De novo and inherited dominant variants in U4 and U6 snRNAs cause retinitis pigmentosa.

The U4 small nuclear RNA (snRNA) forms a duplex with the U6 snRNA and, together with U5 and ∼30 proteins, is part of the U4/U6.U5 tri-snRNP complex, located at the core of the major spliceosome. Recently, recurrent variants in the U4 RNA, transcribed from the gene, and in at least two other genes were discovered to cause neurodevelopmental disorder.

Variants in the AGBL5 gene are responsible for autosomal recessive Retinitis pigmentosa with hearing loss.

The AGBL5 gene encodes for the Cytoplasmic Carboxypeptidase 5 (CCP5), an α-tubulin deglutamylase that cleaves the γ-carboxyl-linked branching point of glutamylated tubulin. To date, pathogenic variants in AGBL5 have been associated only with isolated retinitis pigmentosa (RP). Hearing loss has not been reported in AGBL5-caused retinal disease.

Whole genome sequencing identifies elusive variants in genetically unsolved Italian inherited retinal disease patients.

Inherited retinal diseases (IRDs) are a group of rare monogenic diseases with high genetic heterogeneity (pathogenic variants identified in over 280 causative genes). The genetic diagnostic rate for IRDs is around 60%, mainly thanks to the routine application of next-generation sequencing (NGS) approaches such as extensive gene panels or whole exome analyses. Whole-genome sequencing (WGS) has been reported to improve this diagnostic rate by revealing elusive variants, such as structural variants (SVs) and deep intronic variants (DIVs).

Response of chemical and biochemical soil properties to the spreading of biochar-based treated olive mill wastewater.

Despite the polluting potential olive mill wastewater (OMW) can be a useful source of nutrients and organic compounds to improve soil properties. The aim of this paper was to verify if biochar-based treatment of OMW could be an efficient method to contrast the richness in phenolic compounds and phytotoxicity of OMW making it more suitable. for soil amendment.

Late-onset mucopolysaccharidosis type IIIA mimicking Usher syndrome.

Mucopolysaccharidosis type IIIA (MPS IIIA or Sanfilippo syndrome type A) is an autosomal recessive lysosomal storage disorder caused by pathogenic variants in the SGSH gene encoding N-sulfoglucosamine sulfohydrolase, an enzyme involved in the degradation of heparan sulfate. MPS IIIA is typically characterized by neurocognitive decline and hepatosplenomegaly with childhood onset. Here, we report on a 53-year-old male subject initially diagnosed with Usher syndrome for the concurrence of retinitis pigmentosa and sensorineural hearing loss.

Response of chemical and biochemical soil properties to the spreading of biochar-based treated olive mill wastewater.

Olive mill wastewater (OMW) is the effluent derived from the oil extraction processes from olives. Despite the polluting potential OMW can be a useful source of nutrients and organic compounds to improve soil properties. OMW could negatively affect soil and water quality as this waste is rich in phenolic compounds and has high COD and BOD.

Piwil2 (Mili) sustains neurogenesis and prevents cellular senescence in the postnatal hippocampus.

Adult neural progenitor cells (aNPCs) ensure lifelong neurogenesis in the mammalian hippocampus. Proper regulation of aNPC fate has thus important implications for brain plasticity and healthy aging. Piwi proteins and the small noncoding RNAs interacting with them (piRNAs) have been proposed to control memory and anxiety, but the mechanism remains elusive.

Genetic epidemiology of inherited retinal diseases in a large patient cohort followed at a single center in Italy.

Inherited retinal diseases (IRDs) are the leading cause of vision loss in the working-age population. We performed a retrospective epidemiological study to determine the genetic basis of IRDs in a large Italian cohort (n = 2790) followed at a single referral center. We provided, mainly by next generation sequencing, potentially conclusive molecular diagnosis for 2036 patients (from 1683 unrelated families).

Exploratory analysis of transposable elements expression in the C. elegans early embryo.

Background: Transposable Elements (TE) are mobile sequences that make up large portions of eukaryote genomes. The functions they play within the complex cellular architecture are still not clearly understood, but it is becoming evident that TE have a role in several physiological and pathological processes. In particular, it has been shown that TE transcription is necessary for the correct development of mice embryos and that their expression is able to finely modulate transcription of coding and non-coding genes.

SINEUP Non-coding RNA Targeting GDNF Rescues Motor Deficits and Neurodegeneration in a Mouse Model of Parkinson's Disease.

Glial cell-derived neurotrophic factor (GDNF) has a potent action in promoting the survival of dopamine (DA) neurons. Several studies indicate that increasing GDNF levels may be beneficial for the treatment of Parkinson's disease (PD) by reducing neurodegeneration of DA neurons. Despite a plethora of preclinical studies showing GDNF efficacy in PD animal models, its application in humans remains questionable for its poor efficacy and side effects due to its uncontrolled, ectopic expression.

