Association between vitamin D and metabolic syndrome in older adults

Recently, low serum concentrations of 25-hydroxyvitamin D [25(OH)D] have been linked to disturbances in glucose metabolism, development of type 2 diabetes, and increased risk of metabolic syndrome (MetS). Moreover, deficiency of vitamin D is now recognized to be highly prevalent in the U.S. and worldwide, impacting between 30% and 50% of the general population. Therefore, the objective of this research study is to examine the associations between serum 25-hyroxyvitamin D and MetS. Data were collected from the Nutritional Interventions for Age-Related Muscular Function and Strength Losses Study. From this cohort, 186 independently living males and females over the age of 60, with vitamin D levels between 18 ng/mL and 30 ng/mL, without any existing liver or kidney disease or uncontrolled diabetes mellitus or type 1 diabetes mellitus requiring insulin, provided baseline data. A Pearson correlation coefficient of 0.02 with non-significant p-value of 0.77 was found between MetS score and 25(OH)D. Factors such as average heart rate (p \u3c0.05), weight (p \u3c0.001) , BMI (p \u3c0.001), LDL:HDL ratio (p \u3c0.01), android fat (%) (p \u3c 0.001), gynoid fat mass (p \u3c0.001), and gynoid fat (%) (p \u3c0.01) were found to have significant associations with the MetS score. A backwards stepwise regression indicated that android fat (%) (p \u3c0.001), gynoid fat (%) (p = 0.001), total cholesterol (p \u3c0.001), VLDL cholesterol (p \u3c0.001), and LDL:HDL ratio (p \u3c0.001) were most predictive of the MetS score. In conclusion, the major finding of this study was that the combination of android fat (%), gynoid fat (%), total cholesterol, VLDL cholesterol, and the LDL:HDL ratio were predictive of the MetS score. However, no significant association between low vitamin D status and prevalence of MetS could be established

A Frattini Theory for Leibniz Algebras

A Frattini theory for non-associative algebras was developed by Towers and results for particular classes of algebras have appeared in various articles. Especially plentiful are results on Lie algebras. It is the purpose of this paper to extend some of the Lie algebra results to Leibniz algebras

Cumbria Innovations Platform: student research opportunities

Presented in the 'Employability and Graduateness' theme at this conference

Mutations in FUS lead to synaptic dysregulation in ALS-iPSC derived neurons

Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset neurodegenerative disorder characterized by progressive muscular weakness due to the selective loss of motor neurons. Mutations in the gene Fused in Sarcoma (FUS) were identified as one cause of ALS. Here, we report that mutations in FUS lead to upregulation of synaptic proteins, increasing synaptic activity and abnormal release of vesicles at the synaptic cleft. Consequently, FUS-ALS neurons showed greater vulnerability to glutamate excitotoxicity, which raised neuronal swellings (varicose neurites) and led to neuronal death. Fragile X mental retardation protein (FMRP) is an RNA-binding protein known to regulate synaptic protein translation, and its expression is reduced in the FUS-ALS lines. Collectively, our data suggest that a reduction of FMRP levels alters the synaptic protein dynamics, leading to synaptic dysfunction and glutamate excitotoxicity. Here, we present a mechanistic hypothesis linking dysregulation of peripheral translation with synaptic vulnerability in the pathogenesis of FUS-ALS.</p

Omics-driven identification and elimination of valerolactam catabolism in Pseudomonas putida KT2440 for increased product titer.

Pseudomonas putida is a promising bacterial chassis for metabolic engineering given its ability to metabolize a wide array of carbon sources, especially aromatic compounds derived from lignin. However, this omnivorous metabolism can also be a hindrance when it can naturally metabolize products produced from engineered pathways. Herein we show that P.&nbsp;putida is able to use valerolactam as a sole carbon source, as well as degrade caprolactam. Lactams represent important nylon precursors, and are produced in quantities exceeding one million tons per year (Zhang et&nbsp;al., 2017). To better understand this metabolism we use a combination of Random Barcode Transposon Sequencing (RB-TnSeq) and shotgun proteomics to identify the oplBA locus as the likely responsible amide hydrolase that initiates valerolactam catabolism. Deletion of the oplBA genes prevented P.&nbsp;putida from growing on valerolactam, prevented the degradation of valerolactam in rich media, and dramatically reduced caprolactam degradation under the same conditions. Deletion of oplBA, as well as pathways that compete for precursors L-lysine or 5-aminovalerate, increased the titer of valerolactam from undetectable after 48 h of production to ~90 mg/L. This work may serve as a template to rapidly eliminate undesirable metabolism in non-model hosts in future metabolic engineering efforts

Omics-driven identification and elimination of valerolactam catabolism in Pseudomonas putida KT2440 for increased product titer.

Pseudomonas putida is a promising bacterial chassis for metabolic engineering given its ability to metabolize a wide array of carbon sources, especially aromatic compounds derived from lignin. However, this omnivorous metabolism can also be a hindrance when it can naturally metabolize products produced from engineered pathways. Herein we show that P. putida is able to use valerolactam as a sole carbon source, as well as degrade caprolactam. Lactams represent important nylon precursors, and are produced in quantities exceeding one million tons per year (Zhang et al., 2017). To better understand this metabolism we use a combination of Random Barcode Transposon Sequencing (RB-TnSeq) and shotgun proteomics to identify the oplBA locus as the likely responsible amide hydrolase that initiates valerolactam catabolism. Deletion of the oplBA genes prevented P. putida from growing on valerolactam, prevented the degradation of valerolactam in rich media, and dramatically reduced caprolactam degradation under the same conditions. Deletion of oplBA, as well as pathways that compete for precursors L-lysine or 5-aminovalerate, increased the titer of valerolactam from undetectable after 48 h of production to ~90 mg/L. This work may serve as a template to rapidly eliminate undesirable metabolism in non-model hosts in future metabolic engineering efforts

Add-on topiramate reduces weight in overweight patients with affective disorders: a clinical case series

BACKGROUND: The weight-gain caused by many psychotropic drugs is a major cause for poor compliance with such medications and could also increase cardio-vascular morbidity among psychiatric patients. Recent reports have shown that the anticonvulsant topiramate causes weight loss in various patient groups. The drug has also shown effectiveness in open trials as a mood stabilizer in patients with affective disorders, but not in controlled trials in the acute treatment of mania. We used topiramate to treat 12 patients with affective disorders who had a body-mass index >30 kg/m(2). METHODS: Topiramate was prescribed as part of our routine clinical practice, as an add-on medication, or as a replacement of a mood stabilizer. Patients' weight was recorded in 1 to 2 monthly intervals. Patients were followed up for between 6 and 12 months. The final dose of topiramate varied from 200 to 600 mg/day. RESULTS: Topiramate was effective in reducing the weight in 10 out of the 12 patients. At six months the 12 patients had lost a mean of 7.75 kg (SD = 6.9 kg, p < 0.001) and at 12 months 9 patients had lost a mean of 9.61 kg (SD = 6.7 kg, p = 0.003). Three patients stopped the treatment: one due to side effects, one due to possible side effects, and one suffered a manic relapse and showed no sustained weight loss. There were no other clear changes in the course of illness of the patients. CONCLUSION: The evidence of a strong weight-reducing potential of topiramate is indisputable and clinically significant. Topiramate could be considered in the treatment of bipolar patients who are overweight, or whose concerns about weight gain compromise their compliance with long-term prophylactic medication. So far there is no evidence that topiramate has anti-manic effect and it should not be used as monotherapy