Nighttime mesospheric ozone enhancements during the 2002 southern hemispheric major stratospheric warming

Sudden Stratospheric Warmings (SSW) affect the chemistry and dynamics of the middle atmosphere. Major warmings occur roughly every second winter in the Northern Hemisphere (NH), but has only been observed once in the Southern Hemisphere (SH), during the Antarctic winter of 2002. Observations by the Global Ozone Monitoring by Occultation of Stars (GOMOS, an instrument on board Envisat) during this rare event, show a 40% increase of ozone in the nighttime secondary ozone layer at subpolar latitudes compared to non-SSW years. This study investigates the cause of the mesospheric nighttime ozone increase, using the National Center for Atmospheric Research (NCAR) Whole Atmosphere Community Climate Model with specified dynamics (SD-WACCM). The 2002 SH winter was characterized by several reductions of the strength of the polar night jet in the upper stratosphere before the jet reversed completely, marking the onset of the major SSW. At the time of these wind reductions, corresponding episodic increases can be seen in the modelled nighttime secondary ozone layer. This ozone increase is attributed largely to enhanced upwelling and the associated cooling of the altitude region in conjunction with the wind reversal. This is in correspondence to similar studies of SSW induced ozone enhancements in NH. But unlike its NH counterpart, the SH secondary ozone layer appeared to be impacted less by episodic variations in atomic hydrogen. Seasonally decreasing atomic hydrogen plays however a larger role in SH compared to NH

High Resolution Genome-Wide Analysis of Chromosomal Alterations in Burkitt's Lymphoma

Additional chromosomal abnormalities are currently detected in Burkitt's lymphoma. They play major roles in the progression of BL and in prognosis. The genes involved remain elusive. A whole-genome oligonucleotide array CGH analysis correlated with karyotype and FISH was performed in a set of 27 Burkitt's lymphoma-derived cell lines and primary tumors. More than half of the 145 CNAs<2 Mb were mapped to Mendelian CNVs, including GSTT1, glutathione s-transferase and BIRC6, an anti-apoptotic protein, possibly predisposing to some cancers. Somatic cell line-specific CNVs localized to the IG locus were consistently observed with the 244 K aCGH platform. Among 136 CNAs >2 Mb, gains were found in 1q (12/27), 13q (7/27), 7q (6/27), 8q(4/27), 2p (3/27), 11q (2/27) and 15q (2/27). Losses were found in 3p (5/27), 4p (4/27), 4q (4/27), 9p (4/27), 13q (4/27), 6p (3/27), 17p (3/27), 6q (2/27),11pterp13 (2/27) and 14q12q21.3 (2/27). Twenty one minimal critical regions (MCR), (range 0.04–71.36 Mb), were delineated in tumors and cell lines. Three MCRs were localized to 1q. The proximal one was mapped to 1q21.1q25.2 with a 6.3 Mb amplicon (1q21.1q21.3) harboring BCA2 and PIAS3. In the other 2 MCRs, 1q32.1 and 1q44, MDM4 and AKT3 appeared as possible drivers of these gains respectively. The 13q31.3q32.1 <89.58–96.81> MCR contained an amplicon and ABCC4 might be the driver of this amplicon. The 40 Kb 2p16.1 <60.96–61> MCR was the smallest gained MCR and specifically encompassed the REL oncogene which is already implicated in B cell lymphomas. The most frequently deleted MCR was 3p14.1 <60.43–60.53> that removed the fifth exon of FHIT. Further investigations which combined gene expression and functional studies are essential to understand the lymphomagenesis mechanism and for the development of more effective, targeted therapeutic strategies

Broad-Range Papillomavirus Transcriptome as a Biomarker of Papillomavirus-Associated Cervical High-Grade Cytology

