BABEL3&3a : Crustal-Scale Structures of the Precambrian Svecofennian Accretionary Orogen in the Fennoscandian Shield

obs typo in the title: The title will be changed to FIRE3&3A: Crustal-Scale Structures of the Precambrian Svecofennian Accretionary Orogen in the Fennoscandian Shield. in the second printed version.Peer reviewe

The demonstration of a herpesvirus, related to bovine herpesvirus 1, in reindeer with ulcerative and necrotizing lesions of the upper alimentary tract and nose

In 11 male reindeer, all esposed to transportation stress, signs of conjunctivitis and later on ulcerative and necrotizing lesions of the mucosa of the nostrils and mouth were recorded. Blood and secretions from the nose were sampled. Antibodies to bovine herpesvirus 1 (BHV-1) were detected in 2 animals. No animal had antibodies to bovine viral diarrhoea virus (BVDV). Virus isolation was negative. The sampling was repeated 2 weeks later and complemented with biopsies from the mouth lesions, fixed in formalin. At this occasion 3 animals were seropositive to BHV-1 and in biopsies from 2 of these intranuclear herpesvirus-like particles were found by means of electron microscopy. Four animals, 3 of them seropositive, were treated with cortison during 8 days. The size of the ulcers in the mouth increased in all animals. A herpesvirus was isolated from 3 of them at 10 different occasions. The ultrastructural investigation of the virus suspension demonstrated the presence of typical herpesvirus particles. On day 11 all 4 animals suffered from a severe diarrhoea and anorexia. On day 12 one animal died and on day 13 post challenge with cortison two additional animals died. The remaining animal was slaughtered on day 13. Bacteriological investigation revealed growth of Fusobacterium necrophorum from the spleen and oral wounds of all 4 animals. The animals were obviously subjected to an infection with a herpesvirus colsely related to BHV-1. Virus could be liberated by cortison treatment. It is possible that infections with the found herpesvirus, and the lesions caused by it, may be the background to earlier recorded severe outbreaks of necrobacillosis of the alimentary tract in reindeer herds

Survival Analysis and Cox Proportional Hazards Model Reporting in Pediatric Leukemia Studies : a Systematic Review

Survival (overall, event free, etc.) is the most-used outcome in clinical oncology studies. This study analyzed methodological reporting of survival analysis in pediatric leukemia studies, focusing on Cox proportional hazards (PH). We performed a systematic review of studies published between 2012 and 2021 in the five highest-ranking oncology and five highest-ranking hematology journals. The included studies had to focus on pediatric leukemia and utilize survival analyses. We extracted data on how the survival analysis methodology was reported and focused on Cox proportional hazards modeling and whether the PH assumption was checked. We screened 561 studies and included 103 in the analysis. The most-used crude survival analysis method was Kaplan–Meier, as 96 (94%) of the 103 studies applied it. Adjusted survival analysis was performed in 80 (78%) of the included studies, and the Cox PH model was used in 77 (96%) of these studies. The PH assumption was mentioned in 18 (23%) of the 77 studies that used the Cox PH model. Only nine studies (12%) stated how the PH assumption was assessed. We noted 10 (13%) studies with possible violations of the PH assumption. Overall, we found a need for improvement in the reporting of survival analysis and especially PH assumption in pediatric leukemia studies. The Cox PH model was the most-used adjusted survival analysis method but checking of the background assumption was not reported in most of the studies.publishedVersionPeer reviewe

