Gut Microbial Signatures Associated with Cryptosporidiosis: A Case Series.

spp. are zoonotic protozoan parasites with a global prevalence, with both gastrointestinal and pulmonary involvement. Though symptoms can often be relatively mild, they can become severe and even fatal in children under five, the elderly, and in immunocompromised individuals, making cryptosporidiosis a leading cause of morbidity and mortality in fragile populations.

Pneumonia Severity Is Associated with Taxonomic Shifts in the Respiratory Microbiota.

Pneumonia caused by infection (PCP) is a potentially life-threatening illness, particularly affecting the immunocompromised. The past two decades have shown an increase in PCP incidence; however, the underlying factors that promote disease severity and fatality have yet to be fully elucidated. Recent evidence suggests that the microbiota of the respiratory tract may play a role in stimulating or repressing pulmonary inflammation, as well as the progression of both bacterial and viral pneumonia.

Changes in the pharyngeal and nasal microbiota in pediatric patients with adenotonsillar hypertrophy.

Unlabelled: The present study aimed to investigate the pharyngeal and nasal microbiota composition in children with adenotonsillar hypertrophy (AH) and assess longitudinal alterations in both microbiota after a probiotic oral spray treatment. A cohort of 57 AH patients were enrolled and randomly assigned to the probiotic and placebo groups for a 5-month treatment course. Pharyngeal and nasal swabs were collected before and after treatment and analyzed by 16S rRNA-based metataxonomics and axenic cultures for pathobiont identification.

Actin-nucleation promoting factor N-WASP influences alpha-synuclein condensates and pathology.

Abnormal intraneuronal accumulation of soluble and insoluble α-synuclein (α-Syn) is one of the main pathological hallmarks of synucleinopathies, such as Parkinson's disease (PD). It has been well documented that the reversible liquid-liquid phase separation of α-Syn can modulate synaptic vesicle condensates at the presynaptic terminals. However, α-Syn can also form liquid-like droplets that may convert into amyloid-enriched hydrogels or fibrillar polymorphs under stressful conditions.

The pediatric gut bacteriome and virome in response to SARS-CoV-2 infection.

Introduction: Since the beginning of the SARS-CoV-2 pandemic in early 2020, it has been apparent that children were partially protected from both infection and the more severe forms of the disease. Many different mechanisms have been proposed to explain this phenomenon, including children's frequent exposure to other upper respiratory infections and vaccines, and which inflammatory cytokines they are more likely to produce in response to infection. Furthermore, given the presence of SARS-CoV-2 in the intestine and its ability to infect enterocytes, combined with the well described immunomodulatory capabilities of the microbiome, another potential contributing factor may be the presence of certain protective microbial members of the gut microbiota (GM).

The metaproteome of the gut microbiota in pediatric patients affected by COVID-19.

Introduction: The gut microbiota (GM) play a significant role in the infectivity and severity of COVID-19 infection. However, the available literature primarily focuses on adult patients and it is known that the microbiota undergoes changes throughout the lifespan, with significant alterations occurring during infancy and subsequently stabilizing during adulthood. Moreover, children have exhibited milder symptoms of COVID-19 disease, which has been associated with the abundance of certain protective bacteria.

Case Report: The impact of severe cryptosporidiosis on the gut microbiota of a pediatric patient with CD40L immunodeficiency.

is a protozoan parasite and one of the leading causes of gastroenteritis in the world, primarily affecting very young children and immunocompromised patients. While infection is usually self-limiting, it can become chronic and even lethal in these vulnerable populations, in whom treatments are generally ineffective, due to their acting in concert with a functioning immune system. Here, we describe a case of chronic cryptosporidiosis in a European child with severe CD40L immunodeficiency infected with of the IIa20G1 subgenotype, a lineage which has thus far only ever been described in the Middle East.

Integrated analysis of transcriptomic and proteomic alterations in mouse models of ALS/FTD identify early metabolic adaptions with similarities to mitochondrial dysfunction disorders.

Objective: Sporadic and familial amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease that results in loss of motor neurons and, in some patients, associates with frontotemporal dementia (FTD). Apart from the accumulation of proteinaceous deposits, emerging literature indicates that aberrant mitochondrial bioenergetics may contribute to the onset and progression of ALS/FTD. Here we sought to investigate the pathophysiological signatures of mitochondrial dysfunction associated with ALS/FTD.

Extremely small and incredibly close: Gut microbes as modulators of inflammation and targets for therapeutic intervention.

Chronic inflammation is a hallmark for a variety of disorders and is at least partially responsible for disease progression and poor patient health. In recent years, the microbiota inhabiting the human gut has been associated with not only intestinal inflammatory diseases but also those that affect the brain, liver, lungs, and joints. Despite a strong correlation between specific microbial signatures and inflammation, whether or not these microbes are disease markers or disease drivers is still a matter of debate.

Impact of helminth-microbiome interactions on childhood health and development-A clinical perspective.

Humans have co-existed with parasites for virtually the entirety of our existence as a species. Today, nearly one third of the human population is infected with at least one helminthic species, most of which reside in the intestinal tract, where they have co-evolved alongside the human gut microbiota (GM). Appreciation for the interconnected relationship between helminths and GM has increased in recent years.

Comparative analysis of CI- and CIV-containing respiratory supercomplexes at single-cell resolution.

