A randomized controlled trial of exercise in spinal and bulbar muscular atrophy.

OBJECTIVE: To determine the safety and efficacy of a home-based functional exercise program in spinal and bulbar muscular atrophy (SBMA). METHODS: Subjects were randomly assigned to participate in 12 weeks of either functional exercises (intervention) or a stretching program (control) at the National Institutes of Health in Bethesda, MD. A total of 54 subjects enrolled, and 50 completed the study with 24 in the functional exercise group and 26 in the stretching control group. The primary outcome measure was the Adult Myopathy Assessment Tool (AMAT) total score, and secondary measures included total activity by accelerometry, muscle strength, balance, timed up and go, sit-to-stand test, health-related quality of life, creatine kinase, and insulin-like growth factor-1. RESULTS: Functional exercise was well tolerated but did not lead to significant group differences in the primary outcome measure or any of the secondary measures. The functional exercise did not produce significantly more adverse events than stretching, and was not perceived to be difficult. To determine whether a subset of the subjects may have benefited, we divided them into high and low functioning based on baseline AMAT scores and performed a post hoc subgroup analysis. Low-functioning individuals receiving the intervention increased AMAT functional subscale scores compared to the control group. INTERPRETATION: Although these trial results indicate that functional exercise had no significant effect on total AMAT scores or on mobility, strength, balance, and quality of life, post hoc findings indicate that low-functioning men with SBMA may respond better to functional exercises, and this warrants further investigation with appropriate exercise intensity

Supersize me - new insights into cortical expansion and gyration of the mammalian brain

During evolution, the mammalian brain massively expanded its size. However, the exact roles of distinct neural precursors, identified in the developing cortex during embryogenesis, for size expansion and surface folding (i.e., gyration) remain largely unknown. New findings by Nonaka-Kinoshita et al advance our understanding of embryonic neural precursor function by identifying cell type-selective functions for size expansion and folding, and challenge previously held concepts of mammalian brain development

A rapid method for detection of cell adhesion molecules (CAMs) on human umbilical vein endothelial cells (HUVECs)

Detection of cell surface proteins is widely used as molecular markers for initiation, progression and severity of many diseases. In particular, detection of cell adhesion molecules (CAMs) on endothelial cells is important as it indicates the extent of inflammation associated with several diseases including arthritis, asthma, tumor metastasis, etc. Here, we report, a rapid method for detection of CAMs on endothelial cells by covalently immobilizing TNF-α induced cells on a photoactivated polystyrene microtiter plate at 50 °C in 45 min followed by performing enzyme-linked immunosorbent assay (ELISA) technique at elevated temperature. Our method reduced the time of cell-ELISA to 3 h with results akin to conventional cell-ELISA carried out in 38 h. The method thus described herein could be potentially useful in clinical and research laboratories for rapid detection of cell surface proteins including CAMs on intact cell samples

Asian Journal of Medical and Biological Research Segregation pattern and inbreeding depression in F 2 generation of some hybrid okra varieties

Abstract: An experiment was conducted in randomized complete block design (RCBD) with three replications in the experimental field of Regional Horticulture Research Station (RHRS), Bangladesh Agriculture Research Institute (BARI), Lebukhali, Patuakhali during April, 2014 to October, 2014 for assessing the inbreeding depression, genetic parameters, gene action and segregation pattern of Okra [Abelmoschusesculentus (L.) Moench]. The experiment was comprised of five commercial hybrid Okra genotypes such as Tara sonali, Bimala, Juboraj, Suvo 1and Noor, their respective F 2 progenies along with a check variety named as BARI Dherosh 1. Results of the experiment indicated that there were considerable variability among the F 1 and their F 2 . The yield were in-between 14.81 to 7.92 Kg plot -1 in case of F 1 generation, which deteriorate to 10.32 to 5.32 Kg plot -1 in F 2 generation. Broad sense heritability computed through variance component method showed that all the quantitative traits were moderate to highly heritable. The trait yield per plot exhibited 68.83% broad sense heritability coupled with 50.96% genetic advance suggesting the existence of sufficient amount of genetic variability for improvement of this trait and also indicates that the trait is more amenable to selection and could be improved easily. In case of segregation pattern, plant height and pod pubescence content exhibit as polygenic trait. Leaf shape, fruit base shape and branching pattern showed complete dominance and fruit color displayed incomplete dominance. The present investigation thus provide information about the nature and magnitude of genetic variation, segregation pattern and inbreeding depression for yield and its components in okra so as to formulate suitable breeding strategy and isolate potential parents and promising crosses for further breeding program

Stem cell-derived motor neurons from spinal and bulbar muscular atrophy patients

AbstractSpinal and bulbar muscular atrophy (SBMA, Kennedy's disease) is a motor neuron disease caused by polyglutamine repeat expansion in the androgen receptor. Although degeneration occurs in the spinal cord and muscle, the exact mechanism is not clear. Induced pluripotent stem cells from spinal and bulbar muscular atrophy patients provide a useful model for understanding the disease mechanism and designing effective therapy. Stem cells were generated from six patients and compared to control lines from three healthy individuals. Motor neurons from four patients were differentiated from stem cells and characterized to understand disease-relevant phenotypes. Stem cells created from patient fibroblasts express less androgen receptor than control cells, but show androgen-dependent stabilization and nuclear translocation. The expanded repeat in several stem cell clones was unstable, with either expansion or contraction. Patient stem cell clones produced a similar number of motor neurons compared to controls, with or without androgen treatment. The stem cell-derived motor neurons had immunoreactivity for HB9, Isl1, ChAT, and SMI-32, and those with the largest repeat expansions were found to have increased acetylated α-tubulin and reduced HDAC6. Reduced HDAC6 was also found in motor neuron cultures from two other patients with shorter repeats. Evaluation of stably transfected mouse cells and SBMA spinal cord showed similar changes in acetylated α-tubulin and HDAC6. Perinuclear lysosomal enrichment, an HDAC6 dependent process, was disrupted in motor neurons from two patients with the longest repeats. SBMA stem cells present new insights into the disease, and the observations of reduced androgen receptor levels, repeat instability, and reduced HDAC6 provide avenues for further investigation of the disease mechanism and development of effective therapy