Neurons have a constantly high glucose demand, and unlike muscle cells they cannot accommodate episodic glucose uptake under the influence of insulin. Neuronal glucose uptake depends on the ...extracellular concentration of glucose, and cellular damage can ensue after persistent episodes of hyperglycaemia--a phenomenon referred to as glucose neurotoxicity. This article reviews the pathophysiological manifestation of raised glucose in neurons and how this can explain the major components of diabetic neuropathy.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Objective
The aim of the current research was to identify the extent to which reward sensitivity and impulsivity were related to food addiction.
Method
Forty‐five studies, published from 2009 to June ...2019, investigating reward sensitivity and/or impulsivity with food addiction as measured by the Yale Food Addiction Scale were reviewed.
Results
Reward sensitivity, as measured by the Sensitivity to Reward (SR) scale, was positively associated with food addiction in two studies, but failed to yield consistent results in other studies when measured with the Behavioral Inhibition/Behavioral Activation Scales. Self‐report impulsivity, as measured by the Barratt Impulsiveness Scale (BIS‐11), was consistently associated with food addiction, with attentional impulsivity and motor impulsivity the most consistent subscales. Similarly, food addiction was also consistently associated with Negative Urgency, Positive Urgency, and Lack of Perseverance as measured by the UPPS‐P Impulsive Behavior Scale. Food addiction was inconsistently associated with disinhibition, as measured by behavioral tasks, indicating food addiction appears more aligned with self‐report measures of impulsivity.
Conclusions
Research in this field is dominated by university student, overweight and obese samples. Additional research is required to further tease out these relationships.
Introduction
The human genome-scale metabolic reconstruction details all known metabolic reactions occurring in humans, and thereby holds substantial promise for studying complex diseases and ...phenotypes. Capturing the whole human metabolic reconstruction is an on-going task and since the last community effort generated a consensus reconstruction, several updates have been developed.
Objectives
We report a new consensus version, Recon 2.2, which integrates various alternative versions with significant additional updates. In addition to re-establishing a consensus reconstruction, further key objectives included providing more comprehensive annotation of metabolites and genes, ensuring full mass and charge balance in all reactions, and developing a model that correctly predicts ATP production on a range of carbon sources.
Methods
Recon 2.2 has been developed through a combination of manual curation and automated error checking. Specific and significant manual updates include a respecification of fatty acid metabolism, oxidative phosphorylation and a coupling of the electron transport chain to ATP synthase activity. All metabolites have definitive chemical formulae and charges specified, and these are used to ensure full mass and charge reaction balancing through an automated linear programming approach. Additionally, improved integration with transcriptomics and proteomics data has been facilitated with the updated curation of relationships between genes, proteins and reactions.
Results
Recon 2.2 now represents the most predictive model of human metabolism to date as demonstrated here. Extensive manual curation has increased the reconstruction size to 5324 metabolites, 7785 reactions and 1675 associated genes, which now are mapped to a single standard. The focus upon mass and charge balancing of all reactions, along with better representation of energy generation, has produced a flux model that correctly predicts ATP yield on different carbon sources.
Conclusion
Through these updates we have achieved the most complete and best annotated consensus human metabolic reconstruction available, thereby increasing the ability of this resource to provide novel insights into normal and disease states in human. The model is freely available from the Biomodels database (
http://identifiers.org/biomodels.db/MODEL1603150001
).
Analysis of global microRNA (miRNA) expression in postmortem cortical grey matter from the superior temporal gyrus, revealed significant up-regulation of miR-181b expression in schizophrenia. This ...finding was supported by quantitative real-time RT–PCR analysis of miRNA expression in a cohort of 21 matched pairs of schizophrenia and non-psychiatric controls. The implications of this finding are substantial, as this miRNA is predicted to regulate many target genes with potential significance to the development of schizophrenia. They include the calcium sensor gene visinin-like 1 (VSNL1) and the ionotropic AMPA glutamate receptor subunit (GRIA2), which were found to be down-regulated in the same cortical tissue from the schizophrenia group. Both of these genes were also suppressed in miR-181b transfected cells and shown to contain functional miR-181b miRNA recognition elements by reporter gene assay. This study suggests altered miRNA levels could be a significant factor in the dysregulation of cortical gene expression in schizophrenia.
Abstract Peripheral blood mononuclear cells (PBMCs) represent an accessible tissue source for gene expression profiling in schizophrenia that could provide insight into the molecular basis of the ...disorder. This study used the Illumina HT_12 microarray platform and quantitative real time PCR (QPCR) to perform mRNA expression profiling on 114 patients with schizophrenia or schizoaffective disorder and 80 non-psychiatric controls from the Australian Schizophrenia Research Bank (ASRB). Differential expression analysis revealed altered expression of 164 genes (59 up-regulated and 105 down-regulated) in the PBMCs from patients with schizophrenia compared to controls. Bioinformatic analysis indicated significant enrichment of differentially expressed genes known to be involved or associated with immune function and regulating the immune response. The differential expression of 6 genes, EIF2C2 ( Ago 2 ), MEF2D , EVL , PI3 , S100A12 and DEFA4 was confirmed by QPCR. Genome-wide expression analysis of PBMCs from individuals with schizophrenia was characterized by the alteration of genes with immune system function, supporting the hypothesis that the disorder has a significant immunological component in its etiology.
ObjectivesThe aim of this study was to explore the barriers and facilitators faced by clinical academics (CAs) in the Greater Manchester region, with particular attention to the experiences of ...minoritised groups.DesignA qualitative study using semistructured interviews and focus groups was conducted. A reflexive thematic analysis was applied to identify key themes.SettingUniversity of Manchester and National Health Service Trusts in the Greater Manchester region.ParticipantsThe sample of this study was composed of 43 participants, including CAs, senior stakeholders, clinicians and medical and dental students.ResultsSix themes were identified. CAs face several barriers and facilitators, some of which—(1) funding insecurity and (2) high workload between the clinic and academia—are common to all the CAs. Other barriers, including (3) discrimination that translates into struggles with self-worth and feeling of not belonging, (4) being or being perceived as foreign and (5) unequal distribution of care duties, particularly affect people from minoritised groups. In contrast, (6) mentorship was commonly identified as one of the most important facilitators.ConclusionsCultural and structural interventions are needed, such as introducing financial support for early career CAs and intercalating healthcare students to promote wider social and cultural change and increase the feelings of belonging and representation across the entire CA pipeline.
High glucose levels in the peripheral nervous system (PNS) have been implicated in the pathogenesis of diabetic neuropathy (DN). However, our understanding of the molecular mechanisms that cause the ...marked distal pathology is incomplete. We performed a comprehensive, system-wide analysis of the PNS of a rodent model of DN. We integrated proteomics and metabolomics from the sciatic nerve (SN), the lumbar 4/5 dorsal root ganglia (DRG), and the trigeminal ganglia (TG) of streptozotocin-diabetic and healthy control rats. Even though all tissues showed a dramatic increase in glucose and polyol pathway intermediates in diabetes, a striking upregulation of mitochondrial oxidative phosphorylation and perturbation of lipid metabolism was found in the distal SN that was not present in the corresponding cell bodies of the DRG or the cranial TG. This finding suggests that the most severe molecular consequences of diabetes in the nervous system present in the SN, the region most affected by neuropathy. Such spatial metabolic dysfunction suggests a failure of energy homeostasis and/or oxidative stress, specifically in the distal axon/Schwann cell-rich SN. These data provide a detailed molecular description of the distinct compartmental effects of diabetes on the PNS that could underlie the distal-proximal distribution of pathology.
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