A neurotoxic peripherin splice variant in a mouse model of ALS

Peripherin, a neuronal intermediate filament (nIF) protein found associated with pathological aggregates in motor neurons of patients with amyotrophic lateral sclerosis (ALS) and of transgenic mice overexpressing mutant superoxide dismutase-1 (SOD1G37R), induces the selective degeneration of motor neurons when overexpressed in transgenic mice. Mouse peripherin is unique compared with other nIF proteins in that three peripherin isoforms are generated by alternative splicing. Here, the properties of the peripherin splice variants Per 58, Per 56, and Per 61 have been investigated in transfected cell lines, in primary motor neurons, and in transgenic mice overexpressing peripherin or overexpressing SOD1G37R. Of the three isoforms, Per 61 proved to be distinctly neurotoxic, being assembly incompetent and inducing degeneration of motor neurons in culture. Using isoform-specific antibodies, Per 61 expression was detected in motor neurons of SOD1G37R transgenic mice but not of control or peripherin transgenic mice. The Per 61 antibody also selectively labeled motor neurons and axonal spheroids in two cases of familial ALS and immunoprecipitated a higher molecular mass peripherin species from disease tissue. This evidence suggests that expression of neurotoxic splice variants of peripherin may contribute to the neurodegenerative mechanism in ALS

Optogenetics and deep brain stimulation neurotechnologies

Brain neural network is composed of densely packed, intricately wired neurons whose activity patterns ultimately give rise to every behavior, thought, or emotion that we experience. Over the past decade, a novel neurotechnique, optogenetics that combines light and genetic methods to control or monitor neural activity patterns, has proven to be revolutionary in understanding the functional role of specific neural circuits. We here briefly describe recent advance in optogenetics and compare optogenetics with deep brain stimulation technology that holds the promise for treating many neurological and psychiatric disorders

Genotyping and drug resistance patterns of M. tuberculosis strains in Pakistan

<p>Abstract</p> <p>Background</p> <p>The incidence of tuberculosis in Pakistan is 181/100,000 population. However, information about transmission and geographical prevalence of <it>Mycobacterium tuberculosis </it>strains and their evolutionary genetics as well as drug resistance remains limited. Our objective was to determine the clonal composition, evolutionary genetics and drug resistance of <it>M. tuberculosis </it>isolates from different regions of the country.</p> <p>Methods</p> <p><it>M. tuberculosis </it>strains isolated (2003–2005) from specimens submitted to the laboratory through collection units nationwide were included. Drug susceptibility was performed and strains were spoligotyped.</p> <p>Results</p> <p>Of 926 <it>M. tuberculosis </it>strains studied, 721(78%) were grouped into 59 "shared types", while 205 (22%) were identified as "Orphan" spoligotypes. Amongst the predominant genotypes 61% were Central Asian strains (CAS ; including CAS1, CAS sub-families and Orphan Pak clusters), 4% East African-Indian (EAI), 3% Beijing, 2% poorly defined TB strains (T), 2% Haarlem and LAM (0.2). Also TbD1 analysis (<it>M. tuberculosis </it>specific deletion 1) confirmed that CAS1 was of "modern" origin while EAI isolates belonged to "ancestral" strain types.</p> <p>Prevalence of CAS1 clade was significantly higher in Punjab (P < 0.01, Pearsons Chi-square test) as compared with Sindh, North West Frontier Province and Balochistan provinces. Forty six percent of isolates were sensitive to five first line antibiotics tested, 45% were Rifampicin resistant, 50% isoniazid resistant. MDR was significantly associated with Beijing strains (P = 0.01, Pearsons Chi-square test) and EAI (P = 0.001, Pearsons Chi-square test), but not with CAS family.</p> <p>Conclusion</p> <p>Our results show variation of prevalent <it>M. tuberculosis </it>strain with greater association of CAS1 with the Punjab province. The fact that the prevalent CAS genotype was not associated with drug resistance is encouraging. It further suggests a more effective treatment and control programme should be successful in reducing the tuberculosis burden in Pakistan.</p

Evaluation of the Indices of Post-Traumatic Stress Disorder in Trauma-Suffered Individuals Referred to Fars Province General Administration of Forensic Medicine

Background & aim: Post-traumatic stress disorder (PTSD) is the most common psychological consequence of traumatic events, which is usually accompanied by functional impairment, which is often accompanied by other psychological disorders. The purpose of this study was to investigate the indicators of post-traumatic stress disorder (PTSD) in trauma patients referred to the examination department of the General Administration of Forensic Medicine of Fars province. Methods: The present study was a cross-sectional one conducted in the years 2020 and 2021. In the present study, 160 participants were selected accidentally among people who experienced trauma and referred to the forensic medical examination centers in Shiraz. In this study, people with the age of 18 years or more who agreed to participate in the study and who were referred for the purpose of evaluating injuries caused by trauma, were included in the study. In this study, the participants were evaluated using the Trauma Exposure Questionnaire (PCL-5) and DSM-5 post-traumatic stress disorder levels. Results: In the present study, 160 people referred to the forensic medical examination unit were examined, including 91 men (56.87%) and 69 women (43.12%). Of these, 75 people (46.87%) qualified for PTSD based on ICD-10 criteria. The average age of the subjects was 45.67 ± 11.96 years, the youngest of whom was 18 years old and the oldest was 75 years old. Among the subjects studied, 9 people (12.00%) had a history of drinking alcoholic beverages, 6 people (8.00%) had a history of addiction, and 26 people (34.66%) had a history of smoking. On the other hand, 13 of the participants in this study had a history of visiting psychiatrists and psychologists and taking medication for psychological disorders. PTSD clinical evaluations measured in the studied subjects showed subclinical PTSD in 15 people, clinical form in 31 people, sub-group I PTSD in 7 people, sub-group II PTSD in 13 people, sub-group III PTSD in 6 people and Subgroup IV PTSD was observed in 3 people. Conclusion: The results of this study indicate a considerable frequency of post-traumatic stress disorder (PTSD) in trauma clients referred to the examination department of the General administration of Forensic Medicine in Shiraz. Psychological support for victims of traumatic events is of great importance in order to prevent secondary complications and prevent chronic PTSD in people

Decentralized Control of Distributed Actuation in a Segmented Soft Robot Arm

Continuum robot manipulators present challenges for controller design due to the complexity of their infinite-dimensional dynamics. This paper develops a practical dynamics-based approach to synthesizing state feedback controllers for a soft continuum robot arm composed of segments with local sensing, actuation, and control capabilities. Each segment communicates its states to its two adjacent neighboring segments, requiring a tridiagonal feedback matrix for decentralized controller implementation. A semi-discrete numerical approximation of the Euler-Bernoulli beam equation is used to represent the robot arm dynamics. Formulated in state space representation, this numerical approximation is used to define an H-infinity optimal control problem in terms of a Bilinear Matrix Inequality. We develop three iterative algorithms that solve this problem by computing the tridiagonal feedback matrix which minimizes the H-infinity norm of the map from disturbances to regulated outputs. We confirm through simulations that all three controllers successfully dampen the free vibrations of a cantilever beam that are induced by an initial sinusoidal displacement, and we compare the controllers' performance.Office of Naval Research (ONR) [N00014-17-1-2117]This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]