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The Research Centers in Minority Institutions (RCMI) program was established by the US Congress to support the development of biomedical research infrastructure at minority-serving institutions granting doctoral degrees in the health professions or in a health-related science. RCMI institutions also conduct research on diseases that disproportionately affect racial and ethnic minorities (ie, African Americans/Blacks, American Indians and Alaska Natives, Hispanics, Native Hawaiians and Other Pacific Islanders), those of low socioeconomic status, and rural persons. Quantitative metrics, including the numbers of doctoral science degrees granted to underrepresented students, NIH peer-reviewed research funding, peer-reviewed publications, and numbers of racial and ethnic minorities participating in sponsored research, demonstrate that RCMI grantee institutions have made substantial progress toward the intent of the Congressional legislation, as well as the NIH/NIMHD-linked goals of addressing workforce diversity and health disparities. Despite this progress, nationally, many challenges remain, including persistent disparities in research and career development awards to minority investigators. The continuing underrepresentation of minority investigators in NIH-sponsored research across multiple disease areas is of concern, in the face of unrelenting national health inequities. With the collaborative network support by the RCMI Translational Research Network (RTRN), the RCMI community is uniquely positioned to address these challenges through its community engagement and strategic partnerships with non-RCMI institutions. Funding agencies can play an important role by incentivizing such collaborations, and incorporating metrics for research funding that address underrepresented populations, workforce diversity and health equity.

MoMo30 is an antiviral protein isolated from aqueous extracts of Momordica balsamina L. (Senegalese bitter melon). Previously, we demonstrated MoMo30's antiviral activity against HIV-1. Here, we explore whether MoMo30 has antiviral activity against the COVID-19 virus, SARS-CoV-2. MLV particles pseudotyped with the SARS-CoV-2 Spike glycoprotein and a Luciferase reporter gene (SARS2-PsV) were developed from a three-way co-transfection of HEK293-T17 cells. MoMo30's inhibition of SARS2-PsV infection was measured using a luciferase assay and its cytotoxicity using an XTT assay. Additionally, MoMo30's interactions with the variants and domains of Spike were determined by ELISA. We show that MoMo30 inhibits SARS2-PsV infection. We also report evidence of the direct interaction of MoMo30 and SARS-CoV-2 Spike from WH-1, Alpha, Delta, and Omicron variants. Furthermore, MoMo30 interacts with both the S1 and S2 domains of Spike but not the receptor binding domain (RBD), suggesting that MoMo30 inhibits SARS-CoV-2 infection by inhibiting fusion of the virus and the host cell via interactions with Spike. [ABSTRACT FROM AUTHOR]

The chemokine co-receptors CXCR4 and CCR5 mediate HIV entry and signal transduction necessary for viral infection. However, to date only the CCR5 antagonist maraviroc is approved for treating HIV-1 infection. Given that approximately 50% of late-stage HIV patients also develop CXCR4-tropic virus, clinical anti-HIV CXCR4 antagonists are needed. Here, we describe a novel allosteric CXCR4 antagonist TIQ-15 which inhibits CXCR4-tropic HIV-1 infection of primary and transformed CD4 T cells. TIQ-15 blocks HIV entry with an IC50 of 13 nM. TIQ-15 also inhibits SDF-1α/CXCR4-mediated cAMP production, cofilin activation, and chemotactic signaling. In addition, TIQ-15 induces CXCR4 receptor internalization without affecting the levels of the CD4 receptor, suggesting that TIQ-15 may act through a novel allosteric site on CXCR4 for blocking HIV entry. Furthermore, TIQ-15 did not inhibit VSV-G pseudotyped HIV-1 infection, demonstrating its specificity in blocking CXCR4-tropic virus entry, but not CXCR4-independent endocytosis or post-entry steps. When tested against a panel of clinical isolates, TIQ-15 showed potent inhibition against CXCR4-tropic and dual-tropic viruses, and moderate inhibition against CCR5-tropic isolates. This observation was followed by a co-dosing study with maraviroc, and TIQ-15 demonstrated synergistic activity. In summary, here we describe a novel HIV-1 entry inhibitor, TIQ-15, which potently inhibits CXCR4-tropic viruses while possessing low-level synergistic activities against CCR5-tropic viruses. TIQ-15 could potentially be co-dosed with the CCR5 inhibitor maraviroc to block viruses of mixed tropisms. Author summary: HIV uses the chemokine co-receptors CXCR4 or CCR5 for cell fusion and entry. While the CCR5-tropic viruses predominate early in HIV infection, the emergence of the CXCR4-tropic viruses at later stages in 50% of patients is associated with rapid disease progression. The CCR5 antagonist maraviroc has been approved for treating HIV infection. However, currently, there is no clinical anti-HIV CXCR4 inhibitor. Here we report a novel CXCR4 antagonist TIQ-15 that potently blocked CXCR4-tropic HIV infection of human CD4 T cells. TIQ-15 in combination with maraviroc also demonstrated synergistic activities against CCR5-tropic viruses and could be potentially used with maraviroc to block viruses of mixed tropisms. [ABSTRACT FROM AUTHOR]

