1,254 research outputs found
"Investigation on the role of Cl- homeostasis and GABAergic transmission in sleep disorders of Down syndrome and in Prader Willi syndrome: a possible contributor to cognitive impairment"
GABA is the main inhibitory neurotransmitter of the central nervous system (CNS). Recently,
GABAergic transmission has been reported to be depolarizing and possibly excitatory rather than
inhibitory in a number of neurodevelopmental disorders both in patients and mouse models.
In particular, the Ts65Dn mouse model of Down syndrome (DS) exhibits depolarizing GABA due to
upregulation of the Cl- importer NKCC1 both in the hippocampus and in the cortex. Moreover,
NKCC1 inhibition by the FDA-approved diuretic bumetanide is able to rescue inhibitory GABAergic
transmission, synaptic plasticity and cognitive functions in Ts65Dn mice.
Beside cognitive impairment, DS mice and people with DS show sleep disturbaces. Since sleep
pattern is regulated by GABAergc transmission, we reasoned that the alteration of GABAergic
transmission due to upregulation of NKCC1 might be underlying at least some of the sleep
disturbances in DS mice. So, we characterized sleep in Ts65Dn mice and investigated the effects of
a chronic treatment with bumetanide. We found that bumetanide ameliorates the quality of sleep
in NREM and REM sleep phases before and after sleep deprivation and decreases abnormal
wakefulness during light phase at baseline in Ts65Dn mice. Moreover, we also found abnormalities
in other parameters, which could contribute to sleep abnormalities of Ts65Dn mice: an increase of
food intake and activity (partially rescued by bumetanide) with a reduction of body temperature
during dark phase.
Because of the association of altered GABAergic signaling by dysregulation of the expression of
NKCC1 (but also of the Cl- exporter KCC2) in many neurodevelopmental disorders characterized by
cognitive or social impairment, and sleep disorders, we extended our studies to Prader Willi
syndrome (PWS). PWS is a neurodevelopmental disorder, caused by defects of genomic imprinting
and characterized by cognitive, social and sleep abnormalities. Here, we observed that the Snord116
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mutant mouse model of PWS, PWScrm+/p− show an increased expression of NKCC1, specifically in the
hippocampus in comparison to their wild-type mice. Moreover, we report that PWS mice have
altered cognition and the circadian period in free-running conditions. In particular, mutant mice
present defects of long-term memory and a reduced shortening of their circadian period together
with an increase of alpha activity in dark-dark (DD). Moreover, they also show alteration of pain
sensitivity, that could be linked to defects in the thermoregulation. Interestingly, in constrast with
PWS people, Snord116 mutant mice showed no alterations of anxiety, repetivive, obsessive and
social behaviors.
In an effort to rescue cognition and the circadian phenotype by rescuing NKCC1 inhibition, we
treated Snord116 mutant mice with bumetanide. Remarkably, bumetanide treatment resulted in a
complete rescue of the cognitive defects and circadian alteration in DD, with no effects in controls.
Our results suggest an important link between GABA transmission and the regulation of cognition
and the circadian clock in PWS. In addition, the current study extends the repertoire of disorders in
which NKCC1 inhibition attenuates behavioural deficits and proposes a new potential mechanism
for the investigation of PWS
Inherent Safe and Sustainable Process Design applied to Polyhydroxyalkanoates Bioproduction from Wastes
Nowadays, the environmental impact deriving from plastic waste represents a global challenge due to its persistence in natural ecosystems, directly associated to its difficulty in disposal. These issues heightened the urgency to find sustainable alternatives to conventional plastics. Polyhydroxyalkanoates offer a promising solution as biodegradable biopolymers, but their large-scale introduction is hindered by high production costs, primarily due to the use of food-based carbon sources such as glucose, which account for around 50% of the total expenses. This issue can be addressed through the use of alternative carbon substrates like agro-food wastes, which are able to lower the overall production costs and reduce the waste accumulation, becoming powerful resources and introducing polyhydroxyalkanoates production within the biorefinery concept.
