Loss-of-Function Myeloperoxidase Mutations Are Associated with Increased Neutrophil Counts and Pustular Skin Disease.

The identification of disease alleles underlying human autoinflammatory diseases can provide important insights into the mechanisms that maintain neutrophil homeostasis. Here, we focused our attention on generalized pustular psoriasis (GPP), a potentially life-threatening disorder presenting with cutaneous and systemic neutrophilia. Following the whole-exome sequencing of 19 unrelated affected individuals, we identified a subject harboring a homozygous splice-site mutation (c.

Congenital cytomegalovirus infection and audiological follow-up: electrophysiological auditory threshold before 3 months of age as a predictor of hearing outcome at 3 years of age.

Objective: We aimed to evaluate whether electrophysiological auditory thresholds (EATs) before 3 month of age, as assessed by the auditory brainstem responses (ABR) test and the auditory steady state responses (ASSR) test, can predict hearing outcome at 3 years of age among children born with congenital cytomegalovirus (cCMV) infection.

Study Design: Audiological assessment was performed before 3 months of age, and every 6 months thereafter until 3 years of age, in a population of 63 children (126 ears). EATs before 3 months of age and at 3 years of age were compared.

IL-36 Promotes Systemic IFN-I Responses in Severe Forms of Psoriasis.

Psoriasis is an immune-mediated skin disorder associated with severe systemic comorbidities. Whereas IL-36 is a key disease driver, the pathogenic role of this cytokine has mainly been investigated in skin. Thus, its effects on systemic immunity and extracutaneous disease manifestations remain poorly understood.

Determination of the Global Pattern of Gene Expression in Yeast Cells by Intracellular Levels of Guanine Nucleotides.

Correlations between gene transcription and the abundance of high-energy purine nucleotides in have often been noted. However, there has been no systematic investigation of this phenomenon in the absence of confounding factors such as nutrient status and growth rate, and there is little hard evidence for a causal relationship. Whether transcription is fundamentally responsive to prevailing cellular energetic conditions via sensing of intracellular purine nucleotides, independently of specific nutrition, remains an important question.

Bacterial Signaling Nucleotides Inhibit Yeast Cell Growth by Impacting Mitochondrial and Other Specifically Eukaryotic Functions.

We have engineered to inducibly synthesize the prokaryotic signaling nucleotides cyclic di-GMP (cdiGMP), cdiAMP, and ppGpp in order to characterize the range of effects these nucleotides exert on eukaryotic cell function during bacterial pathogenesis. Synthetic genetic array (SGA) and transcriptome analyses indicated that, while these compounds elicit some common reactions in yeast, there are also complex and distinctive responses to each of the three nucleotides. All three are capable of inhibiting eukaryotic cell growth, with the guanine nucleotides exhibiting stronger effects than cdiAMP.