Prolonged Replication of a Type 1 Vaccine-Derived Poliovirus in an Immunodeficient Patient

VP1 sequences were determined for poliovirus type 1 isolates obtained over a 189-day period from a poliomyelitis patient with common variable immunodeficiency syndrome (a defect in antibody formation). The isolate from the first sample, taken 11 days after onset of paralysis, contained two poliovirus populations, differing from the Sabin 1 vaccine strain by ~10%, differing from diverse type 1 wild polioviruses by 19 to 24%, and differing from each other by 5.5% of nucleotides. Specimens taken after day 11 appeared to contain only one major poliovirus population. Evolution of VP1 sequences at synonymous third-codon positions occurred at an overall rate of ~3.4% per year over the 189-day period. Assuming this rate to be constant throughout the period of infection, the infection was calculated to have started ~9.3 years earlier. This estimate is about the time (6.9 years earlier) the patient received his last oral poliovirus vaccine dose, approximately 2 years before the diagnosis of immunodeficiency. These findings may have important implications for the strategy to eliminate poliovirus immunization after global polio eradication.     

Sequence of centromere separation: Occurrence,possible significance,and control

This review describes the existence of a phenomenon, sequential separation of centromeres, in mitotic cells of various species including both animals and plants. Critical observations at metaanaphase show that the centromeres of chromosomes in a given genome do not separate into two sister units randomly, but that there is a genetically controlled, nonrandom, species-specific sequence which is independent of the length of the chromosome or the position of the centromere. A stricter control appears to exist for late-separating than for early-separating chromosomes. At early stages of metaanaphase several chromosomes initiate onset of separation simultaneously or in rapid succession, but late-separating chromosomes are better defined in their sequential position. The effect of Colcemid on the sequence of separation is minimal. It is proposed that aneuploidy in humans and other organisms may result from out-of-phase separation of a given chromosome. With the exception of chromosome No. 16, it appears that very early- or very late-separating centromeres are involved in human trisomies more often than those in between.Perhaps one function of centromeric heterochromatin is the control of centromere separation. The amount of such chromatin shows a positive correlation with the timing of separation of the centromeres. Superimposed upon this quantitative influence is the qualitative aspect, as discussed for various genomes. This suggestion explains a lack of extremely large quantities of heterochromatin near the centromere. Its existence in the form of homogeneously staining regions distal to the centromere, as in some cancer cells or in sex chromosomes, seemingly has no influence on the separation of centromeres.A brief discussion of centromere separation errors in human disease is provided, and suggestions for further studies are made.     

The structure of human S-phase chromosome fibres

Recentin situ hybridization studies suggested that within the range of 0.1–1.0 Mb, human interphase chromosomes follow a random walk model (i.e. they behave as flexible polymers without major constraints). However, chromosome structure may differ in the G1, S, and G2 phases, and phase-specific constraints may be masked if the chromosome analysis does not discriminate between the phases. Therefore, using confocal microscopy, we examined the structure of S-phase chromosomes labelled with 5-iododeoxyuridine after prolonged treatment with 5-fluorodeoxyuridine. In the S-phase, labelled 0.32 µ chromosome fibres mostly appear as semi-circles with an average diameter of 0.83 ±0.03 µ. These semi-circles are joined together to form different 3D structures, and two semicircles frequently adopt s- or-like conformations involving about 2.5 µ of the chromosome contour length (L). Morphometric analysis of the S-phase fibres suggests that our data fit both the random flexible polymer model and also a model in which two constrained semi-circles are attached to each other by a flexible joint, thus eliminating constraints at long distances (L more than 2 µ).     

Complete genome sequence analysis of Japanese encephalitis virus isolated from a horse in India

The complete genome of the Japanese encephalitis virus (JEV) strain JEV/eq/India/H225/2009(H225), isolated from an infected horse in India, was sequenced and compared to previously published JEV genomes. H225 genome was 10,977-nucleotides long, comprising a single ORF of 10,299-nucleotides, a 5′-UTR of 95 nucleotides and a 3′-UTR of 582 nucleotides. The H225 genome showed high levels of sequence identity with 47 fully sequenced JEV genomes, ranging from 99.3 % to 75.5 % for nucleotides and 99.2 % to 91.5 % for amino acid sequences. Phylogenetic analysis of the full-length sequence indicated that the H225 strain belongs to genotype III and is closely related to the Indian JEV strain Vellore P20778. A comparison of amino acids associated with neurovirulence in the E proteins and non-structural proteins of known virulent and attenuated JEV strains suggested H225 to be a highly virulent strain. This is the first report of whole-genome sequencing of a genotype III JEV genome isolated from equines.     

