Detectable Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Human Breast Milk of a Mildly Symptomatic Patient With Coronavirus Disease 2019 (COVID-19).

SARS-CoV-2 is a novel coronavirus and causative pathogen to the pandemic illness COVID-19. Although RNA has been detected in various clinical samples, no reports to date have documented SARS-CoV-2 in human milk. This case report describes an actively breastfeeding patient with COVID-19 infection with detectable viral RNA in human milk.

Mitochondrial DNA of protohistoric remains of an Arikara population from South Dakota: implications for the macro-Siouan language hypothesis.

Mitochondrial DNA (mtDNA) was extracted from skeletal remains excavated from three Arikara sites in South Dakota occupied between AD 1600 and 1832. The diagnostic markers of four mtDNA haplogroups to which most Native Americans belong (A, B, C, and D) were successfully identified in the extracts of 55 (87%) of the 63 samples studied. The frequencies of the four haplogroups were 42%, 29%, 22%, and 7%, respectively, and principal coordinates analysis and Fisher's exact tests were conducted to compare these haplogroup frequencies with those from other populations. Both analyses showed closer similarity among the Mohawk, Arikara, and Sioux populations than between any of these three and any other of the comparison populations. Portions of the first hypervariable segment (HVSI) of the mitochondrial genome were successfully amplified and sequenced for 42 of these 55 samples, and haplotype networks were constructed for two of the four haplogroups. The sharing of highly derived lineages suggests that some recent admixture of the Arikara with Algonquian-speaking and Siouan-speaking groups has occurred. The Arikara shared more ancient lineages with both Siouan and Cherokee populations than with any other population, consistent with the Macro-Siouan language hypothesis that Iroquoian, Siouan, and Caddoan languages share a relatively recent common ancestry.

CXCR4 and CXCL12 (SDF-1) in prostate cancer: inhibitory effects of human single chain Fv antibodies.

PURPOSE: Metastasis is a major cause of morbidity in prostate cancer (PCa). Several studies have shown that the chemokine receptor CXCR4 and its ligand, CXCL12 (stromal cell-derived factor-1), regulate tumor cell metastasis to specific organs. Recently, it was demonstrated that CXCL12 enhances PCa cell adhesion, migration, and invasion, implicating CXCR4 in PCa metastasis. In this study, we examined the inhibitory effects of anti-CXCR4 antibodies on CXCL12-mediated PCa cell activities. EXPERIMENTAL DESIGN: We developed fully human single chain Fv antibodies (scFv), Ab124 and Ab125, against CXCR4 using the yeast two-hybrid system. We performed immunofluorescent staining, flow cytometry, and ELISA-binding assays to measure scFv binding to PCa cells. We also examined the effects of scFv on CXCL12-mediated calcium mobilization, cell migration, and invasion. RESULTS: Our results confirmed that PCa cell lines express cell-surface CXCR4. Real-time quantitative reverse transcription-PCR and immunohistochemical staining also verified that CXCR4 is expressed in primary cultures of prostate epithelial cells from adenocarcinomas and in human prostate tissues. Ab124 and Ab125 demonstrated specific binding to PCa cell lines by flow cytometry and in binding assays. Preincubation with scFv resulted in significant reduction of CXCL12-induced calcium mobilization in PC-3 and LNCaP cells. Ab124 and Ab125 also inhibited PCa cell migration toward CXCL12, as well as invasion through extracellular matrix gels. CONCLUSIONS: Ab124 and Ab125 inhibit CXCL12-mediated cellular activities by binding the receptor CXCR4. Recombinant scFv are an efficient mode of targeting tumor antigens. Considering the high incidence of PCa, the development of fully human scFv may be a useful therapeutic approach in the prevention and treatment of PCa metastasis.

CXCR4-mediated adhesion and MMP-9 secretion in head and neck squamous cell carcinoma.

