The quantification of mRNA in cerebellum tissue: diagnosis, genotype, methylation and expression

Background: The COMT gene is located on chromosome 22q11, a region strongly implicated in the aetiology of several psychiatric disorders, in particular schizophrenia. Previous research has suggested that activity and expression of COMT is altered in schizophrenia, and is mediated by one or more polymorphisms within the gene, including the functional Val(158)Met polymorphism. Method: In this study we examined the expression levels of COMT mRNA using quantitative RTPCR in 60 post mortem cerebellum samples derived from individuals with schizophrenia, bipolar disorder, depression, and no history of psychopathology. Furthermore, we have examined the methylation status of two CpG sites in the promoter region of the gene. Results: We found no evidence of altered COMT expression or methylation in any of the psychiatric diagnoses examined. We did, however, find evidence to suggest that genotype is related to COMT gene expression, replicating the findings of two previous studies. Specifically, val(158)met (rs165688; Val allele) rs737865 ( G allele) and rs165599 ( G allele) all showed reduced expression ( P <0.05). Finally, we observe a strong sexual dimorphism in COMT expression, with females exhibiting significantly greater levels of COMT mRNA. Conclusion: The expression of COMT does not appear to be altered in the cerebellum of individuals suffering from schizophrenia, bipolar disorder or depression, but does appear to be influenced by single nucleotide polymorphisms within the gen

Resolving the neural circuits of anxiety

Although anxiety disorders represent a major societal problem demanding new therapeutic targets, these efforts have languished in the absence of a mechanistic understanding of this subjective emotional state. While it is impossible to know with certainty the subjective experience of a rodent, rodent models hold promise in dissecting well-conserved limbic circuits. The application of modern approaches in neuroscience has already begun to unmask the neural circuit intricacies underlying anxiety by allowing direct examination of hypotheses drawn from existing psychological concepts. This information points toward an updated conceptual model for what neural circuit perturbations could give rise to pathological anxiety and thereby provides a roadmap for future therapeutic development.National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (NIH Director’s New Innovator Award DP2-DK-102256-01)National Institute of Mental Health (U.S.) (NIH) R01-MH102441-01)JPB Foundatio

Adaptive Management of Riverine Socio-ecological Systems

If ongoing change in ecosystems and society can render inflexible policies obsolete, then management must dynamically adapt as a counter to perennial uncertainty. This chapter describes a general synthesis of how to make decision-making more adaptive and then explores the barriers to learning in management. We then describe how one such process, known as adaptive management (AM), has been applied in different river basins, on which basis we discuss AM’s strengths and limitations in various resource management contexts

Depth-specific fluctuations of gene expression and protein abundance modulate the photophysiology in the seagrass Posidonia oceanica

Here we present the results of a multiple organizational level analysis conceived to identify acclimative/adaptive strategies exhibited by the seagrass Posidonia oceanica to the daily fluctuations in the light environment, at contrasting depths. We assessed changes in photophysiological parameters, leaf respiration, pigments, and protein and mRNA expression levels. The results show that the diel oscillations of P. oceanica photophysiological and respiratory responses were related to transcripts and proteins expression of the genes involved in those processes and that there was a response asynchrony between shallow and deep plants probably caused by the strong differences in the light environment. The photochemical pathway of energy use was more effective in shallow plants due to higher light availability, but these plants needed more investment in photoprotection and photorepair, requiring higher translation and protein synthesis than deep plants. The genetic differentiation between deep and shallow stands suggests the existence of locally adapted genotypes to contrasting light environments. The depth-specific diel rhythms of photosynthetic and respiratory processes, from molecular to physiological levels, must be considered in the management and conservation of these key coastal ecosystems.Portuguese funds from FCT - Foundation for Science and Technology [UID/Multi/04326/2013]; SZN PhD fellowship via the Open University; ESF COST Action Seagrass Productivity: From Genes to Ecosystem Management [ES0906]info:eu-repo/semantics/publishedVersio

Financial difficulties but not other types of recent negative life events show strong interactions with 5-HTTLPR genotype in the development of depressive symptoms

Several studies indicate that 5-HTTLPR mediates the effect of childhood adversity in the development of depression, while results are contradictory for recent negative life events. For childhood adversity the interaction with genotype is strongest for sexual abuse, but not for other types of childhood maltreatment; however, possible interactions with specific recent life events have not been investigated separately. The aim of our study was to investigate the effect of four distinct types of recent life events in the development of depressive symptoms in a large community sample. Interaction between different types of recent life events measured by the List of Threatening Experiences and the 5-HTTLPR genotype on current depression measured by the depression subscale and additional items of the Brief Symptom Inventory was investigated in 2588 subjects in Manchester and Budapest. Only a nominal interaction was found between life events overall and 5-HTTLPR on depression, which failed to survive correction for multiple testing. However, subcategorising life events into four categories showed a robust interaction between financial difficulties and the 5-HTTLPR genotype, and a weaker interaction in the case of illness/injury. No interaction effect for the other two life event categories was present. We investigated a general non-representative sample in a cross-sectional approach. Depressive symptoms and life event evaluations were self-reported. The 5-HTTLPR polymorphism showed a differential interaction pattern with different types of recent life events, with the strongest interaction effects of financial difficulties on depressive symptoms. This specificity of interaction with only particular types of life events may help to explain previous contradictory findings