A new class of bactericidal agents against S. aureus,MRSA and VRE derived from bisindolylmethane

A series of bisindolylmethanes (BIMs) (1a–7j) including hybrid BIMs 6a–6c were prepared for bioevaluation. The results of initial antimicrobial screening of compounds 1a–6c showed compounds 2b, 2m, 4a and 5b to be the most potent inhibitors, exhibiting MIC as well as MBC values equal to or less than that of ciprofloxacin (0.5–2 μg/mL) against Staphylococcus aureus, MRSA and VRE. Compound 2m was selected further to study the effect of N,N′ disubstitution towards antibacterial and antitumor activity. It was observed that substitution at N,N′ position (7a–7j) of 2m diminishes its antibacterial activity though in vitro antitumour activity against a panel of prostate, cervical and lung cancer cell lines remains more or less intact.     

Correction: Bakuchiol – a natural meroterpenoid: structure,isolation, synthesis and functionalization approaches

Correction for ‘Bakuchiol – a natural meroterpenoid: structure, isolation, synthesis and functionalization approaches’ by T. P. Adarsh Krishna et al., RSC Adv., 2022, 12, 8815–8832, DOI: 10.1039/D1RA08771A.

The authors regret that the first sentence in Section 2 (Occurrence and isolation) contained errors. The correct sentence is the following:“Bakuchiol (Syn. Chiba) was first extracted from the seeds of Psoralea corylifolia L. Medik (Bakuchi, now Cullen corylifolium L.) by a team of scientists at the National Chemical Laboratory (NCL), Pune, India.”The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Mechanism of participation of medial preotic area in the hippocampal inhibition of ovulation

Bilateral hippocampal (HPC) stimulation with anodal direct current on the afternoon of proestrus blocked sponstaneous ovulation in 87.5% of the Wistar rats subjected to the experiments. The incidence of the ovulation block by this procedure was reduced to 16.7% on bilateral injection of 0.25 μg picrotoxin into the medial preoptic area (mPOA) preceding as well as following the stimulation. Ovulation was also blocked in 53.8% of the animals by bilateral injection of 50.0 μg GABA into mPOA, while only 20.0% animals showed a blockade of ovulation of HPC stimulation can be simulated mPOA. These observations indicate that blockade of ovulation by saline injection into by local injection of GABA into mPOA while the effect of stimulation can be blocked by local injection of picrotoxin. Thus, indicating the possibility of GABA being neurotransmitter involved at the level of mPOA for mediating the inhibitory hippocampal influence on ovulation.     

Green tea polyphenol-induced epidermal keratinocyte differentiation is associated with coordinated expression of p57/KIP2 and caspase 14

Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, exerts chemopreventive effects by selectively inducing apoptosis in tumor cells. In contrast, EGCG accelerates terminal differentiation in normal human epidermal keratinocytes (NHEK) mediated partially by up-regulation of p57/KIP2, a cyclin-dependent kinase inhibitor that confers growth arrest and differentiation. However, it is unclear if EGCG modulates caspase 14, a unique regulator of epithelial cell terminal differentiation associated with cornification. Here, we examined the effect of EGCG on caspase 14 expression in NHEK and correlated the protein and mRNA expression of p57/KIP2 with those of caspase 14 in either normal keratinocytes or p57/KIP2-expressing tumor cells (OSC2, an oral squamous cell carcinoma cell line). Additionally, paraffin-embedded normal and untreated psoriatic (aberrant keratinization) skin sections from humans were assessed for caspase 14 by immunohistochemistry. In NHEK, EGCG induced the expression of caspase 14 mRNA and protein levels within a 24-h period. The expression of p57/KIP2 in OSC2 cells was adequate to induce caspase 14 in the absence of EGCG; this induction of caspase 14 was down-regulated by transforming growth factor-beta1. In human psoriatic skin samples, caspase 14 staining in the upper epidermis was reduced, especially in nuclear areas. These results suggest that, in addition to p57/KIP2, EGCG-induced terminal differentiation of epidermal keratinocytes involves up-regulation of caspase 14. Further understanding of how EGCG modulates cellular differentiation may be useful in developing green tea preparations for selected clinical applications.     

Chemoprevention of oral cancer by green tea

Green tea has been a popular beverage for many centuries. Only recently, however, has the anti-cancer power of green tea constituents been unveiled. Green tea polyphenols are found to induce apoptosis (programmed cell death) in many types of tumor cells, including oral cancer cells. However, mechanisms that enable normal cells to evade the apoptotic effect still are not understood. In this study, cell growth and invasion assays combined with apoptosis assays were used to examine the effects of green tea extracts, green tea polyphenols, and the most potent green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), on normal human keratinocytes and oral carcinoma cells. The results showed that green tea and its constituents selectively induce apoptosis only in oral carcinoma cells, while EGCG was able to inhibit the growth and invasion of oral carcinoma cells. These differential responses to green tea and its constituents between normal and malignant cells were correlated with the induction of p57, a cell cycle regulator. These data suggest that the chemopreventive effects of green tea polyphenols may involve a p57 mediated survival pathway in normal epithelial cells, while oral carcinoma cells undergo an apoptotic pathway. Therefore, regular consumption of green tea could be beneficial in the prevention of oral cancer.