Divergent roles of RIPK3 and MLKL in high-fat diet-induced obesity and MAFLD in mice.

Cell death frequently occurs in the pathogenesis of obesity and metabolic dysfunction-associated fatty liver disease (MAFLD). However, the exact contribution of core cell death machinery to disease manifestations remains ill-defined. Here, we show via the direct comparison of mice genetically deficient in the essential necroptotic regulators, receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like (MLKL), as well as mice lacking apoptotic caspase-8 in myeloid cells combined with RIPK3 loss, that RIPK3/caspase-8 signaling regulates macrophage inflammatory responses and drives adipose tissue inflammation and MAFLD upon high-fat diet feeding.

Dominant negative OTULIN-related autoinflammatory syndrome.

OTU deubiquitinase with linear linkage specificity (OTULIN) regulates inflammation and cell death by deubiquitinating linear ubiquitin chains generated by the linear ubiquitin chain assembly complex (LUBAC). Biallelic loss-of-function mutations causes OTULIN-related autoinflammatory syndrome (ORAS), while OTULIN haploinsuffiency has not been associated with spontaneous inflammation. However, herein, we identify two patients with the heterozygous mutation p.

RIPK3 cleavage is dispensable for necroptosis inhibition but restricts NLRP3 inflammasome activation.

Caspase-8 activity is required to inhibit necroptosis during embryogenesis in mice. In vitro studies have suggested that caspase-8 directly cleaves RIPK1, CYLD and the key necroptotic effector kinase RIPK3 to repress necroptosis. However, recent studies have shown that mice expressing uncleavable RIPK1 die during embryogenesis due to excessive apoptosis, while uncleavable CYLD mice are viable.

The HeRO score: Enhancing prognosis and predicting nosocomial infections in newborns: Insights from the neonatal intensive care unit.

Background: Nosocomial infections pose a significant health risk to neonates, and traditional biomarkers used for diagnosis often fall short in predicting such infections. In this study, we evaluate the efficacy of the HeRO (Heart Rate Observation score), a novel predictive tool for late-onset neonatal sepsis, in improving neonatal prognosis and reducing morbidity and mortality rates.

Methods: A prospective study was conducted from September 2020 to May 2021, reviewing patient evaluation for all neonates admitted to the neonatal intensive care unit during this period after the implementation of the HeRO score.

A1 is induced by pathogen ligands to limit myeloid cell death and NLRP3 inflammasome activation.

Programmed cell death pathways play an important role in innate immune responses to infection. Activation of intrinsic apoptosis promotes infected cell clearance; however, comparatively little is known about how this mode of cell death is regulated during infections and whether it can induce inflammation. Here, we identify that the pro-survival BCL-2 family member, A1, controls activation of the essential intrinsic apoptotic effectors BAX/BAK in macrophages and monocytes following bacterial lipopolysaccharide (LPS) sensing.

Clinical, biochemical and molecular characterization of Wilson's disease in Moroccan patients.

Background: Wilson Disease (WD) is an autosomal recessive inherited metabolic disease caused by mutations in the gene. WD is characterized by heterogeneous clinical presentations expressed by hepatic and neuropsychiatric phenotypes. The disease is difficult to diagnose, and misdiagnosed cases are commonly seen.

RIPK3 controls MAIT cell accumulation during development but not during infection.

Cell death mechanisms in T lymphocytes vary according to their developmental stage, cell subset and activation status. The cell death control mechanisms of mucosal-associated invariant T (MAIT) cells, a specialized T cell population, are largely unknown. Here we report that MAIT cells express key necroptotic machinery; receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) protein, in abundance.

Gold nanoparticle-based supramolecular approach for dye-sensitized H-evolving photocathodes.

Solar conversion of water into the storable energy carrier H can be achieved through photoelectrochemical water splitting using light adsorbing anodes and cathodes bearing O and H evolving catalysts, respectively. Herein a novel photocathode nanohybrid system is reported. This photocathode consists of a dye-sensitized p-type nickel oxide (NiO) with a perylene-based chromophore () and a tetra-adamantane modified cobaloxime reduction catalyst () that photo-reduces aqueous protons to H.

Lactobacillus supports Clostridiales to restrict gut colonization by multidrug-resistant Enterobacteriaceae.

Infections by multidrug-resistant Enterobacteriaceae (MRE) are life-threatening to patients. The intestinal microbiome protects against MRE colonization, but antibiotics cause collateral damage to commensals and open the way to colonization and subsequent infection. Despite the significance of this problem, the specific commensals and mechanisms that restrict MRE colonization remain largely unknown.

Genetic Diversity and Virulence Profile of Methicillin and Inducible Clindamycin-Resistant Isolates in Western Algeria.

causes a wide range of life-threatening infections. In this study, we determined its prevalence in the hospital environment and investigated nasal carriage among healthcare workers and patients admitted to a hospital in western Algeria. A total of 550 specimens were collected.

Ubiquitylation of RIPK3 beyond-the-RHIM can limit RIPK3 activity and cell death.

Pathogen recognition and TNF receptors signal via receptor interacting serine/threonine kinase-3 (RIPK3) to cause cell death, including MLKL-mediated necroptosis and caspase-8-dependent apoptosis. However, the post-translational control of RIPK3 is not fully understood. Using mass-spectrometry, we identified that RIPK3 is ubiquitylated on K469.

