Muscle-Specific SIRT1 Gain-of-Function Increases Slow-Twitch Fibers and Ameliorates Pathophysiology in a Mouse Model of Duchenne Muscular Dystrophy

SIRT1 is a metabolic sensor and regulator in various mammalian tissues and functions to counteract metabolic and age-related diseases. Here we generated and analyzed mice that express SIRT1 at high levels specifically in skeletal muscle. We show that SIRT1 transgenic muscle exhibits a fiber shift from fast-to-slow twitch, increased levels of PGC-1α, markers of oxidative metabolism and mitochondrial biogenesis, and decreased expression of the atrophy gene program. To examine whether increased activity of SIRT1 protects from muscular dystrophy, a muscle degenerative disease, we crossed SIRT1 muscle transgenic mice to mdx mice, a genetic model of Duchenne muscular dystrophy. SIRT1 overexpression in muscle reverses the phenotype of mdx mice, as determined by histology, creatine kinase release into the blood, and endurance in treadmill exercise. In addition, SIRT1 overexpression also results in increased levels of utrophin, a functional analogue of dystrophin, as well as increased expression of PGC-1α targets and neuromuscular junction genes. Based on these findings, we suggest that pharmacological interventions that activate SIRT1 in skeletal muscle might offer a new approach for treating muscle diseases.American Heart Association (Postdoctoral Fellowship)National Institutes of Health (U.S.)Glenn Foundation for Medical Researc

Strategies for employees to effect change to improve performance of public organizations

Seventy percent of organizations fail in their organizational change initiatives because of failure to involve employees in the change process. Some managers lack the strategies to implement change initiatives successfully. Using Kotter’s eight-step change model as the conceptual framework, this qualitative case study was conducted to explore public sector managers’ strategies to include employees in implementing organizational change. Semi-structured interviews were used to identify public sector managers’ strategies that include employees in implementing organizational change. Interviews were conducted with eight participants who met the inclusion criteria for this study. Data analysis included methodological triangulation and Yin’s five-phase data analysis. The five resulting principal themes are effective communication, creating and sustaining employee engagement, leadership style effect, developing training programs and processes, and strengthening organizational culture. The findings indicate that managers should focus on how well their subordinates understand the overarching goals of the vision and mission of change initiatives. These findings have potential implications for positive social change that include catalyzing employees to have a healthier attitude at work, have a better sense of work–life balance, and have a sense of belonging. Understanding the contribution of an engaging workforce may enable organizations to improve performance and profits by catalyzing monetary and non-monetary contributions to benefit citizens

Magnetic Pollution of Soil Samples at Some Industrial Sites in Jos Metropolis, Plateau State, Nigeria

Magnetic susceptibility of polluted material can give a general view of the degree of heavy metal pollution, prior to a more expensive and time- consuming chemical analyses. In this study, magnetic susceptibility measurements of 40 soil samples collected from some industrial sites of Jos  Metropolis, were made using MS2G Sensor connected to Bartington MS 2 susceptibility meter. Volume magnetic susceptibility values ranged from  0.00026 x 10-5 SI to 0.0650 x 10-5 SI while low frequency mass specific susceptibility values ranged from 0.1181 x 10-6 m3kg-1 to 20.3 x 10- 6 m3kg-1. In both cases least and highest values are recorded at Zuma Steel and Dilimi respectively. Comparing low frequency mass specific susceptibility  values obtained from industrial sites to that obtained from non-industrial sites, it was observed that samples 11 and 12 from JIB and all samples collected from Dilimi recorded values higher than the  background soil samples thus indicating magnetic enhancement of soil at these locations by anthropogenic sources. The relationship between the volume magnetic susceptibility and mass specific susceptibility showed correlation of 0.983 implying that volume magnetic susceptibility results can be accepted in the absence of low frequency mass specific susceptibility measurement to assess magnetic pollution. The study also revealed that the magnetic behaviour of the dried soil samples collected from the industrial sites are controlled by concentration of ferrimagnetic minerals. Keywords: Magnetic, Pollution, Ferrimagnetic, Susceptibility, Anthropogenic, Dilim

The impact of competitive scenarios on individual and team behaviour

In this thesis, we study the impact of competitive scenarios on individual and team behaviour. In chapter one, we study experimentally the role of leadership in teams facing a game with a complex strategy space. Teams of three members face an instance of a team dispatching problem, in which the members jointly devise then separately implement a plan to visit a set of locations on a map. Some teams have one member designated as a “leader”, although this role does not confer any distinct responsibility or capability in the game. We compare the performance of teams with elected leaders, appointed leaders, and no leaders. We find that teams with leaders perform better than those without, while teams with elected leaders and teams with appointed leaders perform similarly. Our results indicate that electing a leader serves as a device to coordinate team activity, and is valuable primarily when a team needs to be able to deliver well immediately. We find that teams with leaders are more confident than those without, but this additional confidence is in line with those teams’ superior performance. In chapter two, we study experimentally the effects of individual skill in a real-performance task and the responsiveness of individual skill to various incentive schemes. Participants faced instances of the Truck Dispatch Problem, in which they devised three journeys which visit a set of locations on a map. Some participants were remunerated under a rank order tournament incentive scheme, some participants were informed of their performance ranking and were given a fixed rate whilst some participants were remunerated under a fixed rate incentive scheme. We find evidence for individual skill differences in the task, but that the distribution of these differences does not depend on the incentive treatment. In chapter three, we study empirically the effects of domestic and international football tournaments on domestic abuse in England and Wales and how these effects vary with people’s expectations of the football match outcomes. Previous studies on domestic abuse and football in England and Wales have focused primarily on international tournaments and have not taken into account the effects of expected match outcomes. This is surprising given the visibility of the English Premier League (EPL). We find in our analysis, that the existence of an EPL fixture is associated with a 1% percent increase in domestic violence while the existence of a FIFA World Cup fixture is associated with a 3% increase in domestic violence in England and Wales. Our results, also suggest that expected match outcomes have strong effects on domestic violence in England and Wales

