Prevalence, comorbidities, and profiles of neurodevelopmental disorders according to the DSM-5-TR in children aged 6 years old in a European region.

Background: There are no studies that measure the prevalence and real comorbidities of neurodevelopmental disorders (NDDs) according to the DSM-5-TR in 6-year-old children in population and clinical samples or studies that measure them as a whole. The data on the prevalence of these disorders are usually disparate because of the estimation methods (direct/indirect), the type of sample (population/clinical/school), and the ages studied.

Methods: The initial sample (289 subjects) was representative of 6-year-old children in the entire population of Menorca, obtained from pediatric primary care services (100% of the sample).

P-TEFb regulation of transcription termination factor Xrn2 revealed by a chemical genetic screen for Cdk9 substrates.

The transcription cycle of RNA polymerase II (Pol II) is regulated at discrete transition points by cyclin-dependent kinases (CDKs). Positive transcription elongation factor b (P-TEFb), a complex of Cdk9 and cyclin T1, promotes release of paused Pol II into elongation, but the precise mechanisms and targets of Cdk9 action remain largely unknown. Here, by a chemical genetic strategy, we identified ∼ 100 putative substrates of human P-TEFb, which were enriched for proteins implicated in transcription and RNA catabolism.

The Stimulatory Mechanism of Hepatitis C Virus NS5A Protein on the NS5B Catalyzed Replication Reaction In Vitro.

The Hepatitis C Virus RNA dependent RNA polymerase, NS5B, is stimulated by the NS5A protein in vitro. To explore this stimulatory mechanism, we compared the activity of a mutant of NS5B containing a deletion of the β-loop region with that of the full length NS5B in response to NS5A. While the NS5A protein does stimulate full length NS5B, NS5A does not stimulate the NS5B deletion mutant during either replication initiation or elongation.

Transition step during assembly of HIV Tat:P-TEFb transcription complexes and transfer to TAR RNA.

Transcription factors regulate eukaryotic RNA polymerase II (Pol II) activity by assembling and remodeling complexes at multiple steps in the transcription cycle. In HIV, we previously proposed a two-step model where the viral Tat protein first preassembles at the promoter with an inactive P-TEFb:7SK snRNP complex and later transfers P-TEFb to TAR on the nascent transcript, displacing the inhibitory snRNP and resulting in Pol II phosphorylation and stimulation of elongation. It is unknown how the Tat:P-TEFb complex transitions to TAR to activate the P-TEFb kinase.

The Hepatitis C Virus NS5A Stimulates NS5B During In Vitro RNA Synthesis in a Template Specific Manner.

The hepatitis C virus (HCV) NS5B protein contains the RNA dependent RNA polymerase (RdRp) activity that catalyzes the synthesis of the viral genome with other host and viral factors. NS5A is an HCV-encoded protein previously shown to localize to the replisome and be necessary for viral replication. However, its role in replication has not been defined.