QSAR model to develop newer generation GSK-3β inhibitors targeting Alzheimer

In the year 2022 most of the patients affected by the disease was around 65 year age. Among total number of patients, 73% were near 75 year or older age. It was also stated that maximum numbers of patients were women. Black Americans were more affected by Alzheimer than white Americans. GSK-3β was also linked with hyperphosphorylation of tau protein followed by the increasing number of amyloid-beta plaques and other inflammatory responses followed by activation of microglial cells to develop neurotoxic inflammatory factors along with reducing the concentration of acetylcholine; these factors cumulatively create Alzheimer disease. GSK-3β modulated the inflammatory stress related to endoplasmic reticulum and mitochondrial abnormalities. But all the molecules those were used in the treatment not so much effective to fully cure the patient. So, to break this jinx to develop of newer generation anti Alzheimer drug molecules, computational approaches played an essential role. The most effective QSAR model was pIC50 = -5.47052 +2.60572 IC1 +1.64642 GATS2e +2.088 mindssC -0.01441 ATSC7s -13.5191 AVP-0 +0.16712 minssNH -0.15369 minaaN +0.01777 VR2_Dt +1.52684 MATS8s +0.04725 nAtomP with all necessary acceptance criteria Q^2: 0.60111, r^2: 0.65711, |r0^2-r'0^2|: 0.07866, k: 0.99121 [(r^2-r0^2)/r^2] 0.00543 or k': 0.92437 [(r^2-r'0^2)/r^2] 0.12513. It can be easily concluded that if in near future we want to develop a small molecule effective as GSK-3β inhibitor active against Alzheimer disease, this QSAR model will work as a boon for the mankind

The academy for future science faculty:randomized controlled trial of theory-driven coaching to shape development and diversity of early-career scientists

Background: Approaches to training biomedical scientists have created a talented research community. However, they have failed to create a professional workforce that includes many racial and ethnic minorities and women in proportion to their representation in the population or in PhD training. This is particularly true at the faculty level. Explanations for the absence of diversity in faculty ranks can be found in social science theories that reveal processes by which individuals develop identities, experiences, and skills required to be seen as legitimate within the profession. Methods/Design: Using the social science theories of Communities of Practice, Social Cognitive Career Theory, identity formation, and cultural capital, we have developed and are testing a novel coaching-based model to address some of the limitations of previous diversity approaches. This coaching intervention (The Academy for Future Science Faculty) includes annual in-person meetings of students and trained faculty Career Coaches, along with ongoing virtual coaching, group meetings and communication. The model is being tested as a randomized controlled trial with two cohorts of biomedical PhD students from across the U.S., one recruited at the start of their PhDs and one nearing completion. Stratification into the experimental and control groups, and to coaching groups within the experimental arms, achieved equal numbers of students by race, ethnicity and gender to the extent possible. A fundamental design element of the Academy is to teach and make visible the social science principles which highly influence scientific advancement, as well as acknowledging the extra challenges faced by underrepresented groups working to be seen as legitimate within the scientific communities. Discussion: The strategy being tested is based upon a novel application of the well-established principles of deploying highly skilled coaches, selected and trained for their ability to develop talents of others. This coaching model is intended to be a complement, rather than a substitute, for traditional mentoring in biomedical research training, and is being tested as such

Interactions among motility, fertilizing ability, and testosterone binding on spermatozoa of bonnet monkey (Macaca radiata)

Fresh ejaculates of bonnet monkeys were separated into fractions rich with highly motile and sluggishly motile spermatozoa. The motility, ability to fertilize zona-free hamster eggs, and distribution of testosterone-binding sites on spermatozoa were assessed to determine the relation between these sperm functions. Two parameters of objective assessment of motility—velocity and degree of flagellar bending—were significantly correlated with the ability to form pronuclei in zona-free hamster eggs. Only spermatozoa with good motility could form pronuclei, which might be important for assessment of the fertilizing ability. The motility was directly related to the distribution of testosterone-binding sites; the fraction having mostly motile spermatozoa was distributed over the sperm surface. The technique is simple and may be used to evaluate semen of nonhuman primates

Status of the down-regulated canine testis using two different GNRH agonist implants in comparison with the juvenile testis

Testicular function in the dog was down-regulated using two different GNRH agonist implants, with adult and juvenile testes serving as controls. Treatment resulted in an increased percentage of the interstitial area and decreased area of Leydig cell nuclei. Expression of StAR and the steroidogenic enzymes cytochrome P450 side-chain cleavage enzyme (P450scc, CYP11A1) and cytochrome P450 17α-hydroxylase-17,20-lyase (P450c17, CYP17A1) in Leydig cells was blocked at the mRNA and protein level, showing no differences between the two agonists. Staining for androgen receptor (AR) by immunohistochemistry was positive in Sertoli, Leydig and peritubular cells and some spermatogonia, with in situ hybridization confirming expression in Sertoli cells. At the mRNA level, expression of AR was not affected; however, translation was blocked (reduced percentage of AR-positive Sertoli cells), with the number of nuclei in basal position being decreased. In the juvenile testes, mRNA expression of StAR, CYP11A1 and CYP17A1 was higher compared with the other groups but distinctly lower for the AR. At the protein level, the expression was at the limit of detection for StAR; AR-positive Sertoli cells were not detected. Our observations show that the down-regulated testis is different from the juvenile one rather resembling the testicular status in seasonal breeders out of season