The ULK1 effector BAG2 regulates autophagy initiation by modulating AMBRA1 localization.

Autophagy initiation is regulated by the ULK1 kinase complex. To gain insights into functions of the holo-complex, we generated a deep interactome by combining affinity purification- and proximity labeling-mass spectrometry of all four complex members: ULK1, ATG13, ATG101, and RB1CC1/FIP200. Under starvation conditions, the ULK1 complex interacts with several protein and lipid kinases and phosphatases, implying the formation of a signalosome.

Role of AMBRA1 in mitophagy regulation: emerging evidence in aging-related diseases.

Aging is a gradual and irreversible physiological process that significantly increases the risks of developing a variety of pathologies, including neurodegenerative, cardiovascular, metabolic, musculoskeletal, and immune system diseases. Mitochondria are the energy-producing organelles, and their proper functioning is crucial for overall cellular health. Over time, mitochondrial function declines causing an increased release of harmful reactive oxygen species (ROS) and DNA, which leads to oxidative stress, inflammation and cellular damage, common features associated with various age-related pathologies.

Drugs for treating infections caused by non-tubercular mycobacteria: a narrative review from the study group on mycobacteria of the Italian Society of Infectious Diseases and Tropical Medicine.

Background: Non-tuberculous mycobacteria (NTM) are generally free-living organism, widely distributed in the environment, with sporadic potential to infect. In recent years, there has been a significant increase in the global incidence of NTM-related disease, spanning across all continents and an increased mortality after the diagnosis has been reported. The decisions on whether to treat or not and which drugs to use are complex and require a multidisciplinary approach as well as patients' involvement in the decision process.

KRAS is a molecular determinant of platinum responsiveness in glioblastoma.

Background: KRAS is the undisputed champion of oncogenes, and despite its prominent role in oncogenesis as mutated gene, KRAS mutation appears infrequent in gliomas. Nevertheless, gliomas are considered KRAS-driven cancers due to its essential role in mouse malignant gliomagenesis. Glioblastoma is the most lethal primary brain tumor, often associated with disturbed RAS signaling.

Transglutaminase Type 2-MITF axis regulates phenotype switching in skin cutaneous melanoma.

Skin cutaneous melanoma (SKCM) is the deadliest form of skin cancer due to its high heterogeneity that drives tumor aggressiveness. Melanoma plasticity consists of two distinct phenotypic states that co-exist in the tumor niche, the proliferative and the invasive, respectively associated with a high and low expression of MITF, the master regulator of melanocyte lineage. However, despite efforts, melanoma research is still far from exhaustively dissecting this phenomenon.

The ubiquitin ligase TRIM32 promotes the autophagic response to Mycobacterium tuberculosis infection in macrophages.

Mycobacterium tuberculosis (Mtb) is known to evade host immune responses and persist in macrophages for long periods. A mechanism that the host uses to combat Mtb is xenophagy, a selective form of autophagy that targets intracellular pathogens for degradation. Ubiquitination of Mtb or Mtb-containing compartments is a key event to recruit the autophagy machinery and mediate the bacterial delivery to the lysosome.

A microRNA Arising from the Negative Strand of SARS-CoV-2 Genome Targets FOS to Reduce AP-1 Activity.

Virus-encoded microRNAs were first reported in the Epstein-Barr virus in 2004. Subsequently, a few hundred viral miRNAs have been identified, mainly in DNA viruses belonging to the family. To date, only 30 viral miRNAs encoded by RNA viruses are reported by miRBase.

Qualitative and semi-quantitative ultrasound assessment in delta and Omicron Covid-19 patients: data from high volume reference center.

Objective: to evaluate the efficacy of US, both qualitatively and semi-quantitatively, in the selection of treatment for the Covid-19 patient, using patient triage as the gold standard.

Methods: Patients admitted to the Covid-19 clinic to be treated with monoclonal antibodies (mAb) or retroviral treatment and undergoing lung ultrasound (US) were selected from the radiological data set between December 2021 and May 2022 according to the following inclusion criteria: patients with proven Omicron variant and Delta Covid-19 infection; patients with known Covid-19 vaccination with at least two doses. Lung US (LUS) was performed by experienced radiologists.

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions.

NAADP-Evoked Ca Signaling Leads to Mutant Huntingtin Aggregation and Autophagy Impairment in Murine Astrocytes.

Huntington's disease (HD) is a progressive neurodegenerative disease characterized by mutations in the huntingtin gene (mHtt), causing an unstable repeat of the CAG trinucleotide, leading to abnormal long repeats of polyglutamine (poly-Q) in the N-terminal region of the huntingtin, which form abnormal conformations and aggregates. Alterations in Ca signaling are involved in HD models and the accumulation of mutated huntingtin interferes with Ca homeostasis. Lysosomes are intracellular Ca storages that participate in endocytic and lysosomal degradation processes, including autophagy.

