THE ROLE OF BROCA’S AREA IN SYNTAX: A TMS STUDY ON WRITTEN GREEK LANGUAGE

A number of recent papers have addressed the potential of transcranial magnetic stimulation (TMS) to interfere with linguistic processes or speech production. In this paper we present an experiment with TMS to clarify the role of Broca’s area in syntactic processing. An experimental paradigm contrasted sentences that require syntactic and semantic decisions on written Greek language. We found a clue of selective priming effects on syntactic decisions but not on semantic decisions. Our results provide evidence of the involvement of Broca’s area in syntax

F TACHEODISPERSION. A NEW NEUROPHYSIOLOGICAL METHOD FOR THE INVESTIGATION OF PERIPHERAL NERVE DISORDERS

F WAVE IS A LATE, EVOKED MUSCLE RESPONSE PRODUCED BY RECURRENT DISCHARGES OF ANTIDROMICALLY ACTIVATED MOTOR NEURONES. IN F TACHEODISPERSION, THE NEW NEUROPHYSIOLOGICAL METHOD APPLIED IN THIS STUDY, A SIGNIFICANT NUMBER OF CONSECUTIVELYRECORDED F WAVES ARE USED TO ESTIMATE THE DISTRIBUTION OF CONDUCTION VELOCITIES (FCV)OF INDIVIDUAL OF SMALL GROUPS OF MOTOR NERVE FIBRES. WE STUDIED 39 HEALTHY SUBJECTS AND 52 PATIENTS WITH POLYNEUROPATHY. ANALYSIS OF F TACHEODISPERSION IN THE HEALTHY VOLUNTEERS SUGGESTED AN AGE RELATED SLOWING