Double Gate PbS Quantum Dot Field-Effect Transistors for Tuneable Electrical Characteristics

In this work colloidal quantum dots double gate transistors are introduced. A high-k (k = 43) relaxor ferroelectric polymer is used as a dielectric material for the top gate in a device where the other gate is fabricated from SiO2. The device in double gate configuration is characterized by reduced hysteresis in the transfer curves measured by separately sweeping the voltage of the SiO2 and of the polymer gate. Gating with the relaxor polymer leads to mobility values of μe = 1.1 cm2 V−1s−1 and μh = 6 × 10−3 cm2 V−1s−1 that exceed those extracted from the SiO2 gating: μe = 0.5 cm2 V−1s−1 and μh = 2 × 10−3 cm2 V−1s−1. Measurements under double gating conditions prove that the device works in a single channel mode that is delocalized over the whole film thickness. Double gating allows for shifting the threshold voltage into a desired position and also allows increasing the on-current of the devices

Inhibition of microglia overactivation restores neuronal survival in a mouse model of CDKL5 deficiency disorder

open9noFunding: This work was supported by the Telethon foundation (grant number GGP19045 to EC), by the Italian parent associations “CDKL5 insieme verso la cura” to EC and by the CARISBO foundation (grant number 2020.0400 to ST).CDKL5 deficiency disorder (CDD), a severe neurodevelopmental disorder characterized by early onset epilepsy, intellectual disability, and autistic features, is caused by mutations in the CDKL5 gene. Evidence in animal models of CDD showed that absence of CDKL5 negatively affects neuronal survival, as well as neuronal maturation and dendritic outgrowth; however, knowledge of the substrates underlying these alterations is still limited. Neuroinflammatory processes are known to contribute to neuronal dysfunction and death. Recent evidence shows a subclinical chronic inflammatory status in plasma from CDD patients. However, to date, it is unknown whether a similar inflammatory status is present in the brain of CDD patients and, if so, whether this plays a causative or exacerbating role in the pathophysiology of CDD.openGalvani, Giuseppe; Mottolese, Nicola; Gennaccaro, Laura; Loi, Manuela; Medici, Giorgio; Tassinari, Marianna; Fuchs, Claudia; Ciani, Elisabetta; Trazzi, StefaniaGalvani, Giuseppe; Mottolese, Nicola; Gennaccaro, Laura; Loi, Manuela; Medici, Giorgio; Tassinari, Marianna; Fuchs, Claudia; Ciani, Elisabetta; Trazzi, Stefani

Population Saturation in Trivalent Erbium Sensitized by Organic Molecular Antennae

We investigate sensitization efficiency of near-infrared emission and population saturation of trivalent erbium in erbium quincilinolato complexes photoexcited into the absorption band of the organic sensitizer. At low excitation levels, we find high (similar to 80%) sensitization efficiencies. We observe excited state population saturation at inversion threshold under subnanosecond pumping at the level of one injected photoexcitation per complex

Localization and subcellular association of Grapevine Pinot Gris Virus in grapevine leaf tissues

Despite the increasing impact of Grapevine Pinot gris disease (GPG-disease) worldwide, etiology about this disorder is still uncertain. The presence of the putative causal agent, the Grapevine Pinot Gris Virus (GPGV), has been reported in symptomatic grapevines (presenting stunting, chlorotic mottling, and leaf deformation) as well as in symptom-free plants. Moreover, information on virus localization in grapevine tissues and virus-plant interactions at the cytological level is missing at all. Ultrastructural and cytochemical investigations were undertaken to detect virus particles and the associated cytopathic effects in field-grown grapevine showing different symptom severity. Asymptomatic greenhouse-grown grapevines, which tested negative for GPGV by real time RT-PCR, were sampled as controls. Multiplex real-time RT-PCR and ELISA tests excluded the presence of viruses included in the Italian certification program both in field-grown and greenhouse-grown grapevines. Conversely, evidence was found for ubiquitous presence of Grapevine Rupestris Stem Pitting-associated Virus (GRSPaV), Hop Stunt Viroid (HSVd), and Grapevine Yellow Speckle Viroid 1 (GYSVd-1) in both plant groups. Moreover, in every field-grown grapevine, GPGV was detected by real-time RT-PCR. Ultrastructural observations and immunogold labelling assays showed filamentous flexuous viruses in the bundle sheath cells, often located inside membrane-bound organelles. No cytological differences were observed among field-grown grapevine samples showing different symptom severity. GPGV localization and associated ultrastructural modifications are reported and discussed, in the perspective of assisting management and control of the disease. \ua9 2017 The Author(s

