The Paleo-Indian Entry into South America According to Mitogenomes

Recent and compelling archaeological evidence attests to human presence 14.5 ka at multiple sites in South America and a very early exploitation of extreme high-altitude Andean environments. Considering that, according to genetic evidence, human entry into North America from Beringia most likely occurred 16 ka, these archeological findings would imply an extremely rapid spread along the double continent. To shed light on this issue from a genetic perspective, we first completely sequenced 217 novel modern mitogenomes of Native American ancestry from the northwestern area of South America (Ecuador and Peru); we then evaluated them phylogenetically together with other available mitogenomes (430 samples, both modern and ancient) from the same geographic area and, finally, with all closely related mitogenomes from the entire double continent. We detected a large number (N¼ 48) of novel subhaplogroups, often branching into further subclades, belonging to two classes: those that arose in South America early after its peopling and those that instead originated in North or Central America and reached South America with the first settlers. Coalescence age estimates for these subhaplogroups provide time boundaries indicating that early Paleo-Indians probably moved from North America to the area corresponding to modern Ecuador and Peru over the short time frame of 1.5 ka comprised between 16.0 and 14.6 ka

Reconstructing the Deep Population History of Central and South America

We report genome-wide ancient DNA from 49 individuals forming four parallel time transects in Belize, Brazil, the Central Andes, and the Southern Cone, each dating to at least 9,000 years ago. The common ancestral population radiated rapidly from just one of the two early branches that contributed to Native Americans today. We document two previously unappreciated streams of gene flow between North and South America. One affected the Central Andes by 4,200 years ago, while the other explains an affinity between the oldest North American genome associated with the Clovis culture and the oldest Central and South Americans from Chile, Brazil, and Belize. However, this was not the primary source for later South Americans, as the other ancient individuals derive from lineages without specific affinity to the Clovis-associated genome, suggesting a population replacement that began at least 9,000 years ago and was followed by substantial population continuity in multiple regions

Dead migrants in the Mediterranean: genetic analysis of bone samples exposed to seawater

In April 2015, a fishing boat that departed from Libya with about 1,000 migrants on board sank in the Mediterranean Sea. Most of the migrants were packed in the hull of the boat and drowned in the shipwreck. After fifteen months, the ship was recovered from the seabed and brought to a Sicilian naval area for forensic investigations. Skeletal remains belonging to more than 700 people were retrieved. A selected sample composed of 80 victims was considered in order to evaluate the possibility of achieving genetic profiles useful for a positive identification from these challenging specimens. The molecular features of the DNA recovered from a significant number of real casework samples exposed to seawater for long periods of time were described for the first time. Three different DNA extraction protocols and three different commercial kits were employed in order to generate genetic profiles based on the characterization of 21 autosomal STR loci. The combination of multiple DNA extractions and the cross-checking of multiple PCR amplifications with different kits allowed to obtain reliable genetic profiles characterized by at least 16 STR markers in more than 70% of the samples. The factors that could have affected the different quality of the genetic profiles were investigated and the bone preservation was examined through microscopic and macroscopic analyses. The approach presented in this study could be useful in the management of the genetic analysis of bone samples collected in other similar DVI scenarios. The genetic profiles recovered from the bone samples will be compared in kinship analysis to putative relatives of the victims collected in Africa in order to obtain positive identifications

Markers of Immune Activation and Inflammation, and Non-Hodgkin Lymphoma: A Meta-Analysis of Prospective Studies.

BackgroundChronic inflammation and immune activation are reported to play a key role in the etiology of non-Hodgkin lymphoma (NHL). We conducted a meta-analysis on the associations between prediagnosis circulating levels of immune stimulatory markers, interleukin 6 (IL-6), IL-10, tumor necrosis factor α (TNF-α), CXCL13, soluble CD23 (sCD23), sCD27, sCD30, and the risk of NHL.MethodsRelevant studies were identified from PubMed, EMBASE, and Web of Science up to January 1, 2017. We calculated summary odds ratio (OR) estimates for the association between one natural log increase in concentration of each biomarker and NHL using random-effects models for NHL as a composite outcome and for several histological subtypes of NHL.ResultsSeventeen nested case control studies were included. Elevated levels of several biomarkers were more strongly associated with increased odds of NHL: TNF-α, OR = 1.18 (95% confidence interval [CI] = 1.04 to 1.34); CXCL13, OR = 1.47 (95% CI = 1.03 to 2.08); sCD23, OR = 1.57 (95% CI = 1.21 to 2.05); sCD27, OR = 2.18 (95% CI = 1.20 to 3.98); sCD30, OR = 1.65 (95% CI = 1.22 to 2.22). In stratified analyses, IL-6, TNF-α, sCD27, and sCD30 were more strongly associated with NHL in HIV-infected individuals compared to HIV-uninfected individuals. Between-study heterogeneity was observed across multiple biomarkers for overall NHL and by subtypes.ConclusionThis meta-analysis provides evidence that elevated circulating levels of TNF-α, CXCL13, sCD23, sCD27, and sCD30 are consistently associated with an increased risk of NHL, suggesting the potential utility of these biomarkers in population risk stratification and prediction

