Explore the vast range of titles available.

The Bcl-xL apoptosis inhibitor plays a major role in vertebrate development. In addition to its effect on apoptosis, Bcl-xL is also involved in cell migration and mitochondrial metabolism. These effects may favour the onset and dissemination of metastasis. However, the underlying molecular mechanisms remain to be fully understood. Here we focus on the control of cell migration by Bcl-xL in the context of breast cancer cells. We show that Bcl-xL silencing led to migration defects in Hs578T and MDA-MB231 cells. These defects were rescued by re-expressing mitochondria-addressed, but not endoplasmic reticulum-addressed, Bcl-xL. The use of BH3 mimetics, such as ABT-737 and WEHI-539 confirmed that the effect of Bcl-xL on migration did not depend on interactions with BH3-containing death accelerators such as Bax or BH3-only proteins. In contrast, the use of a BH4 peptide that disrupts the Bcl-xL/VDAC1 complex supports that Bcl-xL by acting on VDAC1 permeability contributes to cell migration through the promotion of reactive oxygen species production by the electron transport chain. Collectively our data highlight the key role of Bcl-xL at the interface between cell metabolism, cell death, and cell migration, thus exposing the VDAC1/Bcl-xL interaction as a promising target for anti-tumour therapy in the context of metastatic breast cancer.

Senescence is defined as a stress-induced durable cell cycle arrest. We herein revisit the origin of two of these stresses, namely mitochondrial metabolic compromise, associated with reactive oxygen species (ROS) production, and replicative senescence, activated by extreme telomere shortening. We discuss how replication stress-induced DNA damage of telomeric DNA (telDNA) and mitochondrial DNA (mtDNA) can be considered a common origin of senescence in vitro, with consequences on ageing in vivo. Unexpectedly, mtDNA and telDNA share common features indicative of a high degree of replicative stress, such as G-quadruplexes, D-loops, RNA:DNA heteroduplexes, epigenetic marks, or supercoiling. To avoid these stresses, both compartments use similar enzymatic strategies involving, for instance, endonucleases, topoisomerases, helicases, or primases. Surprisingly, many of these replication helpers are active at both telDNA and mtDNA (e.g., RNAse H1, FEN1, DNA2, RecQ helicases, Top2α, Top2β, TOP3A, DNMT1/3a/3b, SIRT1). In addition, specialized telomeric proteins, such as TERT (telomerase reverse transcriptase) and TERC (telomerase RNA component), or TIN2 (shelterin complex), shuttle from telomeres to mitochondria, and, by doing so, modulate mitochondrial metabolism and the production of ROS, in a feedback manner. Hence, mitochondria and telomeres use common weapons and cooperate to resist/prevent replication stresses, otherwise producing common consequences, namely senescence and ageing.

According to the Source Monitoring Framework, the origin of a memory is remembered through the retrieval of specific features ( e.g . perceptive, sensitive, affective signals). In two source discrimination tasks, we studied the ability of cuttlefish to remember the modality in which an item had been presented several hours ago. In Experiment 1, cuttlefish were able to retrieve the modality of presentation of a crab (visual vs olfactory) sensed before 1 h and 3 hrs delays. In Experiment 2, cuttlefish were trained to retrieve the modality of the presentation of fish, shrimp, and crabs. After training, cuttlefish performed the task with another item never encountered before (e.g. mussel). The cuttlefish successfully passed transfer tests with and without a delay of 3 hrs. This study is the first to show the ability to discriminate between two sensory modalities ( i.e . see vs smell) in an animal. Taken together, these results suggest that cuttlefish can retrieve perceptual features of a previous event, namely whether they had seen or smelled an item.

Purpose of Review This review aims at reporting the current evidence of the impact of COVID-19 pandemic on grief in children. Recent Findings Evidence from the scientific literature shows that the severity of grief in children is impacted by numerous risk factors which can lead to prolonged grief disorder (PGD). Summary Among these risk factors are the unpredictability of the death, the lack of understanding about what is happening by the child, the global insecurity raised by the context of the pandemic or again the impossibility for the child to find comfort with his peers due to the lock-down. No medical-based approach has proven efficient on PGD in children. However, cognitive based therapy can lower the severity of the symptoms. Future efforts should focus on developing therapeutic strategies to specifically fit the needs of children with PGD, in the context of a major crisis such as this pandemic.

The paper reports an electrophysiological (EEG) study investigating how language is involved in perception–action relations in musically trained and untrained participants. Using an original backward priming paradigm, participants were exposed to muted point-light videos of violinists performing piano or forte nuances followed by a congruent vs. incongruent word. After the video presentation, participants were asked to decide whether the musician was playing a piano or forte musical nuance. EEG results showed a greater P200 event-related potential for trained participants at the occipital site, and a greater N400 effect for untrained participants at the central site. Musically untrained participants were more accurate when the word was semantically congruent with the gesture than when it was incongruent. Overall, language seems to influence the performance of untrained participants, for which perception–action couplings are less automatized.