Discovery of Sexual Dimorphisms in Metabolic and Genetic Biomarkers

Metabolomic profiling and the integration of whole-genome genetic association data has proven to be a powerful tool to comprehensively explore gene regulatory networks and to investigate the effects of genetic variation at the molecular level. Serum metabolite concentrations allow a direct readout of biological processes, and association of specific metabolomic signatures with complex diseases such as Alzheimer's disease and cardiovascular and metabolic disorders has been shown. There are well-known correlations between sex and the incidence, prevalence, age of onset, symptoms, and severity of a disease, as well as the reaction to drugs. However, most of the studies published so far did not consider the role of sexual dimorphism and did not analyse their data stratified by gender. This study investigated sex-specific differences of serum metabolite concentrations and their underlying genetic determination. For discovery and replication we used more than 3,300 independent individuals from KORA F3 and F4 with metabolite measurements of 131 metabolites, including amino acids, phosphatidylcholines, sphingomyelins, acylcarnitines, and C6-sugars. A linear regression approach revealed significant concentration differences between males and females for 102 out of 131 metabolites (p-values<3.8 x 10(-4); Bonferroni-corrected threshold). Sex-specific genome-wide association studies (GWAS) showed genome-wide significant differences in beta-estimates for SNPs in the CPS1 locus (carbamoyl-phosphate synthase 1, significance level: p<3.8 x 10(-10); Bonferroni-corrected threshold) for glycine. We showed that the metabolite profiles of males and females are significantly different and, furthermore, that specific genetic variants in metabolism-related genes depict sexual dimorphism. Our study provides new important insights into sex-specific differences of cell regulatory processes and underscores that studies should consider sex-specific effects in design and interpretation

Non-Sterilized Fermentative Production of Polymer-Grade L-Lactic Acid by a Newly Isolated Thermophilic Strain Bacillus sp. 2–6

-lactic acid is another limitation for PLA polymers to compete with conventional plastics.-lactic acid concentration of 182.0 g/liter was obtained from 30-liter fed-batch fermentation with an average productivity of 3.03 g/liter/h and product optical purity of 99.4%.-lactic acid production from renewable resources

Psychiatric (Axis I) and personality (Axis II) disorders and subjective psychiatric symptoms in chronic tinnitus

Objective: Chronic tinnitus has been associated with several psychiatric disorders. Only few studies have investigated these disorders using validated diagnostic interviews. The aims were to diagnose psychiatric and personality disorders with structured interviews, to assess self-rated psychiatric symptoms and elucidate temporal relations between psychiatric disorders and tinnitus. Design: Current and lifetime DSM-IV diagnoses of axis-I (psychiatric disorders) and axis-II (personality disorders) were assessed using structured clinical interviews (SCID-I and -II). Current subjective psychiatric symptoms were evaluated via self-rating instruments: the Symptom Check List-90 (SCL-90), the Beck Depression Inventory, and the Dissociative Experiences Scale (DES). Study sample: 83 patients (mean age 51.7, 59% men) with chronic, disturbing tinnitus and a median Tinnitus Handicap Inventory score of 32. Results: The rates of lifetime and current major depression were 26.5% and 2.4%. The lifetime rate of obsessive-compulsive personality disorder (type C) was 8.4%. None of the patients had cluster B personality disorder or psychotic symptoms. The SCL-90 subscales did not differ from the general population, and median DES score was low, 2.4. Conclusions: Tinnitus patients are prone to episodes of major depression and often also have obsessive-compulsive personality features. Psychiatric disorders seem to be comorbid or predisposing conditions rather than consequences of tinnitus.Clinical trial reference: ClinicalTrials.gov (ID NCT 01929837).</p

Mutation screening of the RNF8, UBC13 and MMS2 genes in Northern Finnish breast cancer families

