Investigating differing degrees of FoxO3a expression in adult neural stem cells between age groups in zebrafish

One factor influencing organismal longevity is the activity of transcription factors of the “fork head domain” family, otherwise known as “Forkhead box” (Fox) proteins. Studies of the four isoforms of the “O” subclass of Fox proteins found in human genes have revealed a direct relationship between FoxO3a-dependent gene expression and the conservation of neural stem cell (NSC) in the adult brain, specifically in the subgranular zone of the dentate gyrus in the hippocampus and the subventricular zone of the cortex. This transcription factor has also been shown to regulate apoptosis in nervous tissue during embryonic development in zebrafish. The current study aimed to investigate the differences in FoxO3a expression in adult zebrafish across two different age groups. The primary hypothesis of this study was that a significant positive correlation would be found between expression of FoxO3a in the medial pallium of the brain and progressive organismal aging. Tissue samples from the MP of one- and two-year-old zebrafish were dissected and cDNA was isolated for analyses via qPCR and Western Blot. The resulting data showed no significant difference in FoxO3a expression between younger and older fish

Label-free affinity screening, design and synthesis of inhibitors targeting the <i>Mycobacterium tuberculosis</i> L-alanine dehydrogenase

The ability of Mycobacterium tuberculosis (Mtb) to persist in its host may enable an evolutionary advantage for drug resistant variants to emerge. A potential strategy to prevent persistence and gain drug efficacy is to directly target the activity of enzymes that are crucial for persistence. We present a method for expedited discovery and structure-based design of lead compounds by targeting the hypoxia-associated enzyme L-alanine dehydrogenase (AlaDH). Biochemical and structural analyses of AlaDH confirmed binding of nucleoside derivatives and showed a site adjacent to the nucleoside binding pocket that can confer specificity to putative inhibitors. Using a combination of dye-ligand affinity chromatography, enzyme kinetics and protein crystallographic studies, we show the development and validation of drug prototypes. Crystal structures of AlaDH-inhibitor complexes with variations at the N6 position of the adenyl-moiety of the inhibitor provide insight into the molecular basis for the specificity of these compounds. We describe a drug-designing pipeline that aims to block Mtb to proliferate upon re-oxygenation by specifically blocking NAD accessibility to AlaDH. The collective approach to drug discovery was further evaluated through in silico analyses providing additional insight into an efficient drug development strategy that can be further assessed with the incorporation of in vivo studies

Effect of B7.1 Costimulation on T-Cell Based Immunity against TAP-Negative Cancer Can Be Facilitated by TAP1 Expression

Tumors deficient in expression of the transporter associated with antigen processing (TAP) usually fail to induce T-cell-mediated immunity and are resistant to T-cell lysis. However, we have found that introduction of the B7.1 gene into TAP-negative (TAP−) or TAP1-transfected (TAP1+) murine lung carcinoma CMT.64 cells can augment the capacity of the cells to induce a protective immune response against wild-type tumor cells. Differences in the strength of the protective immune responses were observed between TAP− and TAP1+ B7.1 expressing CMT.64 cells depending on the doses of γ-irradiated cell immunization. While mice immunized with either high or low dose of B7.1-expressing TAP1+ cells rejected TAP− tumors, only high dose immunization with B7.1-expressing TAP− cells resulted in tumor rejection. The induced protective immunity was T-cell dependent as demonstrated by dramatically reduced antitumor immunity in mice depleted of CD8 or CD4 cells. Augmentation of T-cell mediated immune response against TAP− tumor cells was also observed in a virally infected tumor cell system. When mice were immunized with a high dose of γ-irradiated CMT.64 cells infected with vaccinia viruses carrying B7.1 and/or TAP1 genes, we found that the cells co-expressing B7.1 and TAP1, but not those expressing B7.1 alone, induced protective immunity against CMT.64 cells. In addition, inoculation with live tumor cells transfected with several different gene(s) revealed that only B7.1- and TAP1-coexpressing tumor cells significantly decreased tumorigenicity. These results indicate that B7.1-provoked antitumor immunity against TAP− cancer is facilitated by TAP1-expression, and thus both genes should be considered for cancer therapy in the future

