Fragile X mental retardation protein (FMRP) and metabotropic glutamate receptor subtype 5 (mGlu5) control stress granule formation in astrocytes

Fragile X syndrome (FXS) is a common form of intellectual disability and autism caused by the lack of Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein involved in RNA transport and protein synthesis. Upon cellular stress, global protein synthesis is blocked and mRNAs are recruited into stress granules (SGs), together with RNA-binding proteins including FMRP. Activation of group-I metabotropic glutamate (mGlu) receptors stimulates FMRP-mediated mRNA transport and protein synthesis, but their role in SGs formation is unexplored. To this aim, we pre-treated wild type (WT) and Fmr1 knockout (KO) cultured astrocytes with the group-I-mGlu receptor agonist (S)-3,5-Dihydroxyphenylglycine (DHPG) and exposed them to sodium arsenite (NaAsO2), a widely used inducer of SGs formation. In WT cultures the activation of group-I mGlu receptors reduced SGs formation and recruitment of FMRP into SGs, and also attenuated phosphorylation of eIF2α, a key event crucially involved in SGs formation and inhibition of protein synthesis. In contrast, Fmr1 KO astrocytes, which exhibited a lower number of SGs than WT astrocytes, did not respond to agonist stimulation. Interestingly, the mGlu5 receptor negative allosteric modulator (NAM) 2-methyl-6-(phenylethynyl)pyridine (MPEP) antagonized DHPG-mediated SGs reduction in WT and reversed SGs formation in Fmr1 KO cultures. Our findings reveal a novel function of mGlu5 receptor as modulator of SGs formation and open new perspectives for understanding cellular response to stress in FXS pathophysiology

Stop-event-related potentials from intracranial electrodes reveal a key role of premotor and motor cortices in stopping ongoing movements

In humans, the ability to withhold manual motor responses seems to rely on a right-lateralized frontal–basal ganglia–thalamic network, including the pre-supplementary motor area and the inferior frontal gyrus (IFG). These areas should drive subthalamic nuclei to implement movement inhibition via the hyperdirect pathway. The output of this network is expected to influence those cortical areas underlying limb movement preparation and initiation, i.e., premotor (PMA) and primary motor (M1) cortices. Electroencephalographic (EEG) studies have shown an enhancement of the N200/P300 complex in the event-related potentials (ERPs) when a planned reaching movement is successfully stopped after the presentation of an infrequent stop-signal. PMA and M1 have been suggested as possible neural sources of this ERP complex but, due to the limited spatial resolution of scalp EEG, it is not yet clear which cortical areas contribute to its generation. To elucidate the role of motor cortices, we recorded epicortical ERPs from the lateral surface of the fronto-temporal lobes of five pharmacoresistant epileptic patients performing a reaching version of the countermanding task while undergoing presurgical monitoring. We consistently found a stereotyped ERP complex on a single-trial level when a movement was successfully cancelled. These ERPs were selectively expressed in M1, PMA, and Brodmann's area (BA) 9 and their onsets preceded the end of the stop process, suggesting a causal involvement in this executive function. Such ERPs also occurred in unsuccessful-stop (US) trials, that is, when subjects moved despite the occurrence of a stop-signal, mostly when they had long reaction times (RTs). These findings support the hypothesis that motor cortices are the final target of the inhibitory command elaborated by the frontal–basal ganglia–thalamic network

Role of Spinophilin in Group I Metabotropic Glutamate Receptor Endocytosis, Signaling, and Synaptic Plasticity

Activation of Group I metabotropic glutamate receptors (mGluRs) activates signaling cascades, resulting in calcium release from intracellular stores, ERK1/2 activation, and long term changes in synaptic activity that are implicated in learning, memory, and neurodegenerative diseases. As such, elucidating the molecular mechanisms underlying Group I mGluR signaling is important for understanding physiological responses initiated by the activation of these receptors. In the current study, we identify the multifunctional scaffolding protein spinophilin as a novel Group I mGluR-interacting protein. We demonstrate that spinophilin interacts with the C-terminal tail and second intracellular loop of Group I mGluRs. Furthermore, we show that interaction of spinophilin with Group I mGluRs attenuates receptor endocytosis and phosphorylation of ERK1/2, an effect that is dependent upon the interaction of spinophilin with the C-terminal PDZ binding motif encoded by Group I mGluRs. Spinophilin knock-out results in enhanced mGluR5 endocytosis as well as increased ERK1/2, AKT, and Ca2+ signaling in primary cortical neurons. In addition, the loss of spinophilin expression results in impaired mGluR5-stimulated LTD. Our results indicate that spinophilin plays an important role in regulating the activity of Group I mGluRs as well as their influence on synaptic activity

The incremental role of trait emotional intelligence on perceived cervical screening barriers

