The effect of endurance and circuit resistance training on serum brain-derived neurotrophic factor and cortisol in inactive male students: A randomized clinical trial

زمینه و هدف: عامل رشد عصبی مشتق از مغز نقش مهمی در رشد و تکامل دستگاه عصبی دارد. تحقیقات حیوانی نشان داده اند که سطوح سرمی این فاکتور تحت تأثیر فعالیت ورزشی قرار می گیرد. هدف از انجام تحقیق حاضر تعیین تأثیر تمرین استقامتی و مقاومتی دایره ای بر عامل رشد عصبی مشتق شده از مغز و کورتیزول سرمی در مردان غیر فعال بود. روش بررسی: در این مطالعه کارآزمایی بالینی، 30 دانشجوی پسر غیر فعال به طور تصادفی به سه گروه تمرین استقامتی، تمرین مقاومتی و کنترل تقسیم شدند. آزمودنی های گروه استقامتی برنامه تمرینی استقامتی شامل 45-30 دقیقه دوی تناوبی با شدت 75-60 درصد ضربان قلب بیشینه را به مدت چهار هفته اجرا کردند. آزمودنی های گروه های تمرین مقاومتی نیز سه جلسه در هفته، به مدت چهار هفته تمرین مقاومتی دایره ای با شدت 75-60 درصد یک تکرار بیشینه را انجام دادند. قبل و 48 ساعت بعد از دوره‌ی تحقیق، نمونه گیری خونی برای سنجش مقادیر سرمی عامل رشد عصبی مشتق شده از مغز و کورتیزول از آزمودنی ها به عمل آمد. یافته ها: تمرین استقامتی و مقاومتی دایره ای غلظت سرمی عامل رشد عصبی مشتق شده از مغز را به طور معنی داری افزایش داد. در بررسی نتایج پس آزمون تفاوتی بین گروه های تمرینی مشاهده نشد؛ ولی بین دو گروه تمرین استقامتی و گروه کنترل تفاوت معنی دار بود. تمرین استقامتی و مقاومتی تأثیر معنی داری بر سطوح کورتیزول سرمی نداشت. نتیجه گیری: بر اساس یافته های این مطالعه، تمرین استقامتی و مقاومتی دایره ای باعث افزایش فاکتورهای نروتروفیک می شود که ممکن است بدین طریق باعث ایجاد سازگاری های ساختاری و عملکردی در دستگاه عصبی شود

Development of NMR and thermal shift assays for the evaluation of Mycobacterium tuberculosis isocitrate lyase inhibitors.

The enzymes isocitrate lyase (ICL) isoforms 1 and 2 are essential for Mycobacterium tuberculosis survival within macrophages during latent tuberculosis (TB). As such, ICLs are attractive therapeutic targets for the treatment of tuberculosis. However, there are few biophysical assays that are available for accurate kinetic and inhibition studies of ICL in vitro. Herein we report the development of a combined NMR spectroscopy and thermal shift assay to study ICL inhibitors for both screening and inhibition constant (IC50) measurement. Operating this new assay in tandem with virtual high-throughput screening has led to the discovery of several new ICL1 inhibitors

A transfer-learning approach to feature extraction from cancer transcriptomes with deep autoencoders

Publicado en Lecture Notes in Computer Science.The diagnosis and prognosis of cancer are among the more challenging tasks that oncology medicine deals with. With the main aim of fitting the more appropriate treatments, current personalized medicine focuses on using data from heterogeneous sources to estimate the evolu- tion of a given disease for the particular case of a certain patient. In recent years, next-generation sequencing data have boosted cancer prediction by supplying gene-expression information that has allowed diverse machine learning algorithms to supply valuable solutions to the problem of cancer subtype classification, which has surely contributed to better estimation of patient’s response to diverse treatments. However, the efficacy of these models is seriously affected by the existing imbalance between the high dimensionality of the gene expression feature sets and the number of sam- ples available for a particular cancer type. To counteract what is known as the curse of dimensionality, feature selection and extraction methods have been traditionally applied to reduce the number of input variables present in gene expression datasets. Although these techniques work by scaling down the input feature space, the prediction performance of tradi- tional machine learning pipelines using these feature reduction strategies remains moderate. In this work, we propose the use of the Pan-Cancer dataset to pre-train deep autoencoder architectures on a subset com- posed of thousands of gene expression samples of very diverse tumor types. The resulting architectures are subsequently fine-tuned on a col- lection of specific breast cancer samples. This transfer-learning approach aims at combining supervised and unsupervised deep learning models with traditional machine learning classification algorithms to tackle the problem of breast tumor intrinsic-subtype classification.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2