The influence of the fatigue on bioelectrical signal value in MVC at patients with gonarthritis

Celem pracy była ocena zmian amplitudy sygnału bioelektrycznego mięśnia czworogłowego uda, rejestrowanego podczas maksymalnego skurczu izometrycznego {maximum voluntary contraction - MVC) przed i po serii testów funkcjonalnych. Badaniu poddano 22 osoby zakwalifikowane do zabiegu endoplastyki stawu kolanowego. Zaobserwowano wzrost wartości amplitudy sygnału bioelektrycznego poszczególnych głów mięśnia czworogłowego podczas maksymalnego skurczu izometrycznego (MVC) po wykonanych testach funkcjonalnych. Mogłoby to świadczyć o zmęczeniu mięśnia i konieczności uwzględnienia tego efektu w procedurach normalizacji zapisu EMG oraz podczas interpretacji wyników lub modyfikacji metodyki prowadzonych testów funkcjonalnych.The aim of this paper was the evaluation of the change of the bioelectrical signal amplitude of the guadriceps femoris muscle traffic recorded during the maximal voluntary isometric contraction (MVC test) before and after functional tests are conducted, which could influence the analysis and interpretation of the normalized bioelectrical signal. The research was conducted at the Orthopaedics and Musculoskeletal Traumatology Department at the, Silesian Medical University in Katowice. Twenty-two people with gonarthrosis underwent the clinical evaluation and were qualifited for the endoplastic surgery. The EMG was used register the tension of the quadriceps femoris muscle MyoTrace (Noraxon, USA). It has been observed, the amplitude value executed after the functional test increase statiscially with respect of the conducted. However, not all of the examinet quadriceps femoris muscle showed significant differences. It could prove the muscle’s fatigue and the necesity of considering this effect in the normalization procedures of EMG as well as during the interpretation of the results all the modification of the methodology of the conduction functional tests

The effect of the training with the different combinations of frequency and peak-to-peak vibration displacement of whole-body vibration on the strength of knee flexors and extensors

Whole-body vibration training has become a popular method used in sports and physiotherapy. The study aimed to evaluate the effect of different vibration frequency and peak-to-peak displacement combinations on men knee flexors and extensors strength in isokinetic conditions. The sample consisted of 49 male subjects randomly allocated to seven comparative groups, six of which exercised on a vibration platform with parameters set individually for the groups. The experimental groups were exposed to vibrations 3 times a week for 4 weeks. The pre- and post- isokinetic strength tests, with the angular velocities of 240°/s and 30°/s, were recorded prior to and 2 days after the training. After 4 weeks of whole-body vibration training, a significant increase was noted regarding the mean values of peak torque, average peak torque and total work for knee flexors at high angular velocity in Groups I (60 Hz/ 4 mm) and V (40 Hz/ 2 mm) (p<0.05). The mean percentage values of post-training changes to study parameters suggest that the training had the most beneficial effect in Groups I (60 Hz/4 mm) and IV (60 Hz/2 mm) (p<0.05). Whole-body vibrations during static exercise beneficially affected knee flexor strength profile in young men at high angular velocity. The combinations of 60 Hz/4 mm seem to have the most advantageous effects on muscle strength parameters

The effect of short- and long-term vibration training on postural stability in men

The study aimed to establish the short- and long-term effects of vibration on postural stability in young men. A single set of exercises and a 4-week vibration training were assessed for their impact on the center of foot pressure (COP) sway. The sample consisted of 49 male subjects randomly allocated to seven comparative groups, six of which exercised on a vibration platform whose parameters were set individually for the groups. Group VII was the control group. The stabilographic signal was recorded before the test commenced, after a single application of vibration, before the last set of exercises of the 4-week vibration training, immediately afterwards, as well as one week and one month after the training ended. The subjects were exposed to vibration 3 times a week for 4 weeks. Both a single application of vibration and the 4-week vibration training had an effect on all parameter values, but most changes were statistically insignificant. Group III was the only one where the COP sway in the anterior-posterior direction significantly increased after a single exposure to vibration and significantly decreased in both anterior-posterior and medio-lateral planes one week after vibration training compared with the pre-test recordings