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Good, S. V.

Publications and source records attributed to Good, S. V..

3 recordsLinked to original sources

The germline-specific region of the sea lamprey genome plays a key role in spermatogenesis

The sea lamprey genome undergoes programmed genome rearrangement (PGR) in which [~]20% is jettisoned from somatic cells soon after fertilization. Although the role of PGR in embryonic development has been studied, the role of the germline-specific region (GSR) in gonad development is unknown. We analysed RNA-sequence data from 28 sea lamprey gonads sampled across life-history stages, generated a genome-guided de novo superTransciptome with annotations, and identified genes in the GSR. We found that the 638 genes in the GSR are enriched for reproductive processes, exhibit 36x greater odds of being expressed in testes than ovaries, show little evidence of conserved synteny with other chordates, and most have putative paralogues in the GSR and/or somatic genomes. Further, several of these genes play known roles in sex determination and differentiation in other vertebrates. We conclude that the GSR of sea lamprey plays an important role in testicular differentiation and potentially sex determination.

genomics

Insertive vaginal sex has a profound impact on the penile immune correlates of HIV susceptibility

The penis is the primary site of HIV acquisition in heterosexual men. Elevated penile inflammatory cytokines increase sexual acquisition risk, and topically applied cytokines enhance foreskin HIV susceptibility in an explant model. However, the impact of penile-vaginal sex on these immune parameters is undefined. Heterosexual couples were recruited to the Sex, Couples and Science (SECS) Study, with the collection of penile swabs, semen, cervico-vaginal secretions, and blood after a period of abstinence, and repeated sampling up to 72 hours after either condomless (n=30) or condom-protected (n=8) penile-vaginal sex. Soluble immune parameters were quantified by multiplex immunoassay. Co-primary immune endpoints were penile levels of IL-8 and MIG, cytokines previously linked to penile HIV acquisition. One hour after sex there were dramatic increases in penile IL-8 and MIG levels, regardless of condom use, with a gradual return to baseline by 72 hours; similar patterns were observed for other chemoattractant chemokines. Penile cytokine changes were similar in circumcised and uncircumcised men, and repeated measures ANOVA and ANCOVA models demonstrated that the degree of change after condomless sex was explained by cytokine levels in their partners cervico-vaginal secretions. This may have important implications for the biology of penile HIV acquisition. Author summaryIn heterosexual men, the penis is the primary site of Human Immunodeficiency Virus (HIV) acquisition. Levels of inflammatory cytokines in the coronal sulcus are associated with an increased HIV risk, and we hypothesized that these may be altered after insertive penile sex. Therefore, we designed the Sex, Couples and Science Study (SECS study) to define the impact of penile-vaginal sex on the penile immune correlates of HIV susceptibility. We found that multiple coronal sulcus cytokines increased dramatically and rapidly after sex, regardless of condom use, with a return to baseline levels by 72 hours. The changes observed after condomless sex were strongly predicted by cytokine concentrations in the vaginal secretions of the female partner, and were similar in circumcised and uncircumcised men. We believe that these findings have important implications for understanding the immunopathogenesis of penile HIV acquisition; in addition, they have important implications for the design of clinical studies of penile HIV acquisition and prevention.

immunology

N-myristoyltransferase: Tracing Steps Backwards to Find a Way Forward

N-myristoylation refers to the attachment of a 14-carbon fatty acid onto the N-terminal glycine residue of a target protein. The myristoylation reaction, catalyzed by N-myristoyltrasnferase (NMT), is essential for regulating cellular activities such as signal transduction, proliferation, migration, differentiation, and transformation. Although a considerable amount of research is performed on the overexpression of NMT in pathogenic conditions, a fundamental knowledge gap exists on the evolution of NMT and the functional impact of myristoylation for normal cellular development and functions. We performed evolutionary analyses of the NMT gene and found that most non-vertebrates harbor a single nmt gene and all vertebrates examined harbor two genes; nmt1 and nmt2. For the first time, we report that teleosts harbor two copies of nmt1, named nmt1a and nmt1b. We traced the evolutionary history of the chromosomal fragments hosting NMT1 and NMT2 in humans and found that NMT1 and NMT2 trace back to a single vertebrate ancestral chromosome. We also report the presence of putative nuclear localization sequence (NLS) and amino acid residues flanking NLS. The presence of phosphorylatable amino acid residues flanking the NLS suggests that nuclear localization of NMT is regulated by phosphorylation. The nuclear localization of NMT suggest its potential role in gene transcription.

evolutionary biology