Inferring the cellular origin of voltage and calcium alternans from the spatial scales of phase reversal during discordant alternans

Beat-to-beat alternation of the action potential duration (APD) in paced cardiac cells has been linked to the onset of lethal arrhythmias. Both experimental and theoretical studies have shown that alternans at the single cell level can be caused by unstable membrane voltage (V(m)) dynamics linked to steep APD-restitution, or unstable intracellular calcium (Ca) cycling linked to high sensitivity of Ca release from the sarcoplasmic reticulum on sarcoplasmic reticulum Ca load. Identifying which of these two mechanisms is the primary cause of cellular alternans, however, has remained difficult since Ca and V(m) are bidirectionally coupled. Here, we use numerical simulations of a physiologically detailed ionic model to show that the origin of alternans can be inferred by measuring the length scales over which APD and Ca(i) alternans reverse phase during spatially discordant alternans. The main conclusion is that these scales are comparable to a few millimeters and equal when alternans is driven by APD restitution, but differ markedly when alternans is driven predominantly by unstable Ca cycling. In the latter case, APD alternans still reverses phase on a millimeter tissue scale due to electrotonic coupling, while Ca alternans reverses phase on a submillimeter cellular scale. These results show that experimentally accessible measurements of Ca(i) and V(m) in cardiac tissue can be used to shed light on the cellular origin of alternans.     

Ethiopian Population Dermatoglyphic Study Reveals Linguistic Stratification of Diversity

The manifestation of ethnic, blood type, & gender-wise population variations regarding Dermatoglyphic manifestations are of interest to assess intra-group diversity and differentiation. The present study reports on the analysis of qualitaive and quantitative finger Dermatoglyphic traits of 382 individuals cross-sectionally sampled from an administrative region of Ethiopia, consisting of five ethnic cohorts from the Afro-Asiatic & Nilo-Saharan affiliations. These Dermatoglyphic parameters were then applied in the assessment of diversity & differentiation, including Heterozygosity, Fixation, Panmixia, Wahlund’s variance, Nei’s measure of genetic diversity, and thumb & finger pattern genotypes, which were inturn used in homology inferences as summarized by a Neighbour-Joining tree constructed from Nei’s standard genetic distance. Results revealed significant correlation between Dermatoglyphics & population parameters that were further found to be in concordance with the historical accounts of the ethnic groups. Such inductions as the ancient north-eastern presence and subsequent admixure events of the Oromos (PII= 15.01), the high diversity of the Amharas (H= 0.1978, F= 0.6453, and P= 0.4144), and the Nilo-Saharan origin of the Berta group (PII= 10.66) are evidences to this. The study has further tested the possibility of applying Dermatoglyphics in population genetic & anthropologic research, highlighting on the prospect of developing a method to trace back population origins & ancient movement patterns. Additionally, linguistic clustering was deemed significant for the Ethiopian population, coinciding with recent genome wide studies that have ascertained that linguistic clustering as to being more crucial than the geographical patterning in the Ethiopian context. Finally, Dermatoglyphic markers have been proven to be endowed with a strong potential as non-invasive preliminary tools applicable prior to genetic studies to analyze ethnically sub-divided populations and also to reveal the stratification mechanism in play.     

Synthesis of enantiomerically pure isotopomers of 2-phenylpropionic acids

A series of enantiomerically pure [D,(13)C]-labeled isotopomeric 2-phenylpropionic acids were efficiently synthesized using a diastereoselective alkylation and kinetic resolution strategy.     

Interfacial and lipid transfer properties of human phospholipid transfer protein: implications for the transfer mechanism of phospholipids

In circulation the phospholipid transfer protein (PLTP) facilitates the transfer of phospholipid-rich surface components from postlipolytic chylomicrons and very low density lipoproteins (VLDL) to HDL and thereby regulates plasma HDL levels. To study the molecular mechanisms involved in PLTP-mediated lipid transfer, we studied the interfacial properties of PLTP using Langmuir phospholipid monolayers and asymmetrical flow field-flow fractionation (AsFlFFF) to follow the transfer of 14C-labeled phospholipids and [35S]PLTP between lipid vesicles and HDL particles. The AsFlFFF method was also used to determine the sizes of spherical and discoidal HDL particles and small unilamellar lipid vesicles. In Langmuir monolayer studies high-activity (HA) and low-activity (LA) forms of PLTP associated with fluid phosphatidylcholine monolayers spread at the air/buffer interphase. Both forms also mediated desorption of [14C]dipalmitoylphosphatidylcholine (DPPC) from the phospholipid monolayer into the buffer phase, even when it contained no physiological acceptor such as HDL. After the addition of HDL3 to the buffer, HA-PLTP caused enhanced lipid transfer to them. The particle diameter of HA-PLTP was approximately 6 nm and that of HDL3 approximately 8 nm as determined by AsFlFFF analysis. Using this method, it could be demonstrated that in the presence of HA-PLTP, but not LA-PLTP, [14C]DPPC was transferred from small unilamellar vesicles (SUV) to acceptor HDL3 molecules. Concomitantly, [35S]-HA-PLTP was transferred from the donor to acceptor, and this transfer was not observed for its low-activity counterpart. These observations suggest that HA-PLTP is capable of transferring lipids by a shuttle mechanism and that formation of a ternary complex between PLTP, acceptor, and donor particles is not necessary for phospholipid transfer.     