Strategies for Employees to Effect Change to Improve Performance of Public Organizations

Seventy percent of organizations fail in their organizational change initiatives because of failure to involve employees in the change process. Some managers lack the strategies to implement change initiatives successfully. Using Kotter’s eight-step change model as the conceptual framework, this qualitative single case study was conducted to explore public sector managers’ strategies to include employees in implementing organizational change. Semistructured interviews were used to identify the strategies public sector managers use to include employees in implementing organizational change. Interviews were conducted with eight participants who met the inclusion criteria for this study. Data analysis included methodological triangulation and Yin’s 5 steps of organizing the data. The five resulting principal themes were (a) effective communication, (b) creating and sustaining employee engagement, (c) leadership style effect, (d) developing training programs and processes, and (e) strengthening organizational culture. The findings indicate that managers should focus on how well their subordinates understand the overarching goals of the vision and the mission of change initiatives. These findings have potential implications for positive social change that include catalyzing employees to have a healthier attitude at work, having a better sense of work–life balance, and having pride in belonging. Understanding the contribution of an engaging workforce may enable organizations to improve performance and profits by catalyzing monetary and nonmonetary contributions to benefit citizens

ENVIRONMENTAL CHANGE: AN IMPERATIVE FOR EMPLOYEE SATISFACTION IN PRIVATE UNIVERSITIES IN NORTH-CENTRAL NIGERIA

This research empirically examines the impact of organisational environmental change on employee job satisfaction within private universities in North-Central Nigeria. Specifically, it explores the impact of regulatory changes, market competition, and funding pressures on employee satisfaction. Adopting a descriptive survey research approach, responses were collected from 528 participants drawn from seven private universities using a structured questionnaire. The data were analysed through multiple regression analysis to ascertain the relationship between employee satisfaction and organisational change. The findings reveal that regulatory change significantly contributes positively to employee satisfaction (0.4000, 0.0145), implying that effective management of regulatory policies enhances job security and workplace stability. Market competition also significantly and positively affects satisfaction (0.4961, 0.0033), indicating that increased competitive pressures compel universities to improve employee welfare, thereby leading to greater satisfaction. Financial pressures negatively and significantly impact employee satisfaction (0.2759, 0.0118), suggesting that financial demands result in uncertainty, delayed salaries, and decreased job morale. These results support organisational justice theory by highlighting the importance of procedural, distributive, and interactional justice in organisational change management. The following recommendations are proposed for private universities based on these results: sustaining transparency in regulatory changes, maintaining competitive and fair reward systems, and involving employees in financial decision-making to enhance job satisfaction despite environmental pressures

Assessment of biological role and insight into druggability of the Plasmodium falciparum protease plasmepsin V

Upon infecting a red blood cell (RBC), the malaria parasit

Activation of the Plasmodium egress effector subtilisin-like protease 1 is mediated by plasmepsin X destruction of the prodomain

Following each round of replication, daughter merozoites of the malaria parasite Plasmodium falciparum escape (egress) from the infected host red blood cell (RBC) by rupturing the parasitophorous vacuole membrane (PVM) and the RBC membrane (RBCM). A proteolytic cascade orchestrated by a parasite serine protease, subtilisin-like protease 1 (SUB1), regulates the membrane breakdown. SUB1 activation involves primary autoprocessing of the 82-kDa zymogen to a 54-kDa (p54) intermediate that remains bound to its inhibitory propiece (p31) postcleavage. A second processing step converts p54 to the terminal 47-kDa (p47) form of SUB1. Although the aspartic protease plasmepsin X (PM X) has been implicated in the activation of SUB1, the mechanism remains unknown. Here, we show that upon knockdown of PM X, the inhibitory p31-p54 complex of SUB1 accumulates in the parasites. Using recombinant PM X and SUB1, we show that PM X can directly cleave both p31 and p54. We have mapped the cleavage sites on recombinant p31. Furthermore, we demonstrate that the conversion of p54 to p47 can be effected by cleavage at either SUB1 or PM X cleavage sites that are adjacent to one another. Importantly, once the p31 is removed, p54 is fully functional inside the parasites, suggesting that the conversion to p47 is dispensable for SUB1 activity. Relief of propiece inhibition via a heterologous protease is a novel mechanism for subtilisin activation

Quantifying Nematodes through Images: Datasets, Models, and Baselines of Deep Learning

Every year, plant parasitic nematodes, one of the major groups of plant pathogens, cause a significant loss of crops worldwide. To mitigate crop yield losses caused by nematodes, an efficient nematode monitoring method is essential for plant and crop disease management. In other respects, efficient nematode detection contributes to medical research and drug discovery, as nematodes are model organisms. With the rapid development of computer technology, computer vision techniques provide a feasible solution for quantifying nematodes or nematode infections. In this paper, we survey and categorise the studies and available datasets on nematode detection through deep-learning models. To stimulate progress in related research, this survey presents the potential state-of-the-art object detection models, training techniques, optimisation techniques, and evaluation metrics for deep learning beginners. Moreover, seven state-of-the-art object detection models are validated on three public datasets and the AgriNema dataset for plant parasitic nematodes to construct a baseline for nematode detection.Comment: The 26th IEEE International Conference on Computational Science and Engineering (CSE-2023