Researchers have become increasingly interested in investigating the role of the psychological aspects related to the perception of cervical screening barriers. This study investigates the influence of trait EI on perceived cervical screening barriers. Furthermore, this study investigates the incremental validity of trait EI beyond the Big Five, as well as emotion regulation in the perceived barrier towards the Pap test as revealed in a sample of 206 Italian women that were undergoing cervical screening. Results have shown that trait EI is negatively related to cervical screening barriers. Furthermore, trait EI can be considered as a strong incremental predictor of a woman's perception of screening over and above the Big Five, emotion regulation, age, sexual intercourse experience and past Pap test. Detailed information on the study findings and future research directions are discussed

Quantum transport in ultracold atoms

Ultracold atoms confined by engineered magnetic or optical potentials are ideal systems for studying phenomena otherwise difficult to realize or probe in the solid state because their atomic interaction strength, number of species, density, and geometry can be independently controlled. This review focuses on quantum transport phenomena in atomic gases that mirror and oftentimes either better elucidate or show fundamental differences with those observed in mesoscopic and nanoscopic systems. We discuss significant progress in performing transport experiments in atomic gases, contrast similarities and differences between transport in cold atoms and in condensed matter systems, and survey inspiring theoretical predictions that are difficult to verify in conventional setups. These results further demonstrate the versatility offered by atomic systems in the study of nonequilibrium phenomena and their promise for novel applications.Comment: 24 pages, 7 figures. A revie

Involvement of the endocannabinoid system in the physiological response to transient common carotid artery occlusion and reperfusion

Background: The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) may trigger a physiological response in an attempt to preserve tissue and function integrity. There are several candidate molecules among which the endocannabinoid system (ECS) and/or peroxisome-proliferator activated receptor-alpha (PPAR-alpha) may play a role in modulating oxidative stress and inflammation. The aims of the present study are to evaluate whether the ECS, the enzyme cyclooxygenase-2 (COX-2) and PPAR-alpha are involved during BCCAO/R in rat brain, and to identify possible markers of the ongoing BCCAO/R-induced challenge in plasma. Methods: Adult Wistar rats underwent BCCAO/R with 30 min hypoperfusion followed by 60 min reperfusion. The frontal and temporal-occipital cortices and plasma were analyzed by high performance liquid chromatography-mass spectrometry (HPLC-MS) to determine concentrations of endocannabinoids (eCBs) and related molecules behaving as ligands of PPAR-alpha, and of oxidative-stress markers such as lipoperoxides, while Western Blot and immunohistochemistry were used to study protein expression of cannabinoid receptors, COX-2 and PPAR-alpha. Unpaired Student's t-test was used to evaluate statistical differences between groups. Results: The acute BCCAO/R procedure is followed by increased brain tissue levels of the eCBs 2-arachidonoylglycerol and anandamide, palmitoylethanolamide, an avid ligand of PPAR-alpha, lipoperoxides, type 1 (CB1) and type 2 (CB2) cannabinoid receptors, and COX-2, and decreased brain tissue concentrations of docosahexaenoic acid (DHA), one of the major targets of lipid peroxidation. In plasma, increased levels of anandamide and lipoperoxides were observed. Conclusions: The BCCAO/R stimulated early molecular changes that can be easily traced in brain tissue and plasma, and that are indicative of the tissue physiological response to the reperfusion-induced oxidative stress and inflammation. The observed variations suggest that the positive modulation of the ECS and the increase of proinflammatory substances are directly correlated events. Increase of plasmatic levels of anandamide and lipoperoxides further suggests that dysregulation of these molecules may be taken as an indicator of an ongoing hypoperfusion/reperfusion challenge

Perinatal care in SARS-CoV-2 infected women: the lesson learnt from a national prospective cohort study during the pandemic in Italy

Background: Despite the growing importance given to ensuring high-quality childbirth, perinatal good practices have been rapidly disrupted by SARS-CoV-2 pandemic. This study aimed at describing the childbirth care provided to infected women during two years of COVID-19 emergency in Italy. Methods: A prospective cohort study enrolling all women who gave birth with a confirmed SARS-CoV-2 infection within 7 days from hospital admission in the 218 maternity units active in Italy during the periods February 25, 2020-June 30, 2021, and January 1-May 31, 2022. Perinatal care was assessed by evaluating the prevalence of the following indicators during the pandemic: presence of a labour companion; skin-to-skin; no mother-child separation at birth; rooming-in; breastfeeding. Logistic regression models including women' socio-demographic, obstetric and medical characteristics, were used to assess the association between the adherence to perinatal practices and different pandemic phases. Results: During the study period, 5,360 SARS-CoV-2 positive women were enrolled. Overall, among those who had a vaginal delivery (n = 3,574; 66.8%), 37.5% had a labour companion, 70.5% of newborns were not separated from their mothers at birth, 88.1% were roomed-in, and 88.0% breastfed. These four indicators showed similar variations in the study period with a negative peak between September 2020 and January 2021 and a gradual increase during the Alpha and Omicron waves. Skin-to-skin (mean value 66.2%) had its lowest level at the beginning of the pandemic and gradually increased throughout the study period. Among women who had a caesarean section (n = 1,777; 33.2%), all the indicators showed notably worse outcomes with similar variations in the study period. Multiple logistic regression analyses confirm the observed variations during the pandemic and show a lower adherence to good practices in southern regions and in maternity units with a higher annual number of births. Conclusions: Despite the rising trend in the studied indicators, we observed concerning substandard childbirth care during the SARS-CoV-2 pandemic. Continued efforts are necessary to underscore the significance of the experience of care as a vital component in enhancing the quality of family-centred care policies