<p>Abstract</p> <p>Background</p> <p>Currently known susceptibility genes such as <it>BRCA1 </it>and <it>BRCA2 </it>explain less than 25% of familial aggregation of breast cancer, which suggests the involvement of additional susceptibility genes. RNF8, UBC13 and MMS2 are involved in the DNA damage response pathway and play important roles in BRCA1-mediated DNA damage recognition. Based on the evidence that several players in the ubiquitin-mediated BRCA1-dependent DDR seem to contribute to breast cancer predisposition, <it>RNF8, UBC13 </it>and <it>MMS2 </it>were considered plausible candidate genes for susceptibility to breast cancer.</p> <p>Methods</p> <p>The entire coding region and splice junctions of <it>RNF8, UBC13 </it>and <it>MMS2 </it>genes were screened for mutations in affected index cases from 123 Northern Finnish breast cancer families by using conformation sensitive gel electrophoresis, high resolution melting (HRM) analysis and direct sequencing.</p> <p>Results</p> <p>Mutation analysis revealed several changes in <it>RNF8 </it>and <it>UBC13</it>, whereas no aberrations were observed in <it>MMS2</it>. None of the found sequence changes appeared to associate with breast cancer susceptibility.</p> <p>Conclusions</p> <p>The present data suggest that mutations in <it>RNF8, UBC13 </it>and <it>MMS2 </it>genes unlikely make any sizeable contribution to breast cancer predisposition in Northern Finland.</p

Secretor Genotype (FUT2 gene) Is Strongly Associated with the Composition of Bifidobacteria in the Human Intestine

Intestinal microbiota plays an important role in human health, and its composition is determined by several factors, such as diet and host genotype. However, thus far it has remained unknown which host genes are determinants for the microbiota composition. We studied the diversity and abundance of dominant bacteria and bifidobacteria from the faecal samples of 71 healthy individuals. In this cohort, 14 were non-secretor individuals and the remainders were secretors. The secretor status is defined by the expression of the ABH and Lewis histo-blood group antigens in the intestinal mucus and other secretions. It is determined by fucosyltransferase 2 enzyme, encoded by the FUT2 gene. Non-functional enzyme resulting from a nonsense mutation in the FUT2 gene leads to the non-secretor phenotype. PCR-DGGE and qPCR methods were applied for the intestinal microbiota analysis. Principal component analysis of bifidobacterial DGGE profiles showed that the samples of non-secretor individuals formed a separate cluster within the secretor samples. Moreover, bifidobacterial diversity (p<0.0001), richness (p<0.0003), and abundance (p<0.05) were significantly reduced in the samples from the non-secretor individuals as compared with those from the secretor individuals. The non-secretor individuals lacked, or were rarely colonized by, several genotypes related to B. bifidum, B. adolescentis and B. catenulatum/pseudocatenulatum. In contrast to bifidobacteria, several bacterial genotypes were more common and the richness (p<0.04) of dominant bacteria as detected by PCR-DGGE was higher in the non-secretor individuals than in the secretor individuals. We showed that the diversity and composition of the human bifidobacterial population is strongly associated with the histo-blood group ABH secretor/non-secretor status, which consequently appears to be one of the host genetic determinants for the composition of the intestinal microbiota. This association can be explained by the difference between the secretor and non-secretor individuals in their expression of ABH and Lewis glycan epitopes in the mucosa

Metabolic Regulation in Progression to Autoimmune Diabetes

Recent evidence from serum metabolomics indicates that specific metabolic disturbances precede β-cell autoimmunity in humans and can be used to identify those children who subsequently progress to type 1 diabetes. The mechanisms behind these disturbances are unknown. Here we show the specificity of the pre-autoimmune metabolic changes, as indicated by their conservation in a murine model of type 1 diabetes. We performed a study in non-obese prediabetic (NOD) mice which recapitulated the design of the human study and derived the metabolic states from longitudinal lipidomics data. We show that female NOD mice who later progress to autoimmune diabetes exhibit the same lipidomic pattern as prediabetic children. These metabolic changes are accompanied by enhanced glucose-stimulated insulin secretion, normoglycemia, upregulation of insulinotropic amino acids in islets, elevated plasma leptin and adiponectin, and diminished gut microbial diversity of the Clostridium leptum group. Together, the findings indicate that autoimmune diabetes is preceded by a state of increased metabolic demands on the islets resulting in elevated insulin secretion and suggest alternative metabolic related pathways as therapeutic targets to prevent diabetes