bluuebunny/crossref_metadata_2025_split huggingface dataset:
SDHC mutation in an elderly patient without familial antecedents
Authors: López‐Jiménez Elena , De Campos José M. , Kusak Elena M. , Landa Iñigo , Leskelä Susanna , Montero‐Conde Cristina , Leandro‐García Luis J. , Vallejo Luis A. , Madrigal Beatriz , Rodríguez‐Antona Cristina , Robledo Mercedes , Cascón Alberto 
Published: August 2008

SummaryHead and neck paragangliomas are usually asymptomatic and benign tumours arising mainly from the carotid body and the vagal, tympanic or jugular glomus. The majority of patients develop sporadic masses, and around 30% of cases harbour germline mutations in one of the succinate dehydrogenase genes: SDHB, SDHC or SDHD. In these hereditary cases, the presence of familial antecedents of the disease, multiplicity/bilaterality, young age at onset, and more recently, presence of gastrointestinal stromal tumours, are main factors to be considered. Here we describe a new mutation (c.256–257insTTT) affecting the SDHC gene in a 60‐year‐old‐patient with a single head and neck paraganglioma, and without familial antecedents of the disease. In silico splice site analysis showed that this variant created a cryptic splice acceptor site and loss of heterozygosity (LOH) supported the pathogenic role of the mutation. Control population analyses did not detect this variant but revealed a novel SDHC polymorphism that exhibited a frequency of 0·3% (3/1020). This latter finding highlights the importance of assessing the clinical relevance of variants of unknown significance by means of analysing sufficient controls. Despite having found a germline mutation in an older, apparently sporadic patient, we consider that the high costs of analysing all susceptibility genes related to the disease support the recommendation of screening for mutations only in patients fulfilling the above criteria.
Phylogenetic analyses and molecular epidemiology of European salmonid alphaviruses (SAV) based on partial E2 and nsP3 gene nucleotide sequences
Authors: Fringuelli E , Rowley H M , Wilson J C , Hunter R , Rodger H , Graham D A 
Published: August 2008

AbstractSequence data were generated for portions of the E2 and nsP3 genes of 48 salmonid alphaviruses from farmed Atlantic salmon (AS), Salmo salar L., and rainbow trout (RT), Oncorhynchus mykiss (Walbaum), in marine and freshwater environments, respectively, from the Republic of Ireland, Northern Ireland, England, Scotland, Norway, France, Italy and Spain between 1991 and 2007. Based on these sequences, and those of six previously published reference strains, phylogenetic trees were constructed using the parsimony method. Trees generated with both gene segments were similar. Clades corresponding to the three previously recognized subtypes were generated and in addition, two further new clades of viruses were identified. A single further strain (F96‐1045) was found to be distinct from all of the other strains in the study. The percentage of nucleotide divergence within clades was generally low (0–4.8% for E2, 0–6.6% for nsP3). Interclade divergence tended to be higher (3.4–19.7% for E2, 6.5–28.1% for nsP3). Based on these results and using current SAV terminology, the two new clades and F96‐1045 were termed SAV subtypes 4, 5 and 6, respectively. SAV4 contained AS strains from Ireland and Scotland, while SAV5 contained only Scottish AS strains. Recently identified SAV strains from RT in Italy and Spain were shown to belong to SAV2. In addition, marine AS strains belonging to SAV2 were identified for the first time. Analysis of the origin of several clusters of strains with identical E2 and nsP3 sequences strongly support horizontal transmission of virus between farms and aquaculture companies. Evidence in support of vertical transmission was not found.
Genetic diversity of Flavobacterium psychrophilum recovered from commercially raised rainbow trout, Oncorhynchus mykiss (Walbaum), and spawning coho salmon, O. kisutch (Walbaum)
Authors: Chen Y‐C , Davis M A , LaPatra S E , Cain K D , Snekvik K R , Call D R 
Published: August 2008