Luteolin Treatment Ameliorates Brain Development and Behavioral Performance in a Mouse Model of CDKL5 Deficiency Disorder

CDKL5 deficiency disorder (CDD), a rare and severe neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene, is characterized by early-onset epilepsy, intellectual disability, and autistic features. Although pharmacotherapy has shown promise in the CDD mouse model, safe and effective clinical treatments are still far off. Recently, we found increased microglial activation in the brain of a mouse model of CDD, the Cdkl5 KO mouse, suggesting that a neuroinflammatory state, known to be involved in brain maturation and neuronal dysfunctions, may contribute to the pathophysiology of CDD. The present study aims to evaluate the possible beneficial effect of treatment with luteolin, a natural flavonoid known to have anti-inflammatory and neuroprotective activities, on brain development and behavior in a heterozygous Cdkl5 (+/-) female mouse, the mouse model of CDD that best resembles the genetic clinical condition. We found that inhibition of neuroinflammation by chronic luteolin treatment ameliorates motor stereotypies, hyperactive profile and memory ability in Cdkl5 +/- mice. Luteolin treatment also increases hippocampal neurogenesis and improves dendritic spine maturation and dendritic arborization of hippocampal and cortical neurons. These findings show that microglia overactivation exerts a harmful action in the Cdkl5 +/- brain, suggesting that treatments aimed at counteracting the neuroinflammatory process should be considered as a promising adjuvant therapy for CDD

Treatment with a GSK-3β/HDAC Dual Inhibitor Restores Neuronal Survival and Maturation in an In Vitro and In Vivo Model of CDKL5 Deficiency Disorder

open11noFunding: This research was funded by the Telethon foundation (grant number GGP19045, awarded to E.C.), and by the Italian parent association “CDKL5 insieme verso la cura” (to E.C.).Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene cause a rare neurodevelopmental disorder characterized by early-onset seizures and severe cognitive, motor, and visual impairments. To date there are no therapies for CDKL5 deficiency disorder (CDD). In view of the severity of the neurological phenotype of CDD patients it is widely assumed that CDKL5 may influence the activity of a variety of cellular pathways, suggesting that an approach aimed at targeting multiple cellular pathways simultaneously might be more effective for CDD. Previous findings showed that a single-target therapy aimed at normalizing impaired GSK-3β or histone deacetylase (HDAC) activity improved neurodevelopmental and cognitive alterations in a mouse model of CDD. Here we tested the ability of a first-in-class GSK-3β/HDAC dual inhibitor, Compound 11 (C11), to rescue CDD-related phenotypes. We found that C11, through inhibition of GSK-3β and HDAC6 activity, not only restored maturation, but also significantly improved survival of both human CDKL5-deficient cells and hippocampal neurons from Cdkl5 KO mice. Importantly, in vivo treatment with C11 restored synapse development, neuronal survival, and microglia over-activation, and improved motor and cognitive abilities of Cdkl5 KO mice, suggesting that dual GSK-3β/HDAC6 inhibitor therapy may have a wider therapeutic benefit in CDD patients.openLoi, Manuela; Gennaccaro, Laura; Fuchs, Claudia; Trazzi, Stefania; Medici, Giorgio; Galvani, Giuseppe; Mottolese, Nicola; Tassinari, Marianna; Giorgini, Roberto Rimondini; Milelli, Andrea; Ciani, ElisabettaLoi, Manuela; Gennaccaro, Laura; Fuchs, Claudia; Trazzi, Stefania; Medici, Giorgio; Galvani, Giuseppe; Mottolese, Nicola; Tassinari, Marianna; Giorgini, Roberto Rimondini; Milelli, Andrea; Ciani, Elisabett

