Discovery of new potential triplet acting inhibitor for Alzheimer’s disease via X-ray crystallography,molecular docking and molecular dynamics

Abstract

The most common brain disorder of late life is Alzheimer’s disease (AD), which is highly complicating dementia. There are several drug targets which are reported to control the severe level of AD; notably, acetylcholinesterase, β-Secretase and glycogen synthase kinase enzymes are approached as a good drug targets for AD. Hence, the present study mainly focused to discover newly synthesized molecule (7-propyl-6H-pyrano[3,2-c:5,6-c']dichromene-6,8(7H)-dione) as a potential triplet acting drug for above said enzymes through the analysis of X-ray crystallography, molecular docking, molecular dynamics and quantum chemical calculation. The target drug molecule was crystallized in the monoclinic crystal structure with P21/n space group. The structure was solved by SHELXS and refined by SHELXL. The crystal packing is stabilized by C???H···O type of interactions. Further, the induced fit docking shows that the molecule has high docking score, glide energy, favorable hydrogen bonding and hydrophobic interactions on the protein targets. The molecular dynamics simulation was performed to understand the stability of the molecule in the presence of active site environment. Finally, quantum chemical calculation has been carried out for the molecule in gas phase and for the corresponding molecule lifted from the active site region. The structural comparison between gas phase and active site helps to understand the conformational modification of the molecule in the active site.

Communicated by Ramaswamy H. Sarma     

Age‐ and sex‐related dietary specialization facilitate seasonal resource partitioning in a migratory shorebird

1. Dietary specialization is common in animals and has important implications for individual fitness, inter‐ and intraspecific competition, and the adaptive potential of a species. Diet composition can be influenced by age‐ and sex‐related factors including an individual''s morphology, social status, and acquired skills; however, specialization may only be necessary when competition is intensified by high population densities or increased energetic demands.
2. To better understand the role of age‐ and sex‐related dietary specialization in facilitating seasonal resource partitioning, we inferred the contribution of biofilm, microphytobenthos, and benthic invertebrates to the diets of western sandpipers (Calidris mauri) from different demographic groups during mid‐winter (January/February) and at the onset of the breeding migration (April) using stable isotope mixing models. Western sandpipers are sexually dimorphic with females having significantly greater body mass and bill length than males.
3. Diet composition differed between seasons and among demographic groups. In winter, prey consumption was similar among demographic groups, but, in spring, diet composition differed with bill length and body mass explaining 31% of the total variation in diet composition. Epifaunal invertebrates made up a greater proportion of the diet in males which had lesser mass and shorter bills than females. Consumption of Polychaeta increased with increasing bill length and was greatest in adult females. In contrast, consumption of microphytobenthos, thought to be an important food source for migrating sandpipers, increased with decreasing bill length and was greatest in juvenile males.
4. Our results provide the first evidence that age‐ and sex‐related dietary specialization in western sandpipers facilitate seasonal resource partitioning that could reduce competition during spring at the onset of the breeding migration.
5. Our study underscores the importance of examining resource partitioning throughout the annual cycle to inform fitness and demographic models and facilitate conservation efforts.

     

Bioethics in the Malay‐Muslim Community in Malaysia: A Study on the Formulation of Fatwa on Genetically Modified Food by the National Fatwa Council

The field of bioethics aims to ensure that modern scientific and technological advancements have been primarily developed for the benefits of humankind. This field is deeply rooted in the traditions of Western moral philosophy and socio‐political theory. With respect to the view that the practice of bioethics in certain community should incorporate religious and cultural elements, this paper attempts to expound bioethical tradition of the Malay‐Muslim community in Malaysia, with shedding light on the mechanism used by the National Fatwa Council to evaluate whether an application of biological sciences is ethical or not. By using the application of the genetically modified food as a case study, this study has found that the council had reviewed the basic guidelines in the main references of shari'ah in order to make decision on the permissibility of the application. The fatwa is made after having consultation with the experts in science field. The council has taken all factors into consideration and given priority to the general aim of shari'ah which to serve the interests of mankind and to save them from harm.     

The importance of well protected forests for the conservation genetics of West African colobine monkeys

In tropical forests, anthropogenic activities are major drivers of the destruction and degradation of natural habitats, causing severe biodiversity loss. African colobine monkeys (Colobinae) are mainly folivore and strictly arboreal primates that require large forests to subsist, being among the most vulnerable of all nonhuman primates. The Western red colobus Piliocolobus badius and the King colobus Colobus polykomos inhabit highly fragmented West African forests, including the Cantanhez Forests National Park (CFNP) in Guinea-Bissau. Both species are also found in the largest and best-preserved West African forest—the Taï National Park (TNP) in Ivory Coast. Colobine monkeys are hunted for bushmeat in both protected areas, but these exhibit contrasting levels of forest fragmentation, thus offering an excellent opportunity to investigate the importance of well-preserved forests for the maintenance of evolutionary potential in these arboreal primates. We estimated genetic diversity, population structure, and demographic history by using microsatellite loci and mitochondrial DNA. We then compared the genetic patterns of the colobines from TNP with the ones previously obtained for CFNP and found contrasting genetic patterns. Contrary to the colobines from CFNP that showed very low genetic diversity and a strong population decline, the populations in TNP still maintain high levels of genetic diversity and we found no clear signal of population decrease in Western red colobus and a limited decrease in King colobus. These results suggest larger and historically more stable populations in TNP compared to CFNP. We cannot exclude the possibility that the demographic effects resulting from the recent increase of bushmeat hunting are not yet detectable in TNP using genetic data. Nevertheless, the fact that the TNP colobus populations are highly genetically diverse and maintain large effective population sizes suggests that well-preserved forests are crucial for the maintenance of populations, species, and probably for the evolutionary potential in colobines.