Abstract Flavobacterium psychrophilum is the aetiological agent of rainbow trout fry syndrome and bacterial cold water disease. This study examined the genetic diversity of F. psychrophilum isolates retrieved from multiple epizootics at rainbow trout, Oncorhynchus mykiss, rearing facilities and from spawning coho salmon, O. kisutch. A total of 139 isolates were confirmed as F. psychrophilum by PCR assay and were further typed using pulsed‐field gel electrophoresis (PFGE). Multiple epizootics at three proximally located rainbow trout rearing facilities were numerically dominated by three PFGE profiles, which accounted for 76% of all trout isolates. In coho salmon, 19 PFGE profiles were differentiated by PFGE and four numerically dominant PFGE profiles represented 56% of all coho salmon isolates. PFGE analysis also indicated that the average similarity of macrorestriction patterns of F. psychrophilum isolates was greater in rainbow trout than in coho salmon (88% vs. 70%). Furthermore, it was not unusual to isolate multiple PFGE profiles from a single coho salmon sample whereas only two PFGE profiles were shared between two sample dates separated by 1 month. It is clear that the domestic rainbow trout aquaculture facilities studied here were primarily affected by a complex of genetically related strains whereas spawning coho salmon supported a much more genetically diverse collection of F. psychrophilum.
The first report of viral haemorrhagic septicaemia in farmed rainbow trout, Oncorhynchus mykiss (Walbaum), in the United Kingdom
Authors: Stone D M , Ferguson H W , Tyson P A , Savage J , Wood G , Dodge M J , Woolford G , Dixon P F , Feist S W , Way K 
Published: August 2008

AbstractViral haemorrhagic septicaemia (VHS) was diagnosed in rainbow trout in the UK in May 2006. VHS virus (VHSV) was isolated from fingerlings showing typical histopathological lesions at a single rainbow trout farm site experiencing high mortality. The virus was confirmed as VHSV by serological and molecular biological tests. Phylogenetic analysis based on the complete glycoprotein gene sequence revealed that the isolate was closely related (99% nucleotide identity) to several Danish isolates from 1991 to 2000 and was assigned to VHSV genogroup Ia. The pathogenicity of the isolate was determined in infection experiments using rainbow trout fry. Following waterborne challenge, cumulative mortalities reached 96.67–100% by 12 days post‐infection. This represents the first isolation of a pathogenic freshwater VHSV in the UK.
Farnesol induces the transcriptional accumulation of the Aspergillus nidulans Apoptosis‐Inducing Factor (AIF)‐like mitochondrial oxidoreductase
Authors: Savoldi Marcela , Malavazi Iran , Soriani Frederico Marianetti , Capellaro José Luiz , Kitamoto Katsuhiko , da Silva Ferreira Márcia Eliana , Goldman Maria Helena S. , Goldman Gustavo Henrique 
Published: August 2008

SummaryFarnesol (FOH) is a non‐sterol isoprenoid produced by dephosphorylation of farnesyl pyrophosphate, a catabolite of the cholesterol biosynthetic pathway. These isoprenoids inhibit proliferation and induce apoptosis. It has been shown previously that FOH triggers morphological features characteristic of apoptosis in the filamentous fungus Aspergillus nidulans. Here, we investigate which pathways are influenced through FOH by examining the transcriptional profile of A. nidulans exposed to this isoprenoid. We observed decreased mRNA abundance of several genes involved in RNA processing and modification, transcription, translation, ribosomal structure and biogenesis, amino acid transport and metabolism, and ergosterol biosynthesis. We also observed increased mRNA expression of genes encoding a number of mitochondrial proteins and characterized in detail one of them, the aifA, encoding the Apoptosis‐Inducing Factor (AIF)‐like mitochondrial oxidoreductase. The ΔaifA mutant is more sensitive to FOH (about 8.0% and 0% survival when exposed to 10 and 100 μM FOH respectively) than the wild type (about 97% and 3% survival when exposed to 10 and 100 μM FOH respectively). These results suggest that AifA is possibly important for decreasing the effects of FOH and reactive oxygen species. Furthermore, we showed an involvement of autophagy and protein kinase C in A. nidulans FOH‐induced apoptosis.
RloC: a wobble nucleotide‐excising and zinc‐responsive bacterial tRNase
Authors: Davidov Elena , Kaufmann Gabriel 
Published: August 2008