OF FCVMAX FCVMIN FCV MEAN WHICH WAS MORE PROMINENT IN THE PERONEAL THAN THE ULNAR. PATIENT'S NERVES WERE DIVIDED INTO 4 GROUPS. F TACHEODISPERSION IN THE FIRST GROUP (NORMAL CONVENTIONAL MEASUREMENTS) SHOWED MILD SHIFT OF FCV TOWARDS THE LOWER NORMAL LIMIT. (ABSTRACT TRUNCATED)ΤO F ΚΥΜΑ ΕΙΝΑΙ ΕΝΑ ΚΑΘΥΣΤΕΡΗΜΕΝΟ ΠΡΟΚΛΗΤΟ ΜΥΙΚΟΔΥΝΑΜΙΚΟ ΠΟΥ ΠΑΡΑΓΕΤΑΙ ΑΠΟ ΠΑΛΙΝΔΡΟΜΕΣ ΕΚΦΟΡΤΙΣΕΙΣ ΚΙΝΗΤΙΚΩΝ ΚΥΤΤΑΡΩΝ ΤΩΝ ΠΡΟΣΘΙΩΝ ΚΕΡΑΤΩΝ ΤΟΥ ΝΩΤΙΑΙΟΥ ΜΥΕΛΟΥ ΜΕΤΑ ΑΠΟ ΠΕΡΙΦΕΡΙΚΟ ΕΡΕΘΙΣΜΟ ΤΩΝ ΝΕΥΡΑΞΟΝΩΝ ΤΟΥΣ. ΕΝΑΣ ΣΤΑΤΙΣΤΙΚΩΣ ΣΗΜΑΝΤΙΚΟΣ ΑΡΙΘΜΟΣ F ΚΥΜΑΤΩΝ ΧΡΗΣΙΜΟΠΟΙΕΙΤΑΙ ΣΤΗ ΜΕΘΟΔΟ ΤΗΣ F ΤΑΧΕΟΔΙΑΣΠΟΡΑΣ, ΤΗ ΝΕΑ ΝΕΥΡΟΦΥΣΙΟΛΟΓΙΚΗ ΜΕΘΟΔΟ ΠΟΥ ΕΦΑΡΜΟΖΕΤΑΙ ΣΤΗΝ ΕΡΓΑΣΙΑ ΑΥΤΗ, ΓΙΑ ΤΟΝ ΥΠΟΛΟΓΙΣΜΟΤΗΣ ΚΑΤΑΝΟΜΗΣ ΤΩΝ ΤΑΧΥΤΗΤΩΝ ΑΓΩΓΗΣ ΜΕΜΟΝΩΜΕΝΩΝ Η ΜΙΚΡΩΝ ΟΜΑΔΩΝ ΚΙΝΗΤΙΚΩΝ ΝΕΥΡΙΚΩΝ ΙΝΩΝ. ΣΤΗ ΜΕΛΕΤΗ 39 ΥΓΙΗ ΑΤΟΜΑ ΚΑΙ 52 ΑΣΘΕΝΕΙΣ ΕΞΕΤΑΣΤΗΚΑΝ. ΣΤΑ ΥΓΙΗ ΑΤΟΜΑ ΔΙΑΠΙΣΤΩΘΗΚΕ ΜΙΑ ΜΕΙΩΣΗ ΤΟΥ ΣΥΝΟΛΟΥ ΤΩΝ ΤΑΧΥΤΗΤΩΝ ΜΕ ΤΗΝ ΠΑΡΟΔΟ ΤΗΣ ΗΛΙΚΙΑΣ Η ΟΠΟΙΑ ΕΙΝΑΙ ΠΙΟ ΕΜΦΑΝΗΣ ΣΤΟ ΠΕΡΟΝΙΑΙΟ ΠΑΡΑ ΣΤΟ ΩΛΕΝΙΟ. ΑΝΑΓΝΩΡΙΣΤΗΚΑΝ 4 ΚΑΤΗΓΟΡΙΕΣ ΝΕΥΡΩΝ ΣΤΟΥΣ ΑΣΘΕΝΕΙΣ ΑΝΑΛΟΓΑ ΜΕ ΤΑ ΕΥΡΗΜΑΤΑ ΤΩΝ ΣΥΜΒΑΤΙΚΩΝ ΗΛΕΚΤΡΟΦΥΣΙΟΛΟΓΙΚΩΝ ΜΕΤΡΗΣΕΩΝ. ΣΤΗΝ ΠΡΩΤΗ ΚΑΤΗΓΟΡΙΑ (ΦΥΣΙΟΛΟΓΙΚΕΣ ΣΥΜΒΑΤΙΚΕΣ ΜΕΤΡΗΣΕΙΣ) ΠΑΡΑΤΗΡΗΘΗΚΕ ΗΠΙΑ ΜΕΙΩΣΗ ΤΗΣ ΜΕΓΙΣΤΗΣ ΚΑΙ ΕΛΑΧΙΣΤΗΣ ΤΑΧΥΤΗΤΑΣ ΠΟΥ ΕΚΤΙΜΗΘΗΚΑΝ ΜΕ F ΤΑΧΕΟΔΙΑΣΠΟΡΑ (F-TXΜΕΓ. F-TXΜΙΚ.) (ΠΕΡΙΚΟΠΗ ΠΕΡΙΛΗΨΗΣ

