Preparing For Extended Field Tests of the Intelligent Water System

The Intelligent Water System, which improves access to clean water by autonomously monitoring and reporting on the health of hand pumps in developing countries, has been under development for several years. This development has included short-term prototype field tests in several countries. The design has matured to the point that an extended field trial to demonstrate performance and reliability has been requested by our client. In light of this, the team has implemented design changes to address issues from our most recent prototype field test and begun manufacture of the first five systems intended for installation in Burkina Faso. This poster highlights the code changes enabling more accurate determination of the volume of water pumped and the simplified mounting of the system’s Handle Motion Sensor.https://mosaic.messiah.edu/engr2021/1006/thumbnail.jp

PNF 2.0? Initial evidence that gamification can increase the efficacy of brief, web-based personalized normative feedback alcohol interventions

Gamified interventions exploit the motivational characteristics of a game in order to provide prevention information and promote behavior change. Despite the modest effect sizes observed in increasingly popular web-based personalized normative feedback (PNF) alcohol interventions for college students, previous research has yet to consider how gamification might be used to enhance efficacy. This study examines whether a novel, gamified PNF intervention format, which includes a point-based reward system, the element of chance, and personal icons to visually represent users, is more effective in reducing short-term alcohol use than the standard web-based style of PNF currently used on college campuses. Two-hundred and thirty-seven college students were randomly assigned to receive either a standard brief, web-based PNF alcohol intervention or the same alcohol intervention components delivered within a Facebook-connected social game called CampusGANDR (Gamified Alcohol Norm Discovery and Readjustment). In both study conditions participants answered identical questions about their perceptions of peer drinking norms and own drinking and then received the same PNF slides. Two weeks following PNF delivery, participants again reported their perceptions of peers\u27 alcohol use and own drinking. Students in the CampusGANDR condition reported significantly reduced peer drinking norms and alcohol use at the two-week follow-up relative to students who received identical PNF delivered by standard online survey. Further, a mediation model demonstrated that this effect was driven by larger reductions in perceived drinking norms among participants assigned to receive CampusGANDR, relative to control. As web-based PNF is becoming an increasingly universal prevention strategy, findings from this study suggest gamification may represent one method by which intervention efficacy could be substantially improved. The potential methodological and economic benefits associated with gamified PNF interventions are emphasized and directions for future research are discussed

Remote Hand Pump Monitoring in Africa

Millions of communities in developing countries rely on hand pumps installed by various non-governmental organizations (NGOs). Studies have shown that these pumps are often broken with significant delays before maintenance people arrive. During the last few years, the Intelligent Water Project (IWP), in cooperation with World Vision and AlignedWorks has successfully produced sensor units, installed on each water pump to provide state of operation information, which proves the feasibility of remote monitoring through a real-time web-based database. Currently, we are working to demonstrate reliability, improve accuracy, and prepare for production on a larger scale to expand the impact to more communities all over Africa. Recently we have been moving toward this goal by producing all necessary documentation to manufacture our system and prove its functionality with quality control procedures. This involves creating drawings of each component and assembly and using these along with complete manufacturing, quality control check, and installation instructions.https://mosaic.messiah.edu/engr2020/1009/thumbnail.jp

Pseudomonas aeruginosa Adaptation to Lungs of Cystic Fibrosis Patients Leads to Lowered Resistance to Phage and Protist Enemies

Pathogenic life styles can lead to highly specialized interactions with host species, potentially resulting in fitness trade-offs in other ecological contexts. Here we studied how adaptation of the environmentally transmitted bacterial pathogen, Pseudomonas aeruginosa, to cystic fibrosis (CF) patients affects its survival in the presence of natural phage (14/1, ΦKZ, PNM and PT7) and protist (Tetrahymena thermophila and Acanthamoebae polyphaga) enemies. We found that most of the bacteria isolated from relatively recently intermittently colonised patients (1-25 months), were innately phage-resistant and highly toxic for protists. In contrast, bacteria isolated from long time chronically infected patients (2-23 years), were less efficient in both resisting phages and killing protists. Moreover, chronic isolates showed reduced killing of wax moth larvae (Galleria mellonella) probably due to weaker in vitro growth and protease expression. These results suggest that P. aeruginosa long-term adaptation to CF-lungs could trade off with its survival in aquatic environmental reservoirs in the presence of microbial enemies, while lowered virulence could reduce pathogen opportunities to infect insect vectors; factors that are both likely to result in poorer environmental transmission. From an applied perspective, phage therapy could be useful against chronic P. aeruginosa lung infections that are often characterized by multidrug resistance: chronic isolates were least resistant to phages and their poor growth will likely slow down the emergence of beneficial resistance mutations

Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10-36), SULT2A1 (rs2637125; p = 2.61×10-19), ARPC1A (rs740160; p = 1.56×10-16), TRIM4 (rs17277546; p = 4.50×10-11), BMF (rs7181230; p = 5.44×10-11), HHEX (rs2497306; p = 4.64×10-9), BCL2L11 (rs6738028; p = 1.72×10-8), and CYP2C9 (rs2185570; p = 2.29×10-8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS

Elevated AKR1C3 expression promotes prostate cancer cell survival and prostate cell-mediated endothelial cell tube formation: implications for prostate cancer progressioan