Analysis of polyethylene wear in plain radiographs: The number of radiographs influences the results

Background and purpose Two-dimensional computerized radiographic techniques are frequently used to measure in vivo polyethylene (PE) wear after total hip arthroplasty (THA), and several variables in the clinical set-up may influence the amount of wear that is measured. We compared the repeatability and concurrent validity of linear PE wear on plain radiographs using the same software but a different number of radiographs

Reviewing The Benefits of Health Workforce Stability

This paper examines the issue of workforce stability and turnover in the context of policy attempts to improve retention of health workers. The paper argues that there are significant benefits to supporting policy makers and managers to develop a broader perspective of workforce stability and methods of monitoring it. The objective of the paper is to contribute to developing a better understanding of workforce stability as a major aspect of the overall policy goal of improved retention of health workers. The paper examines some of the limited research on the complex interaction between staff turnover and organisational performance or quality of care in the health sector, provides details and examples of the measurement of staff turnover and stability, and illustrates an approach to costing staff turnover. The paper concludes by advocating that these types of assessment can be valuable to managers and policy makers as they examine which policies may be effective in improving stability and retention, by reducing turnover. They can also be used as part of advocacy for the use of new retention measures. The very action of setting up a local working group to assess the costs of turnover can in itself give managers and staff a greater insight into the negative impacts of turnover, and can encourage them to work together to identify and implement stability measures

Prospective object search in dogs: mixed evidence for knowledge of What and Where

We investigated whether two dogs that had been specially trained to retrieve objects by their names were able to integrate information about the identity (What) as well as the location (Where) of those objects so that they could plan their search accordingly. In a first study, two sets of objects were placed in two separate rooms and subjects were asked to retrieve the objects, one after the other. Both dogs remembered the identity of the objects as they reliably retrieved the correct objects. One of the dogs was also able to integrate information about the object’s location as he chose the correct location in which the object had been placed. Further investigation of the second dog’s behavior revealed that she followed a more stereotyped search strategy. Despite this variation in performance, this study provides evidence for the memory of What and Where in a domestic dog and shows the prospective use of such information in a search task

Polymorphisms in the bovine HSP90AB1 gene are associated with heat tolerance in Thai indigenous cattle

Heat shock proteins act as molecular chaperones that have preferentially been transcribed in response to severe perturbations of the cellular homeostasis such as heat stress. Here the traits respiration rate (RR), rectal temperature (RT), pack cell volume (PCV) and the individual heat tolerance coefficient (HTC) were recorded as physiological responses on heat stress (environmental temperatures) in Bos taurus (crossbred Holstein Friesian; HF) and B. indicus (Thai native cattle: White Lamphun; WL and Mountain cattle; MT) animals (n = 47) in Thailand. Polymorphisms of the heat shock protein 90-kDa beta gene (HSP90AB1) were evaluated by comparative sequencing. Nine single nucleotide polymorphisms (SNP) were identified, i.e. three in exons 10 and 11, five in introns 8, 9, 10 and 11, and one in the 3′UTR. The exon 11 SNP g.5082C>T led to a missense mutation (alanine to valine). During the period of extreme heat (in the afternoon) RR and RT were elevated in each of the three breeds, whereas the PCV decreased. Mountain cattle and White Lamphun heifers recorded significantly better physiologic parameters (p < 0.05) in all traits considered, including or particularly HTC than Holstein Friesian heifers. The association analysis revealed that the T allele at SNP g.4338T>C within intron 3 improved the heat tolerance (p < 0.05). Allele T was exclusively found in White Lamphun animals and to 84% in Mountain cattle. Holstein Friesian heifers revealed an allele frequency of only 18%. Polymorphisms within HSP90AB1 were not causative for the physiological responses; however, we propose that they should at least be used as genetic markers to select appropriate breeds for hot climates

RTN4IP1 is required for the final stages of mitochondrial complex I assembly and CoQ biosynthesis

\ua9 The Author(s) 2025.A biochemical deficiency of mitochondrial complex I (CI) underlies approximately 30% of cases of primary mitochondrial disease, yet the inventory of molecular machinery required for CI assembly remains incomplete. We previously characterised patients with isolated CI deficiency caused by segregating variants in RTN4IP1, a gene that encodes a mitochondrial NAD(P)H oxidoreductase. Here, we demonstrate that RTN4IP1 deficiency causes a CI assembly defect in both patient fibroblasts and knockout cells, and report that RTN4IP1 is a bona fide CI assembly factor. Complexome profiling revealed accumulation of unincorporated ND5-module and impaired N-module production. RTN4IP1 patient fibroblasts also exhibited defective coenzyme Q biosynthesis, substantiating a second function of RTN4IP1. Thus, our data reveal RTN4IP1 plays necessary and independent roles in both the terminal stages of CI assembly and in coenzyme Q metabolism, and that pathogenic RTN4IP1 variants impair both functions in patients with mitochondrial disease