Development of a dimethylarginine dimethylaminohydrolase (DDAH) assay for high-throughput chemical screening

Nitric oxide (NO) is a potent signaling molecule that needs to be tightly regulated to maintain metabolic and cardiovascular homeostasis. The nitric oxide synthase (NOS)/dimethylarginine dimethylaminohydrolase (DDAH)/asymmetric dimethylarginine (ADMA) pathway is central to this regulation. Specifically, the small-molecule ADMA competitively inhibits NOS, thus lowering NO levels. The majority of ADMA is physiologically metabolized by DDAH, thus maintaining NO levels at a physiological concentration. However, under pathophysiological conditions, DDAH activity is impaired, in part as a result of its sensitivity to oxidative stress. Therefore, the application of high-throughput chemical screening for the discovery of small molecules that could restore or enhance DDAH activity might have significant potential in treating metabolic and vascular diseases characterized by reduced NO levels, including atherosclerosis, hypertension, and insulin resistance. By contrast, excessive generation of NO (primarily driven by inducible NOS) could play a role in idiopathic pulmonary fibrosis, sepsis, migraine headaches, and some types of cancer. In these conditions, small molecules that inhibit DDAH activity might be therapeutically useful. Here, we describe optimization and validation of a highly reproducible and robust assay successfully used in a high-throughput screen for DDAH modulators.     

Rate of Belowground Carbon Allocation Differs with Successional Habit of Two Afromontane Trees

Background

Anthropogenic disturbance of old-growth tropical forests increases the abundance of early successional tree species at the cost of late successional ones. Quantifying differences in terms of carbon allocation and the proportion of recently fixed carbon in soil CO₂ efflux is crucial for addressing the carbon footprint of creeping degradation.

Methodology

We compared the carbon allocation pattern of the late successional gymnosperm Podocarpus falcatus (Thunb.) Mirb. and the early successional (gap filling) angiosperm Croton macrostachyus Hochst. es Del. in an Ethiopian Afromontane forest by whole tree ¹³CO₂ pulse labeling. Over a one-year period we monitored the temporal resolution of the label in the foliage, the phloem sap, the arbuscular mycorrhiza, and in soil-derived CO₂. Further, we quantified the overall losses of assimilated ¹³C with soil CO₂ efflux.

Principal Findings

¹³C in leaves of C. macrostachyus declined more rapidly with a larger size of a fast pool (64% vs. 50% of the assimilated carbon), having a shorter mean residence time (14 h vs. 55 h) as in leaves of P. falcatus. Phloem sap velocity was about 4 times higher for C. macrostachyus. Likewise, the label appeared earlier in the arbuscular mycorrhiza of C. macrostachyus and in the soil CO₂ efflux as in case of P. falcatus (24 h vs. 72 h). Within one year soil CO₂ efflux amounted to a loss of 32% of assimilated carbon for the gap filling tree and to 15% for the late successional one.

Conclusions

Our results showed clear differences in carbon allocation patterns between tree species, although we caution that this experiment was unreplicated. A shift in tree species composition of tropical montane forests (e.g., by degradation) accelerates carbon allocation belowground and increases respiratory carbon losses by the autotrophic community. If ongoing disturbance keeps early successional species in dominance, the larger allocation to fast cycling compartments may deplete soil organic carbon in the long run.     

Isotope signatures in winter moulted feathers predict malaria prevalence in a breeding avian host

It is widely accepted that animal distribution and migration strategy might have co-evolved in relation to selection pressures exerted by parasites. Here, we first determined the prevalence and types of malaria blood parasites in a breeding population of great reed warblers Acrocephalus arundinaceus using PCR. Secondly, we tested for differences in individual feather stable isotope signatures (delta (13)C, delta (15)N, deltaD and delta (34)S) to investigate whether malaria infected and non-infected birds had occupied different areas in winter. We show that birds moulting in Afro-tropical habitats with significantly higher delta (13)C and delta (15)N but lower deltaD and delta(34)S values were more frequently infected with malaria parasites. Based on established patterns of isotopic distributions, our results indicate that moulting sites with higher incidence of malaria are generally drier and situated further to the north in West Africa than sites with lower incidence of malaria. Our findings are pertinent to the general hypothesis that animal distribution and particularly avian migration strategy might evolve in response to selection pressures exerted by parasites at different geographic scales. Tradeoffs between investment in energy demanding life history traits (e.g. migration and winter moult) and immune function are suggested to contribute to the particular choice of habitat during migration and at wintering sites.     

Welternährung im 21. Jahrhundert. Eine umfassende Herausforderung (Teil 1)

Nutrition of the world's population in the 21st century often appears as an unsolved problem. The challenges are bigger than an increase in agricultural production. From a brief review on the history of food production diverse aspects of the development become evident: innovations with their beneficial and non‐beneficial aspects, e.g. the, green revolution' increasing the rice yields on one hand and the number of landless people on the other. Great differences can be found in agricultural productivity: the yields of the presently area under the plough can be increased. Climate change impacts on the framework of agricultural production with losses and gains of arable land. The challenges of global nutrition cannot be met by innovations in plant breeding and cultivation alone. Socioeconomic factors, education, and health become increasingly important.     