<p>Abstract</p> <p>Background</p> <p>Aldo-keto reductase (AKR) 1C family member 3 (AKR1C3), one of four identified human AKR1C enzymes, catalyzes steroid, prostaglandin, and xenobiotic metabolism. In the prostate, AKR1C3 is up-regulated in localized and advanced prostate adenocarcinoma, and is associated with prostate cancer (PCa) aggressiveness. Here we propose a novel pathological function of AKR1C3 in tumor angiogenesis and its potential role in promoting PCa progression.</p> <p>Methods</p> <p>To recapitulate elevated AKR1C3 expression in cancerous prostate, the human PCa PC-3 cell line was stably transfected with an AKR1C3 expression construct to establish PC3-AKR1C3 transfectants. Microarray and bioinformatics analysis were performed to identify AKR1C3-mediated pathways of activation and their potential biological consequences in PC-3 cells. Western blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and an <it>in vitro </it>Matrigel angiogenesis assays were applied to validate the pro-angiogenic activity of PC3-AKR1C3 transfectants identified by bioinformatics analysis.</p> <p>Results</p> <p>Microarray and bioinformatics analysis suggested that overexpression of AKR1C3 in PC-3 cells modulates estrogen and androgen metabolism, activates insulin-like growth factor (IGF)-1 and Akt signaling pathways, as well as promotes tumor angiogenesis and aggressiveness. Levels of IGF-1 receptor (IGF-1R) and Akt activation as well as vascular endothelial growth factor (VEGF) expression and secretion were significantly elevated in PC3-AKR1C3 transfectants in comparison to PC3-mock transfectants. PC3-AKR1C3 transfectants also promoted endothelial cell (EC) tube formation on Matrigel as compared to the AKR1C3-negative parental PC-3 cells and PC3-mock transfectants. Pre-treatment of PC3-AKR1C3 transfectants with a selective IGF-1R kinase inhibitor (AG1024) or a non-selective phosphoinositide 3-kinases (PI3K) inhibitor (LY294002) abolished ability of the cells to promote EC tube formation.</p> <p>Conclusions</p> <p>Bioinformatics analysis followed by functional genomics demonstrated that AKR1C3 overexpression promotes angiogenesis and aggressiveness of PC-3 cells. These results also suggest that AKR1C3-mediated tumor angiogenesis is regulated by estrogen and androgen metabolism with subsequent IGF-1R and Akt activation followed by VEGF expression in PCa cells.</p

Genome organization and chromatin analysis identify transcriptional downregulation of insulin-like growth factor signaling as a hallmark of aging in developing B cells.

BACKGROUND: Aging is characterized by loss of function of the adaptive immune system, but the underlying causes are poorly understood. To assess the molecular effects of aging on B cell development, we profiled gene expression and chromatin features genome-wide, including histone modifications and chromosome conformation, in bone marrow pro-B and pre-B cells from young and aged mice. RESULTS: Our analysis reveals that the expression levels of most genes are generally preserved in B cell precursors isolated from aged compared with young mice. Nonetheless, age-specific expression changes are observed at numerous genes, including microRNA encoding genes. Importantly, these changes are underpinned by multi-layered alterations in chromatin structure, including chromatin accessibility, histone modifications, long-range promoter interactions, and nuclear compartmentalization. Previous work has shown that differentiation is linked to changes in promoter-regulatory element interactions. We find that aging in B cell precursors is accompanied by rewiring of such interactions. We identify transcriptional downregulation of components of the insulin-like growth factor signaling pathway, in particular downregulation of Irs1 and upregulation of Let-7 microRNA expression, as a signature of the aged phenotype. These changes in expression are associated with specific alterations in H3K27me3 occupancy, suggesting that Polycomb-mediated repression plays a role in precursor B cell aging. CONCLUSIONS: Changes in chromatin and 3D genome organization play an important role in shaping the altered gene expression profile of aged precursor B cells. Components of the insulin-like growth factor signaling pathways are key targets of epigenetic regulation in aging in bone marrow B cell precursors

Escherichia coli heat-stable enterotoxin b (STb) in vivo internalization within rat intestinal epithelial cells

Heat-stable enterotoxin b (STb) is a low molecular weight toxin known to bind sulfatide, its receptor. The fate of STb bound to rat intestinal epithelium cells was followed using an anti-toxin gold labeled assay and transmission electron microscopy. The data suggest that STb toxin and the fusion protein maltose binding protein (MBP)-STb were internalized whereas its mutant I41E-M42R with reduced hydrophobicity did not show internalization. There was a significant difference in the mean of gold particles per field between rat intestine incubated with STb or the fusion protein MBP-STb and the negative control consisting of intestine incubated with PBS alone. No subcellular compartment seems to be particularly aimed by the toxin as gold particles were randomly distributed within the cell.Internalisation in vivo de l'entérotoxine b (STb) d'Escherichia coli dans les cellules épithéliales d'intestin de rat. L'entérotoxine b thermostable (STb) est une toxine de faible masse moléculaire qui se lie au sulfatide, son récepteur. À l'aide d'un essai avec un anticorps anti-STb marqué à l'or suivi d'une visualisation en microscopie électronique, nous avons observé les évènements suivant l'attachement de STb aux cellules épithéliales d'intestin de rat. La toxine STb et la protéine de fusion Maltose Binding Protein-STb (MBP-STb) ont été internalisées tandis que le mutant I41E-M42R avec une hydrophobicité réduite ne présentait pas d'internalisation. Nous avons observé une différence significative de la moyenne de particules d'or par champ entre l'intestin de rat incubé avec STb ou la protéine de fusion MBP-STb et le contrôle négatif, soit le tampon PBS seul. Aucun organelle cellulaire ne semble particulièrement visé par la toxine puisque les particules d'or étaient distribuées aléatoirement dans la cellule