SummaryThe conserved bacterial protein RloC, a distant homologue of the tRNALys anticodon nuclease (ACNase) PrrC, is shown here to act as a wobble nucleotide‐excising and Zn++‐responsive tRNase. The more familiar PrrC is silenced by a genetically linked type I DNA restriction‐modification (R‐M) enzyme, activated by a phage anti‐DNA restriction factor and counteracted by phage tRNA repair enzymes. RloC shares PrrC's ABC ATPase motifs and catalytic ACNase triad but features a distinct zinc‐hook/coiled‐coil insert that renders its ATPase domain similar to Rad50 and related DNA repair proteins. Geobacillus kaustophilus RloC expressed in Escherichia coli exhibited ACNase activity that differed from PrrC's in substrate preference and ability to excise the wobble nucleotide. The latter specificity could impede reversal by phage tRNA repair enzymes and account perhaps for RloC's more frequent occurrence. Mutagenesis and functional assays confirmed RloC's catalytic triad assignment and implicated its zinc hook in regulating the ACNase function. Unlike PrrC, RloC is rarely linked to a type I R‐M system but other genomic attributes suggest their possible interaction in trans. As DNA damage alleviates type I DNA restriction, we further propose that these related perturbations prompt RloC to disable translation and thus ward off phage escaping DNA restriction during the recovery from DNA damage.
The Vibrio harveyi master quorum‐sensing regulator, LuxR, a TetR‐type protein is both an activator and a repressor: DNA recognition and binding specificity at target promoters
Authors: Pompeani Audra J. , Irgon Joseph J. , Berger Michael F. , Bulyk Martha L. , Wingreen Ned S. , Bassler Bonnie L. 
Published: August 2008

SummaryQuorum sensing is the process of cell‐to‐cell communication by which bacteria communicate via secreted signal molecules called autoinducers. As cell population density increases, the accumulation of autoinducers leads to co‐ordinated changes in gene expression across the bacterial community. The marine bacterium, Vibrio harveyi, uses three autoinducers to achieve intra‐species, intra‐genera and inter‐species cell–cell communication. The detection of these autoinducers ultimately leads to the production of LuxR, the quorum‐sensing master regulator that controls expression of the genes in the quorum‐sensing regulon. LuxR is a member of the TetR protein superfamily; however, unlike other TetR repressors that typically repress their own gene expression and that of an adjacent operon, LuxR is capable of activating and repressing a large number of genes. Here, we used protein binding microarrays and a two‐layered bioinformatics approach to show that LuxR binds a 21 bp consensus operator with dyad symmetry. In vitro and in vivo analyses of two promoters directly regulated by LuxR allowed us to identify those bases that are critical for LuxR binding. Together, the in silico and biochemical results enabled us to scan the genome and identify novel targets of LuxR in V. harveyi and thus expand the understanding of the quorum‐sensing regulon.
A new Vibrio cholerae sRNA modulates colonization and affects release of outer membrane vesicles
Authors: Song Tianyan , Mika Franziska , Lindmark Barbro , Liu Zhi , Schild Stefan , Bishop Anne , Zhu Jun , Camilli Andrew , Johansson Jörgen , Vogel Jörg , Wai Sun Nyunt 
Published: August 2008

SummaryWe discovered a new small non‐coding RNA (sRNA) gene, vrrA of Vibrio cholerae O1 strain A1552. A vrrA mutant overproduces OmpA porin, and we demonstrate that the 140 nt VrrA RNA represses ompA translation by base‐pairing with the 5′ region of the mRNA. The RNA chaperone Hfq is not stringently required for VrrA action, but expression of the vrrA gene requires the membrane stress sigma factor, σE, suggesting that VrrA acts on ompA in response to periplasmic protein folding stress. We also observed that OmpA levels inversely correlated with the number of outer membrane vesicles (OMVs), and that VrrA increased OMV production comparable to loss of OmpA. VrrA is the first sRNA known to control OMV formation. Moreover, a vrrA mutant showed a fivefold increased ability to colonize the intestines of infant mice as compared with the wild type. There was increased expression of the main colonization factor of V. cholerae, the toxin co‐regulated pili, in the vrrA mutant as monitored by immunoblot detection of the TcpA protein. VrrA overproduction caused a distinct reduction in the TcpA protein level. Our findings suggest that VrrA contributes to bacterial fitness in certain stressful environments, and modulates infection of the host intestinal tract.
Association between perceived security of the neighbourhood and small‐for‐gestational‐age birth
Authors: Auger Nathalie , Daniel Mark , Platt Robert W. , Wu Yuquan , Luo Zhong‐Cheng , Choinière Robert 
Published: August 2008

