ASPETTI ULTRASTRUTTURALI DELLA CELLULA UOVO E DELLE CELLULE FOLLICOLARI DI PHYTOPTUS AVELLANAE NAL. (ACARINA: ERIOPHYOIDEA)

The ultrastructure of the egg and of the follicle cells of Phytoptus avellanae Nal. (Acarina: Eriophyoidea) was examined by transmission electron microscopy with special regard to the mechanism of the production and the accumulation into the oocyte of yolk and lipoid substances.The follicle cells show endoplasmic reticulum, Golgi bodies, mitochondria and many vesicles which might be interpreted as containing secretory products. Secretory vesicles originate from mitochondria which are composed of numerous layers of electron-dense lipoid and often containing one or several yolk or lipoid droplets. In addition to those myelin fìgures », there were numerous mitochondria with ordinary cristae and dense matrix and also partly myelinated mitochondria losing their cristae. Basing on these observations we can conclude that the secretory substance is originated from myelinated mitochondria and fìnally lipoid and yolk globules are formed. The accumulation of the secretory substance into the oocyte was by pinocytotic mechanism and by pores of vitelline membrane.  Gli autori descrivono gli aspetti ultrastrutturali dell'uovo e delle cellule follicolari di un Acaro Eriofìde: Phytoptus avellanae Nal. che vive nelle gemme del Nocciolo determinando ipertrofìe a carico delle stesse. Lo studio delle ultrastrutture delle cellule uovo e follicolari appare di notevole importanza poiché ha messo in evidenza, soprattutto a carico dei mitocondri, variazioni strutturali che dimostrano la loro evoluzione sino alla formazione, da una parte, di corpi lipidici e, dall'altra, di granuli di vitello (questa ultima trasformazione è certa solo per i mitocondri delle cellule follicolari). Un'ulteriore evoluzione dei mitocondri è quella che porta alla formazione di complessi mitocondriali del tipo delle condriosfere. Sono stati messi in evidenza fenomeni trofìci da parte delle cellule follicolari rispetto alle cellule uovo con il passaggio di materiale di riserva attraverso i pori della membrana vitellina e mediante fenomeni di pinocitosi. Il materiale trofìco è rappresentato soprattutto da lipidi, da granuli di glicogeno e, in modo più abbondante, da granuli di vitello che nelle cellule uovo diventano più evidenti come placche vitelline

Extended regular use of kinetic oscillation stimulation (KOS) in refractory chronic migraine: case report of a first, single-subject experience

Background: Kinetic Oscillation Stimulation (KOS) is a novel and non-invasive neuromodulation method for migraine therapy. Emerging evidence suggests that applying low-frequency intranasal vibrations to the sphenopalatine ganglion (SPG) could be a safe and effective option for migraine treatment. Case report: We present a case of a 60-year-old man affected by refractory chronic migraine with a history of failure or progressive ineffectiveness of multiple approved therapies. Given the limited available options, we proposed the patient a 6-week treatment cycle with KOS. After 1 month, monthly migraine days (MMD) dropped from 18 to 7, with significant pain reduction by week 6. However, the benefits were not sustained after discontinuation, requiring a second stimulation cycle after 3 months, which yielded an even faster and more significant response. Conclusions: This experience reveals KOS safety and effectiveness for long-term SPG neuromodulation, highlighting the potential of focusing treatment on the trigeminal-autonomic reflex (TAR) as a promising direction to pursue

The Emerging Roles of Long Non-Coding RNAs in Intellectual Disability and Related Neurodevelopmental Disorders

In the human brain, long non-coding RNAs (lncRNAs) are widely expressed in an exquisitely temporally and spatially regulated manner, thus suggesting their contribution to normal brain development and their probable involvement in the molecular pathology of neurodevelopmental disorders (NDD). Bypassing the classic protein-centric conception of disease mechanisms, some studies have been conducted to identify and characterize the putative roles of non-coding sequences in the genetic pathogenesis and diagnosis of complex diseases. However, their involvement in NDD, and more specifically in intellectual disability (ID), is still poorly documented and only a few genomic alterations affecting the lncRNAs function and/or expression have been causally linked to the disease endophenotype. Considering that a significant fraction of patients still lacks a genetic or molecular explanation, we expect that a deeper investigation of the non-coding genome will unravel novel pathogenic mechanisms, opening new translational opportunities. Here, we present evidence of the possible involvement of many lncRNAs in the etiology of different forms of ID and NDD, grouping the candidate disease-genes in the most frequently affected cellular processes in which ID-risk genes were previously collected. We also illustrate new approaches for the identification and prioritization of NDD-risk lncRNAs, together with the current strategies to exploit them in diagnosis

