Molecular HIV Clustering Among Individuals with Mpox and HIV Co-Morbidity in New York State, Excluding New York City.

The 2022 global mpox outbreak created an opportunity to test the utility of molecular HIV surveillance (MHS) to identify high-risk transmission networks. Individuals diagnosed with mpox in New York State (NYS) outside New York City-[Rest of State (ROS)] were matched to the NYS HIV and sexually transmitted infection registries. The demographic characteristics of individuals diagnosed with mpox in ROS mirror national trends. HIV-mpox comorbid individuals were more likely to be included in HIV molecular clusters compared to persons living with diagnosed HIV in ROS overall, men who have sex with men (MSM) in ROS, and age-adjusted MSM (to match individuals with mpox diagnosis) in ROS. For the 3-year 0.5% clusters, which are used to define national priority clusters, the HIV-mpox comorbid individuals clustered 2.4 times more frequently than the age/risk-adjusted control group. This study supports the use of HIV MHS to identify populations for priority public health interventions.

Investigation of Presumptive HIV Transmission Associated with Hospitalization Using Nucleotide Sequence Analysis - New York, 2017.

Since implementation of Standard Precautions* for the prevention of bloodborne pathogen transmission in 1985, health care-associated transmission of human immunodeficiency virus (HIV) in the United States has been rare (1). In October 2017, the New York City Department of Health and Mental Hygiene (NYCDOHMH) and the New York State Department of Health (NYSDOH) were notified by a clinician of a diagnosis of acute HIV infection in a young adult male (patient A) without recognized risk factors (i.e., he was monogamous, had an HIV-negative partner, and had no injection drug use) who had recently been hospitalized for a chronic medical condition. The low risk coupled with the recent hospitalization and medical procedures prompted NYSDOH, NYCDOHMH, and CDC to investigate this case as possible health care-associated transmission of HIV. Among persons with known HIV infection who had hospitalization dates overlapping those of patient A, one person (patient B) had an HIV strain highly similar to patient A's strain by nucleotide sequence analysis. The sequence relatedness, combined with other investigation findings, indicated a likely health care-associated transmission. Nucleotide sequence analysis, which is increasingly used for detecting HIV clusters (i.e., persons with closely related HIV strains) and to inform public health response (2,3), might also be used to identify possible health care-associated transmission of HIV to someone with health care exposure and no known HIV risk factors (4).

Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease.

Parkinson's disease is a common disorder that leads to motor and cognitive disability. We performed a genome-wide association study of 2,000 individuals with Parkinson's disease (cases) and 1,986 unaffected controls from the NeuroGenetics Research Consortium (NGRC). We confirmed associations with SNCA and MAPT, replicated an association with GAK (using data from the NGRC and a previous study, P = 3.2 x 10(-9)) and detected a new association with the HLA region (using data from the NGRC only, P = 2.9 x 10(-8)), which replicated in two datasets (meta-analysis P = 1.9 x 10(-10)). The HLA association was uniform across all genetic and environmental risk strata and was strong in sporadic (P = 5.5 x 10(-10)) and late-onset (P = 2.4 x 10(-8)) disease. The association peak we found was at rs3129882, a noncoding variant in HLA-DRA. Two studies have previously suggested that rs3129882 influences expression of HLA-DR and HLA-DQ. The brains of individuals with Parkinson's disease show upregulation of DR antigens and the presence of DR-positive reactive microglia, and nonsteroidal anti-inflammatory drugs reduce Parkinson's disease risk. The genetic association with HLA supports the involvement of the immune system in Parkinson's disease and offers new targets for drug development.

Molecular phylogeny and biogeography of langurs and leaf monkeys of South Asia (Primates: Colobinae).