The Seine-Saint-Denis is the French metropolitan department with the highest incidence of tuberculosis (TB). Our aim was to explore epidemiological and phylogenetic characteristics of TB strains in this hotspot department. We performed WGS on 227 strains of Mycobacterium tuberculosis complex isolated from patients at the Avicenne Hospital from 2016 to 2021 and randomly selected to represent the clinical diversity of French TB localization. Clinical and demographic data were recorded for each TB patient. The mean age of patients was 36 years old. They came from Africa (44%), Asia (27%), Europe (26%) and America (3%). Strains isolated from extrapulmonary samples were associated with Asian patients, whereas strains isolated from pulmonary samples were associated with European patients. We observed a high level of lineage diversity in line with the known worldwide diversity. Interestingly, lineage 3 was associated with lymph node TB. Additionally, the sensitivity of WGS for predicting resistance was 100% for rifampicin, isoniazid and ethambutol and 66.7% for pyrazinamide. The global concordance with drug-susceptibility testing using the phenotypic approach was 97%. In microbiology laboratories, WGS turns out to be an essential tool for better understanding local TB epidemiology, with direct access to circulating lineage identification and to drug susceptibilities to first- and second-line anti-TB drugs.

The Seine-Saint-Denis is the French metropolitan department with the highest incidence of tuberculosis (TB). Our aim was to explore epidemiological and phylogenetic characteristics of TB strains in this hotspot department. We performed WGS on 227 strains of Mycobacterium tuberculosis complex isolated from patients at the Avicenne Hospital from 2016 to 2021 and randomly selected to represent the clinical diversity of French TB localization. Clinical and demographic data were recorded for each TB patient. The mean age of patients was 36 years old. They came from Africa (44%), Asia (27%), Europe (26%) and America (3%). Strains isolated from extrapulmonary samples were associated with Asian patients, whereas strains isolated from pulmonary samples were associated with European patients. We observed a high level of lineage diversity in line with the known worldwide diversity. Interestingly, lineage 3 was associated with lymph node TB. Additionally, the sensitivity of WGS for predicting resistance was 100% for rifampicin, isoniazid and ethambutol and 66.7% for pyrazinamide. The global concordance with drug-susceptibility testing using the phenotypic approach was 97%. In microbiology laboratories, WGS turns out to be an essential tool for better understanding local TB epidemiology, with direct access to circulating lineage identification and to drug susceptibilities to first- and second-line anti-TB drugs.

The discovery of jumbo phages and giant viruses of microeukaryotes has transformed our perception of the virosphere. Metagenomic and metatranscriptomic data further highlight their diversity and ecological impact. Nevertheless, sequence-based approaches fail to take into account the morphological diversity of non-cultivated viruses, resulting in our fragmented understanding of their nature and role in the environment. Here, we combined flow cytometry and electron microscopy to uncover both previously unsuspected morphological diversity and significant abundances of large virus-like particles in aquatic environments. We discovered new viral morphotypes, all likely to be associated with microeukaryotes. We also obtained insights into the multi-year dynamics of the abundances of both giant microeukaryotic virus-like particles and jumbo phage-like particles. This work deepens our understanding of large virus and reveals their key role as regulators of microbial communities.

The discovery of Jumbo phages and giant viruses of microeukaryotes has transformed our perception of the virosphere. Metagenomic and metatranscriptomic data further highlight their diversity and ecological impact. Nevertheless, sequence-based approaches fail to take into account the morphological diversity of non-cultivated viruses, resulting in our fragmented understanding of their nature and role in the environment. Here, we combined flow cytometry and electron microscopy to uncover both previously unsuspected morphological diversity as well as significant abundances of large viruses in aquatic environments. We discovered four new viral morphotypes, all of which were associated with microeukaryotes. We also obtained insights into the multi-year dynamics of the abundances of both giant microeukaryotic viruses and Jumbo phages. This work deepens our understanding of large viruses and reveals their key role as regulators of microbial communities.

Whole genome sequencing of Mycobacterium tuberculosis complex (MTBC) strains is a new and rapidly growing tool to obtain results regarding resistance, virulence factors and phylogeny of the strains. Bioinformatics tools presented as user-friendly and easy to use are available online. The objective of this work was to evaluate the performances of two bioinformatics tools, easily accessible on the internet, for the analysis of sequencing data of MTBC strains. Two hundred and twenty-seven MTBC strains isolated at the laboratory of the Avicenne Hospital between 2015 and 2021 were sequenced using Illumina®(USA) MiSeq technology. An analysis of the sequencing data was performed using the two tools Mykrobe and PhyResSE. Sequencing quality, resistance or susceptibility status and phylogeny were investigated for each strain. Genotypic resistance results were compared to the results obtained by phenotypic drug susceptibility testing performed in the hospital’s routine laboratory. Using the PhyResSE tool we found an average coverage of 98% against the reference strain H37Rv and an average depth of 119X. No information on sequencing quality was obtained with the Mykrobe tool. The concordance of each tool with the phenotypic method for determining susceptibility to first-line anti-tuberculosis drugs was 95%. Mykrobe and PhyResSE tools identified resistance to second-line anti-tuberculosis drugs in 5.3% and 5.7% of cases respectively. The sensitivity and specificity of each tool compared to the phenotypic method was respectively 70% and 98% for Mykrobe and 76% and 97% for PhyResSE. Finally, the two tools showed 99.5% agreement in lineage determination. The Mykrobe and PhyResSE bioinformatics tools were easy to use, fast and efficient. The Mykrobe tool had the advantage of being offline and its interface was more user-friendly. The use of these platforms depends on their accessibility and updating. However, their use is accessible to people not trained in bioinformatics and would allow a complementary approach to phenotypic methods for the study of MTBC strains.