APOL1 CKD Risk Alleles in New Mexico African American and American Indian Populations: Racial Disparity

Purpose/Background: Two haplotypes of human apolipoprotein L1 gene (gene: APOL1; protein: ApoL1) harboring three coding sequence mutations have been demonstrated as risk variants associated with non-diabetic chronic kidney diseases (CKD) in African Americans. The first one, termed G1, is a two non-synonymous SNP haplotype (rs73885319 (A\u3eG; p.S342G) and rs60910145 (G\u3eT; p.I384M). The second one, termed G2, is a two codon deletion haplotype rs71785313 (6-bp in frame deletion) These two coding-sequence variants have been discovered in CKD patients of African ancestry and linked to the pathogenesis of primary focal and segmental glomerulosclerosis (FSGS), hypertension-attributed kidney disease, and HIV-associated nephropathy (HIVAN), under a recessive inheritance pattern. Marked disparities exist in races, rates, and etiological classifications of CDK between African Americans (AAs) and European Americans. Sequencing and genotyping analysis of known APOL1 SNPs showed that only APOL1 G1 and G2 confer kidney risk, and other common and rare APOL1 missense variants, including the G3 haplotype, do not contribute to FSGS and HIVAN in the US population. According to the report of US census bureau, African American and American Indian (AI) citizens in New Mexico make up nearly 2.5% and 10.9% of the state\u27s entire population in 2018 (2). However, whether APOL1 G1 and G2 kidney-risk alleles are linked with hypertension-attributed CKD in AAs and AIs in New Mexico has not been investigated. Materials & Methods: We analyzed the published results of a retrospective analysis of inpatient and discharge data from hospitals across the state of New Mexico, known as Hospital Inpatient and Discharge Dataset (HIDD; 3). Results: A pattern persisted for all three years (2012-2014) that AAs had the highest rate of CKD followed by AIs per 10,000 population in New Mexico. AAs had the highest age adjusted rate of CKD with hypertension at 102.6 per 10,000 population (29.7% (102.6/345.7) of all CKD with hypertension patients) followed by American Indians at 91.9 (26.6% (91.9/345.7) of all CKD with hypertension patients). Interestingly, in terms of CKD with diabetes, AIs had the highest age adjusted rate at 79.9 per 10,000 followed by AAs at 66.5. Discussion/Conclusion: The prevalence of CKD with hypertension in AA and AI populations is significantly high in New Mexico, To understand the etiology of CKD in AAs and AIs in New Mexico, genotyping the APOL1 G1 and G2 risk alleles in these two populations is warranted. Detection of APOL1 associations with CKD and delineation of injury pathways (autophagy, necroptosis and ferroptosis) would bring hope for effective treatment for these kidney diseases. In addition, modifier loci can influence APOL1 risk for the development of CKD. ‘Second hits’, for example viral and environmental, may alter the outcome of APOL1 risk variants

A stable mode of bookmarking by TBP recruits RNA polymerase II to mitotic chromosomes.

Maintenance of transcription programs is challenged during mitosis when chromatin becomes condensed and transcription is silenced. How do the daughter cells re-establish the original transcription program? Here, we report that the TATA-binding protein (TBP), a key component of the core transcriptional machinery, remains bound globally to active promoters in mouse embryonic stem cells during mitosis. Using live-cell single-molecule imaging, we observed that TBP mitotic binding is highly stable, with an average residence time of minutes, in stark contrast to typical TFs with residence times of seconds. To test the functional effect of mitotic TBP binding, we used a drug-inducible degron system and found that TBP promotes the association of RNA Polymerase II with mitotic chromosomes, and facilitates transcriptional reactivation following mitosis. These results suggest that the core transcriptional machinery promotes efficient transcription maintenance globally

Development and Evaluation of Methodologies for Vulnerability Analysis of Ad-hoc Routing Protocols

