SIRT3 Regulation Under Cellular Stress: Making Sense of the Ups and Downs

Sirtuin 3 (SIRT3) is an NAD+ dependent deacetylase that resides primarily in mitochondria and functions to maintain mitochondrial homeostasis under stress. SIRT3 expression has been observed to change under a number of different stresses in multiple tissues and model systems. Inconsistencies in the literature with regards to how and when SIRT3 protein levels change indicates that the mechanism of SIRT3 regulation is multi-faceted. Alterations in SIRT3 have been observed in experimental models of cellular stress, however, the effect these changes have on mitochondrial health remain unknown. Neurons are highly dependent on proper mitochondrial function for their survival. SIRT3 dynamics and function have been studied using models of genotoxic, metabolic, and oxidative stresses, although it remains unclear how SIRT3 is being regulated under these conditions. A closer look into SIRT3 regulation under stress conditions in various model systems will help incorporate the many SIRT3 regulatory mechanisms at play in disease states. In this review, we describe the observations that have been made about SIRT3 protein modulation under basic stress conditions. We then point out consistencies and contradictions in these observations and what they mean. Lastly, we present the observations made in the complicated neuronal stress of stroke. We hope that this review will help consolidate the ambiguous SIRT3 literature and provide a framework for investigation of SIRT3 regulation during stress response

Analysis of optimal operating modes of the induction traction drives for establishing a control algorithm over a semiconductor transducer

Оптимізовано режими роботи тягового асинхронного приводу тепловоза за критерієм ефективності. Ідентифіковано оптимальні режими керування автономного інвертору напруги при різних температурах обмоток тягових двигунів. Проаналізовано оптимальні режими роботи тягового приводу тепловоза та трамваю, що дозволило встановити відмінності розташування точки переходу з просторово-векторної до однократної ШІМ від температури двигуна

Antidepressant-like Effect of Extracts From Urtica Dioica in Mice Model of Depression

Urtica dioica (Stinging nettle) leaves have been used as a traditional medicine to treatrheumatoid arthritis, to alleviate rheumatic pain benign prostatic hyperplasia (BPH), diuretic and prevention of kidney stones by local people in Middle East region especially in Iran, Turkey and East Europe. Hence, this investigation evaluates the antidepressant effect of selected crude extracts in the forced swimming test (FST) and tail suspension test (TST), two models predictive of antidepressant activity. The acute treatment of mice with extracts by intra-peritoneal (i.p.) route significantly reduced the immobility time in the FST (50 and 100 mg/kg) and TST (50 and 100 mg/kg), as compared to positive controls (haloperidol and fluoxetine) at 1 and 10 mg/kg, respectively. On the third day of experiment, a significant decrease of mobility was observed for chloroform extract (CE I) and butanol extract (BE II) compared to first day. CE I and BE II led to reduction of immobility time, as the selected extracts with two doses administered were different compared to the control, in the FST method by 65.37% and53.92% for 100 mg/kg, respectively. However, CE I showed the best result compared to our positive controls. Similar results of increased antidepressant effect, that was, of immobility time depending on the concentration administered, were obtained with the TST method. Also our data showed that there was no significant differences between doses (50 and 100 mg/kg). The results suggested that the antidepressant action of the butanol extract and of U. dioica its fraction (BE II2) was mediated by an interaction with 5-hydroxytrptamine (5-HT). U. dioica showed a potential source for the isolation of important natural products with antidepressant-like properties. However, further studies are still require

A Comparison of quality of life outcomes following different techniques of mastoid surgery

- Background: Mastoid surgery carried out to treat chronic otitis media (COM) can lead to an improvement in objective and subjective measures post-operatively. This study aims to look at the subjective change in quality of life using the Glasgow Benefit Inventory relative to the type of mastoid surgery undertaken. - Method: A retrospective multi-centre postal questionnaire survey of 157 patients who underwent mastoid surgery from 2008-2012. - Results: 83 questionnaire responses were received from patients having the surgery at 3 different hospitals (a response rate of 53%). 57% of patients had a Glasgow benefit Score of 0 indicating no change in quality of life post-operatively. 35% scored +50 indicating a significant improvement. The only significant difference found was that women fare worse after surgery than men. - Conclusions: The choice of mastoid surgery technique should be determined by clinical need and surgeon preference. There is no improvement in quality of life for most patients

Result of 2004 extended trypanosomosis survey of ruminants at Kachia Grazing Reserve, North Central Nigeria

