Distribution of UDPglucuronosyltransferase in rat tissue.

UDPglucuronosyltransferase [UDPglucuronate beta-D-glucuronosyltransferase (acceptor-unspecific), EC 2.4.1.17] is a group of enzymes with distinct but partially overlapping substrate specificity. A rabbit antiserum raised against one purified rat liver UDPglycuronosyltransferase isoform was specific for UDPglucuronosyltransferase and recognized all transferase isoforms by immunodiffusion or immunotransblot analysis. The transferase activity toward all substrates was immunoabsorbed from solubilized rat liver microsomes by IgG purified from the antiserum. The purified IgG was used for immunocytochemical localization of UDP-glucuronosyltransferase in rat liver, jejunum, kidney, and adrenal gland. In the liver, UDPglucuronosyltransferase was present exclusively in hepatocytes and was uniformly distributed within all zones of the hepatic lobule. In the jejunum, the transferase was present exclusively in the epithelial cells and showed a progressive increase in concentration from the crypt to the villar tip. In the kidney, the greatest concentration of the transferase was observed in the epithelial cells of the proximal convoluted tubule. Adrenal medullary cells showed intense immunocytochemical staining; the zona glomerulosa and the zona reticularis of the adrenal cortex were more intensely stained than the zona fasciculata. By light microscopy, UDPglucuronosyltransferase was found in the endoplasmic reticulum and nuclear envelope of all the four organs; this was confirmed in the hepatocyte by electron microscopy. The transferase was not observed in mitochondria, Golgi apparatus, lysosomes, peroxisomes, and plasma membrane, even after 3- to 4-fold induction of various substrate-specific UDPglucuronosyltransferase activities.     

Primary structure of Euplotes raikovi pheromones: comparison of five sequences of pheromones from cells with variable mating interactions.

The amino acid sequences of five pheromones, Er-2, Er-3, Er-9, Er-11, and Er-20, secreted by cells of different mating types of the ciliated protozoa Euplotes raikovi, have been determined by automated Edman analyses of the whole proteins and germane fragments. In each case, the molecular mass was determined by plasma desorption or laser desorption mass spectrometry and was in excellent agreement with the calculated values. Where available, the determined sequences were also in accord with the corresponding segments of the precursor molecules predicted from relevant nucleic acid sequences. Of the five, two were found to be identical (Er-2 and Er-9) and one (Er-3) was identical to a pheromone previously sequenced (Er-1), even though mating pair formation was found to take place (although to a limited extent) when cells secreting those pheromones were combined in a mixture. Comparison of the five unique sequences suggested a closer relationship between Er-1 (Er-3) and Er-10 and between Er-11 and Er-20 (44% and 56% identity, respectively) than was generally observed among the other members. This pairing was also supported by hydrophobicity analyses. Interestingly, Er-20 cannot, as a rule, induce cell union in any of the other cell types, including cells secreting Er-11, despite the fact that Er-20 and Er-11 are the most similar of the five unique sequences. Thus sequence identity and secondary structure profiles are not a good indicator of biological relatedness as manifested in heterologous receptor interaction.     

Trends of HIV-1 risk reduction among initiates into intravenous drug use 1982-1987

To assess how injection practices may have changed during the course of the AIDS epidemic, active intravenous drug users (IVDUs) recruited from the community were asked to report year of first injection as well as specific details about the first 3 months after initial injection: frequencies of injection, using sterile needles, sharing needles and other equipment. For the analysis, the users were sorted into successive cohorts of initiation (by year of first injection), and tests for trends were completed using Mantel-Haenszel statistics. Among the 421 IVDUs who reported first injection between 1982 and 1987, the use of new sterile needles to self-administer drugs increased (p less than .05) along with its corollary behavior (i.e., using equipment one is sure that no one else had used before). Conversely, there was a decrease in the proportion of those who always used equipment previously used by another IVDU (p less than .05) and a decrease in the number of needle-sharing partners (p less than .01). Over the 6 years, heroin as first drug decreased and cocaine increased (p less than .01). Although these data are from a cross-sectional interview study, they suggest a shift toward lower risk practices among new IVDUs between 1982 and 1987. The shift from heroin to cocaine is compatible with other evidence on the cocaine epidemic.     

Gender identity shows a high correlation with Prader score in patients with disorders of sex development (DSD) presenting in mid childhood

Objective

In developing countries like Bangladesh, delayed presentation for disorders of sex development (DSD) is common, and provides some special problems for management. There remains significant controversy about appropriate sex assignment in this group. We aimed, therefore, to assess gender identity (GI) in 50 consecutive patients with DSD presenting to a referral centre in Chittagong, Bangladesh, and correlate it with Prader score, to see if the latter could be used to predict GI.

Methods

A cross-sectional, case–control study of 50 consecutive children with DSD and 50 children with vascular anomalies was conducted in the Pediatric Surgical Clinic, Chittagong Medical College and Hospital. After informed consent, patients and controls provided oral answers to a GI questionnaire and had a detailed history and physical examination. Sex-typed activities were assessed by observations of a structured toy play and the child’s selection of a toy to keep. Both patients and parents then completed the Child Game Participation Questionnaire.

Results

There were no differences in age (2–16 years, mean 8.74) between controls and DSD patients (11 46, XX DSD, 32 46, XY DSD, 4 MGD, 3 ovo-testicular DSD). Fifteen of the DSD patients (30 %) came from consanguineous marriages and only 2 of the control patients had consanguinity of their parents. For the 13-question GI interview, there was no overall difference between DSD cases and controls. For the 46, XX DSD subgroup, there was a significantly higher score (11.1 ± 7.1) compared with control girls (4.5 ± 4.7) (p < 0.05), while for DSD and control boys, there was a positive correlation with age and GI (p < 0.01). Prader score correlated with GI score in both control (r = 0.91) and DSD patients (r = 0.75) (p < 0.01), DSD girls played significantly less with girls’ toys than controls (p < 0.01), but there was no differences for the boys. Composite scores on GI and gender-related behaviour correlated with Prader score for DSD patients (r = 0.61) (p < 0.01).

Conclusion

This study supports the view that GI and gender-role behaviour should be assessed routinely in DSD patients presenting after the neonatal period, so that sex assignment is in accordance with behaviour. Prader scores showed a good correlation with GI and gender role behaviour.     

Whole genome sequencing for revealing the point mutations of SARS-CoV-2 genome in Bangladeshi isolates and their structural effects on viral proteins

Coronavirus disease-19 (COVID-19) caused by SARS-CoV-2 has already killed more than one million people worldwide. Since novel coronavirus is a new virus, mining its genome sequence is of crucial importance for drug/vaccine(s) development. Whole genome sequencing is a helpful tool in identifying genetic changes that occur in a virus when it spreads through the population. In this study, we performed complete genome sequencing of SARS-CoV-2 to unveil the genomic variation and indel, if present. We discovered thirteen (13) mutations in Orf1ab, S and N gene where seven (7) of them turned out to be novel mutations from our sequenced isolate. Besides, we found one (1) insertion and seven (7) deletions from the indel analysis among the 323 Bangladeshi isolates. However, the indel did not show any effect on proteins. Our energy minimization analysis showed both stabilizing and destabilizing impact on viral proteins depending on the mutation. Interestingly, all the variants were located in the binding site of the proteins. Furthermore, drug binding analysis revealed marked difference in interacting residues in mutants when compared to the wild type. Our analysis also suggested that eleven (11) mutations could exert damaging effects on their corresponding protein structures.

SARS-CoV-2 mutational impact analysis.