Marine climate change risks to biodiversity and society in the ROPME Sea Area

The subtropical ROPME Sea Area (RSA), comprising the Gulf, the Gulf of Oman and the northern Arabian Sea, is a heavily exploited sea region that experiences extreme environmental conditions, and for which climate change is expected to further impact marine ecosystems and coastal communities, sectors and industries. Climate change risk assessments provide a valuable tool to inform decision-making and adaptation planning through identifying and prioritising climate risks and/or opportunities. Using the first UK Climate Change Risk Assessment as an example, a marine climate change risk assessment was undertaken for the marine and coastal environment of the RSA for the first time. Through an extensive literature review and a workshop involving regional experts, marine and coastal climate change risks were identified, scored and prioritised. A total of 45 risks were identified, which spanned two key themes: ‘Risks to Biodiversity’ and ‘Risks to Economy and Society’. Of these, 13 were categorised as ‘severe’, including degradation of coral reefs and their associated ecological assemblages, shifts in the distribution of wild-capture fisheries resources, changes to phytoplankton primary productivity, impacts on coastal communities, threats to infrastructure and industries, and impacts on operations and safety in maritime transport. The diversity of risks identified and their transboundary nature highlight that climate change adaptation responses will require coordinated action and cooperation at multiple scales across the RSA. This risk assessment provides a crucial baseline for a largely overlooked geographic area, that can be used to underpin future decision-making and adaptation planning on climate change, and serve as a ‘blueprint’ for similar assessments for other regional shared seas

Exome-wide Rare Variant Analysis Identifies TUBA4A Mutations Associated with Familial ALS

Exome sequencing is an effective strategy for identifying human disease genes. However, this methodology is difficult in late-onset diseases where limited availability of DNA from informative family members prohibits comprehensive segregation analysis. To overcome this limitation, we performed an exome-wide rare variant burden analysis of 363 index cases with familial ALS (FALS). The results revealed an excess of patient variants within TUBA4A, the gene encoding the Tubulin, Alpha 4A protein. Analysis of a further 272 FALS cases and 5,510 internal controls confirmed the overrepresentation as statistically significant and replicable. Functional analyses revealed that TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability. These results further emphasize the role of cytoskeletal defects in ALS and demonstrate the power of gene-based rare variant analyses in situations where causal genes cannot be identified through traditional segregation analysis

Dominant Cone-Rod Dystrophy: A Mouse Model Generated by Gene Targeting of the GCAP1/Guca1a Gene

Cone dystrophy 3 (COD3) is a severe dominantly inherited retinal degeneration caused by missense mutations in GUCA1A, the gene encoding Guanylate Cyclase Activating Protein 1 (GCAP1). The role of GCAP1 in controlling cyclic nucleotide levels in photoreceptors has largely been elucidated using knock-out mice, but the disease pathology in these mice cannot be extrapolated directly to COD3 as this involves altered, rather than loss of, GCAP1 function. Therefore, in order to evaluate the pathology of this dominant disorder, we have introduced a point mutation into the murine Guca1a gene that causes an E155G amino acid substitution; this is one of the disease-causing mutations found in COD3 patients. Disease progression in this novel mouse model of cone dystrophy was determined by a variety of techniques including electroretinography (ERG), retinal histology, immunohistochemistry and measurement of cGMP levels. It was established that although retinal development was normal up to 3 months of age, there was a subsequent progressive decline in retinal function, with a far greater alteration in cone than rod responses, associated with a corresponding loss of photoreceptors. In addition, we have demonstrated that accumulation of cyclic GMP precedes the observed retinal degeneration and is likely to contribute to the disease mechanism. Importantly, this knock-in mutant mouse has many features in common with the human disease, thereby making it an excellent model to further probe disease pathogenesis and investigate therapeutic interventions

Do we have any solid evidence of clinical utility about the pathophysiology of schizophrenia?

A diagnosis of schizophrenia, as in most of psychiatric practice, is made largely by eliciting symptoms with reference to subjective, albeit operationalized, criteria. This diagnosis then provides some rationale for management. Objective diagnostic and therapeutic tests are much more desirable, provided they are reliably measured and interpreted. Definite advances have been made in our understanding of schizophrenia in recent decades, but there has been little consideration of how this information could be used in clinical practice. We review here the potential utility of the strongest and best replicated risk factors for and manifestations of schizophrenia within clinical, epidemiological, cognitive, blood biomarker and neuroimaging domains. We place particular emphasis on the sensitivity, specificity and predictive power of pathophysiological indices for making a diagnosis, establishing an early diagnosis or predicting treatment response in schizophrenia. We conclude that a number of measures currently available have the potential to increase the rigour of clinical assessments in schizophrenia. We propose that the time has come to more fully evaluate these and other well replicated abnormalities as objective potential diagnostic and prognostic guides, and to steer future clinical, therapeutic and nosological research in this direction

Delta-9-tetrahydrocannabinol, neural oscillations above 20 Hz and induced acute psychosis

Rationale: An acute challenge with delta-9-tetrahydrocannabinol (THC) can induce psychotic symptoms including delusions. High electroencephalography (EEG) frequencies, above 20 Hz, have previously been implicated in psychosis and schizophrenia. Objectives: The objective of this study is to determine the effect of intravenous THC compared to placebo on high-frequency EEG. Methods: A double-blind cross-over study design was used. In the resting state, the high-beta to low-gamma magnitude (21–45 Hz) was investigated (n=13 pairs+4 THC only). Also, the event-related synchronisation (ERS) of motor-associated high gamma was studied using a self-paced button press task (n=15). Results: In the resting state, there was a significant condition × frequency interaction (p=0.00017), consisting of a shift towards higher frequencies under THC conditions (reduced high beta [21–27 Hz] and increased low gamma [27–45 Hz]). There was also a condition × frequency × location interaction (p=0.006), such that the reduction in 21–27-Hz magnitude tended to be more prominent in anterior regions, whilst posterior areas tended to show greater 27–45-Hz increases. This effect was correlated with positive symptoms, as assessed on the Positive and Negative Syndrome Scale (PANSS) (r=0.429, p=0.042). In the motor task, there was a main effect of THC to increase 65–130-Hz ERS (p=0.035) over contra-lateral sensorimotor areas, which was driven by increased magnitude in the higher, 85–130-Hz band (p=0.02) and not the 65–85-Hz band. Conclusions: The THC-induced shift to faster gamma oscillations may represent an over-activation of the cortex, possibly related to saliency misattribution in the delusional state

Cross-tolerance to abiotic stresses in halophytes: Application for phytoremediation of organic pollutants

International audienceHalopytes are plants able to tolerate high salt concentrations but no clear definition was retained for them. In literature, there are more studies that showed salt-enhanced tolerance to other abiotic stresses compared to investigations that found enhanced salt tolerance by other abiotic stresses in halophytes. The phenomenon by which a plant resistance to a stress induces resistance to another is referred to as cross-tolerance. In this work, we reviewed cross-tolerance in halophytes at the physiological, biochemical, and molecular levels. A special attention was accorded to the cross-tolerance between salinity and organic pollutants that could allow halophytes a higher potential of xenobiotic phytoremediation in comparison with glycophytes