Major Role for TRPV1 and InsP3R in PAR2-Elicited Inflammatory Mediator Production in Differentiated Human Keratinocytes

International audienc

Reconstructing the Deep Population History of Central and South America.

We report genome-wide ancient DNA from 49 individuals forming four parallel time transects in Belize, Brazil, the Central Andes, and the Southern Cone, each dating to at least ∼9,000 years ago. The common ancestral population radiated rapidly from just one of the two early branches that contributed to Native Americans today. We document two previously unappreciated streams of gene flow between North and South America. One affected the Central Andes by ∼4,200 years ago, while the other explains an affinity between the oldest North American genome associated with the Clovis culture and the oldest Central and South Americans from Chile, Brazil, and Belize. However, this was not the primary source for later South Americans, as the other ancient individuals derive from lineages without specific affinity to the Clovis-associated genome, suggesting a population replacement that began at least 9,000 years ago and was followed by substantial population continuity in multiple regions

Reconstructing the Deep Population History of Central and South America.

We report genome-wide ancient DNA from 49 individuals forming four parallel time transects in Belize, Brazil, the Central Andes, and the Southern Cone, each dating to at least ∼9,000 years ago. The common ancestral population radiated rapidly from just one of the two early branches that contributed to Native Americans today. We document two previously unappreciated streams of gene flow between North and South America. One affected the Central Andes by ∼4,200 years ago, while the other explains an affinity between the oldest North American genome associated with the Clovis culture and the oldest Central and South Americans from Chile, Brazil, and Belize. However, this was not the primary source for later South Americans, as the other ancient individuals derive from lineages without specific affinity to the Clovis-associated genome, suggesting a population replacement that began at least 9,000 years ago and was followed by substantial population continuity in multiple regions

COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study

International audienceBackground: Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases.Methods: In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609.Findings: Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66-6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46-0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55-3·19, p=0·53).Interpretation: Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases

Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients

International audienceObjectives: There is little known about the impact of SARS-CoV-2 on patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). We examined epidemiological characteristics associated with severe disease, then with death. We also compared mortality between patients hospitalised for COVID-19 with and without iRMD.Methods: Individuals with suspected iRMD-COVID-19 were included in this French cohort. Logistic regression models adjusted for age and sex were used to estimate adjusted ORs and 95% CIs of severe COVID-19. The most significant clinically relevant factors were analysed by multivariable penalised logistic regression models, using a forward selection method. The death rate of hospitalised patients with iRMD-COVID-19 (moderate-severe) was compared with a subset of patients with non-iRMD-COVID-19 from a French hospital matched for age, sex, and comorbidities.Results: Of 694 adults, 438 (63%) developed mild (not hospitalised), 169 (24%) moderate (hospitalised out of the intensive care unit (ICU) and 87 (13%) severe (patients in ICU/deceased) disease. In multivariable imputed analyses, the variables associated with severe infection were age (OR=1.08, 95% CI: 1.05-1.10), female gender (OR=0.45, 95% CI: 0.25-0.80), body mass index (OR=1.07, 95% CI: 1.02-1.12), hypertension (OR=1.86, 95% CI: 1.01-3.42), and use of corticosteroids (OR=1.97, 95% CI: 1.09-3.54), mycophenolate mofetil (OR=6.6, 95% CI: 1.47-29.62) and rituximab (OR=4.21, 95% CI: 1.61-10.98). Fifty-eight patients died (8% (total) and 23% (hospitalised)). Compared with 175 matched hospitalised patients with non-iRMD-COVID-19, the OR of mortality associated with hospitalised patients with iRMD-COVID-19 was 1.45 (95% CI: 0.87-2.42) (n=175 each group).Conclusions: In the French RMD COVID-19 cohort, as already identified in the general population, older age, male gender, obesity, and hypertension were found to be associated with severe COVID-19. Patients with iRMD on corticosteroids, but not methotrexate, or tumour necrosis factor alpha and interleukin-6 inhibitors, should be considered as more likely to develop severe COVID-19. Unlike common comorbidities such as obesity, and cardiovascular or lung diseases, the risk of death is not significantly increased in patients with iRMD