, immunological, and bioactive properties and bactericidal activity of human milk can be altered during refrigeration. Pyrex bottles and polyethylene bags are 2 commonly used containers for human milk storage. Objective: The aim of this study was to compare the association between storage container type on the bactericidal activity of human milk for different durations of refrigeration (fresh, and at 24 and 48 hours). Methods: Forty-four samples of human milk were collected from 22 lactating mothers. Two samples of breast milk (approximately 10 mL each) were obtained by manual expression from each mother. One was collected directly into sterile Pyrex bottles and the other into polyethylene bags. One mL of human milk from each container was processed immediately after arrival to the laboratory. The remaining human milk was kept in the Pyrex and polyethylene containers at 4°C until analysis at 24 and 48 hours. The bactericidal activity of each sample was studied. A strain of Escherichia coli ATCC 25922 was used to determine the bactericidal effect of human milk. Results: Bactericidal activity was significantly reduced in milk samples stored in polyethylene bags compared to those stored in Pyrex bottles when milk samples were stored at 4°C for 24 and 48 hours ( P < .05). Conclusion: Short-term storage of human milk in Pyrex bottles is more appropriate than polyethylene bags for preserving its bactericidal activity against E coli.
Urinary neutrophil gelatinase-associated lipocalin as a marker of severe lupus nephritis in children
Authors: Hammad A , Mosaad Y , Elhanbly S , Youssef H , Refaaey A El , Elhusseini F , Bakr A 
Published: April 2013

Introduction More than 60% of children with systemic lupus erythematosus (SLE) develop lupus nephritis (LN). Neutrophil gelatinase-associated lipocalin (NGAL) is a protein secreted by leukocytes during inflammation and is overexpressed in the kidneys following ischemic and nephrotoxic damage. Aim To study urinary and serum NGAL in children with SLE and investigate their possible role as markers of renal involvement. Methods Urinary and serum levels of NGAL were assessed in 33 children with active SLE (22 with and 11 without LN) and compared to 15 matched controls. Results Children with SLE had elevated urinary NGAL as compared to controls ( P < 0.001). Levels of urinary NGAL were higher in patients with LN than those without LN ( P < 0.001). In patients with LN, serum levels of NGAL were not significantly different from controls ( P = 0.4) and urinary NGAL correlated with the renal score of the Systemic Lupus Erythematosus Disease Activity Index ( r = 0.5, P = 0.02) but not with serum NGAL ( P = 0.5). Urinary NGAL was significantly predictive of class III and IV LN ( P = 0.005) with 91% sensitivity and 70% specificity to levels ≥10.07 ng/mg creatinine. Conclusions Urinary NGAL is a sensitive marker of proliferative nephritis in juvenile SLE.
High mobility group box1 (HMGB1) in relation to cutaneous inflammation in systemic lupus erythematosus (SLE)
Authors: Abdulahad DA , Westra J , Reefman E , Zuidersma E , Bijzet J , Limburg PC , Kallenberg CGM , Bijl M 
Published: April 2013

Summary Photosensitivity is characteristic of systemic lupus erythematosus (SLE). Upon ultraviolet B (UVB) exposure, patients develop inflammatory skin lesions in the vicinity of sunburn cells (SBCs). High mobility group box 1 (HMGB1) is released from apoptotic and activated cells and exerts inflammatory actions through ligation to its receptors. Methods Eleven SLE patients and 10 healthy controls (HCs) were exposed to UVB. Skin biopsies were taken before and at one, three and 10 days after irradiation. Sections were stained for SBC, HMGB1, CD3, CD68, interferon-induced protein MxA and cleaved caspase 3. In vitro experiments with UVB-irradiated keratinocytes were also performed. Higher numbers of cells that had released HMGB1 were seen in the skin of SLE patients compared to HCs before and after irradiation. HMGB1-negative nuclei correlated with the presence of SBCs, and with the number of cleaved caspase 3 positive cells in lupus skin. Results HMGB1 release is increased in the skin of SLE patients compared to HCs. Upon UVB exposure, HMGB1 release further increases in SLE patients and is related to the number of apoptotic cells. Our data suggest that HMGB1, probably released from apoptotic keratinocytes, contributes to the development of inflammatory lesions in the skin of SLE patients upon UVB exposure.