Bruce Protocol Test affects Postural Stability in Healthy Young Adults

Maintaining balance is key in avoiding falls and injury. However, little is known on how increased cardiac activity may affect postural stability. This study investigated if increase in cardiac activity to 85% maximal heart rate (HR) when exercising with standard Bruce Protocol Test (BPT) influence postural sway. Ten young adults were tested for three postural stances, quiet bilateral standing with i) eyes open, ii) eyes closed, and iii) tandem stance, before and after performing the BPT. Resting Heart Rate (HR) and HR variability along with standard postural sway parameters like sway velocity, sway area, turn index, and power frequency in the anterior-posterior (AP) and medial-lateral (ML) directions were evaluated. We found significant increases in postural sway values for turn index values due to HR changes. Thus, balance demanding tasks may be avoided immediately after performing submaximal cardiac activities in order to avoid fall risk and injury

Agroinoculation of Grapevine Pinot Gris Virus in tobacco and grapevine provides insights on viral pathogenesis

The Grapevine Pinot Gris disease (GPG-d) is a novel disease characterized by symptoms such as leaf mottling and deformation, which has been recently reported in grapevines, and mostly in Pinot gris. Plants show obvious symptoms at the beginning of the growing season, while during summer symptom recovery frequently occurs, manifesting as symptomless leaves. A new Trichovirus, named Grapevine Pinot gris virus (GPGV), which belongs to the family Betaflexiviridae was found in association with infected plants. The detection of the virus in asymptomatic grapevines raised doubts about disease aetiology. Therefore, the primary target of this work was to set up a reliable system for the study of the disease in controlled conditions, avoiding interfering factor(s) that could affect symptom development. To this end, two clones of the virus, pRI::GPGV-vir and pRI::GPGV-lat, were generated from total RNA collected from one symptomatic and one asymptomatic Pinot gris grapevine, respectively. The clones, which encompassed the entire genome of the virus, were used in Agrobacterium-mediated inoculation of Vitis vinifera and Nicotiana benthamiana plants. All inoculated plants developed symptoms regardless of their inoculum source, demonstrating a correlation between the presence of GPGV and symptomatic manifestations. Four months post inoculum, the grapevines inoculated with the pRI::GPGV-lat clone developed asymptomatic leaves that were still positive to GPGV detection. Three to four weeks later (i.e. ca. 5 months post inoculum), the same phenomenon was observed in the grapevines inoculated with pRI::GPGV-vir. This observation perfectly matches symptom progression in infected field-grown grapevines, suggesting a possible role for plant antiviral mechanisms, such as RNA silencing, in the recovery process.</div

Cardiac Functional and Structural Abnormalities in a Mouse Model of CDKL5 Deficiency Disorder

CDKL5 (cyclin-dependent kinase-like 5) deficiency disorder (CDD) is a severe neurodevelopmental disease that mostly affects girls, who are heterozygous for mutations in the X-linked CDKL5 gene. Mutations in the CDKL5 gene lead to a lack of CDKL5 protein expression or function and cause numerous clinical features, including early-onset seizures, marked hypotonia, autistic features, gastrointestinal problems, and severe neurodevelopmental impairment. Mouse models of CDD recapitulate several aspects of CDD symptomology, including cognitive impairments, motor deficits, and autistic-like features, and have been useful to dissect the role of CDKL5 in brain development and function. However, our current knowledge of the function of CDKL5 in other organs/tissues besides the brain is still quite limited, reducing the possibility of broad-spectrum interventions. Here, for the first time, we report the presence of cardiac function/structure alterations in heterozygous Cdkl5 +/- female mice. We found a prolonged QT interval (corrected for the heart rate, QTc) and increased heart rate in Cdkl5 +/- mice. These changes correlate with a marked decrease in parasympathetic activity to the heart and in the expression of the Scn5a and Hcn4 voltage-gated channels. Interestingly, Cdkl5 +/- hearts showed increased fibrosis, altered gap junction organization and connexin-43 expression, mitochondrial dysfunction, and increased ROS production. Together, these findings not only contribute to our understanding of the role of CDKL5 in heart structure/function but also document a novel preclinical phenotype for future therapeutic investigation