Absence of HTLV I from New Zealand

Sera from 1,943 individuals from Auckland, New Zealand, were tested for the presence of serum antibodies to human T cell lymphotropic virus I (HTLV I), mainly with an enzyme-linked immunosorbent assay (ELISA) with cell extracts as target antigen. The individuals tested were blood donors and mostly Caucasian, but included indigenous Maoris and representatives of several groups of Pacific islanders now resident in New Zealand. Also included were 37 patients with various hematological malignancies, including seven with T cell leukemias. Although 1% of samples were positive by ELISA, none of these were confirmed as positives by Western blotting. On the basis of these results we consider that it is unlikely that HTLV I infection occurs in Auckland; however, we cannot exclude the possibility that pockets of virus infection may occur in other parts of New Zealand or the South Pacific.     

Genotoxicity of naturally occurring indole compounds: correlation between covalent DNA binding and other genotoxicity tests

3-Methylindole (3MI), melatonin (Mel), serotonin (Ser), and tryptamine (Tryp) were evaluated in vitro for their potential to induce DNA adducts, DNA strand breaks, chromosomal aberrations (Abs), inhibition of DNA synthesis, and mutations. All compounds produced DNA adducts in calf thymus DNA in the presence of rat liver S9. In cultured rat hepatocytes, all produced DNA adducts but none induced DNA strand breaks. In Chinese hamster ovary cells, 3MI and Mel produced DNA adducts, Abs, and inhibition of DNA synthesis with and without S9, except that Mel without S9 did not form adducts. Ser formed DNA adducts, was an equivocal Abs inducer, and suppressed DNA synthesis. Tryp induced neither adducts nor Abs, but did suppress DNA synthesis with S9. Ser and Tryp were less cytotoxic than 3MI and Mel. Mel, Ser, and Tryp failed to induce mutations in Salmonella and E. coli strains with or without S9. 3MI and Mel produced DNA adducts but not mutations in Salmonella TA100 with S9. 3MI and its metabolite indole 3-carbinol also did not induce mutations in a shuttle vector system in human cells. The lack of correlation between DNA adducts and other genotoxicity endpoints for these indole compounds may be due to the higher sensitivity of the (32)P-postlabeling adduct assay or it may indicate that the indole-DNA adducts per se are not mutagenic and are not able to induce strand breaks or alkali-labile lesions. The indole-induced Abs may result from cytotoxicity and suppression of DNA synthesis with minimal if any contribution from DNA adducts.     

STXBP1: the second synaptic vesicle release gene involved in epilepsy

De novo mutations in the gene encoding STXBP1 (MUNC18‐1) cause early infantile epileptic encephalopathy
Saitsu et al. (2008)
Nature Genetics 40: 782–788     

Presenting characteristics,comorbidities, and outcomes of patients coinfected with COVID-19 and Mycoplasma pneumoniae in the USA

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is spreading at a rapid pace, and the World Health Organization declared it as pandemic on 11 March 2020. Mycoplasma pneumoniae is an "atypical" bacterial pathogen commonly known to cause respiratory illness in humans. The coinfection from SARS-CoV-2 and mycoplasma pneumonia is rarely reported in the literature to the best of our knowledge. We present a study in which 6 of 350 patients confirmed with COVID-19 were also diagnosed with M. pneumoniae infection. In this study, we described the clinical characteristics of patients with coinfection. Common symptoms at the onset of illness included fever (six [100%] patients); five (83.3%) patients had a cough, shortness of breath, and fatigue. The other symptoms were myalgia (66.6%), gastrointestinal symptoms (33.3%-50%), and altered mental status (16.7%). The laboratory parameters include lymphopenia, elevated erythrocyte sedimentation rate, C-reactive protein, lactate dehydrogenase, interleukin-6, serum ferritin, and D-dimer in all six (100%) patients. The chest X-ray at presentation showed bilateral infiltrates in all the patients (100%). We also described electrocardiogram findings, complications, and treatment during hospitalization in detail. One patient died during the hospital course.     

Predominance of null mutations in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a Pl 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the Pl 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T.      