The two recently proposed taxonomies of the langurs and leaf monkeys (Subfamily Colobinae) provide different implications to our understanding of the evolution of Nilgiri and purple-faced langurs. Groves (2001) [Groves, C.P., 2001. Primate Taxonomy. Smithsonian Institute Press, Washington], placed Nilgiri and purple-faced langurs in the genus Trachypithecus, thereby suggesting disjunct distribution of the genus Trachypithecus. [Brandon-Jones, D., Eudey, A.A., Geissmann, T., Groves, C.P., Melnick, D.J., Morales, J.C., Shekelle, M., Stewart, C.-B., 2003. Asian primate classification. Int. J. Primatol. 25, 97-162] placed these langurs in the genus Semnopithecus, which suggests convergence of morphological characters in Nilgiri and purple-faced langurs with Trachypithecus. To test these scenarios, we sequenced and analyzed the mitochondrial cytochrome b gene and two nuclear DNA-encoded genes, lysozyme and protamine P1, from a variety of colobine species. All three markers support the clustering of Nilgiri and purple-faced langurs with Hanuman langur (Semnopithecus), while leaf monkeys of Southeast Asian (Trachypithecus) form a distinct clade. The phylogenetic position of capped and golden leaf monkeys is still unresolved. It is likely that this species group might have evolved due to past hybridization between Semnopithecus and Trachypithecus clades.

Genomic and evolutionary analyses of asymmetrically expressed genes in human fetal left and right cerebral cortex.

In the human brain, the left and right hemispheres are anatomically asymmetric and have distinctive cognitive function, although the molecular basis for this asymmetry has not yet been characterized. We compared gene expression levels in the perisylvian regions of human left-right cortex at fetal weeks 12, 14, and 19 using serial analysis of gene expression (SAGE). We identified dozens of genes with evidence of differential expression by SAGE and confirmed these by quantitative reverse transcriptase-polymerase chain reaction. Most genes with differential levels of expression in the left and right hemispheres function in signal transduction and gene expression regulation during early cortical development. By comparing genes differentially expressed in left and right fetal brains with those previously reported to be differently expressed in human versus chimpanzee adult brains, we identified a subset of genes that shows evidence of asymmetric expression in humans and altered expression levels between chimps and humans. We also compared the coding sequences of genes differentially expressed between left and right hemispheres and found genes that show both asymmetric expression and evidence of positive evolutionary selection in the primate lineage leading to humans. Our results identify candidate genes involved in the evolution of human cerebral cortical asymmetry.

Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome.

Joubert syndrome is a congenital brain malformation of the cerebellar vermis and brainstem with abnormalities of axonal decussation (crossing in the brain) affecting the corticospinal tract and superior cerebellar peduncles. Individuals with Joubert syndrome have motor and behavioral abnormalities, including an inability to walk due to severe clumsiness and 'mirror' movements, and cognitive and behavioral disturbances. Here we identified a locus associated with Joubert syndrome, JBTS3, on chromosome 6q23.2-q23.3 and found three deleterious mutations in AHI1, the first gene to be associated with Joubert syndrome. AHI1 is most highly expressed in brain, particularly in neurons that give rise to the crossing axons of the corticospinal tract and superior cerebellar peduncles. Comparative genetic analysis of AHI1 indicates that it has undergone positive evolutionary selection along the human lineage. Therefore, changes in AHI1 may have been important in the evolution of human-specific motor behaviors.

Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion.

Primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes) consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size.

Spatial Pattern of Expression of Cyl Actin-ß-Galactosidase Fusion Genes injected into Sea Urchin Eggs.

The Cyl actin gene of the sea urchin Strongylocentrotus purpuratus displays a pattern of expression that is correlated with cell division; the gene is initially activated in all cells of the early blastula stage embryo, but after 18 hours Cyl actin transcripts disappear from the aboral ectoderm at a time when these cells are withdrawing from the cell cycle. As part of our investigation of the transcriptional regulation of Cyl, we tested various Cyl-ß-gal fusion genes for their spatial pattern of expression by microinjection into fertilized eggs of the sea urchin, Lytechinus pictus. The plasmid Cyl-ß-gal containing 2.5 kb of upstream sequence displayed a pattern of expression which reflected the endogenous Cyl actin gene. Most of the staining was seen in the gut, oral ectoderm, and mesenchyme cells, while fewer embryos had stained cells in the aboral ectoderm cells. Deletions in the upstream sequences to-195 bp resulted in a decrease in the mean number of stained cells, but the overall pattern of expression was similar to Cyl-ß-gal. These results indicate that sequences required for correct spatial expression of Cyl are located in the first 195 bp upstream of the Cyl start of transcription and/or within the first intron. A mutation in the highly conserved serum response element and an adjacent protein binding site did not increase the percentage of aboral ectoderm staining nor decrease the relative level of CAT activity from a Cyl-CAT fusion gene containing the same mutation. The implications of these rsults are discussed.