Avian claw morphometry and growth determine the temporal pattern of archived stable isotopes

Detailed knowledge about claw formation and growth rate is a prerequisite for the interpretation of avian claw stable isotopes, as is commonly done with feather stable isotopes to e.g. infer habitat use, dietary specialisations, and spatial occurrence. In this study, we provide basic information about claw formation and empirical evidence about the time scale of archiving isotopic information to develop a reliable assessment of archived isotopic pattern in claws of passerines. Avian claws grow conically from the tip of the bone of the phalanx. The length of the tip of an avian claw, suitable for stable isotope analysis, is about 42 ± 6.8% (SD) of total linear claw length and can also be estimated from the body mass of a given species. Claw growth rate in adult songbirds typically ranged between 0.03 and 0.05 mm d^?1, but differed between front and back toes, and varied seasonally. From the claw growth rate, the archiving period of a given claw length can be estimated. In long‐distance migrant species, δ¹³C of claws matched δ¹³C of feathers grown during the same period (wintering or breeding period). In Palaearctic‐African migrants sampled in the breeding season, δ¹³C of the distal half of the claw tip reflected the African wintering site, while the proximal half reflected a blend of African and European δ¹³C signatures, as expected. Hence there is empirical evidence that entire claw tips mirror the isotopic environments over longer periods (up to months), and over weeks when parts can be analysed. However any part of a claw contains a blend of material formed at different times due to the claw's conical (i.e. longitudinal and lateral) growth. Avian claws provide a complementary isotope archive for investigations, but its applicability may vary according to the ecology of the study species.     

Evaluation of structurally diverse neuronal nicotinic receptor ligands for selectivity at the α61 subtype

Direct comparison of pyridine versus pyrimidine substituents on a small but diverse set of ligands indicates that the pyrimidine substitution has the potential to enhance affinity and/or functional activity at α6 subunit-containing neuronal nicotinic receptors (NNRs) and decrease activation of ganglionic nicotinic receptors, depending on the scaffold. The ramifications of this structure–activity relationship are discussed in the context of the design of small molecules targeting smoking cessation.     

Evaluation of different botanical for the management of cowpea bruchid (Callosobruchus maculatus) in north-eastern Ethiopia

The pesticide efficacy of locally available seven botanicals “Gime” (Chenopodium ambrosioides), “Ayderke” (Jatropha curcas), Neem (Azadirachta indica), Melia (Melia azadirach), “Chobe” (Cisus rotonifolia), “Kelewa” (Maesa lanceolata) and “Antharfa” at a rate of 4% weight by weight was evaluated for the control of cowpea bruchid using 200?g cowpea seeds in 500?cm³ volume jar in 2010 and 2011 under laboratory condition at Sirinka Agricultural Research Centre. The combined analysis showed that “Gime” (both leaf and seed) had high speed of pesticide effect as it showed significantly higher per cent of parent adult mortality (84 and 71%, respectively) as to the standard check Malathion 5% dust (100%) in the first day of adult mortality count. “Antharfa” and “Ayderke” also have shown significantly higher per cent of parent adult mortality as to Malathion in the third and fifth day of adult mortality count, respectively. In the seventh day, all botanicals showed significantly higher per cent of adult mortality as compared to untreated check. “Gime” leaf and seed powder, “Ayderke” seed, Neem seed and “Antharfa” leaf powders significantly reduced the number of progeny emergence per day as compared to all other treatments. Moreover, these botanicals were effective in reducing per cent seed damage (0.00, 0.00, 0.57, 5.86 and 10.86%, respectively) and storage loss (0.00, 0.00, 0.073, 1.02 and 2.27%, respectively). Gime (both leaf and seed powder), “Ayderke” seed and Neem seed are locally available, simple for preparation and environmentally friendly. Therefore, these three botanicals can be recommended to satisfy the demand for organic food and save the seed damage and yield loss of cowpea caused by Callosobruchus maculates and bean bruchid (Zabrotes subfasciatus) which has similar biology with Callosobruchus maculatus.