DataSheet1_Loss of ARHGAP15 affects the directional control of migrating interneurons in the embryonic cortex and increases susceptibility to epilepsy.pdf

GTPases of the Rho family are components of signaling pathways linking extracellular signals to the control of cytoskeleton dynamics. Among these, RAC1 plays key roles during brain development, ranging from neuronal migration to neuritogenesis, synaptogenesis, and plasticity. RAC1 activity is positively and negatively controlled by guanine nucleotide exchange factors (GEFs), guanosine nucleotide dissociation inhibitors (GDIs), and GTPase-activating proteins (GAPs), but the specific role of each regulator in vivo is poorly known. ARHGAP15 is a RAC1-specific GAP expressed during development in a fraction of migrating cortical interneurons (CINs) and in the majority of adult CINs. During development, loss of ARHGAP15 causes altered directionality of the leading process of tangentially migrating CINs, along with altered morphology in vitro. Likewise, time-lapse imaging of embryonic CINs revealed a poorly coordinated directional control during radial migration, possibly due to a hyper-exploratory behavior. In the adult cortex, the observed defects lead to subtle alteration in the distribution of CALB2-, SST-, and VIP-positive interneurons. Adult Arhgap15-knock-out mice also show reduced CINs intrinsic excitability, spontaneous subclinical seizures, and increased susceptibility to the pro-epileptic drug pilocarpine. These results indicate that ARHGAP15 imposes a fine negative regulation on RAC1 that is required for morphological maturation and directional control during CIN migration, with consequences on their laminar distribution and inhibitory function.</p

Video1_Loss of ARHGAP15 affects the directional control of migrating interneurons in the embryonic cortex and increases susceptibility to epilepsy.AVI

GTPases of the Rho family are components of signaling pathways linking extracellular signals to the control of cytoskeleton dynamics. Among these, RAC1 plays key roles during brain development, ranging from neuronal migration to neuritogenesis, synaptogenesis, and plasticity. RAC1 activity is positively and negatively controlled by guanine nucleotide exchange factors (GEFs), guanosine nucleotide dissociation inhibitors (GDIs), and GTPase-activating proteins (GAPs), but the specific role of each regulator in vivo is poorly known. ARHGAP15 is a RAC1-specific GAP expressed during development in a fraction of migrating cortical interneurons (CINs) and in the majority of adult CINs. During development, loss of ARHGAP15 causes altered directionality of the leading process of tangentially migrating CINs, along with altered morphology in vitro. Likewise, time-lapse imaging of embryonic CINs revealed a poorly coordinated directional control during radial migration, possibly due to a hyper-exploratory behavior. In the adult cortex, the observed defects lead to subtle alteration in the distribution of CALB2-, SST-, and VIP-positive interneurons. Adult Arhgap15-knock-out mice also show reduced CINs intrinsic excitability, spontaneous subclinical seizures, and increased susceptibility to the pro-epileptic drug pilocarpine. These results indicate that ARHGAP15 imposes a fine negative regulation on RAC1 that is required for morphological maturation and directional control during CIN migration, with consequences on their laminar distribution and inhibitory function.</p

Video2_Loss of ARHGAP15 affects the directional control of migrating interneurons in the embryonic cortex and increases susceptibility to epilepsy.AVI

GTPases of the Rho family are components of signaling pathways linking extracellular signals to the control of cytoskeleton dynamics. Among these, RAC1 plays key roles during brain development, ranging from neuronal migration to neuritogenesis, synaptogenesis, and plasticity. RAC1 activity is positively and negatively controlled by guanine nucleotide exchange factors (GEFs), guanosine nucleotide dissociation inhibitors (GDIs), and GTPase-activating proteins (GAPs), but the specific role of each regulator in vivo is poorly known. ARHGAP15 is a RAC1-specific GAP expressed during development in a fraction of migrating cortical interneurons (CINs) and in the majority of adult CINs. During development, loss of ARHGAP15 causes altered directionality of the leading process of tangentially migrating CINs, along with altered morphology in vitro. Likewise, time-lapse imaging of embryonic CINs revealed a poorly coordinated directional control during radial migration, possibly due to a hyper-exploratory behavior. In the adult cortex, the observed defects lead to subtle alteration in the distribution of CALB2-, SST-, and VIP-positive interneurons. Adult Arhgap15-knock-out mice also show reduced CINs intrinsic excitability, spontaneous subclinical seizures, and increased susceptibility to the pro-epileptic drug pilocarpine. These results indicate that ARHGAP15 imposes a fine negative regulation on RAC1 that is required for morphological maturation and directional control during CIN migration, with consequences on their laminar distribution and inhibitory function.</p