Modifying L-type calcium current kinetics: consequences for cardiac excitation and arrhythmia dynamics

The L-type Ca current (I_Ca,L), essential for normal cardiac function, also regulates dynamic action potential (AP) properties that promote ventricular fibrillation. Blocking I_Ca,L can prevent ventricular fibrillation, but only at levels suppressing contractility. We speculated that, instead of blocking I_Ca,L, modifying its shape by altering kinetic features could produce equivalent anti-fibrillatory effects without depressing contractility. To test this concept experimentally, we overexpressed a mutant Ca-insensitive calmodulin (CaM₁₂₃₄) in rabbit ventricular myocytes to inhibit Ca-dependent I_Ca,L inactivation, combined with the ATP-sensitive K current agonist pinacidil or I_Ca,L blocker verapamil to maintain AP duration (APD) near control levels. Cell shortening was enhanced in pinacidil-treated myocytes, but depressed in verapamil-treated myocytes. Both combinations flattened APD restitution slope and prevented APD alternans, similar to I_Ca,L blockade. To predict the arrhythmogenic consequences, we simulated the cellular effects using a new AP model, which reproduced flattening of APD restitution slope and prevention of APD/Ca_i transient alternans but maintained a normal Ca_i transient. In simulated two-dimensional cardiac tissue, these changes prevented the arrhythmogenic spatially discordant APD/Ca_i transient alternans and spiral wave breakup. These findings provide a proof-of-concept test that I_Ca,L can be targeted to increase dynamic wave stability without depressing contractility, which may have promise as an antifibrillatory strategy.     

Factors associated with uptake of post-abortion family planning in Shire town,Tigray, Ethiopia

Objectives

Post-abortion contraceptive service is pivotal for the prevention of unwanted pregnancy and alleviation of its complication. Worldwide half of the pregnancy is unplanned, whereas unwanted pregnancy ends up with abortion. This study assessed post-abortion contraceptive uptake and associated factors among abortion service users at health institution in Shire town, North Ethiopia. Institutional based cross-sectional study was conducted from December 15/2016 to March 15, 2017, in Shire town. Data were collected using systematic random sampling technique. Bivariate and multivariable analyses were done to determine the association of each independent variable with the dependent variable.

Results

Overall post-abortion contraceptive utilization in this study was 61.5%. Married [AOR 2.59, 95% CI (1.16, 5.65)], completed College education [AOR 5.69, 95% CI (1.61, 20.11)], previous contraceptive used [AOR 3.62, 95% CI (1.77, 7.40)], counseling of family planning [AOR 3.53 95% CI (1.69, 7.37)], grand multipara [AOR 7.91, 95% CI (1.66, 37.74)] and public health institution [AOR 5.95, 95% CI (3.03, 11.72)] were significantly associated with the post-abortion contraceptive utilization. In this study, post-abortion contraceptive utilization was about two-third. Being married, had been completing a college education, had been receiving family planning counseling, previous contraceptive usage, abortion care service at public health institution, and being grand multiparty were determinants of post-abortion contraceptive utilization.

     

Dynamic origin of spatially discordant alternans in cardiac tissue

Alternans, a condition in which there is a beat-to-beat alternation in the electromechanical response of a periodically stimulated cardiac cell, has been linked to the genesis of life-threatening ventricular arrhythmias. Optical mapping of membrane voltage (V_m) and intracellular calcium (Ca_i) on the surface of animal hearts reveals complex spatial patterns of alternans. In particular, spatially discordant alternans has been observed in which regions with a large-small-large action potential duration (APD) alternate out-of-phase adjacent to regions of small-large-small APD. However, the underlying mechanisms that lead to the initiation of discordant alternans and govern its spatiotemporal properties are not well understood. Using mathematical modeling, we show that dynamic changes in the spatial distribution of discordant alternans can be used to pinpoint the underlying mechanisms. Optical mapping of V_m and Ca_i in paced rabbit hearts revealed that spatially discordant alternans induced by rapid pacing exhibits properties consistent with a purely dynamical mechanism as shown in theoretical studies. Our results support the viewpoint that spatially discordant alternans in the heart can be formed via a dynamical pattern formation process which does not require tissue heterogeneity.     

Child undernutrition in war-torn society: the Ethiopian experience.

Using data from a cross-sectional nutrition survey conducted in rural Ethiopia between March and April 1992, roughly a year after the end of one of the longest civil wars in modern human history, this study attempts to document the magnitude and correlates of childhood undernutrition in Ethiopia. Findings from the study reveal that, at the time of the survey, 59% of children in the country were exposed to long-term or chronic undernutrition (stunted); about 4% were suffering from acute problems (wasted); and about the same proportion were both stunted and wasted. Less than a third of the country's children had normal growth. The logistic-binomial regression results demonstrated the existence of significant clustering of risks of undernutrition within areas of residence and notable differentials by age of child, duration of breast-feeding, age at introduction of supplementary foods and number of under-five siblings. Significant variations were also noted by age of household head, per capita land holding, religious affiliation and prevalence of endemic diseases in an area.     

Passerine migration strategies and body mass variation along geographic sectors across East Africa, the Middle East and the Arabian Peninsula

Using the body mass estimates of 12 long-distance migrating Palearctic passerine species monitored at successive sites across the Eastern Africa flyway, we tested whether birds modulate their body mass according to specific seasonal demands across different geographic sectors. We compared body mass estimates across latitudinal distances and geographic sectors in Europe, the desert, Northeast Africa and East Africa. Our results show that, depending on the species and season considered, the average body mass increase or decrease is variable at and among different geographic sectors. By comparing the variation in body mass between different ecological sectors, we were able to show when and where migrants accumulate their migratory fuel reserves during migration.