The chemokine CXCL12 (SDF-1) and its receptor, CXCR4, have been implicated in organ-specific metastases of several malignancies. Head and neck squamous cell carcinoma (HNSCC) predominantly metastasizes to lymph nodes, and recent evidence has shown that CXCL12 stimulates HNSCC migration. We explored the potential role of CXCR4 in mediating other metastatic processes in HNSCC cells. CXCR4 mRNA and cell-surface expression was assessed in HNSCC cell lines. CXCR4 mRNA expression was detected in five HNSCC cell lines. Cell-surface CXCR4 was also detected in each of the HNSCC cell lines and in resected HNSCC tissues. CXCL12 induced rapid intracellular calcium mobilization in a metastatic HNSCC cell line (HN), as well as rapid phosphorylation of ERK-1/2. HNSCC cell adhesion to fibronectin and collagen was increased by CXCL12 treatment, while the addition of an inhibitor of ERK-1/2 signaling, PD98059, reduced the effects of CXCL12. CXCL12 also increased the active matrix metalloproteinase (MMP)-9 secreted. Thus, HNSCC cells express functional CXCR4 receptors that induce rapid intracellular signaling upon binding to CXCL12. Such binding leads to increased HNSCC cell adhesion and MMP secretion, suggesting that CXCR4 may be a novel regulator of HNSCC metastatic processes.

Expression of CCL5 (RANTES) and CCR5 in prostate cancer.

BACKGROUND: Expression of the inflammatory chemokine CCL5 (RANTES) by tumor cells is thought to correlate with the progression of several cancers. CCL5 was shown to induce breast cancer cell migration, mediated by the receptor CCR5. A CCR5 antagonist was demonstrated to inhibit experimental breast tumor growth. Recently, CCL5 and CCR5 mRNA expression was reported in prostate cancer (PCa) tissues. Herein, we characterized CCL5 and CCR5 expression in cultures of PCa cells and explored possible functions of CCL5 in PCa progression. METHODS: Quantitative RT-PCR, ELISA, and immunohistochemical staining were performed to examine CCL5 expression in prostate cell lines. CCR5 expression was measured by flow cytometry. Proliferation and invasion assays were performed to determine potential functions of CCL5 and CCR5 in PCa. RESULTS: Expression of CCL5 mRNA and protein was found in human PCa cell lines (PC-3; DU-145; LNCaP) and primary prostate adenocarcinoma cells. CCL5 and CCR5 were also detected in human PCa tissues. CCR5 expression was demonstrated on the cell surface of PCa cells, as well as in intracellular pools. Incubation with CCL5 (10-100 ng/ml) induced PCa cell proliferation, and the CCR5 antagonist TAK-779 inhibited CCL5-induced proliferation. CCL5 was found to stimulate PCa cell invasion, and TAK-779 blocked the effects of CCL5. CONCLUSIONS: In light of evidence that inflammation influences the pathogenesis of PCa, these results suggest that inflammatory chemokines, such as CCL5, expressed by prostate cells may act directly on the growth and survival of PCa cells. Chemokine receptor antagonists may thus block autocrine mechanisms of PCa progression.

Patterns of female dominance in Propithecus diadema edwardsi of Ranomafana National Park, Madagascar.

Many lemur species are characterized by some form of female dominance, ranging from female feeding priority to complete female dominance, although this is a rare trait in primates and other mammals. The status of the Milne-Edwards' sifaka (Propithecus diadema edwardsi), a diurnal lemur, is ambiguous. Some short-term studies have found little or no aggression. The aim of the current, long-term study was to quantify the intersexual-dominance patterns of this sifaka. The distribution, outcome, and context of aggressive interactions were studied in four groups of wild sifakas. The majority of intersexual aggressive interactions were decided, with the loser expressing submissive behavior. Intersexual aggressive interactions occurred in all social contexts, and within all social contexts the females won the vast majority (92.7-96.0%) of aggressive interactions. While aggression rates were low (0.22/hr), this evidence suggests female dominance. We propose that female dominance exists because it provides a fitness advantage to both males and females.