Is the G2019S LRRK2 mutation common in all southern European populations?

Mutations in the leucine-rich repeat kinase 2 ( LRRK2) gene, especially the G2019S mutation, have been identified as a common cause of Parkinson’s disease in southern European and other Mediterranean populations (Iberians, Ashkenazi Jews and North African Arabs). Owing to the geographic and historic vicinity of Greece with areas of high prevalence of LRRK2 mutations we studied the frequency of the G2019S mutation in a well characterized cohort of familial and sporadic Parkinson’s disease patients of Greek origin from mainland Greece. The prevalence of the LRRK2 R1441C mutation and the G2385R Asian polymorphism was also determined. We identified no patients with any of the studied mutations/polymorphisms. Very low prevalence of the LRRK2 G2019S mutation has been reported in other southern European populations. LRRK2 mutations appear to be limited in certain populations and differing ancestry and founder effects may explain the reported variability. Accurate estimations of the frequency and penetrance of different LRRK2 mutations are essential for correct and cost-efficient use of genetic testing and proper genetic counseling of patients with Parkinson’s disease

Reconstituted HDL-apoE3 promotes endothelial cell migration through ID1 and its downstream kinases ERK1/2, AKT and p38 MAPK

Introduction: Atherosclerotic Coronary Artery Disease (ASCAD) is the leading cause of mortality worldwide. Novel therapeutic approaches aiming to improve the atheroprotective functions of High Density Lipoprotein (HDL) include the use of reconstituted HDL forms containing human apolipoprotein A-I (rHDL-apoA-I). Given the strong atheroprotective properties of apolipoprotein E3 (apoE3), rHDL-apoE3 may represent an attractive yet largely unexplored therapeutic agent. Objective: To evaluate the atheroprotective potential of rHDL-apoE3 starting with the unbiased assessment of global transcriptome effects and focusing on endothelial cell (EC) migration as a critical process in reendothelial ization and atherosclerosis prevention. The cellular, molecular and functional effects of rHDL-apoE3 on EC migration-associated pathways were assessed, as well as the potential translatability of these findings in vivo. Methods: Human Aortic ECs (HAEC) were treated with rHDL-apoE3 and total RNA was analyzed by whole genome miaoarrays. Expression and phosphorylation changes of key EC migration-associated molecules were validated by qRT-PCR and Western blot analysis in primary HAEC, Human Coronary Artery ECs (HCAEC) and the human EA.hy926 EC line. The capacity of rHDL-apoE3 to stimulate EC migration was assessed by wound healing and transwell migration assays. The contribution of MEK1/2, PI3K and the transcription factor ID1 in rHDL-apoE3-induced EC migration and activation of EC migration-related effectors was assessed using specific inhibitors (PD98059: MEK1/2, LY294002: PI3K) and siRNA-mediated gene silencing, respectively. The capacity of rHDL-apoE3 to improve vascular permeability and hypercholesterolemia in vivo was tested in a mouse model of hypercholesterolemia (apoE KO mice) using Evans Blue assays and lipid/lipoprotein analysis in the serum, respectively. Results: rHDL-apoE3 induced significant expression changes in 198 genes of HAEC mainly involved in reendothelialization and atherosclerosis-associated functions. The most pronounced effect was observed for EC migration, with 42/198 genes being involved in the following EC migration-related pathways: 1) MEK/ERK, 2) PI3K/AKT/eNOS-MMP2/9, 3) RHO-GTPases, 4) integrin. rHDL-apoE3 induced changes in 24 representative transcripts of these pathways in HAEC, increasing the expression of their key proteins PIK3CG, EFNB2, ID1 and FLT1 in HCAEC and EA.hy926 cells. In addition, rHDL-apoE3 stimulated migration of HCAEC and EA.hy926 cells, and the migration was markedly attenuated in the presence of PD98059 or LY294002. rHDL-apoE3 also increased the phosphorylation of ERK1/2, AKT, eNOS and p38 MAPK in these cells, while PD98059 and LY294002 inhibited rHDL-apoE3-induced phosphorylation of ERK1/2, AKT and p38 MAPK, respectively. LY had no effect on rHDL-apoE3-mediated eNOS phosphorylation. ID1 siRNA markedly decreased EA.hy926 cell migration by inhibiting rHDL-apoE3-triggered ERK1/2 and AKT phosphorylation. Finally, administration of a single dose of rHDL-apoE3 in apoE KO mice markedly improved vascular permeability as demonstrated by the reduced concentration of Evans Blue dye in tissues such as the stomach, the tongue and the urinary bladder and ameliorated hypercholesterolemia. Conclusions: rHDL-apoE3 significantly enhanced EC migration in vitro, predominantly via overexpression of ID1 and subsequent activation of MEK1/2 and P13K, and their downstream targets ERK1/2, AKT and p38 MAPK, respectively, and improved vascular permeability in vivo. These novel insights into the rHDL-apoE3 functions suggest a potential clinical use to promote re-endothelialization and retard development of atherosclerosis. (C) 2021 Elsevier Inc. All rights reserved