SummaryEvidence points to an association between a mother's place of residence and her newborn's health, independent of individual characteristics. Neighbourhood constructs such as immigrant density, deprivation and crime have all been separately associated with birth outcomes. Little research has considered the joint influence of variables representing a spectrum of neighbourhood constructs. Subjective vs. objective measures of neighbourhood constructs (e.g. reported vs. perceived crime) are often not considered. We sought to evaluate the relationship between neighbourhood measures of reported crime, neighbourhood perceived security, immigrant density, material/social deprivation, residential stability and the odds of small‐for‐gestational‐age (SGA) birth in an urban setting in Canada. Neighbourhood was defined as police districts (n = 49). We linked Montreal livebirths 1997–2001 (n = 98 330) to police district crime measures, survey data on perceived security, and 2001 census data. We used multi‐level analysis to calculate odds ratios (OR) for neighbourhood effects on SGA birth accounting for individual characteristics.Mothers residing in neighbourhoods with the most favourable perception had a lower odds of SGA birth than neighbourhoods with the least favourable perception [OR 0.87, 95% CI 0.77, 0.97]. Mothers in neighbourhoods with lower proportions of immigrants had lower odds of SGA birth relative to neighbourhoods with the highest proportion of immigrants. Reported crime, residential stability and material/social deprivation (accounting for neighbourhood perception) were not associated with SGA birth. Immigrant density and subjective perceptions of neighbourhood security are associated with SGA birth. Public health strategies to improve fetal growth should target neighbourhoods with low perceived security and high immigrant density.
Diagnostic accuracy of verbal autopsies in ascertaining the causes of stillbirths and neonatal deaths in rural Ghana
Authors: Edmond Karen M. , Quigley Maria A. , Zandoh Charles , Danso Samuel , Hurt Chris , Agyei Seth Owusu , Kirkwood Betty R. 
Published: August 2008

SummaryThis study evaluated the diagnostic accuracy of a verbal autopsy (VA) tool in ascertaining the causes of stillbirths and neonatal deaths in rural Ghana and was nested within a community‐based maternal vitamin A supplementation trial (ObaapaVitA trial). All stillbirths and neonatal deaths between 1 January 2003 and 30 June 2004 were prospectively included. Community VAs were carried out within 6 months of death and were classified with a primary cause of death by three experienced paediatricans. The reference standard diagnosis was obtained by the study paediatrician in 4 district hospitals in the study area.There were 20 317 deliveries, 661 stillbirths and 590 neonatal deaths with a VA diagnosis in the study population. A total of 311 stillbirths and 191 neonatal deaths had both a VA and a hospital reference standard diagnosis. The VA performed poorly for stillbirth diagnoses such as congenital abnormalities and maternal haemorrhage. Accuracy was higher for intrapartum obstetric complications and antepartum maternal disease. For neonatal deaths, sensitivity was >60% for all major causes; specificity was 76% for birth asphyxia but >85% for prematurity and infection. Overall, VA diagnostic accuracy was higher than expected in this rural African setting. Our classification system was based on the expected public health importance of the individual causes of death, differing implications for intervention and the ability to distinguish between the individual causes in low‐resource settings. We believe this system was easier to use than traditional approaches and resulted in high precision and accuracy. However, further simplifications are needed to allow use of the World Health Organisation VA in routine child health programmes. The diagnostic accuracy of the VA tool should also be assessed in other regions and in multicentre studies.
Development of protocols for detection of Colletotrichum acutatum and monitoring of strawberry anthracnose using real‐time PCR
Authors: Garrido C. , Carbú M. , Fernández‐Acero F. J. , Boonham N. , Colyer A. , Cantoral J. M. , Budge G. 
Published: August 2008

