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e calcium sensitivity. We demonstrate that the model can accurately describe twitch contractions for the data and go on to explore the effect of variable mutant incorporation and localization on simulated cardiac muscle twitches.High-throughput experiments suggest that almost 20% of human proteins may be S-palmitoylatable, a post-translational modification (PTM) whereby fatty acyl chains, most commonly palmitoyl chain, are linked to cysteine thiol groups that impact on protein trafficking, distribution and function. In human, protein S-palmitoylation is mediated by a group of 23 palmitoylating ‘Asp-His-His-Cys’ domain-containing (DHHC) enzymes. There is no information on the scope of protein S-palmitoylation, or the pattern of DHHC enzyme expression, in the heart. We used resin-assisted capture to pull down S-palmitoylated proteins from human, dog, and rat hearts, followed by proteomic search to identify proteins in the pulldowns. We identified 454 proteins present in at least 2 species-specific pulldowns. Retatrutide These proteins are operationally called ‘cardiac palmitoylome’. Enrichment analysis based on Gene Ontology terms ‘cellular component’ indicated that cardiac palmitoylome is involved in cell-cell and cell-substrate junctions, plasma membrane microdomain organization, vesicular trafficking, and mitochondrial enzyme organization. Importantly, cardiac palmitoylome is uniquely enriched in proteins participating in the organization and function of t-tubules, costameres and intercalated discs, three microdomains critical for excitation-contraction coupling and intercellular communication of cardiomyocytes. We validated antibodies targeting DHHC enzymes, and detected eleven of them expressed in hearts across species. In conclusion, we provide resources useful for investigators interested in studying protein S-palmitoylation and its regulation by DHHC enzymes in the heart. We also discuss challenges in these efforts, and suggest methods and tools that should be developed to overcome these challenges.

Mild traumatic brain injury (mTBI) in patients on antiplatelet (AP), anticoagulant (AC) or direct oral anticoagulant (DOAC) medication has become a systematic indication for head CT. However, the over-risk and impact of the intracranial hemorrhages (IH) detected with CT in this population remain unclear and need to be assessed.

We prospectively assessed head CTs performed in adults taking AP/AC/DOAC referred after a mTBI to our Emergency Departments between September 2016 and January 2018. Frequency, type and severity of IH were described and frequency was analyzed as a function of treatment.

840 patients were prospectively included. 58.9% were treated with AP, 23.7% with AC, 11.7% with DOAC and 5.7% with a combination of antithrombotic agents. The rate of IH detected with head CT was 5.8% (n = 49), of which 81.6% (n = 40) and 18.4% (n = 9) with minor and intermediate severity respectively. No patient required surgical care and no death occurred. No statistically significant difference was found in treatment distribution between patients with or without IH (p = 0.98). Among the patients who discontinued their antithrombotic treatment after mTBI, three experienced thrombotic events during the hospitalization.

Our results showed a low frequency and severity of IH in mTBI patients indifferently treated with AP, AC or DOAC, without secondary neurological deterioration, death or need of surgical care. Our study suggests the limited benefit of systematic CT head scan as a standard practice for the management of mTBI patients under antithrombotic therapy.

Our results showed a low frequency and severity of IH in mTBI patients indifferently treated with AP, AC or DOAC, without secondary neurological deterioration, death or need of surgical care. Our study suggests the limited benefit of systematic CT head scan as a standard practice for the management of mTBI patients under antithrombotic therapy.To investigate NDM-1-producing atypical Enteroaggregative Escherichia coli (aEAEC) of sequence type 349 from hospitalized patients, the isolates 13ZX28 and 13ZX36 were subjected to antimicrobial susceptibility testing, conjugation and whole genome sequencing. Only one single nucleotide mutation was detected in chromosomes despite different plasmid profiles. Both isolates were positive for blaNDM-1 mediating resistance to carbapenem. A novel plasmid p13ZX28-272 (~272-kb) from 13ZX28 encodes blaNDM-1. Interestingly, its sequence was identical to the two plasmids p13ZX36-200 (~200-kb) and p13ZX36-70 (~70-kb) from 13ZX36. Formation of the former episome possibly involved homologous recombination through a 4948-bp large fragment located on each of the two latter plasmids. Furthermore, plasmid p13ZX28-272 could be resolved into a ~ 98-kb daughter plasmid by IS26 rearrangement following conjugation. The plasticity of the plasmids is recognized, which warrants further investigation to evaluate the underlying public health risk and understand how antibiotic selection pressure drives this process.

Maternal Plasmodium falciparum-specific antibodies may contribute to protect infants against severe malaria. Our main objective was to evaluate the impact of maternal HIV infection and placental malaria on the cord blood levels and efficiency of placental transfer of IgG and IgG subclasses.

In a cohort of 341 delivering HIV-negative and HIV-positive mothers from southern Mozambique, we measured total IgG and IgG subclasses in maternal and cord blood pairs by quantitative suspension array technology against eight P. falciparum antigens Duffy-binding like domains 3-4 of VAR2CSA from the erythrocyte membrane protein 1, erythrocyte-binding antigen 140, exported protein 1 (EXP1), merozoite surface proteins 1, 2 and 5, and reticulocyte-binding-homologue-4.2 (Rh4.2). We performed univariable and multivariable regression models to assess the association of maternal HIV infection, placental malaria, maternal variables and pregnancy outcomes on cord antibody levels and antibody transplacental transfer.

Maternal antibody levels were the main determinants of cord antibody levels. HIV infection and placental malaria reduced the transfer and cord levels of IgG and IgG1, and this was antigen-dependent. Low birth weight was associated with an increase of IgG2 in cord against EXP1 and Rh4.2.

We found lower maternally transferred antibodies in HIV-exposed infants and those born from mothers with placental malaria, which may underlie increased susceptibility to malaria in these children.

We found lower maternally transferred antibodies in HIV-exposed infants and those born from mothers with placental malaria, which may underlie increased susceptibility to malaria in these children.