International audienceHuman Papillomaviruses (HPV) are responsible for over 99% of cervical cancers. Molecular diagnostic tests based on the detection of viral DNA or RNA have low Positive Predictive Values (PPV) for the identification of cancer or precancerous lesions. Triage with the Papanicolaou test lacks sensitivity and even when combined with molecular detection of high-risk HPV results in a significant number of unnecessary colposcopies. We have developed a broad range detection test of HPV transcripts to take a snapshot of the transcriptome of 16 high-risk or putative high-risk HPV in cervical lesions (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73, and 82). The purpose of this novel molecular assay is to detect and type HPV-positive samples and to determine a combination of HPV reads at certain specific viral spliced junctions that can better correlate with high-grade cytology, reflecting the presence of precancerous cells. In a proof-of-concept study conducted on 55 patients, starting from cervical smears, we have shown that (i) HPV RNA-Seq can detect papillomaviruses with performances comparable to a widely used HPV reference molecular diagnostic kit, and (ii) a combination of the number of sequencing reads at specific early vs late HPV transcripts can be used as a marker of high-grade cytology, with encouraging diagnostic performances as a triage test

Antiretroviral Therapy with a Twice-Daily Regimen Containing 400 Milligrams of Indinavir and 100 Milligrams of Ritonavir in Human Immunodeficiency Virus Type 1-Infected Women during Pregnancy▿

We evaluated the safety and efficacy of a twice daily regimen containing 400 mg of indinavir and 100 mg of ritonavir in 32 human immunodeficiency virus (HIV)-infected women during pregnancy. The median indinavir trough concentration was 208 ng/ml during the third trimester. At delivery, 26 of 28 women on indinavir-ritonavir had HIV RNA levels of <200 copies/ml. No infant was HIV infected. These data are encouraging for the use of this combination for prevention of mother-to-child transmission of HIV

Distinct Cellular Origins and Differentiation Process Account for Distinct Oncogenic and Clinical Behaviors of Leiomyosarcomas

In leiomyosarcoma (LMS), a very aggressive disease, a relatively transcriptionally uniform subgroup of well-differentiated tumors has been described and is associated with poor survival. The question raised how differentiation and tumor progression, two apparently antagonist processes, coexist and allow tumor malignancy. We first identified the most transcriptionally homogeneous LMS subgroup in three independent cohorts, which we named ‘hLMS’. The integration of multi-omics data and functional analysis suggests that hLMS originate from vascular smooth muscle cells and show that hLMS transcriptional program reflects both modulations of smooth muscle contraction activity controlled by MYOCD/SRF regulatory network and activation of the cell cycle activity controlled by E2F/RB1 pathway. We propose that the phenotypic plasticity of vascular smooth muscle cells coupled with MYOCD/SRF pathway amplification, essential for hLMS survival, concomitant with PTEN absence and RB1 alteration, could explain how hLMS balance this uncommon interplay between differentiation and aggressiveness

A monocyte/dendritic cell molecular signature of SARS-CoV-2-related multisystem inflammatory syndrome in children with severe myocarditis

International audienceBackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is generally milder than in adults, but a proportion of cases result in hyperinflammatory conditions often including myocarditis.MethodsTo better understand these cases, we applied a multiparametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. Plasma cytokine and chemokine levels and blood cellular composition were measured, alongside gene expression at the bulk and single-cell levels.FindingsThe most severe forms of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 that resulted in myocarditis were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomics analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis characterized by sustained nuclear factor κB (NF-κB) activity and tumor necrosis factor alpha (TNF-α) signaling and associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type I and type II interferons, hyperinflammation, and response to oxidative stress related to increased HIF-1α and Vascular endothelial growth factor (VEGF) signaling.ConclusionsThese results provide potential for a better understanding of disease pathophysiology

A monocyte/dendritic cell molecular signature of SARS-CoV2-related multisystem inflammatory syndrome in children (MIS-C) with severe myocarditis

Posté sur bioRxiv le 23/02/2021SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, we applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe forms of MIS-C (multisystem inflammatory syndrome in children related to SARS-CoV-2), that resulted in myocarditis, were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomic analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis, characterized by sustained NF-κB activity, TNF-α signaling, associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type-I and type-II interferons, hyperinflammation and response to oxidative stress related to increased HIF-1α and VEGF signaling. These results provide potential for a better understanding of disease pathophysiology