This thesis presents a number methodologies for computer assisted vulnerability analysis of routing protocols in ad-hoc networks towards the goal of automating the process of finding vulnerabilities (possible attacks) on such network routing protocols and correcting the protocols. The methodologies developed are (each) based on a different representation (model) of the routing protocol, which model predicated the quantitative methods and algorithms used. Each methodology is evaluated with respect to effectiveness feasibility and possibility of application to realistically sized networks. The first methodology studied is based on formal models of the protocols and associated symbolic partially ordered model checkers. Using this methodology, a simple attack in unsecured AODV is demonstrated. An extension of the Strands model is developed which is suitable for such routing protocols. The second methodology is based on timed-probabilistic formal models which is necessary due to the probabilistic nature of ad-hoc routing protocols. This second methodolgy uses natural extensions of the first one. A nondeterministic-timing model based on partially ordered events is considered for application towards the model checking problem. Determining probabilities within this structure requires the calculation of the volume of a particular type of convex volume, which is known to be #P-hard. A new algorithm is derived, exploiting the particular problem structure, that can be used to reduce the amount of time used to compute these quantities over conventional algorithms. We show that timed-probabilistic formal models can be linked to trace-based techniques by sampling methods, and conversely how execution traces can serve as starting points for formal exploration of the state space. We show that an approach combining both trace-based and formal methods can have faster convergence than either alone on a set of problems. However, the applicability of both of these techniques to ad-hoc network routing protocols is limited to small networks and relatively simple attacks. We provide evidence to this end. To address this limitation, a final technique employing only trace-based methods within an optimization framework is developed. In an application of this third methodology, it is shown that it can be used to evaluate the effects of a simple attack on OLSR. The result can be viewed (from a certain perspective) as an example of automatically discovering a new attack on the OLSR routing protocol

Enhanced fodder yield of maize genotypes under saline irrigation is a function of their increased K accumulation and better K/Na ratio

Poor quality irrigation water adversely affects the growth and yield of crops. This study was designed to evaluate the growth, fodder yield and ionic concentration of three promising maize (Zea mays L.) genotypes under the influence of varying quality irrigation water, with different salinity levels. The genotypes, such as EV-1097, Kisan and Akbar were irrigated with usable (electrical conductivity, EC 1.5 dS m-1), marginal (EC 3.0 dS m-1), poor (EC 4.5 dS m-1) and very poor (EC 7.0 dS m-1) quality irrigationwater. The increasing adverse effects on various growth and yield variables of all three genotypes were observed with the increasing water salinity. Also, soil EC, SAR and ESP values increased linearly with increasing salinity levels of irrigation water. Poor quality irrigation water affected all the growthvariables and yield of maize. Increasing concentrations of sodium and chloride ions, coupled with decreasing concentration of potassium, in flag leaf of maize was observed in response to increasing salinity of irrigation water. The genotypic variation among the three maize genotypes to saline water irrigation was in order of EV-1097 > Kisan > Akbar. The better fresh fodder yield of maize genotypes under poor quality irrigation water was a function of their enhanced accumulation of potassium (K) and better K/Na ratio. The study concluded that, the genotype EV-1097 is a better choice for the maize growers under saline water irrigation condition.Key words: Maize (Zea Mays L.), fodder yield, saline irrigation, K accumulation, K/Na ratio

Association between home layout connectivity and cognitive ability in community dwelling older adults: Implication for occupational therapy

Physical environment has long been recognized within occupational therapy as a key factor contributing to residents’ functional abilities. However, the specific aspects of the physical environment that matter and the extent to which they do so remain less understood. This paper reports a quantitative study of the relationship between a characteristic of the physical home environment—the degree of interconnectedness of its rooms—and the cognitive ability of adults. Working with demographic, health, and home layout data collected from a sample of community-dwelling older adults in Atlanta, Georgia (N=72, Mage=69.5), we found that the cognitive functioning determined by the Montreal Cognitive Assessment (MoCA) score was significantly associated with the average connectivity and mean depth of the homes while controlling participants’ age and education. Regression analysis suggested home connectivity independently explained a little more than 4% of the variance in the MoCA scores. The results further revealed that the relationship may be better modeled using non-linear models, and that the increase in the numbers of circulation rings as average room connectivity rises may be partly, but not entirely, responsible for its association with cognitive ability. The study points to directions for further work, including causal modeling, based on recommendations that could be developed for homes to support older adults’ abilities to continue to reside in their own homes as they grow older

The development of a carbon roadmap investment strategy for carbon intensive food retail industries

This work presents an approach to develop an innovative decarbonisation investment strategy framework for carbon intensive UK industries by using statistical analysis and optimisation modelling. The case study focuses on taking a representative sample of retail buildings and assesses the financial viability of installing low-carbon Combined Heat and Power units (CHPs) and Photovoltaic Solar Panels (PVs) across a portfolio of buildings. Simulation of each building are initially conducted, and the results generate a set of regression coefficients, via a multivariate adaptive regression splines (MARS), which are inputted into a Mixed Integer Linear Programming (MILP) problem. Solving the MILP yields the optimal decarbonisation investment strategy for the case study up to 2050, considering market trends such as electricity prices, gas prices and policy incentives. Results indicate the level of investment required per year, the operational and carbon savings associated, and a program for such investments. This method is reiterated for several scenarios where different parameters such as utility prices, capital costs and grid carbon factors are forecasted up to 2050 (following the Future Energy Scenarios from National Grid). This work shows how a clear mathematical framework can assist decision-makers in commercial organisations to reduce their carbon footprint cost-effectively and thus reach science-based targets