Engineering Reconnaissance Following the October 2016 Central Italy Earthquakes - Version 2

Between August and November 2016, three major earthquake events occurred in Central Italy. The first event, with M6.1, took place on 24 August 2016, the second (M5.9) on 26 October, and the third (M6.5) on 30 October 2016. Each event was followed by numerous aftershocks. As shown in Figure 1.1, this earthquake sequence occurred in a gap between two earlier damaging events, the 1997 M6.1 Umbria-Marche earthquake to the north-west and the 2009 M6.1 L’Aquila earthquake to the south-east. This gap had been previously recognized as a zone of elevated risk (GdL INGV sul terremoto di Amatrice, 2016). These events occurred along the spine of the Apennine Mountain range on normal faults and had rake angles ranging from -80 to -100 deg, which corresponds to normal faulting. Each of these events produced substantial damage to local towns and villages. The 24 August event caused massive damages to the following villages: Arquata del Tronto, Accumoli, Amatrice, and Pescara del Tronto. In total, there were 299 fatalities (www.ilgiornale.it), generally from collapses of unreinforced masonry dwellings. The October events caused significant new damage in the villages of Visso, Ussita, and Norcia, although they did not produce fatalities, since the area had largely been evacuated. The NSF-funded Geotechnical Extreme Events Reconnaissance (GEER) association, with co-funding from the B. John Garrick Institute for the Risk Sciences at UCLA and the NSF I/UCRC Center for Unmanned Aircraft Systems (C-UAS) at BYU, mobilized a US-based team to the area in two main phases: (1) following the 24 August event, from early September to early October 2016, and (2) following the October events, between the end of November and the beginning of December 2016. The US team worked in close collaboration with Italian researchers organized under the auspices of the Italian Geotechnical Society, the Italian Center for Seismic Microzonation and its Applications, the Consortium ReLUIS, Centre of Competence of Department of Civil Protection and the DIsaster RECovery Team of Politecnico di Torino. The objective of the Italy-US GEER team was to collect and document perishable data that is essential to advance knowledge of earthquake effects, which ultimately leads to improved procedures for characterization and mitigation of seismic risk. The Italy-US GEER team was multi-disciplinary, with expertise in geology, seismology, geomatics, geotechnical engineering, and structural engineering. The composition of the team was largely the same for the two mobilizations, particularly on the Italian side. Our approach was to combine traditional reconnaissance activities of on-ground recording and mapping of field conditions, with advanced imaging and damage detection routines enabled by state-of-the-art geomatics technology. GEER coordinated its reconnaissance activities with those of the Earthquake Engineering Research Institute (EERI), although the EERI mobilization to the October events was delayed and remains pending as of this writing (April 2017). For the August event reconnaissance, EERI focused on emergency response and recovery, in combination with documenting the effectiveness of public policies related to seismic retrofit. As such, GEER had responsibility for documenting structural damage patterns in addition to geotechnical effects. This report is focused on the reconnaissance activities performed following the October 2016 events. More information about the GEER reconnaissance activities and main findings following the 24 August 2016 event, can be found in GEER (2016). The objective of this document is to provide a summary of our findings, with an emphasis of documentation of data. In general, we do not seek to interpret data, but rather to present it as thoroughly as practical. Moreover, we minimize the presentation of background information already given in GEER (2016), so that the focus is on the effects of the October events. As such, this report and GEER (2016) are inseparable companion documents. Similar to reconnaissance activities following the 24 August 2016 event, the GEER team investigated earthquake effects on slopes, villages, and major infrastructure. Figure 1.2 shows the most strongly affected region and locations described subsequently pertaining to: 1. Surface fault rupture; 2. Recorded ground motions; 3. Landslides and rockfalls; 4. Mud volcanoes; 5. Investigated bridge structures; 6. Villages and hamlets for which mapping of building performance was performed