In-silico analysis of potential anticancer drug for NEK7 and PPP1CA proteins overexpressed in pancreatic ductal adenocarcinoma.

NIMA-related kinase 7 (NEK7) and phosphoprotein phosphatase-1 catalytic subunit alpha (PPP1CA) are the most common proteins overexpressed in pancreatic ductal adenocarcinoma, which is the most common type of pancreatic cancer. The goal of the current study was to identify a possible NEK7 and PPP1CA therapeutic inhibitor. For this investigation, 5000 compounds were retrieved from the IMPPAT library of phytochemicals, which were docked with our respective target proteins. Also, a reference compound, gemcitabine, which is a Food and Drug Administration (FDA) approved drug, was docked with the target proteins. The binding energy of the reference compound for both the targeted proteins was -6.5 kcal/mol. The common ligand with the lowest binding energy for both targets is boeravinone B (PubChem ID: 14018348) with -9.2 kcal/mol of NEK7 and -7.6 kcal/mol for PPP1CA. The compound was further investigated through density function theory (DFT) and molecular dynamic simulation analysis. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and hydrogen bonding analysis indicated the stability of the boeravinone B with the target proteins (NEK7 and PPP1CA).Communicated by Ramaswamy H. Sarma.

Microsatellites' mutation modeling through the analysis of the Y-chromosomal transmission: Results of a GHEP-ISFG collaborative study.

The Spanish and Portuguese Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) organized a collaborative study on mutations of Y-chromosomal short tandem repeats (Y-STRs). New data from 2225 father-son duos and data from 44 previously published reports, corresponding to 25,729 duos, were collected and analyzed. Marker-specific mutation rates were estimated for 33 Y-STRs. Although highly dependent on the analyzed marker, mutations compatible with the gain or loss of a single repeat were 23.2 times more likely than those involving a greater number of repeats. Longer alleles (relatively to the modal one) showed to be nearly twice more mutable than the shorter ones. Within the subset of longer alleles, the loss of repeats showed to be nearly twice more likely than the gain. Conversely, shorter alleles showed a symmetrical trend, with repeat gains being twofold more frequent than reductions. A positive correlation between the paternal age and the mutation rate was observed, strengthening previous findings. The results of a machine learning approach, via logistic regression analyses, allowed the establishment of algebraic formulas for estimating the probability of mutation depending on paternal age and allele length for DYS389I, DYS393 and DYS627. Algebraic formulas could also be established considering only the allele length as predictor for DYS19, DYS389I, DYS389II-I, DYS390, DYS391, DYS393, DYS437, DYS439, DYS449, DYS456, DYS458, DYS460, DYS481, DYS518, DYS533, DYS576, DYS626 and DYS627 loci. For the remaining Y-STRs, a lack of statistical significance was observed, probably as a consequence of the small effective size of the subsets available, a common difficulty in the modeling of rare events as is the case of mutations. The amount of data used in the different analyses varied widely, depending on how the data were reported in the publications analyzed. This shows a regrettable waste of produced data, due to inadequate communication of the results, supporting an urgent need of publication guidelines for mutation studies.

In silico identification of potential drug-like molecules against G glycoprotein of Nipah virus by molecular docking, DFT studies, and molecular dynamic simulation.

