Kinetics and mechanism for reduction of halo- and haloam(m)ine platinum(IV) complexes by l-ascorbate

Reduction of the model platinum(IV) complexes cis-[PtCl₄(NH₃)₂] (1), trans-[PtCl₄(NH₃)₂] (2), trans-[PtCl₂(en)₂]²⁺ (3), trans-[PtBr₂(NH₃)₄]²⁺ (4), [PtCl₆]²⁻ (5), and [PtBr₆]²⁻ (6) with l-ascorbic acid (H₂Asc) in 1.0 M aqueous medium at 25 °C in the region 1.75≤pH≤7.20 has been investigated using stopped-flow spectrophotometry. The redox reactions follow the rate law: −d[Pt(IV]/dt=k[H₂Asc]_tot[Pt(IV)] where k is a pH-dependent second-order rate constant and [H₂Asc]_tot, the total concentration of ascorbic acid. The pH-dependence of k is attributed to parallel reduction of Pt(IV) by the protolytic species HAsc⁻ and Asc²⁻. Analysis of the kinetics data reveals that the ascorbate anion Asc²⁻ is up to seven orders of magnitude more reactive than HAsc⁻ while H₂Asc is unreactive. Electron transfer from HAsc⁻/Asc²⁻ to the Pt(IV) compounds is suggested to take place by a mechanism involving a reductive attack on any one of the mutually trans-halide ligands by Asc²⁻ and/or HAsc⁻ forming a halide-bridged activated complex. The rapid reduction of these complexes supports the assumption that ascorbate Asc²⁻ might be an important reductant at physiological conditions for anticancer active Pt(IV) pro-drugs capable of undergoing reductive trans elimination. The parameters ΔH^≠ and ΔS^≠ for reduction of Pt(IV) with Asc²⁻ have been determined from the study of the temperature dependence of k.     

Cyanobacterial N2 fixation in presence of nitrogen fertilizers

Anabaena oryzae ARM 570 was examined for its growth (chlorophyll and protein), heterocyst frequency, nitrogenase (acetylene reduction) activity, ammonia excretion, and glutamine synthetase and nitrate reductase in response to two levels of urea-N vis-à-vis N2-N. Growth of cyanobacterium increased with duration of incubation. Reduction in heterocyst frequency (40%) was observed at 30 ppm of urea-N, whereas at 60 ppm of urea-N, filaments were completely devoid of heterocysts and no nitrogenase activity was observed. Maximum excretion of ammonia occurred at 30 ppm of urea-N, which was concomitant with minimum glutamine synthetase activity. These results suggested that A. oryzae could be effectively utilized in cyanobacterial biofertilizer programme even in the presence of combined nitrogen, for improving N-budget in rice cultivation.     

Microarrayed compound screening (microARCS) to identify activators and inhibitors of AMP-activated protein kinase

A novel and innovative high-throughput screening assay was developed to identify both activators and inhibitors of AMP-activated protein kinase (AMPK) using microarrayed compound screening (microARCS) technology. Test compounds were arrayed at a density of 8640 on a polystyrene sheet, and the enzyme and peptide substrate were introduced into the assay by incorporating them into an agarose gel followed by placement of the gels onto the compound sheet. Adenosine triphosphate (ATP) was delivered via a membrane, and the phosphorylated biotinylated substrate was captured onto a streptavidin affinity membrane (SAM trade mark ). For detection, the SAM trade mark was removed, washed, and imaged on a phosphor screen overnight. A library of more than 700,000 compounds was screened using this format to identify novel activators and inhibitors of AMPK.     

Prevalence and Associated Factors of Hypertension: A Crossectional Community Based Study in Northwest Ethiopia

Background

Hypertension, being the root cause of many of the body sytem and organs failure, remains to be a major public health challenge globally. Though the problem is huge in both developed and developing countries, data are scarce in developing countries like Ethiopia. Therefore, this study was aimed to determine the magnitude and associated factors of hypertension in North West Ethiopia.

Methods

A cross-sectional survey was conducted on adults aged 35 years and above in the rural and urban communities of Dabat district and Gondar town in 2012. The data were collected using the WHO STEPwise strategy. Hypertension was defined as having a Systolic blood pressure of ≥140 mmHg and/ or a Diastolic BP of ≥ 90mmHg or a reported use of anti-hypertensive medications for raised blood pressure. Prevalence was computed with a 95% confidence interval. Selected risk factors were assessed using a biviarete logistic regression.

Results

A total of 2200 participants were included in the study. The median age (±SD) was 47 (±12.4) years. The overall prevalence of hypertension was found to be 27.9% [95% CI 26.0, 29.8], with the proportion in the urban and rural residents being 30.7% and 25.3% respectively. The prevalence of hypertension was 29.3% for women and 26.3% for men. Out of the 598 hypertensive patients 241 (40.3%) had blood pressure measurements, and 99 (16.6%) had known hypertension and were on treatment. The proportion of systolic and diastolic hypertension in this subgroup of adults was 133(6.2%). The multivariable logistic regression analysis showed older age (AOR = 1.06; 1.05, 1.07), raised fasting glucose (AOR = 1.01; 1.001, 1.01), alcohol consumption (AOR = 1.71; 1.24, 2.36), and raised BMI (AOR =1.07; 1.04, 1.10) were significantly associated with hypertension.

Conclusion

The prevalence of hypertension was considerably higher in rural areas than previously reported. The health system needs to develop strategies to increase the reach of relevant screening and diagnostic services to both rural and urban populations.     

