Structural architecture supports functional organization in the human aging brain at a regionwise and network level

Functional interactions in the brain are constrained by the underlying anatomical architecture, and structural and functional networks share network features such as modularity. Accordingly, age‐related changes of structural connectivity (SC) may be paralleled by changes in functional connectivity (FC). We provide a detailed qualitative and quantitative characterization of the SC–FC coupling in human aging as inferred from resting‐state blood oxygen‐level dependent functional magnetic resonance imaging and diffusion‐weighted imaging in a sample of 47 adults with an age range of 18–82. We revealed that SC and FC decrease with age across most parts of the brain and there is a distinct age‐dependency of regionwise SC–FC coupling and network‐level SC–FC relations. A specific pattern of SC–FC coupling predicts age more reliably than does regionwise SC or FC alone (r = 0.73, 95% CI = [0.7093, 0.8522]). Hence, our data propose that regionwise SC–FC coupling can be used to characterize brain changes in aging. Hum Brain Mapp 37:2645–2661, 2016. © 2016 Wiley Periodicals, Inc.     

Mutation in the Hepatitis E Virus Polymerase and Outcome of Ribavirin Therapy

Hepatitis E virus (HEV) can lead to chronic infection in solid-organ transplant patients. Ribavirin is efficient for treatment of chronically infected patients. Recently, the1634R mutation in the HEV polymerase has been associated with treatment failure. However, it is unclear if this mutation can be used as a prognostic marker of treatment outcome. We studied the prevalence of the 1634R mutation in the HEV polymerase of patients starting ribavirin therapy, the influence of the 1634R variants on the viral response, the frequency of the 1634R mutation in patients whose treatment failed, and its impact on ribavirin retreatment. We analyzed pretreatment samples from 63 solid-organ transplant patients with chronic hepatitis E using deep sequencing; 42 patients had a sustained virologic response (SVR), and 21 were non-SVR patients. We detected the 1634R variant by deep sequencing in 36.5% (23/63) of the patients (proportions, 1.3 to 100%). The 1634R variant was detected in 31.0% (13/42) of baseline plasma samples from patients with SVR and in 47.6% (10/21) in the other patients (P = 0.2). The presence of this mutation did not influence the initial decrease in viral RNA. Lastly, a second prolonged ribavirin treatment led to SVR in 70% of the patients who initially did not have SVR, despite the presence of the 1634R variant. We conclude that the presence of the 1634R variant at ribavirin initiation does not lead to absolute ribavirin resistance. Although its proportion increased in patients whose treatment failed, the presence of the 1634R variant did not compromise the response to a second ribavirin treatment.     

Always Approach the Bright Side of Life: A General Positivity Training Reduces Stress Reactions in Vulnerable Individuals

Emotional disorders are characterized by cognitive biases towards negative stimuli, and a lack of biases towards positive ones. Therefore, we developed a cognitive bias modification training, modifying approach-avoidance tendencies to diverse emotional pictures. In Study 1, a negative training (pull negative, push positive pictures) was compared to a positive training (vice versa) in 141 students. The pre-existing positivity bias remained after positive training, but reversed into a negativity bias after negative training. This effect transferred to an attentional bias. The training affected neither mood nor emotional vulnerability to stress. In Study 2, we investigated the effects of the positive training in 102 dysphoric and non-dysphoric students, all in a sad mood state. Compared to placebo training, the positive training strengthened a positivity bias, and it reduced emotional vulnerability in dysphoric students. This suggests potential therapeutic value of the training, but further studies are needed.     

Spontaneous hemolytic activity of rat alveolar lining material

During assays of the complement hemolytic activity in lavage fluids (LF) from humans and various laboratory animals (hamsters, rabbits, rats, guinea pigs), we have observed that rat bronchoalveolar lavages had a spontaneous, complement-independent, hemolytic activity to sheep red blood cells (SRBC). Rat lavage fluids were able to lyse sheep and autologous red blood cells at 2°C as well as at 37°C. Together with these observations, the inverse relationship that existed between the LF hemolytic activity and the calcium concentration in the incubation medium suggested that lysis could be due to the presence of large amounts of lysophospholipids in rat lavage fluid. However, thin layer chromatography did not reveal any abnormal amount in lysoderivative, whereas the free fatty acid (FFA) content was very high. Pure palmitic acid, at a concentration similar to that observed in LF from rat, was able to lyse SRBC (8.5μg lyzed 50% of 10⁸ SRBC); its lytic activity decreased when Ca⁺⁺ or bovine serum albumin was added to the incubation mixture. FFA through their detergent effect, appear to account for the hemolytic activity of the rat alveolar lining material.     

