636 research outputs found
Survival Motor Neuron (SMN) protein is required for normal mouse liver development
We would like to thank Lucas Fraga who helped with primer design and Alison Thomson for tissue collection. We would also like to acknowledge the Microscopy and Histology Core Facility at the University of Aberdeen for the use of their facilities. SHP is funded by Anatomical Society, Euan MacDonald Centre for Motor Neurone Disease Research and an Elphinstone Scholarship for ES from the University of Aberdeen. THG is funded by SMA Trust (UK SMA Research Consortium award), Muscular Dystrophy UK, and Anatomical Society (PhD Studentship). FM is funded by Medical Research Council, SMA-Europe and the National Institute for Health Research Biomedical Research Centre and Great Ormond Street Hospital Children’s Charity. HZ is funded by SMA-Europe and the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. Corrigendum: Survival Motor Neuron (SMN) protein is required for normal mouse liver development Published online: 10 November 2016 DOI: 10.1038/srep35898Peer reviewedPublisher PDFOthe
Role of tyrosine M210 in the initial charge separation of reaction centers of Rhodobacter sphaeroides
Femtosecond spectroscopy was used in combination with site-directed mutagenesis to study the
influence of tyrosine M210 (YM210) on the primary electron transfer in the reaction center of Rhodobacter
sphaeroides. The exchange of YM210 to phenylalanine caused the time constant of primary electron transfer
to increase from 3.5 f 0.4 ps to 16 f 6 ps while the exchange to leucine increased the time constant even
more to 22 f 8 ps. The results suggest that tyrosine M210 is important for the fast rate of the primary
electron transfer
Balance Training Reduces Falls Risk in Older Individuals With Type 2 Diabetes
OBJECTIVE - This study assessed the effects of balance/strength training on falls risk and posture in older individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS - Sixteen individuals with type 2 diabetes and 21 age-matched control subjects (aged 50-75 years) participated. Postural stability and falls risk was assessed before and after a 6-week exercise program. RESULTS - Diabetic individuals had significantly higher falls risk score compared with control subjects. The diabetic group also exhibited evidence of mild-to-moderate neuropathy, slower reaction times, and increased postural sway. Following exercise, the diabetic group showed significant improvements in leg strength, faster reaction times, decreased sway, and, consequently, reduced falls risk. CONCLUSIONS - Older individuals with diabetes had impaired balance, slower reactions, and consequently a higher falls risk than age-matched control subjects. However, all these variables improved after resistance/balance training. Together these results demonstrate that structured exercise has wide-spread positive effects on physiological function for older individuals with type 2 diabetes
Survival of motor neurone protein is required for normal postnatal development of the spleen
Funding S.H.P. received an Anatomical Society PhD Studentship award for A.K.T. T.H.G. received an Anatomical Society PhD Studentship award for R.A.P. and funding from the SMA Trust (UK SMA Research Consortium), Euan MacDonald Centre for Motor Neurone Disease Research, and Muscular Dystrophy UK. K.J.S received funding for pathologic studies in human subjects from NICHD grant R01-HD054599.Peer reviewedPostprin
Walking-Induced Fatigue Leads to Increased Risk in Older Adults
Background- For older adults, falls are a serious health problem, with more than 30% of people older than 65 suffering a fall at least once a year. One element often overlooked in the assessment of falls is whether a person\u27s balance, walking ability, and overall falls risk is affected by performing activities of daily living such as walking.
Objective- This study assessed the immediate impact of incline walking at a moderate pace on falls risk, leg strength, reaction time, gait, and balance in 75 healthy adults from 30 to 79 years of age. Subjects were subdivided into 5 equal groups based on their age (group 1, 30-39 years; group 2, 40-49 years; group 3, 50-59 years; group 4, 60-69 years; group 5, 70-79 years).
Methods- Each person\u27s falls risk (using the Physiological Profile Assessment), simple reaction time, leg strength, walking ability, and standing balance were assessed before and after a period of incline walking on an automated treadmill. The walking task consisted of three 5-minute trials at a faster than preferred pace. Fatigue during walking was elicited by increasing the treadmill incline in increments of 2 degrees (from level) every minute to a maximum of 8 degrees.