Nipah virus (NiV) is a novel zoonotic pathogen that belongs to the Paramyxovirus family. The pathogen has infected a number of people in countries like Bangladesh, India, Singapore, and Malaysia with high mortality rates. Although the NiV has been classified as a biosafety level four pathogen (BSL-4), there is no drug approved for treatment against it. In this study, the G glycoprotein of the NiV was chosen as an antiviral target. Based on ADMET criteria, BBB- and BBB + group compounds were screened out of the Gold & platinum Asinex library containing 211620 compounds. After careful evaluation, the selected ligands were then virtually screened to identify the potential inhibitors against the G glycoprotein of the NiV through molecular docking, density functional theory (DFT), and molecular dynamic (MD) simulation studies. In our study we identified 5-(1,3-Benzodioxol-5-yl)-2-[(3-fluorobenzyl)sulfanyl]-5,8-dihydropyrido[2,3-d]pyrimidine-4,7(1H,6H)-dione (from BBB- group) and 7,7-Dimethyl-1-(4-methylphenyl)-3-(4-morpholinylcarbonyl)-7,8-dihydro-2,5(1H,6H)-quinolinedione) (from BBB + group) as potential compounds for the prevention and treatment of NiV related diseases.Communicated by Ramaswamy H. Sarma.

Persistence of Semen on five different fabric types in various water environments.

Evidence collected from biological fluids obtained from a crime scene is essentially important in forensic cases. A potential profile can be generated from these obtained samples and this can help in identifying the victims and/or suspects of sexual assault. The water environments selected for this study are all related to the potential crime scenes from which there is a possibility of finding a dead body or clothing of a sexual assault victim. Tap water, River water, Swimming pool water, and Canal water were selected. Fabric types selected were khaddar, linen, silk, polyester, and chiffon. Detection of seminal stains was carried out by three methods; Alternate Light Source (ALS), Acid phosphatase (AP) testing, and Kernechtrot-Picro-indigo-carmine (KPIC) testing. These tests were performed for each fabric type in each water environment after regular intervals, 24 h, 48 h, 72 h, 4 days, 7 days, and 14 days. This study aimed to compare the ability of five types of fabrics to retain seminal material after immersion in four different types of water environments. Fluorescence was only detected in tap water-soaked silk fabric after 14 days of immersion. Seminal fluid was detected in khaddar, chiffon, silk, and polyester in samples immersed for 14 days in tap water. Spermatozoa were retained by khaddar and silk immersed in tap water, Polyester fabric in tap and river water, Chiffon in only river water and Linen in swimming pool water when immersed for 14 days. However, fluorescence, seminal fluid or spermatozoa were not detected in linen fabric regardless of all the afore mentioned variables.

Familial DNA analysis and criminal investigation: Usage, downsides and privacy concerns.

Since the discovery of Deoxyribonucleic acid (DNA) capability in forensic investigation, it has been an important part of the criminal justice system. In most criminal cases DNA profile originating from evidence sample collected from the crime scene is compared with the DNA profile from the reference sample. However, when a reference sample is not available for comparison, familial DNA analysis can provide important investigation leads in a criminal investigation process by identifying an individual. Moreover, this analysis is also proving effective in the identification of ethnicity and ancestry of an individual. A number of different methodologies and software are being used for familial DNA analysis. This review describes the importance of familial DNA analysis, methodologies used for familial DNA searching and identification, and its advantages in forensic. Moreover, ethical, legal and social issues associated with familial DNA analysis have also been discussed along with future directions for the proper implementation of this technology.

Allele frequency distribution of 10 MiniSTRs in the Pashtun population of Pakistan.

Two hundred individual samples of Pashtun population from Khyber Pakhtunkhwa province of Pakistan were randomly evaluated through 10 MiniSTR loci (CSF1PO, D7S820, TPOX, D18S51, D2S1338, D13S317, FGA, D5S818, D21S11, and D16S539). The PCR product size was reduced in the range of 65 to 280 bp. A total of 112 alleles were observed containing allelic frequency ranging from 0.0025 to 0.4325. Statistical values for forensic and parentage analysis were calculated including combined power of discrimination (PD), combined power of exclusion (PE), and cumulative probability of matching (PM) and equaled to 0.99999999999768, 0.99984944, and 2.33 × 10(-12), respectively. These MiniSTRs show a high degree of polymorphism information content and discriminatory power which would be helpful to resolve forensic cases and establish DNA database for major population groups of Pakistan. In contrast to different populations, significant differences were also observed on these loci.