Genetic diversity of perch rhabdoviruses isolates based on the nucleoprotein and glycoprotein genes

Despite the increasing impact of rhabdoviruses in European percid farming, the diversity of the viral populations is still poorly investigated. To address this issue, we sequenced the partial nucleoprotein (N) and complete glycoprotein (G) genes of nine rhabdoviruses isolated from perch (Perca fluviatilis) between 1999 and 2010, mostly from France, and analyzed six of them by immunofluorescence antibody test (IFAT). Using two rabbit antisera raised against either the reference perch rhabdovirus (PRhV) isolated in 1980 or the perch isolate R6146, two serogroups were distinguished. Meanwhile, based on partial N and complete G gene analysis, perch rhabdoviruses were divided into four genogroups, A-B-D and E, with a maximum of 32.9% divergence (G gene) between isolates. A comparison of the G amino acid sequences of isolates from the two identified serogroups revealed several variable regions that might account for antigenic differences. Comparative analysis of perch isolates with other rhabdoviruses isolated from black bass, pike-perch and pike showed some strong phylogenetic relationships, suggesting cross-host transmission. Similarly, striking genetic similarities were shown between perch rhabdoviruses and isolates from other European countries and various ecological niches, most likely reflecting the circulation of viruses through fish trade as well as putative transfers from marine to freshwater fish. Phylogenetic relationships of the newly characterized viruses were also determined within the family Rhabdoviridae. The analysis revealed a genetic cluster containing only fish viruses, including all rhabdoviruses from perch, as well as siniperca chuatsi rhabdovirus (SCRV) and eel virus X (EVEX). This cluster was distinct from the one represented by spring viraemia of carp vesiculovirus (SVCV), pike fry rhabdovirus (PFRV) and mammalian vesiculoviruses. The new genetic data provided in the present study shed light on the diversity of rhabdoviruses infecting perch in France and support the hypothesis of circulation of these viruses between other hosts and regions within Europe.     

Ascorbic acid inhibits PMP22 expression by reducing cAMP levels

Charcot-Marie-Tooth [CMT] syndrome is the most common hereditary peripheral neuropathy. CMT1A, which accounts for 50% of all CMT cases, usually results from triploidy of the PMP22 gene. Preclinical trials using an animal model show that disabled mice force-fed with high doses of ascorbic acid partially recover muscular strength after a few months of treatment, and suggest that high doses of ascorbic acid repress PMP22 expression. In this study, we demonstrated that ascorbic acid represses PMP22 gene expression by acting on intracellular cAMP levels and adenylate cyclase activity. This action is dose dependent and specific to ascorbic acid, since repression is not observed after treatment with other antioxidants. The new properties of ascorbic acid are discussed, along with the implications of these findings for CMT disease treatment.     

A functional polymorphism of the mu-opioid receptor gene (OPRM1) influences cue-induced craving for alcohol in male heavy drinkers

BACKGROUND: The mu-opioid receptor gene (OPRM1) codes for the mu-opioid receptor, which binds beta-endorphin. The A118G polymorphism in this gene affects beta-endorphin binding such that the Asp40 variant (G allele) binds beta-endorphin 3 times more tightly than the more common Asn40 variant (A allele). This study investigated the influence of the A118G polymorphism on cue reactivity after exposure to an alcoholic beverage in male heavy drinkers. METHODS: Participants were either homozygous for the A allele (n=84) or carrying at least 1 copy of the G allele (n=24). All participants took part in a cue-reactivity paradigm where they were exposed to water and beer in 3-minute trials. The dependent variables of main interest were subjective craving for alcohol, subjective arousal, and saliva production. RESULTS: G allele carriers reported significantly more craving for alcohol than the A allele participants (as indicated by the within-subject difference in craving after beer vs after water exposure). No differences were found for subjective arousal and saliva. Both groups did not differ in family history of alcoholism. Participants with the G allele reported a significantly higher lifetime prevalence of drug use than participants homozygous for the A allele. CONCLUSIONS: A stronger urge to drink alcohol after exposure to an alcoholic beverage might contribute to a heightened risk for developing alcohol-related problems in individuals with a copy of the G allele. The G allele might also predispose to drug use in general.