Results- As predicted, significant age-related differences were observed before the walking activity. In general, increasing age was associated with declines in gait speed, lower limb strength, slower reaction times, and increases in overall falls risk. Following the treadmill task, older adults exhibited increased sway (path length 60-69 years; 10.2 ± 0.7 to 12.1 ± 0.7 cm: 70-79 years; 12.8 ± 1.1 to 15.1 ± 0.8 cm), slower reaction times (70-79 years; 256 ± 6 to 287 ± 8 ms), and declines in lower limb strength (60-69 years; 36 ± 2 to 31 ± 1 kg: 70-79 years; 32.3 ± 2 to 27 ± 1 kg). However, a significant increase in overall falls risk (pre; 0.51 ± 0.17: post; 1.01 ± 0.18) was only seen in the oldest group (70-79 years). For all other persons (30-69 years), changes resulting from the treadmill-walking task did not lead to a significant increase in falls risk. Conclusions: As most falls occur when an individual is moving and/or fatigued, assessing functional properties related to balance, gait, strength, and falls risk in older adults both at rest and following activity may provide additional insight
Detailed studies of the subpicosecond kinetics in the primary electron transfer of reaction centers of Rhodopseudomonas viridis
The primary, light-induced charge separation in reaction centers of Rhodopseudomonas viridis is investigated with femtosecond time resolution. The absorption changes after direct excitation of the primary donor P at 955 nm are investigated in the time range from 100 fs to 600 ps. The experimental data, taken at various probing wavelengths, reveal one subpicosecond and two picosecond time constants: 0.65 ± 0.2 ps, 3.5 ± 0.4 ps, and 200 ± 20 ps. The previously undetected 0.65 ps kinetics can be observed clearly in the spectral range of the Qx and Qy transitions of the monomeric bacteriochlorophylls. The experimental data support the idea that the accessory bacteriochlorophyll B A participates in the electron-transfer process.
Reference
Lamin A/C dysregulation contributes to cardiac pathology in a mouse model of severe spinal muscular atrophy
Cardiac pathology is emerging as a prominent systemic feature of spinal muscular atrophy (SMA), but little is known about the underlying molecular pathways. Using quantitative proteomics analysis, we demonstrate widespread molecular defects in heart tissue from the Taiwanese mouse model of severe SMA. We identify increased levels of lamin A/C as a robust molecular phenotype in the heart of SMA mice and show that lamin A/C dysregulation is also apparent in SMA patient fibroblast cells and other tissues from SMA mice. Lamin A/C expression was regulated in vitro by knockdown of the E1 ubiquitination factor ubiquitin-like modifier activating enzyme 1, a key downstream mediator of SMN-dependent disease pathways, converging on β-catenin signaling. Increased levels of lamin A are known to increase the rigidity of nuclei, inevitably disrupting contractile activity in cardiomyocytes. The increased lamin A/C levels in the hearts of SMA mice therefore provide a likely mechanism explaining morphological and functional cardiac defects, leading to blood pooling. Therapeutic strategies directed at lamin A/C may therefore offer a new approach to target cardiac pathology in SMA
Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy
Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice - including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA
In situ labeling of DNA reveals interindividual variation in nuclear DNA breakdown in hair and may be useful to predict success of forensic genotyping of hair
Hair fibers are formed by keratinocytes of the hair follicle in a process that involves the breakdown of the nucleus including DNA. Accordingly, DNA can be isolated with high yield from the hair bulb which contains living keratinocytes, whereas it is difficult to prepare from the distal portions of hair fibers and from shed hair. Nevertheless, forensic investigations are successful in a fraction of shed hair samples found at crime scenes. Here, we report that interindividual differences in the completeness of DNA removal from hair corneocytes are major determinants of DNA content and success rates of forensic investigations of hair. Distal hair samples were permeabilized with ammonia and incubated with the DNA-specific dye Hoechst 33258 to label DNA in situ. Residual nuclear DNA was visualized under the fluorescence microscope. Hair from some donors did not contain any stainable nuclei, whereas hair of other donors contained a variable number of DNA-positive nuclear remnants. The number of DNA-containing nuclear remnants per millimeter of hair correlated with the amount of DNA that could be extracted and amplified by quantitative PCR. When individual hairs were investigated, only hairs in which DNA could be labeled in situ gave positive results in short tandem repeat typing. This study reveals that the completeness of DNA degradation during cornification of the hair is a polymorphic trait. Furthermore, our results suggest that in situ labeling of DNA in hair may be useful for predicting the probability of success of forensic analysis of nuclear DNA in shed hair
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