Mitochondria sustain the energy demand of the cell. The composition and functional state of the mitochondrial oxidative phosphorylation system are informative indicators of organelle bioenergetic capacity. Here, we describe a highly sensitive and reproducible method for a single-cell quantification of mitochondrial CI- and CIV-containing respiratory supercomplexes (CI∗CIV-SCs) as an alternative means of assessing mitochondrial respiratory chain integrity.

CEST-2.2 overexpression alters lipid metabolism and extends longevity of mitochondrial mutants.

Mitochondrial dysfunction can either extend or decrease Caenorhabditis elegans lifespan, depending on whether transcriptionally regulated responses can elicit durable stress adaptation to otherwise detrimental lesions. Here, we test the hypothesis that enhanced metabolic flexibility is sufficient to circumvent bioenergetic abnormalities associated with the phenotypic threshold effect, thereby transforming short-lived mitochondrial mutants into long-lived ones. We find that CEST-2.

Sphingolipid metabolism in the development and progression of cancer: one cancer's help is another's hindrance.

Cancer development is a multistep process in which cells must overcome a series of obstacles before they can become fully developed tumors. First, cells must develop the ability to proliferate unchecked. Once this is accomplished, they must be able to invade the neighboring tissue, as well as provide themselves with oxygen and nutrients.

Neurodegeneration Caused by S1P-Lyase Deficiency Involves Calcium-Dependent Tau Pathology and Abnormal Histone Acetylation.

We have shown that sphingosine 1-phosphate (S1P) generated by sphingosine kinase 2 (SK2) is toxic in neurons lacking S1P-lyase (SGPL1), the enzyme that catalyzes its irreversible cleavage. Interestingly, patients harboring mutations in the gene encoding this enzyme () often present with neurological pathologies. Studies in a mouse model with a developmental neural-specific ablation of SGPL1 (SGPL1) confirmed the importance of S1P metabolism for the presynaptic architecture and neuronal autophagy, known to be essential for brain health.

Multi-omics identify xanthine as a pro-survival metabolite for nematodes with mitochondrial dysfunction.

Aberrant mitochondrial function contributes to the pathogenesis of various metabolic and chronic disorders. Inhibition of insulin/IGF-1 signaling (IIS) represents a promising avenue for the treatment of mitochondrial diseases, although many of the molecular mechanisms underlying this beneficial effect remain elusive. Using an unbiased multi-omics approach, we report here that IIS inhibition reduces protein synthesis and favors catabolism in mitochondrial deficient We unveil that the lifespan extension does not occur through the restoration of mitochondrial respiration, but as a consequence of an ATP-saving metabolic rewiring that is associated with an evolutionarily conserved phosphoproteome landscape.

A disease-associated Aifm1 variant induces severe myopathy in knockin mice.

Objective: Mutations in the AIFM1 gene have been identified in recessive X-linked mitochondrial diseases. Functional and molecular consequences of these pathogenic AIFM1 mutations have been poorly studied in vivo.

Methods/results: Here we provide evidence that the disease-associated apoptosis-inducing factor (AIF) deletion arginine 201 (R200 in rodents) causes pathology in knockin mice.

WAH-1/AIF regulates mitochondrial oxidative phosphorylation in the nematode .

Impaired mitochondrial energy metabolism contributes to a wide range of pathologic conditions, including neurodegenerative diseases. Mitochondrial apoptosis-inducing factor (AIF) is required for the correct maintenance of mitochondrial electron transport chain. An emerging body of clinical evidence indicates that several mutations in the gene are causally linked to severe forms of mitochondrial disorders.

The SWI/SNF subunit Bcl7a contributes to motor coordination and Purkinje cell function.

Chromatin remodelers have emerged as prominent regulators of epigenetic processes and potential drivers of various human pathologies. The multi-subunit chromatin-remodeling SWI/SNF complex determines gene expression programs and, consequently, contributes to the differentiation, maturation and plasticity of neurons. Here, we investigate the elusive biological function of Bcl7a and Bcl7b, two newly identified subunits of the SWI/SNF complex that are highly expressed throughout the brain.

The histone variant H3.3 claims its place in the crowded scene of epigenetics.

Histones are evolutionarily conserved DNA-binding proteins. As scaffolding molecules, they significantly regulate the DNA packaging into the nucleus of all eukaryotic cells. As docking units, they influence the recruitment of the transcriptional machinery, thus establishing unique gene expression patterns that ultimately promote different biological outcomes.

Replication-Independent Histone Variant H3.3 Controls Animal Lifespan through the Regulation of Pro-longevity Transcriptional Programs.

Chromatin structure orchestrates the accessibility to the genetic material. Replication-independent histone variants control transcriptional plasticity in postmitotic cells. The life-long accumulation of these histones has been described, yet the implications on organismal aging remain elusive.

Functional characterization of drim2, the Drosophila melanogaster homolog of the yeast mitochondrial deoxynucleotide transporter.

The CG18317 gene (drim2) is the Drosophila melanogaster homolog of the Saccharomyces cerevisiae Rim2 gene, which encodes a pyrimidine (deoxy)nucleotide carrier. Here, we tested if the drim2 gene also encodes for a deoxynucleotide transporter in the fruit fly. The protein was localized to mitochondria.