Navigating the kinome

Although it is increasingly being recognized that drug-target interaction networks can be powerful tools for the interrogation of systems biology and the rational design of multitargeted drugs, there is no generalized, statistically validated approach to harmonizing sequence-dependent and pharmacology-dependent networks. Here we demonstrate the creation of a comprehensive kinome interaction network based not only on sequence comparisons but also on multiple pharmacology parameters derived from activity profiling data. The framework described for statistical interpretation of these network connections also enables rigorous investigation of chemotype-specific interaction networks, which is critical for multitargeted drug design.     

Overwintering behavior of the entomopathogenic nematodes Steinernema scarabaei and Heterorhabditis bacteriophora and their white grub hosts

Entomopathogenic nematodes (EPNs) are obligate pathogens known to naturally persist in many habitats. Because survival is a fundamental component of persistence, we investigated whether vertical movement and other avoidance behaviors (i.e., in‐host survival and latent infection), previously speculated as viable survival mechanisms, are exhibited during the cooler months in a temperate turfgrass habitat. The vertical distribution of populations of two EPN species, Steinernema scarabaei Stock & Koppenhöfer (Rhabditida: Steinernematidae) and Heterorhabditis bacteriophora Poinar (Rhabditida: Heterorhabditidae), and two important hosts of these EPN species, the white grub species Popillia japonica Newman and Anomala orientalis Waterhouse (both Coleoptera: Scarabaeidae), were regularly monitored in turf plots from October through April in two consecutive years. Entomopathogenic nematode vertical distribution showed limited changes for H. bacteriophora but none for S. scarabaei. Recovery of H. bacteriophora showed a strong and consistent decline at 0–4 cm depth in the 1st year and a weaker decline at 4–10 cm in the 1st year and at 0–4 cm in the 2nd year. Due to high variability in the data, it was not possible to determine whether the decline in the upper soil layers was due to downward migration or attrition of infective juvenile nematodes. The decline occurred mostly during the first half of the season before the soil froze to any significant extent. The vertical distribution of both white grub species changed with temperature during fall and spring, but not during winter. Overwintering infective juveniles were only recovered in the soil. There was no evidence for successful in‐host survival or latent infection by the nematodes in endemic white grub populations.     

Outpatient Therapeutic Feeding Program Outcomes and Determinants in Treatment of Severe Acute Malnutrition in Tigray,Northern Ethiopia: A Retrospective Cohort Study

Background

Outpatient Therapeutic feeding Program (OTP) brings the services for management of Severe Acute Malnutrition (SAM) closer to the community by making services available at decentralized treatment points within the primary health care settings, through the use of ready-to-use therapeutic foods, community outreach and mobilization. Little is known about the program outcomes. This study revealed the levels of program outcome indictors and determinant factors to recovery rate.

Methods

A retrospective cohort study was conducted on 628 children who had been managed for SAM under OTP from April/2008 to January/2012. The children were selected using systematic random sampling from 12 health posts and 4 health centers. The study relied on information of demographic characteristics, anthropometries, Plumpy''Nut, medical problems and routine medications intakes. The results were estimated using Kaplan-Meier survival curves, log-rank test and Cox-regression.

Results

The recovery, defaulter, mortality and weight gain rates were 61.78%, 13.85%, 3.02% and 5.23 gm/kg/day, respectively. Routine medications were administered partially and children with medical problems were managed inappropriately under the program. As a child consumed one more sachet of Plumpy''Nut, the recovery rate from SAM increased by 4% (HR = 1.04, 95%-CI = 1.03, 1.05, P<0.001). The adjusted hazard ratios to recovery of children with diarrhea, appetite loss with Plumpy''Nut and failure to gain weight were 2.20 (HR = 2.20, 95%-CI = 1.31, 3.41, P = 0.001), 4.49 (HR = 1.74, 95%-CI = 1.07, 2.83, P = 0.046) and 3.88 (HR = 1.95, 95%-CI = 1.17, 3.23, P<0.001), respectively. Children who took amoxicillin and de-worming had 95% (HR = 1.95, 95%-CI = 1.17, 3.23) and 74% (HR = 1.74, 95%-CI = 1.07, 2.83) more probability to recover from SAM as compared to those who didn''t take them.

Conclusions

The OTP was partially successful. Management of children with comorbidities under the program and partial administration of routine drugs were major threats for the program effectiveness. The stakeholders should focus on creating the capacity of the OTP providers on proper management of SAM to achieve fully effective program.     

Geographic distribution of microsatellite alleles in geladas (Primates,Cercopithecidae): Evidence for three evolutionary units

The subspecific taxonomy and distribution of geladas (Theropithecus gelada Rüppell, 1835) remains uncertain. Recent molecular studies based on mitochondrial sequence data revealed a geographically structured, three-deme population, suggesting that there are three evolutionary units of geladas. However, mitochondrial distributions do not always recover population relationships, particularly in taxa with a complex history of isolation and gene flow. We therefore analysed the nuclear genetic population structure of the global gelada population based on 20 microsatellite loci in 43 samples from across its geographic range. F_ST values, a STRUCTURE analysis and a principal coordinate analysis (PCoA) confirmed the three-deme population structure corresponding to the mitochondrial population structure. Therefore, our analyses provide additional support for three evolutionary units in geladas, corresponding to (a) a northern (north of Lake Tana, primarily in the Simien Mountains, previously classified as Theropithecus gelada gelada Rüppell, 1835), (b) a central (between Addis Ababa and the highlands east of Lake Tana, previously classified as Theropithecus gelada obscurus Heuglin, 1863) and (c) a southern (south of the Rift Valley, previously tentatively classified as Theropithecus gelada arsi Shotake et al., 2016, Anthropological Science, 124, 157) population. These results pave the way for future conservation decisions and highlight that the gelada population boundaries need more fine-grained genetic sampling and phenotypic analyses, in particular for their taxonomic ranking.