Isocitrate lyase is important for lipid utilisation by Mycobacterium tuberculosis but its ICL2 isoform is poorly understood. Here we report that binding of the lipid metabolites acetyl-CoA or propionyl-CoA to ICL2 induces a striking structural rearrangement, substantially increasing isocitrate lyase and methylisocitrate lyase activities. Thus, ICL2 plays a pivotal role regulating carbon flux between the tricarboxylic acid (TCA) cycle, glyoxylate shunt and methylcitrate cycle at high lipid concentrations, a mechanism essential for bacterial growth and virulence

Correction to: Destructive Roles of Fibroblast-Like Synoviocytes in Chronic Inflammation and Joint Damage in Rheumatoid Arthritis (Inflammation, (2021), 44, 2, (466-479), 10.1007/s10753-020-01371-1)

Following the publication of the original article, the corresponding author noticed that the second corresponding author has not been mentioned. The below statement must be added to the correspondence section: Jafar Karami; Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. E-mail: [email protected]; [email protected] The original article has been corrected. © 2020, Springer Science+Business Media, LLC, part of Springer Nature

Elevated circulating Hsp70 levels are correlative for malignancies in different mammalian species

Circulating Hsp70 levels were determined in feline and porcine cohorts using two different ELISA systems. These comparative animal models of larger organisms often reflect diseases, and especially malignant tumors, better than conventional rodent models. It is therefore essential to investigate the biology and utility of tumor biomarkers in animals such as cats and pigs. In this study, levels of free Hsp70 in the blood of cats with spontaneously occurring tumors were detected using a commercial Hsp70 ELISA (R&D Systems). Sub-analysis of different tumor groups revealed that animals with tumors of epithelial origin presented with significantly elevated circulating Hsp70 concentrations. In addition to free Hsp70 levels measured with the R&D Systems Hsp70 ELISA, levels of exosomal Hsp70 were determined using the compHsp70 ELISA in pigs. Both ELISA systems detected significantly elevated Hsp70 levels (R&D Systems: median 24.9 ng/mL; compHsp70: median 44.2 ng/mL) in the blood of a cohort of APC$^{1311/+}$ pigs diagnosed with high-grade adenoma polyps, and the R&D Systems Hsp70 ELISA detected also elevated Hsp70 levels in animals with low-grade polyps. In contrast, in flTP53$^{R167H}$ pigs, suffering from malignant osteosarcoma, the compHsp70 ELISA (median 674.32 ng/mL), but not the R&D Systems Hsp70 ELISA (median 4.78 ng/mL), determined significantly elevated Hsp70 concentrations, indicating that in tumor-bearing animals, the dominant form of Hsp70 is of exosomal origin. Our data suggest that both ELISA systems are suitable for detecting free circulating Hsp70 levels in pigs with high-grade adenoma, but only the compHsp70 ELISA can measure elevated, tumor-derived exosomal Hsp70 levels in tumor-bearing animals

Mutations in NKX6-2 Cause Progressive Spastic Ataxia and Hypomyelination

Progressive limb spasticity and cerebellar ataxia are frequently found together in clinical practice and form a heterogeneous group of degenerative disorders that are classified either as pure spastic ataxia or as complex spastic ataxia with additional neurological signs. Inheritance is either autosomal dominant or autosomal recessive. Hypomyelinating features on MRI are sometimes seen with spastic ataxia, but this is usually mild in adults and severe and life limiting in children. We report seven individuals with an early-onset spastic-ataxia phenotype. The individuals come from three families of different ethnic backgrounds. Affected members of two families had childhood onset disease with very slow progression. They are still alive in their 30s and 40s and show predominant ataxia and cerebellar atrophy features on imaging. Affected members of the third family had a similar but earlier-onset presentation associated with brain hypomyelination. Using a combination of homozygozity mapping and exome sequencing, we mapped this phenotype to deleterious nonsense or homeobox domain missense mutations in NKX6-2. NKX6-2 encodes a transcriptional repressor with early high general and late focused CNS expression. Deficiency of its mouse ortholog results in widespread hypomyelination in the brain and optic nerve, as well as in poor motor coordination in a pattern consistent with the observed human phenotype. In-silico analysis of human brain expression and network data provides evidence that NKX6-2 is involved in oligodendrocyte maturation and might act within the same pathways of genes already associated with central hypomyelination. Our results support a non-redundant developmental role of NKX6-2 in humans and imply that NKX6-2 mutations should be considered in the differential diagnosis of spastic ataxia and hypomyelination