MotivationExtracellular vesicles (EVs) are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of the vesicular nomenclatures and components, online searches for EV-related publications and vesicular components are currently challenging.ResultsWe present an improved version of EVpedia, a public database for EVs research. This community web portal contains a database of publications and vesicular components, identification of orthologous vesicular components, bioinformatic tools and a personalized function. EVpedia includes 6879 publications, 172 080 vesicular components from 263 high-throughput datasets, and has been accessed more than 65 000 times from more than 750 cities. In addition, about 350 members from 73 international research groups have participated in developing EVpedia. This free web-based database might serve as a useful resource to stimulate the emerging field of EV research.Availability and implementationThe web site was implemented in PHP, Java, MySQL and Apache, and is freely available at http://evpedia.info.

Harms associated with anabolic androgenic steroids (AAS) use are well-established and a public health concern. Robust estimates of the numbers using AAS are needed to inform responses, however, in the UK these are lacking. Due to the comparative rarity and associated stigma, general population surveys are problematic and data availability limits the use of indirect approaches. To address this, the Delphi method was used to refine the key parameters needed for indirect estimation from attendances at needle and syringe programmes (NSP) for AAS use. An expert panel (n = 63) was surveyed three times (n = 40, 39, and 37) to refine the parameters needed to generate a likely range from data on NSP attendances. A broad agreement was reached on: regional variations in use; the proportion of men using AAS who only use them orally; the proportion of men who inject AAS using NSP; and the proportion of the AAS population who are women. We conclude that previous general population survey-based estimates of recent AAS use appear implausible, with the likely range indicated by NSP data being up to 10-times higher. AAS use in the UK is more common than previously indicated, but further work is needed to refine population size estimation and characteristics. [ABSTRACT FROM AUTHOR]

The HIV envelope protein gp120 can cause cell death in the endothelium, including umbilical vein endothelium. The endothelium is the lining inside blood vessels. gp120 appears to interact with the CXCR4 and CCR5 cell receptors.

Protein kinase C in endothelium increases when exposed to the HIV gp-120 protein. The enzyme appears to be linked to cell death in this tissue, as is the CXCR4 receptor.

A second endogenous Porphyromonas gingivalis insertion element (IS) that is capable of transposition within P. gingivalis was determined. A complete copy of the formerly known IS element called PGIS2 was found to be inserted into IS4351R in Tn4351. The number of copies of PGIS2 per genome was found to vary among various kinds of P. gingivalis strains. PGIS2 had strong homologies to the products encoded by IS1358 from Vibrio cholerae, ISAS1 from Aeromonas salmonicida and H-rpt in Escherichia coli K-12.

Abstract Background Cerebral malaria (CM) is a major cause of malaria mortality. Sequestration of infected red blood cells and leukocytes in brain vessels coupled with the production of pro-inflammatory factors contribute to CM. CXCL-10 a chemokine that is chemotactic to T cells has been linked to fatal CM. Mice deficient for CXCL-10 gene are resistant to murine CM, while antibody ablation of CXCL-10 enhanced the production of regulatory T cells (CD4+Cd25+Foxp3+) and IL-10 which regulate the immune system. Interleukin-2 (IL-2), a pro-inflammatory cytokine implicated in malaria pathogenesis has also been shown to be a key regulator of Foxp3. However the role of Foxp3 in resistant murine CM is not well understood. Methods The hypothesis that resistance of CXCL-10-/- mice to murine CM may be due to enhanced expression of Foxp3 in concert with IL-10 and IL-2 was tested. CXCL-10-/- and WT C57BL/6 mice were infected with Plasmodium berghei ANKA and evaluated for CM symptoms. Brain, peripheral blood mononuclear cells (PBMCs) and plasma were harvested from infected and uninfected mice at days 2, 4 and 8. Regulatory T cells (CD4+CD25+) and non-T regs (CD4+CD25-) were isolated from PBMCs and cultured with P. berghei antigens in vitro with dendritic cells as antigen presenting cells. Regulatory T cell transcription and specific factor Foxp3, was evaluated in mouse brain and PBMCs by realtime-PCR and Western blots while IL-10, and IL-2 were evaluated in plasma and cultured supernatants by ELISA. Results Wild type mice exhibited severe murine CM symptoms compared with CXCL-10-/- mice. Foxp3 mRNA and protein in brain and PBMC's of CXCL-10-/- mice was significantly up-regulated (p < 0.05) by day 4 post-infection (p.i) compared with WT. Plasma levels of IL-10 and IL-2 in infected CXCL-10-/- were higher than in WT mice (p < 0.05) at days 2 and 4 p.i. Ex-vivo CD4+CD25+ T cells from CXCL-10-/- re-stimulated with P. berghei antigens produced more IL-10 than WT CD4+CD25+ T cells. Conclusion The results indicate that in the absence of CXCL-10, the resulting up-regulation of Foxp3, IL-10 and IL-2 may be involved in attenuating fatal murine CM.