Methyl 2-(tert-but­oxy­carbonyl­amino)-1,3-thia­zole-5-carboxyl­ate

The title compound, C10H14N2O4S, was synthesized by the reaction of methyl 2-amino­thia­zole-5-carboxyl­ate and di-tert-butyl carbonate. In this structure, the thia­zole ring is planar (mean deviation = 0.0011 Å). Two weak intra­molecular C—H⋯O hydrogen bonds are formed between two of the methyl groups and one carbonyl O atom, resulting in the formation of two twisted six-membered rings. Inter­molecular N—H⋯N hydrogen bonds link the mol­ecules to form centrosymmetric dimeric units, and the hydrogen-bond scheme is completed by inter­molecular C—H⋯O contacts

Potentiality of benthic dinoflagellate cultures and screening of their bioactivities in Jeju Island, Korea

Eleven strains of benthic dinoflagellates (Amphidinium carterae (D1), Prorocentrum rhathymum (D2),Symbiodinium sp. (D3), Coolia malayensis 1 (D4), Ostreopsis ovata 1 (D5), Ostreopsis ovata 2 (D6),Coolia malayensis 2 (D7), Amphidinium operculatum 1 (D8), Heterocapsa psammophila (D9), Cooliamalayensis 3 (D10) and Amphidinium operculatum 2 (D11)) were collected in Jeju Island, Korea and cultured in 20 L carboys after establishing unialgal cultures. Their growth potential and biomass productivity were evaluated using two different culture media (IMK and f/2 medium); it was found thatIMK medium has the potential to culture benthic dinoflagellates compared to commonly used f/2 medium. Among the benthic dinoflagellates, A. carterae (D1) had the maximum cell density (148.6 × 103 cells mL-1), growth rate (0.317 ± 0.01 divisions day-1) and biomass (0.260 ± 0.03 g L-1 dry weight) in IMK medium at 20 days of culture. Also, screened bioactivities among the methanolic extracts of cultured dinoflagellates showed A. carterae (D1) to have the highest antioxidant and  anti-inflammatory effect and O. ovata 1 (D5) had the highest anticancer activity compared to the other strains. Taken together, this is the first report on the growth potential and biomass production of benthic dinoflagellate strains isolated from Jeju Island in appropriate culture medium as well as their importance in potential pharmacological applications.Key words: Amphidinium carterae, benthic dinoflagellates, biomass, bioactivities, culture conditions, Jeju Island

Cyclohexanedione as the negative electrode reaction for organic redox flow batteries

The electrochemical reduction and oxidation of cyclohexanedione is evaluated for the first time as the negative electrode reaction in an organic redox flow battery. Electrochemical characterization indicates that the redox reaction of cyclohexanedione is a proton-coupled electron transfer process with quasi-reversible behavior in acidic media (pH 2 M) and exhibit reduction process with up to 4 electrons transferred

Infliximab induction regimens in steroid refractory acute severe colitis: a multi-centre retrospective cohort study with propensity score analysis

Background:Accelerated induction regimens of infliximab have been proposed to improve response rates in patients with steroid refractory acute severe colitis. Aims:We aimed to determine differences in outcome for acute severe ulcerative colitis between accelerated and standard-dose infliximab.Methods:We collected data on hospitalised patients receiving differing regimens of rescue therapy for steroid refractory Acute Severe Ulcerative Colitis. Our primary outcome was 30-day colectomy rate. Secondary outcomes were colectomy within index admission, 90 days and 12 months. We used propensity score analysis with optimal calliper matching using a priori defined high-risk covariates to reduce potential provider selection bias.Results:We included 131 patients receiving infliximab rescue therapy; 102 patients received standard induction and 29 received accelerated induction. In the unmatched cohort, there was no difference by type of induction in 30-day colectomy rates (18% vs. 20%, p=0.45), colectomy during index admission (13% vs. 20%, p = 0.26) or overall colectomy (20% vs. 24%, p= 0.38). In the propensity score-matched cohort of 52 patients, 30-day colectomy (57% vs. 27%, p = 0.048) and index admission colectomy (53% vs. 23%,p =0.045) rates were higher in those receiving standard induction compared to accelerated induction but there was no difference in overall colectomy rates between the 2 groups (57% vs. 31%, p =0.09). There was no significant difference in length of stay or in complication and infection rates.Conclusion:In a propensity score matched cohort, steroid refractory Acute Severe Ulcerative Colitis patients, short-term, but not long-term, colectomy rates appear to be lower in those receiving accelerated induction regimen