Metabolic Engineering of Cofactor F420 Production in Mycobacterium smegmatis

Cofactor F420 is a unique electron carrier in a number of microorganisms including Archaea and Mycobacteria. It has been shown that F420 has a direct and important role in archaeal energy metabolism whereas the role of F420 in mycobacterial metabolism has only begun to be uncovered in the last few years. It has been suggested that cofactor F420 has a role in the pathogenesis of M. tuberculosis, the causative agent of tuberculosis. In the absence of a commercial source for F420, M. smegmatis has previously been used to provide this cofactor for studies of the F420-dependent proteins from mycobacterial species. Three proteins have been shown to be involved in the F420 biosynthesis in Mycobacteria and three other proteins have been demonstrated to be involved in F420 metabolism. Here we report the over-expression of all of these proteins in M. smegmatis and testing of their importance for F420 production. The results indicate that co–expression of the F420 biosynthetic proteins can give rise to a much higher F420 production level. This was achieved by designing and preparing a new T7 promoter–based co-expression shuttle vector. A combination of co–expression of the F420 biosynthetic proteins and fine-tuning of the culture media has enabled us to achieve F420 production levels of up to 10 times higher compared with the wild type M. smegmatis strain. The high levels of the F420 produced in this study provide a suitable source of this cofactor for studies of F420-dependent proteins from other microorganisms and for possible biotechnological applications

Risk factor investigation for cardiovascular health through WHO STEPS approach in Ardabil, Iran

Objectives: Reliable evidence is the keystone for any noncommunicable disease (NCD) prevention plan to be initiated. In this study we carried out a risk factor investigation based on the WHO Stepwise approach to Surveillance (STEPS). Methods: The study was conducted on 1000 adults between 15 and 64 years of age living in Ardabil province, north-west Iran during 2006, based on the WHO STEPS approach to surveillance of risk factors for NCD. At this stage only the first and second steps were carried out. Data were collected through standard questionnaires and methods analyzed using STATA version 8 statistical software package. Results: 29.0% of men and 2.6% of women were current daily tobacco smokers. The mean number of manufactured cigarettes smoked per day was 18.9 among current daily smokers. Smoking was most prevalent among men of low-income families and those of lower education The mean body mass index (BMI) was 26.6 kg/m2, and was significantly correlated with systolic blood pressure. 58.9% were overweight or obese; 18.0% had raised blood pressure and 3.7% had isolated systolic hypertension. The mean number of servings of fruit consumed per day was 1.1; 33.1% had low levels of activity. Combined risk factor analysis showed that 4.1%of participants were in the low-risk group (up to 5.1% among men and 3.2% among women).Those in the high-risk group comprised 25.6% in the 25- to 44-year age group and 49.7%in the 45- to 64-year age group. Mean BMI increased by age in both sexes at least at the firstthree decades of adult life. Conclusion: Based on observed status of risk for cardiovascular health, burden of cardiovascular diseases is expected to increase if an effective prevention strategy is not undertaken

SLC25A22 is a novel gene for migrating partial seizures in infancy

Objective To identify a genetic cause for migrating partial seizures in infancy (MPSI). Methods We characterized a consanguineous pedigree with MPSI and obtained DNA from affected and unaffected family members. We analyzed single nucleotide polymorphism 500K data to identify regions with evidence of linkage. We performed whole exome sequencing and analyzed homozygous variants in regions of linkage to identify a candidate gene and performed functional studies of the candidate gene SLC25A22. Results In a consanguineous pedigree with 2 individuals with MPSI, we identified 2 regions of linkage, chromosome 4p16.1-p16.3 and chromosome 11p15.4-pter. Using whole exome sequencing, we identified 8 novel homozygous variants in genes in these regions. Only 1 variant, SLC25A22 c.G328C, results in a change of a highly conserved amino acid (p.G110R) and was not present in control samples. SLC25A22 encodes a glutamate transporter with strong expression in the developing brain. We show that the specific G110R mutation, located in a transmembrane domain of the protein, disrupts mitochondrial glutamate transport. Interpretation We have shown that MPSI can be inherited and have identified a novel homozygous mutation in SLC25A22 in the affected individuals. Our data strongly suggest that SLC25A22 is responsible for MPSI, a severe condition with few known etiologies. We have demonstrated that a combination of linkage analysis and whole exome sequencing can be used for disease gene discovery. Finally, as SLC25A22 had been implicated in the distinct syndrome of neonatal epilepsy with suppression bursts on electroencephalogram, we have expanded the phenotypic spectrum associated with SLC25A22. Ann Neurol 2013;74:873-882 © 2013 American Neurological Association