Tsetse fly and trypanosome prevalence in ruminants were estimated in April and August, peak months of the dry and rainy seasons in the Kachia Grazing Reserve (KGR) of Kaduna State, North Central Nigeria. This study was subsequent to reports of seasonal outmigration of semi nomadic Fulani from the grazing reserve due to death of cattle from trypanosomosis. Result of blood samples showed an overall parasitological infection rate of 17.4%. Infection rates in cattle, sheep and goats were, 18.6%, 9.5% and 5.1% respectively. Over all higher infection rate in the rainy season was attributed to abundance of tsetse and other hematophagus flies. Infection rate in younger animals (21.9%) was higher compared to those of older animals (16.5%). Trypanosoma vivax was the dominant infecting trypanosome specie followed by T. congolense and T. brucei.It was concluded that tsetse fly and trypanosomosis constituted dual plagues limiting economic livestock production and settling of the pastoralists in the grazing reserve. This warrants application of sustainable integrated control measures to enhance utilization of abundant fodder at the reserve.Key words: Kachia grazing reserve, trypanosomosis, ruminants, infection rates, Nigeria. Resultat de l'enquete de trypanosomose extension de 2004 des ruminants a la reserve de piscine Kachia, Nigeria Centrale du NordLa prévalence de la mouche tsé-tsé et du trypanosome chez les ruminants a été estimée en avril et août, les mois de pointe des saisons secanes et pluvieuses dans la réserve de pâturage de Kachia (KGR) de l'État de Kaduna, dans le nord du centre du Nigeria. Cette étude a été postérieure à des rapports d'émigration saisonnière de Fulani semi-nomades provenant de la réserve de pâturage en raison de la mort de bovins de la trypanosomose. Le résultat des échantillons de sang a montré un taux global d'infection parasitaire de 17,4%. Les taux d'infection chez les bovins, les ovins et les chèvres étaient respectivement de 18,6%, 9,5% et 5,1%. Le taux d'infection plus élevé pendant la saison des pluies a été attribué à l'abondance de mouches tsé-tsé et d'autres mouches hématophobes. Le taux d'infection chez les animaux plus jeunes (21,9%) était plus élevé par rapport à ceux des animaux plus âgés (16,5%). Trypanosoma vivax était le trypanosome infectant dominant suivi de T. congolense et T. brucei.On a conclu que la mouche tsé-tsé et la trypanosomose constituaient des fléaux doubles limitant la production d'élevage économique et la colonisation des pasteurs dans la réserve de pâturage. Cela justifie l'application de mesures de contrôle intégrées durables pour améliorer l'utilisation de fourrages abondants dans la réserve.Mots clés: réserve de pâturage de Kachia, trypanosomose, ruminants, taux d'infection, Nigeri

Objective assessment of electrode discrimination with the auditory change complex in adult cochlear implant users

The spatial auditory change complex (ACC) is a cortical response elicited by a change in place of stimulation. There is growing evidence that it provides a useful objective measure of electrode discrimination in cochlear implant (CI) users. To date, the spatial ACC has only been measured in relatively experienced CI users with one type of device. Early assessment of electrode discrimination could allow auditory stimulation to be optimized during a potentially sensitive period of auditory rehabilitation. In this study we used a direct stimulation paradigm to measure the spatial ACC in both pre- and post-lingually deafened adults. We show that it is feasible to measure the spatial ACC in different CI devices and as early as 1 week after CI switch-on. The spatial ACC has a strong relationship with performance on a behavioural discrimination task and in some cases provides information over and above behavioural testing. We suggest that it may be useful to measure the spatial ACC to guide auditory rehabilitation and improve hearing performance in CI users

Ribosomal Protein s15 Phosphorylation Mediates LRRK2 Neurodegeneration in Parkinson’s Disease

SummaryMutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of familial and sporadic Parkinson’s disease (PD). Elevated LRRK2 kinase activity and neurodegeneration are linked, but the phosphosubstrate that connects LRRK2 kinase activity to neurodegeneration is not known. Here, we show that ribosomal protein s15 is a key pathogenic LRRK2 substrate in Drosophila and human neuron PD models. Phosphodeficient s15 carrying a threonine 136 to alanine substitution rescues dopamine neuron degeneration and age-related locomotor deficits in G2019S LRRK2 transgenic Drosophila and substantially reduces G2019S LRRK2-mediated neurite loss and cell death in human dopamine and cortical neurons. Remarkably, pathogenic LRRK2 stimulates both cap-dependent and cap-independent mRNA translation and induces a bulk increase in protein synthesis in Drosophila, which can be prevented by phosphodeficient T136A s15. These results reveal a novel mechanism of PD pathogenesis linked to elevated LRRK2 kinase activity and aberrant protein synthesis in vivo

2005- 2008 UNLV McNair Journal

Journal articles based on research conducted by undergraduate students in the McNair Scholars Program Table of Contents Biography of Dr. Ronald E. McNair Statements: Dr. Neal J. Smatresk, UNLV President Dr. Juanita P. Fain, Vice President of Student Affairs Dr. William W. Sullivan, Associate Vice President for Retention and Outreach Mr. Keith Rogers, Deputy Executive Director of the Center for Academic Enrichment and Outreach McNair Scholars Institute Staf

Expression of BNIP3 in invasive breast cancer: correlations with the hypoxic response and clinicopathological features

<p>Abstract</p> <p>Background</p> <p>Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is a pro-apoptotic member of the Bcl-2 family induced under hypoxia. Low or absent expression has recently been described in human tumors, including gastrointestinal tumors, resulting in poor prognosis. Little is known about BNIP3 expression in invasive breast cancer. The aim of the present study was to investigate the expression of BNIP3 in invasive breast cancer at the mRNA and protein level in correlation with the hypoxic response and clinicopathological features.</p> <p>Methods</p> <p>In 40 cases of invasive breast cancer, BNIP3 mRNA <it>in situ </it>hybridization was performed on frozen sections with a digoxigenin labeled anti-BNIP3 probe. Paraffin embedded sections of the same specimens were used to determine protein expression of BNIP3, Hypoxia Inducible Factor 1 alpha (HIF-1α) and its downstream targets Glucose Transporter 1 (Glut-1) and Carbonic Anhydrase (CAIX) by immunohistochemistry.</p> <p>Results</p> <p>BNIP3 mRNA was expressed in 16/40 (40%) of the cases and correlated with BNIP3 protein expression (p = 0.0218). Neither BNIP3 protein nor mRNA expression correlated with expression of HIF-1α expression or its downstream targets. Tumors which showed loss of expression of BNIP3 had significantly more often lymph node metastases (82% vs 39%, p = 0.010) and showed a higher mitotic activity index (p = 0.027). BNIP3 protein expression was often nuclear in normal breast, but cytoplasmic in tumor cells.</p> <p>Conclusion</p> <p>BNIP3 expression is lost in a significant portion of invasive breast cancers, which is correlated with poor prognostic features such as positive lymph node status and high proliferation, but not with the hypoxic response.</p