Characterization of a very Virulent Marek’s Disease Virus Mutant Expressing the pp38 Protein from the Serotype 1 Vaccine Strain CVI988/Rispens

Marek’s disease virus (MDV), a highly cell-associated oncogenic chicken herpesvirus, causes Marek’s disease in domestic chickens. A unique phosphoprotein of MDV, pp38, has previously been associated with the maintenance of transformation in MDV-induced tumor cell lines. However, recently, the biological properties of a deletion mutant virus (rMd5Δpp38) revealed that pp38 is involved in early cytolytic infection in lymphocytes but not in the induction of tumors. Thus, pp38 is important for early cytolytic infection and not for transformation. The pp38 protein of the MDV serotype 1 vaccine strain CVI988/Rispens differs by one amino acid when compared to the pathogenic strains of MDV. Monoclonal antibody, H19, recognizes all serotype 1 MDV strains except CVI988/Rispens. Previous studies have also shown that the unique pp38 epitope in CVI988/Rispens induced high antibody response. In order to study the role of this epitope in the protective properties of CVI988/Rispens, we generated a mutant rMd5 virus in which the wild type pp38 gene has been substituted with that of CVI988/Rispens (rMd5/pp38CVI). The replication properties of rMd5/pp38CVI, both in vitro and in vivo, and tumor induction were examined. We found that the biological properties of rMd5/pp38CVI were similar to the wild type rMd5 virus with regards to in vivo replication, antibody response and tumor induction. This shows that the pp38 derived from CVI988/Rispens is not involved in protective properties as was previously suggested.     

Genetic evidence on the origins of Indian caste populations

The origins and affinities of the approximately 1 billion people living on the subcontinent of India have long been contested. This is owing, in part, to the many different waves of immigrants that have influenced the genetic structure of India. In the most recent of these waves, Indo-European-speaking people from West Eurasia entered India from the Northwest and diffused throughout the subcontinent. They purportedly admixed with or displaced indigenous Dravidic-speaking populations. Subsequently they may have established the Hindu caste system and placed themselves primarily in castes of higher rank. To explore the impact of West Eurasians on contemporary Indian caste populations, we compared mtDNA (400 bp of hypervariable region 1 and 14 restriction site polymorphisms) and Y-chromosome (20 biallelic polymorphisms and 5 short tandem repeats) variation in approximately 265 males from eight castes of different rank to approximately 750 Africans, Asians, Europeans, and other Indians. For maternally inherited mtDNA, each caste is most similar to Asians. However, 20%-30% of Indian mtDNA haplotypes belong to West Eurasian haplogroups, and the frequency of these haplotypes is proportional to caste rank, the highest frequency of West Eurasian haplotypes being found in the upper castes. In contrast, for paternally inherited Y-chromosome variation each caste is more similar to Europeans than to Asians. Moreover, the affinity to Europeans is proportionate to caste rank, the upper castes being most similar to Europeans, particularly East Europeans. These findings are consistent with greater West Eurasian male admixture with castes of higher rank. Nevertheless, the mitochondrial genome and the Y chromosome each represents only a single haploid locus and is more susceptible to large stochastic variation, bottlenecks, and selective sweeps. Thus, to increase the power of our analysis, we assayed 40 independent, biparentally inherited autosomal loci (1 LINE-1 and 39 Alu elements) in all of the caste and continental populations (approximately 600 individuals). Analysis of these data demonstrated that the upper castes have a higher affinity to Europeans than to Asians, and the upper castes are significantly more similar to Europeans than are the lower castes. Collectively, all five datasets show a trend toward upper castes being more similar to Europeans, whereas lower castes are more similar to Asians. We conclude that Indian castes are most likely to be of proto-Asian origin with West Eurasian admixture resulting in rank-related and sex-specific differences in the genetic affinities of castes to Asians and Europeans.     

Noninvasive Measurement of Acceleration at the Knee Joint in Patients with Rheumatoid Arthritis and Spondyloarthropathy of the Knee

Spondyloarthropathy represents a group of joint diseases with a tendency to reactive new bone formation. Spondyloarthropathy includes Reiter's syndrome, ankylosing spondylitis, and the arthropathy of inflammatory diseases (ulcerative colitis and Crohn's disease). Usually, an extensive investigation is required to distinguish spondyloarthropathy of the knee joint from rheumatoid arthritis. Recently, Reddy et al. (Ann. Biomed. Eng. 23:78–84, 1995) have developed the accelerometry technique to characterize various types of arthritis. The question remains if noninvasive acceleration measurements can be used to distinguish between spondyloarthropathy and rheumatoid arthritis. An ultraminiature accelerometer was placed on the patella, and the subject was asked to rhythmically rotate the knee from 90 flexion to full extension. Results have shown that the mean power of acceleration signal in the range of 100–500 Hz is significantly different (p < 0.05) for spondyloarthropathy patients when compared to rheumatoid arthritis patients. The noninvasive accelerometry technique represents a potential tool for characterization of spondyloarthropathy patients. © 2001 Biomedical Engineering Society. PAC01: 8719St, 8719Xx, 0630Gv