Real‐time PCR (TaqMan®) assays were developed for the specific detection and discrimination of Colletotrichum spp., C. acutatum and C. gloeosporioides causing anthracnose in strawberry using the most divergent area of the internal transcribed spacers (ITS1 and ITS2) and 5·8S ribosomal RNA (rRNA) gene region. The specificity of the new assays was tested using DNA from six species of Colletotrichum and nine fungal species commonly found associated with strawberry material, and additionally by comparing the sequences with those from databases using a blast search. The sequences only showed identity with homologous sequences from the desired target organisms. The new assays were 10–100 times more sensitive than conventional PCR methods previously published for the diagnosis of strawberry anthracnose. When real‐time PCR was compared with ELISA methods, PCR improved the sensitivity of the identification by obtaining positive results for samples of strawberry plant material that tested negative with ELISA. The development of C. acutatum was monitored using artificially infected strawberry crowns from two strawberry cultivars (Camarosa and Ventana) and a real‐time PCR assay specific for this species between January and June 2006. The amount of C. acutatum detected using real‐time PCR varied significantly by month (P < 0·001), but not by cultivar (P = 0·394). The new assays were shown to be useful tools for rapid detection and identification of these pathogens and to allow rapid and accurate assessment of the casual agents of anthracnose in strawberry.
A New Strategy to Induce Effective Antitumour Response In Vitro and In Vivo
Authors: Wang M. , Xie Z. , Shi M. , Lu H. , Yu M. , Hu M. , Lu F. , Ma Y. , Shen B. , Guo N. 
Published: August 2008

AbstractTo induce Her2‐specific cell immune response, we used xenogeneic antigen rat neu L2–S2 domains as the vaccine antigen. The antigenic protein was engineered as a chimeric protein with human IgG1 Fc region (neu‐Fc). Neu‐Fc could stimulate the cell proliferation in mixed lymphocyte reaction effectively. Simultaneous neu‐Fc and IFN‐γ stimulation dramatically elevated IL‐12 secretion and reduced IL‐10 production in PBMC. To further augment the activating effects on Th1‐type response, Bacille Calmette–Guerin (BCG) was utilized as a non‐specific stimulus. Neu‐Fc, IFN‐γ and BCG costimulation exhibited the most conspicuous effects on the reversal of the Th1‐type inhibitory effects by MCF‐7 cell supernatant compared with neu‐Fc alone or IFN‐γ and BCG costimulation. The lytic activity of effector cells to Her2 overexpressing cells was greatly promoted by neu‐Fc, IFN‐γ and BCG stimulation simultaneously. Neu‐Fc led to considerable retardation in EMT6/Her2 tumour growth in Balb/c mice. IFN‐γ and BCG efficiently enhanced the antitumour activity. A large amount of inflammatory cells were found to be accumulated in the tumour tissues or surrounded tumours in mice treated with neu‐Fc, IFN‐γ and BCG but no inflammatory cell infiltration was observed in control tumours, indicating that the strategy is potent enough to support the initiation and propagation of tumour‐specific immune response in an established tumour and generate a proinflammatory environment.
The Liver Mediates Apoptotic Cell‐Induced Immune Regulation
Authors: Wang Y. , Gao Y. , Yuan X. , Xia W. , Luo Y. , Sun E. , Chen Z. K. 
Published: August 2008

AbstractAllogeneic apoptotic cells have been demonstrated to induce allograft tolerance, but the mechanisms for this remain unclear. The study presented here investigates organs in which the tolerogenic immune responses may occur. Distribution of live or apoptotic CFSE+ splenocytes in recipients’ organs and phagocytosis by liver antigen‐presenting cells (APC) were investigated by fluorescence microscopy and flow cytometry, and cytokine expression was analysed by Multiplex and ELISA. It was found that allogeneic or autogenic apoptotic cells preferentially accumulated in the liver within 30 min, peaked at 60 min, and disappeared at 12 h after infusion, whereas these cells scarcely appeared in the spleen. The accumulation in the liver was apoptotic cell‐specific as both allogeneic and autogenic live splenocytes were completely deposited in the spleen. Liver phagocytes, including Kupffer cells, liver sinusoidal endothelial cells and dendritic cells, all efficiently phagocytized apoptotic cells in vitro and in vivo. Although a Th1 cytokine profile found both in the spleen and liver in the recipients of allogeneic apoptotic cells, a rapid and consistent Th2 cytokine profile specifically was initiated in the liver. From this, we conclude that liver APC phagocytize donor apoptotic cells and induce liver‐specific Th2 cytokines, which may contribute to the mechanisms of allograft tolerance induced by donor apoptotic cells.