The STING/TBK1/IRF3/IFN type I pathway is defective in cystic fibrosis.

Cystic fibrosis (CF) is a rare autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The most common mutation is F508del-CFTR (ΔF) which leads the encoded ion channel towards misfolding and premature degradation. The disease is characterized by chronic bronchopulmonary obstruction, inflammation and airways colonization by bacteria, which are the major cause of morbidity and mortality.

Type 2 transglutaminase in the nucleus: the new epigenetic face of a cytoplasmic enzyme.

One of the major mysteries in science is how it is possible to pack the cellular chromatin with a total length of over 1 m, into a small sphere with a diameter of 5 mm "the nucleus", and even more difficult to envisage how to make it functional. Although we know that compaction is achieved through the histones, however, the DNA needs to be accessible to the transcription machinery and this is allowed thanks to a variety of very complex epigenetic mechanisms. Either DNA (methylation) or post-translational modifications of histone proteins (acetylation, methylation, ubiquitination and sumoylation) play a crucial role in chromatin remodelling and consequently on gene expression.

Transglutaminase type 2-dependent crosslinking of IRF3 in dying melanoma cells.

cGAS/STING axis is the major executor of cytosolic dsDNA sensing that leads to the production of type I interferon (IFNI) not only upon bacterial infection, but also in cancer cells, upon DNA damage. In fact, DNA damage caused by ionizing radiations and/or topoisomerase inhibitors leads to a release of free DNA into the cytosol, which activates the cGAS/STING pathway and the induction of IFNI expression. Doxorubicin-induced apoptotic cancer cells release damage-associated molecular patterns (DAMPs), including IFNI, which are able to stimulate the immune system.

Proteomic analysis identifies a signature of disease severity in the plasma of COVID-19 pneumonia patients associated to neutrophil, platelet and complement activation.

Most patients infected with SARS-CoV-2 display mild symptoms with good prognosis, while 20% of patients suffer from severe viral pneumonia and up to 5% may require intensive care unit (ICU) admission due to severe acute respiratory syndrome, which could be accompanied by multiorgan failure.Plasma proteomics provide valuable and unbiased information about disease progression and therapeutic candidates. Recent proteomic studies have identified molecular changes in plasma of COVID-19 patients that implied significant dysregulation of several aspects of the inflammatory response accompanied by a general metabolic suppression.

Non-COVID-19 respiratory viral infection.

Unlabelled: Implemented control measures brought about by the coronavirus disease 2019 (COVID-19) pandemic have changed the prevalence of other respiratory viruses, often relegating them to a secondary plan. However, it must not be forgotten that a diverse group of viruses, including other human coronaviruses, rhinoviruses, respiratory syncytial virus, human metapneumoviruses, parainfluenza and influenza, continue to be responsible for a large burden of disease. In fact, they are among the most common causes of acute upper and lower respiratory tract infections globally.

The contribution of late HIV diagnosis on the occurrence of HIV-associated tuberculosis.

Objectives: To describe the timing of tuberculosis (TB) presentation in relation to diagnosis of HIV infection and antiretroviral therapy (ART) initiation and to evaluate whether the established impact from late presentation to care and late initiation of ART on the risk of TB is retained beyond the observation period of clinical trials.

Design: We used marginal structural models to emulate a clinical trial with up to 5 years of follow-up to evaluate the impact of late initiation on TB risk.

Methods: People with HIV (PWH) were enrolled from 2007 to 2016 in observational cohorts from Uganda, Peru, Mexico and Italy.

Epidemiology, Clinical Presentation and Treatment of Non-Hepatic Hyperammonemia in ICU COVID-19 Patients.

(1) Background: Although COVID-19 is largely a respiratory disease, it is actually a systemic disease that has a wide range of effects that are not yet fully known. The aim of this study was to determine the incidence, predictors and outcome of non-hepatic hyperammonemia (NHH) in COVID-19 in intensive care unit (ICU); (2) Methods: This is a 3-month prospective observational study in a third-level COVID-19 hospital. The authors collected demographic, clinical, severity score and outcome data.

In-Depth Immunophenotyping With Mass Cytometry During TB Treatment Reveals New T-Cell Subsets Associated With Culture Conversion.

Tuberculosis (TB) is a difficult-to-treat infection because of multidrug regimen requirements based on drug susceptibility profiles and treatment observance issues. TB cure is defined by mycobacterial sterilization, technically complex to systematically assess. We hypothesized that microbiological outcome was associated with stage-specific immune changes in peripheral whole blood during TB treatment.