Tankyrase-mediated ADP-ribosylation is a regulator of TNF-induced death.

Tumor necrosis factor (TNF) is a key component of the innate immune response. Upon binding to its receptor, TNFR1, it promotes production of other cytokines via a membrane-bound complex 1 or induces cell death via a cytosolic complex 2. To understand how TNF-induced cell death is regulated, we performed mass spectrometry of complex 2 and identified tankyrase-1 as a native component that, upon a death stimulus, mediates complex 2 poly-ADP-ribosylation (PARylation).

Mycobacterium ulcerans Experimental Dormancy.

Whether Mycobacterium ulcerans, the etiological agent of Buruli ulcer in numerous tropical countries, would exist in a dormant state as reported for closely related Mycobacterium species, has not been established. Six M. ulcerans strains were exposed to a progressive depletion in oxygen for 2 months, using the Wayne model of dormancy previously described for M.

Development and standardization of a specific real-time PCR assay for the rapid detection of Candida auris.

Candida auris is an emerging multiresistant pathogen causing nosocomial fungal infection. Specific detection and identification are necessary. Our goal is to develop a new qPCR system that enables rapid detection of C.

The necroptotic cell death pathway operates in megakaryocytes, but not in platelet synthesis.

Necroptosis is a pro-inflammatory cell death program executed by the terminal effector, mixed lineage kinase domain-like (MLKL). Previous studies suggested a role for the necroptotic machinery in platelets, where loss of MLKL or its upstream regulator, RIPK3 kinase, impacted thrombosis and haemostasis. However, it remains unknown whether necroptosis operates within megakaryocytes, the progenitors of platelets, and whether necroptotic cell death might contribute to or diminish platelet production.

A New Presentation: Aphallia, Vesicoureteral Reflux, Rectovesical Fistula, and Adrenal Insufficiency.

Aphallia or penile agenesis is a rare congenital malformation with an estimated incidence rate of 1 in 10 to 30 million births. More than half of aphallia cases have associated anomalies including caudal axis, cardiovascular, genitourinary, and gastrointestinal anomalies. The penile agenesis associated with adrenal insufficiency has never been reported in an infant.

High HbA levels affect motility parameters and overexpress oxidative stress of human mature spermatozoa.

The aim of this study is to investigate, by a validated in vitro model, the effect of diabetic plasma on ejaculated human spermatozoa. Plasma of 51 male diabetic patients (mean age 62.28 ± 9.

Update of a colorimetric method for quantitative determination of galactose in blood samples: A simple and rapid method for the early detection of inherited metabolic diseases.

Background: A colorimetric microassay for the quantitative determination of galactose in the blood was taken and updated. This method helps in diagnosis and follow-up of several inherited metabolic diseases connected to galactose metabolism deficiency such as galactosemia, glycogenosis, glycosylation, tyrosinemia and citrin deficiency. Galactose assay in the blood presents difficulties due to interference with glucose.

First Clinical Cases of KPC-2-Producing ST258 in Algeria and Outbreak of ST101 Harboring Gene in the Urology Department of Annaba Hospital.

The aim of this study was to characterize the molecular mechanisms of carbapenem resistance in isolated from the urology department of Annaba hospital, Algeria. Between January 2015 and September 2017, 14 carbapenem-resistant strains were isolated during routine surveillance work at Ibn Roched hospital of Annaba, Algeria, from the urology department. Theses strains were recovered, and carbapenem resistance mechanisms were investigated.

What could explain the late emergence of COVID-19 in Africa?

At the end of November 2019, a novel coronavirus responsible for respiratory tract infections emerged in China. Despite drastic containment measures, this virus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread in Asia and Europe. The pandemic is ongoing with a particular hotspot in southern Europe and America in spring 2020.

25 years of research put RIPK1 in the clinic.

Receptor Interacting Protein Kinase 1 (RIPK1) is a key regulator of inflammation. To warrant cell survival and appropriate immune responses, RIPK1 is post-translationally regulated by ubiquitylations, phosphorylations and caspase-8-mediated cleavage. Dysregulations of these post-translational modifications switch on the pro-death function of RIPK1 and can cause inflammatory diseases in humans.

Infections Due to Carbapenem-Resistant Bacteria in Patients With Hematologic Malignancies.

In developed countries, hematological malignancies (HM) account for 8 to 10% of cancers diagnosed annually and one-third of patients with HM (HMP) are expected to die from their disease. The former wide spectrum "magic bullet," imipenem, has been ousted by the emergence of carbapenem resistant (CR) pathogens. In endemic areas, infections with CR-bacteria occur in vulnerable patients, notably in HMP, who suffer from high mortality related to infectious complications.

MLKL trafficking and accumulation at the plasma membrane control the kinetics and threshold for necroptosis.

Mixed lineage kinase domain-like (MLKL) is the terminal protein in the pro-inflammatory necroptotic cell death program. RIPK3-mediated phosphorylation is thought to initiate MLKL oligomerization, membrane translocation and membrane disruption, although the precise choreography of events is incompletely understood. Here, we use single-cell imaging approaches to map the chronology of endogenous human MLKL activation during necroptosis.