Piperazine sulfonamide BACE1 inhibitors: Design,synthesis, and in vivo characterization

With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2′ sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral Aβ₄₀ in transgenic mice with a single subcutaneous dose.     

High‐density molecular characterization and association mapping in Ethiopian durum wheat landraces reveals high diversity and potential for wheat breeding

Durum wheat (Triticum turgidum subsp. durum) is a key crop worldwide, and yet, its improvement and adaptation to emerging environmental threats is made difficult by the limited amount of allelic variation included in its elite pool. New allelic diversity may provide novel loci to international crop breeding through quantitative trait loci (QTL) mapping in unexplored material. Here, we report the extensive molecular and phenotypic characterization of hundreds of Ethiopian durum wheat landraces and several Ethiopian improved lines. We test 81 587 markers scoring 30 155 single nucleotide polymorphisms and use them to survey the diversity, structure, and genome‐specific variation in the panel. We show the uniqueness of Ethiopian germplasm using a siding collection of Mediterranean durum wheat accessions. We phenotype the Ethiopian panel for ten agronomic traits in two highly diversified Ethiopian environments for two consecutive years and use this information to conduct a genome‐wide association study. We identify several loci underpinning agronomic traits of interest, both confirming loci already reported and describing new promising genomic regions. These loci may be efficiently targeted with molecular markers already available to conduct marker‐assisted selection in Ethiopian and international wheat. We show that Ethiopian durum wheat represents an important and mostly unexplored source of durum wheat diversity. The panel analysed in this study allows the accumulation of QTL mapping experiments, providing the initial step for a quantitative, methodical exploitation of untapped diversity in producing a better wheat.     

Ethnobotanical study of medicinal plants in Ganta Afeshum District,Eastern Zone of Tigray,Northern Ethiopia

Background

Starting from the ancient time, the people of Ethiopia use medicinal plants as traditional medicine to heal different human and livestock ailments. This ethnobotanical study of medicinal plants was carried out in Ganta Afeshum District, Eastern Zone of Tigray, Northern Ethiopia, to identify medicinal plant species used by the local community to treat various human and livestock ailments.

Methods

A total of 78 informants (54 men and 24 women) were selected to collect ethnobotanical information from four study sites. Among the 78 informants, 20 key informants were selected purposefully; the other 58 informants were selected randomly by lottery method. Ethnobotanical data were collected using semi-structured interviews, field observations, guided field walks, and group discussions and were analyzed by preference ranking, paired comparison, direct matrix ranking, informant consensus factor, fidelity level (FL), use-value, independent samples t test, and Pearson correlation coefficients.

Results

A total of 173 medicinal plants were collected and identified that were distributed across 77 families and 156 genera. The family Fabaceae stood first by contributing 17 (9.8%) species followed by Lamiaceae and Solanaceae with 9 (5.2%) species each. Rhamnus prinoides was reported for the treatment of many of the described diseases. One hundred sixteen (67.1%) medicinal plant species were collected from natural vegetation, 34 (19.7) were from home gardens, 13 (7.5%) from farmland, and 10 (5.8%) were from natural vegetation and home gardens. The most widely used life form was herbs (69 species, 39.9%) followed by shrubs (58 species, 33.5%). The most commonly used part of the medicinal plants was the leaves followed by roots. The plants were prepared by grinding, powdering, squeezing, roasting, and burning and were administered through oral, dermal, nasal, anal, ocular, and vaginal, and on the surface of the teeth. The most commonly used applications were by drinking, smearing, eating, fumigation, and chewing. There was no difference between men and women informants, showing that the two sexes had similar knowledge in the use of traditional medicinal plants. Educational level and medicinal plant knowledge of informants were negatively correlated; whereas age and medicinal plant knowledge of informants were positively correlated.

Conclusions

Ganta Afeshum District is relatively rich in diversity of medicinal plant resources accompanied with a rich indigenous knowledge within the local communities to harvest and effectively use to prevent different human and livestock ailments. However, nowadays, deforestation, agricultural expansion, overgrazing, drought, and overexploitation are threatening these properties. Therefore, people of the study area should apply complementary conservation approaches (in situ and ex situ) for sustainable use of these resources and to prevent species extinction.

     

Actions of PACAP and VIP on melanotrope cells of Xenopus laevis

The neuropeptides, pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are implicated in the regulation of gene expression and hormone secretion in mammalian melanotrope cells and a mammalian pro-opiomelanocortin (POMC)-producing tumor cell line, but the physiological relevance of this regulation is elusive. The purpose of the present study was to establish if these peptides affect biosynthetic and secretory processes in a well-established physiological model for endocrine cell functioning, the pituitary melanotrope cells of the amphibian Xenopus laevis, which hormonally control the process of skin color adaptation to background illumination. We show that both PACAP and VIP are capable of stimulating the secretory process of the Xenopus melanotrope cell. As the peptides are equipotent, they may exert their actions via a VPAC receptor. Moreover, PACAP stimulated POMC biosynthesis and POMC gene expression. Strong anti-PACAP immunoreactivity was found in the pituitary pars nervosa (PN), suggesting that this neurohemal organ is a source of neurohormonal PACAP action on the melanotropes in the intermediate pituitary. We propose that the PACAP/VIP family of peptides has a physiological function in regulating Xenopus melanotrope cell activity during the process of skin color adaptation.     

Assessing changes in the distribution and range size of demersal fish populations in the Benguela Current Large Marine Ecosystem

Distributional change, expressed as range expansion or contraction , has been observed in many marine populations and related to changes in the environment. The extent of such distributional changes is also expected to increase in response to future climate change. The Benguela Current Large Marine Ecosystem (BCLME) which adjoins the south-western coast of Africa is a global marine hotspot with long-term warming occurring over a large area. The area is also an important centre of marine food production for three countries—South Africa, Namibia and Angola and is considered to be vulnerable to future climate change or increased climate variability. In this study we analysed change in distribution and range size of several demersal fish species in the BCLME over the period 1985–2010, including both commercial and non-commercial fish populations. Some of the observed changes in distribution and range size correspond to what is expected with increased warming whereas others appear to the contrary. Overall the results of the study highlight the complex nature of the response of fish population to climate change.