Short interspersed DNA elements and miRNAs: a novel hidden gene regulation layer in zebrafish?

In this study, we investigated by in silico analysis the possible correlation between microRNAs (miRNAs) and Anamnia V-SINEs (a superfamily of short interspersed nuclear elements), which belong to those retroposon families that have been preserved in vertebrate genomes for millions of years and are actively transcribed because they are embedded in the 3' untranslated region (UTR) of several genes. We report the results of the analysis of the genomic distribution of these mobile elements in zebrafish (Danio rerio) and discuss their involvement in generating miRNA gene loci. The computational study showed that the genes predicted to bear V-SINEs can be targeted by miRNAs with a very high hybridization E-value.

Novel transcription factor variants through RNA-sequencing: the importance of being "alternative".

Alternative splicing is a pervasive mechanism of RNA maturation in higher eukaryotes, which increases proteomic diversity and biological complexity. It has a key regulatory role in several physiological and pathological states. The diffusion of Next Generation Sequencing, particularly of RNA-Sequencing, has exponentially empowered the identification of novel transcripts revealing that more than 95% of human genes undergo alternative splicing.

AnaLysis of Expression on human chromosome 21, ALE-HSA21: a pilot integrated web resource.

Transcriptome studies have shown the pervasive nature of transcription, demonstrating almost all the genes undergo alternative splicing. Accurately annotating all transcripts of a gene is crucial. It is needed to understand the impact of mutations on phenotypes, to shed light on genetic and epigenetic regulation of mRNAs and more generally to widen our knowledge about cell functionality and tissue diversity.

Evidence of Bacteroides fragilis protection from Bartonella henselae-induced damage.

Bartonella henselae is able to internalize endothelial progenitor cells (EPCs), which are resistant to the infection of other common pathogens. Bacteroides fragilis is a gram-negative anaerobe belonging to the gut microflora. It protects from experimental colitis induced by Helicobacter hepaticus through the polysaccharide A (PSA).

Bipolar Disorder: an impossible diagnosis.

Following the recent debates on the discrepancy between the predominant weight of bipolar disorder (BPD) in the clinical reality and its relatively low prevalence figures emerging from epidemiological surveys, the present paper contends the ability of current operational diagnostic system to properly detect the clinical entity of bipolar disorder.As an episode of mania/hypomania is the necessary requirement for a diagnosis of bipolar disorder to be made, in this editorial we maintain that: a) the most severe forms of mania, characterized by cloudy consciousness, mood incongruent delusions, and physical symptoms are likely to escape DSM IV criteria, that are shaped around hypomania or mild mania; b) the impossibility to diagnose mania when this occurs during antidepressant treatments impedes diagnosing those cases whose natural illness pattern is Depression followed by Mania (known as DMI pattern); c) given that approximately 50% of cases have their onset of BPD with affective episodes other than mania/hypomania any prevalence figure necessarily underestimates BPD; d) the sub-threshold forms of BPD, well described in the concept of Bipolar Spectrum, are beyond the possibility to be recognized using operational diagnoses in spite of their utmost clinical relevance.

The Sesto Fiorentino study: point and one-year prevalences of psychiatric disorders in an Italian community sample using clinical interviewers.

Background: It has been argued that lay interviewers' use of fully-structured interviews could lead to a diagnostic pattern different to that by treating physicians. Clinical interviewers in community samples should probably identify cases that are closer to those seen in clinical settings. The greatest advantage of using clinical interviewers consists of the immediate assessment of a possible psychopathology, i.

The Sesto Fiorentino study: background, methods and preliminary results. Lifetime prevalence of psychiatric disorders in an Italian community sample using clinical interviewers.

Background: This paper presents lifetime prevalences and estimated risks of DSM-IV psychiatric disorders from a community survey conducted in Sesto Fiorentino, Italy, using psychiatric interviewers with clinical experience and clinical instruments.

Methods: Two thousand five hundred subjects aged 14 or more were randomly selected from the lists of 15 general practitioners (GPs) regardless of whether or not they had consulted the GP. A three-phase design was adopted, with the GPs using the Mini International Neuropsychiatric Interview (MINI) for the first stage.

A self-controlled, naturalistic study of selective serotonin reuptake inhibitors versus tricyclic antidepressants.

Objective: To compare the effectiveness of serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) for anxiety and mood disorders in a naturalistic setting.

Methods: 114 of 2,000 outpatients drawn from a private facility with a diagnosis of mood or anxiety disorder had two separate episodes during which they were treated once with a SSRI and once with a TCA. The drugs had to be in monotherapy and appropriate according to the recent guidelines.

Onset of panic disorder.

The situations in which the first panic attack occurred were investigated in 44 patients affected by panic disorder. Although the first panic attack was reported to be unexpected and no avoidance was present before it, 75.8% of patients (N = 22) with panic disorder with agoraphobia had their first panic attack in phobogenic situations, compared with 20% of patients (N = 3) with panic disorder without agoraphobia.