Watson Brake, A Middle Archaic Mound Complex in Northeast Louisiana

Middle Archaic earthen mound complexes in the lower Mississippi valley are remote antecedents of the famous but much younger Poverty Point earthworks. Watson Brake is the largest and most complex of these early mound sites. Wry extensive coring and stratigraphic studies, aided by 25 radiocarbon dates and six huninescence dates, show that minor earthworks were begun here at ca. 3500 B.C. in association with an oval arrangement of burned rock middens at the edge of a stream terrace. The full extent of the first earthworks is not yet known. Substantial moundraising began ca. 3350 B.C. and continued in stages until some time after 3000 B.C. when the site was abandoned. All 11 mounds and their connecting ridges were occupied between building bursts. Soils,formed on some of these temporary surfaces, while lithics. fire-cracked rock. and,fired clay/loam objects became scattered throughout the mound fills. Faunal and floral remains from a basal midden indicate all-season occupation, supported by broad-spectrum foraging centered on nuts, fish, and deer All the overlying fills are so acidic that organics have not survived. The area enclosed by the mounds was kept clean of debris, suggesting its use as ritual space. The reasons why such elaborate activities first occurred here remain elusive. However some building bursts covary with very well-documented increases in El Nino/Southern Oscillation events. During such rapid increases in ENSO frequencies, rainfall becomes extremely erratic and unpredictable. It may be that early moundraising was a communal response to new stresses of droughts and flooding that created a suddenly more unpredictable food base

Predictors of HIV Molecular Cluster Membership and Implications for Partner Services

Public health surveillance data used in HIV molecular cluster analyses lack contextual information that is available from partner services (PS) data. Integrating these data sources in retrospective analyses can enrich understanding of the risk profile of people in clusters. In this study, HIV molecular clusters were identified and matched to information on partners and other information gleaned at the time of diagnosis, including coinfection with syphilis. We aimed to produce a more complete understanding of molecular cluster membership in Houston, Texas, a city ranking ninth nationally in rate of new HIV diagnoses that may benefit from retrospective matched analyses between molecular and PS data to inform future intervention. Data from PS were matched to molecular HIV records of people newly diagnosed from 2012 to 2018. By conducting analyses in HIV-TRACE (TRAnsmission Cluster Engine) using viral genetic sequences, molecular clusters were detected. Multivariable logistic regression models were used to estimate the association between molecular cluster membership and completion of a PS interview, number of named partners, and syphilis coinfection. Using data from 4,035 people who had a viral genetic sequence and matched PS records, molecular cluster membership was not significantly associated with completion of a PS interview. Among those with sequences who completed a PS interview (n = 3,869), 45.3% (n = 1,753) clustered. Molecular cluster membership was significantly associated with naming 1 or 3+ partners compared with not naming any partners [adjusted odds ratio, aOR: 1.27 (95% confidence interval, CI: 1.08-1.50), p = .003 and aOR: 1.38 (95% CI: 1.06-1.81), p = .02]. Alone, coinfection with syphilis was not significantly associated with molecular cluster membership. Syphilis coinfection was associated with molecular cluster membership when coupled with incarceration [aOR: 1.91 (95% CI: 1.08-3.38), p = .03], a risk for treatment interruption. Enhanced intervention among those with similar profiles, such as people coinfected with other risks, may be warranted

A Mound Complex in Louisiana at 5400-5500 Years Before the Present

An 11-mound site in Louisiana predates other known mound complexes with earthen enclosures in North America by 1900 years. Radiometric, luminescence, artifactual, geomorphic, and pedogenic data date the site to over 5000 calendar years before present. Evidence suggests that the site was occupied by hunter-gatherers who seasonally exploited aquatic resources and collected plant species that later became the first domesticates in eastern North America

Expression quantitative trait locus fine mapping of the 17q12-21 asthma locus in African American children: a genetic association and gene expression study

BACKGROUND: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12-21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children\u27s Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12-21 locus. METHODS: We first did a genetic association study and meta-analysis using 17q12-21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12-21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12-21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). FINDINGS: 17q12-21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p\u3c0·0055 (for rs2305480_G, odds ratio [OR] 1·36 [95% CI 1·12-1·65], p=0·0014; and for rs8076131_A, OR 1·37 [1·13-1·67], p=0·0010). In upper airway epithelial cells from African American children, genotype at rs2305480 was the most significant eQTL for GSDMB (eQTL effect size [β] 1·35 [95% CI 1·25-1·46], p\u3c0·0001), and to a lesser extent showed an eQTL effect for post-GPI attachment to proteins phospholipase 3 (β 1·15 [1·08-1·22], p\u3c0·0001). No SNPs were eQTLs for ORMDL3. By contrast, in PBMCs, the five core SNPs were associated only with expression of GSDMB and ORMDL3. Genotype at rs12936231 (in zona pellucida binding protein 2) showed the strongest associations across both genes (for GSDMB, eQTLβ 1·24 [1·15-1·32], p\u3c0·0001; and for ORMDL3 (β 1·19 [1·12-1·24], p\u3c0·0001). The eQTL effects of rs2305480 on GSDMB expression were replicated in lower airway cells from African American adults (β 1·29 [1·15-1·44], p\u3c0·0001). INTERPRETATION: Our study suggests that SNPs regulating GSDMB expression in airway epithelial cells have a major role in childhood-onset asthma, whereas SNPs regulating the expression levels of 17q12-21 genes in resting blood cells are not central to asthma risk. Our genetic and gene expression data in African Americans and European Americans indicated GSDMB to be the leading candidate gene at this important asthma locus. FUNDING: National Institutes of Health, Office of the Director

Expression quantitative trait locus fine mapping of the 17q12–21 asthma locus in African American children: a genetic association and gene expression study

BackgroundAfrican ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12-21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12-21 locus.MethodsWe first did a genetic association study and meta-analysis using 17q12-21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12-21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12-21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA).Findings17q12-21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p<0·0055 (for rs2305480_G, odds ratio [OR] 1·36 [95% CI 1·12-1·65], p=0·0014; and for rs8076131_A, OR 1·37 [1·13-1·67], p=0·0010). In upper airway epithelial cells from African American children, genotype at rs2305480 was the most significant eQTL for GSDMB (eQTL effect size [β] 1·35 [95% CI 1·25-1·46], p<0·0001), and to a lesser extent showed an eQTL effect for post-GPI attachment to proteins phospholipase 3 (β 1·15 [1·08-1·22], p<0·0001). No SNPs were eQTLs for ORMDL3. By contrast, in PBMCs, the five core SNPs were associated only with expression of GSDMB and ORMDL3. Genotype at rs12936231 (in zona pellucida binding protein 2) showed the strongest associations across both genes (for GSDMB, eQTLβ 1·24 [1·15-1·32], p<0·0001; and for ORMDL3 (β 1·19 [1·12-1·24], p<0·0001). The eQTL effects of rs2305480 on GSDMB expression were replicated in lower airway cells from African American adults (β 1·29 [1·15-1·44], p<0·0001).InterpretationOur study suggests that SNPs regulating GSDMB expression in airway epithelial cells have a major role in childhood-onset asthma, whereas SNPs regulating the expression levels of 17q12-21 genes in resting blood cells are not central to asthma risk. Our genetic and gene expression data in African Americans and European Americans indicated GSDMB to be the leading candidate gene at this important asthma locus.FundingNational Institutes of Health, Office of the Director