Abstract Background Plasmodium falciparum can cause a diffuse encephalopathy known as cerebral malaria (CM), a major contributor to malaria associated mortality. Despite treatment, mortality due to CM can be as high as 30% while 10% of survivors of the disease may experience short- and long-term neurological complications. The pathogenesis of CM and other forms of severe malaria is multi-factorial and appear to involve cytokine and chemokine homeostasis, inflammation and vascular injury/repair. Identification of prognostic markers that can predict CM severity will enable development of better intervention. Methods Postmortem serum and cerebrospinal fluid (CSF) samples were obtained within 2–4 hours of death in Ghanaian children dying of CM, severe malarial anemia (SMA), and non-malarial (NM) causes. Serum and CSF levels of 36 different biomarkers (IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, Eotaxin, FGF basic protein, CRP, G-CSF, GM-CSF, IFN-γ, TNF-α, IP-10, MCP-1 (MCAF), MIP-1α, MIP-1β, RANTES, SDF-1α, CXCL11 (I-TAC), Fas-ligand [Fas-L], soluble Fas [sFas], sTNF-R1 (p55), sTNF-R2 (p75), MMP-9, TGF-β1, PDGF bb and VEGF) were measured and the results compared between the 3 groups. Results After Bonferroni adjustment for other biomarkers, IP-10 was the only serum biomarker independently associated with CM mortality when compared to SMA and NM deaths. Eight CSF biomarkers (IL-1ra, IL-8, IP-10, PDGFbb, MIP-1β, Fas-L, sTNF-R1, and sTNF-R2) were significantly elevated in CM mortality group when compared to SMA and NM deaths. Additionally, CSF IP-10/PDGFbb median ratio was statistically significantly higher in the CM group compared to SMA and NM groups. Conclusion The parasite-induced local cerebral dysregulation in the production of IP-10, 1L-8, MIP-1β, PDGFbb, IL-1ra, Fas-L, sTNF-R1, and sTNF-R2 may be involved in CM neuropathology, and their immunoassay may have potential utility in predicting mortality in CM.

Abstract Background HLA-G gene is a non-classical MHC class 1 molecule that is highly expressed in the trophoblast at the maternal-fetal interface. In an attempt to elucidate possible immunological mechanisms facilitating protection of infants born to human immunodeficiency virus type (HIV-1) infected mothers, we have been studying genetic variations in the coding and untranslated regions of HLA-G antigen between HIV-1-infected mothers and their infected or uninfected infants. This study investigated whether HLA-G DNA sequence variants are associated with perinatal HIV-1 transmission. Results Genomic DNA samples were obtained from a nested case-control study of 34 mother-child pairs co-enrolled in a cohort of the Perinatal AIDS Collaborative Transmission Study in New York. The samples were from two groups predominantly of African-American and Hispanic origin: In the first group, both mother and child were HIV-1-infected; in the second group, only the mother was infected while the child remained uninfected. Genotyping of HLA-G gene were performed on the extracted DNA from peripheral blood mononuclear cells using PCR based sequencing and restriction fragment-length polymorphism analyses. Among the studied HLA-G exons, dissimilarities in HLA-G DNA sequence variants between the HIV-1 non-transmitting mother child pairs were mostly observed in exon 8-3'-untranslated region at nucleotide positions T3742A, C3743T, G3777C (P = 0.001). Non-transmitting HIV-1 mother child pairs exhibited dissimilarities at nucleotide position C3743T allele with decreased risk of perinatal HIV-1 transmission, compared with HIV-1 transmitting mother-child pairs carrying this allele (odds ratio 0.02 [95% confidence interval 0.00–0.15] P = 0.00001). In addition, heterozygous dissimilarities at nucleotide positions C634G and 714 insT/G in the 5'-upstream regulatory region were observed between the mother child pairs of the HIV-1-non-transmitting group while homozygous similarities of C634C, and either 714insG/G or mother-child pairs with similar 714insT/G were observed among the transmitting group in the same region. Conclusion This study identified new variants in the HLA-G gene and provides further evidence that dissimilarities in the HLA-G DNA sequence variants could influence the transmission of HIV-1 from infected mothers to their infants.