With these regards, the present work focused on the development of an inherent safe and economically sustainable design of polyhydroxyalkanoates, basing on preliminary results obtained at a laboratory scale. Indeed, during the first step of this research, the polyhydroxyalkanoates bioproduction in Cupriavidus necator DSM 545, through the use of spent coffee grounds oil as alternative carbon substrate, was investigated. Sequential spent coffee grounds pre-treatments were initially performed demonstrating the potential of this residue, allowing, at the same time, the extraction of oil and the recovery of commercially valuable compounds like caffeine and polyphenols, addressed to several applications, including food and pharmaceuticals sectors. The obtained results, along with those achieved for the spent coffee grounds powder characterization in terms of flammability and explosivity properties, allowed to perform an early-stage inherent safety design and economic analysis of the process. Even if conventional carbon substrates like fructose represent inherently safer solutions than biomass wastes since they do not comprise additional pre-treatment steps, the latter present the potentialities to obtain both appreciable polyhydroxyalkanoates yields and high-added value subproducts, minimizing the overall biopolymer production costs. Furthermore, considering a trade-off between technical feasibility, safety, and economical sustainability at the basis of the technological transfer of a chemical process, the economic viability of the polyhydroxyalkanoates production in the case spent coffee grounds were used as carbon substrate was verified.
In summary, the topics addressed by this thesis work are organized and subdivided into the following chapters:
Chapter 1 – State of the art. This section was dedicated to a literature review about the main existing inherent safety tools and methodologies, with a focus on the index-based approaches. A second part was dedicated to review the main polyhydroxyalkanoates production processes and conditions starting from wastes as carbon substrates.
Chapter 2 – Polyhydroxyalkanoates production from spent coffee grounds: an experimental study. This section focused on an experimental feasibility study concerning the polyhydroxyalkanoates production from spent coffee grounds, properly pre-treated by sequential extraction steps.
Chapter 3 – Study of the flammability and explosiveness properties of spent coffee grounds. This section concerned the flammability and explosiveness characterization of spent coffee grounds powders, both as such and pre-treated by sequential extraction steps.
Chapter 4 – Inherent safety development applied to polyhydroxyalkanoates production from spent coffee grounds. This section was addressed to an inherent safety design of each polyhydroxyalkanoates production step: bacterium and carbon source selection, pre-treatment of the carbon source, and downstream processing.
Chapter 5 – Polyhydroxyalkanoates production from spent coffee grounds and glucose: an economic comparison. This section focused on an economic comparison between two polyhydroxyalkanoates process routes options, based on the use of spent coffee grounds or glucose as carbon feedstocks
Inventaris de béns personals, 1617-1688
[1] f., [18] p. ; 31 i 21 cmInventario de los bienes del difunto Jaume Bolla, herrero y arrendador de la carnicería de la villa de Sanaüja (La Segarra, Lleida), muerto el 15 de julio pasado, tomado por su viuda Elisabet [Castellà] Bolla, como a heredera universal del difunto, residentes en la calle Mayor de la dicha villa. Inventario "post mortem" fragmentario de los bienes de la difunta doña Maria Torres i Balaguer donde destacan en primer lugar una gran cantidad de cuadros con imágenes de santos y distintas piezas de ropa propias de su ajuar. En la parte final se hace mención a otro inventario "post mortem", en este caso de Josep Torres, quien tenía una serie de objetos que pertenecían a Antonio Hebrat, también difunto. Destaca la descripción de cierta ropa de cam
"Rebellio o defensio licita?". La rivolta di Benevento contro la Bolla “dei Vizi” del 1566
Con l’avvento di Pio V Ghislieri al soglio papale, si assiste a un inasprimento rigoristico della legislazione pontificia che punta alla rigenerazione morale e al controllo sociale, attraverso l’introduzione di nuove procedure giudiziarie per l’individuazione del crimine. A tale genere di provvedimenti è ascrivibile l’emanazione della cosiddetta Bolla “dei Vizi”, tesa a reprimere i peccati di tipo morale: i criteri ispiratori di questo documento manifestano il labile confine intercorrente tra peccato e reato nella fase di affermazione della temperie controriformistica e suscitano i timori della popolazione nei confronti di pratiche giudiziarie ritenute lesive dei diritti cittadini e strumentalmente funzionali al radicamento di un regime di controllo e repressione. La Bolla provoca a Benevento, un’area periferica dello Stato Pontificio, una violenta ribellione contro l’applicazione della temuta procedura per denunzia segreta. Il drammatico episodio registra i tentativi della comunità di resistere a interventi statali verticistici e accentratori, rivelando un complicato intreccio di strategie di “mediazione” tra la periferia e il centro, che si ispirano ad una visione contrattualistica del potere: un’ottica “pattizia” destinata ad essere pesantemente ridimensionata dalla progressiva estensione della sfera del crimine di lesa maestà, in concomitanza col sopravanzare dell’assolutismo monarchico. Diritto di resistenza comunitario e logiche di natura fazionaria appaiono sottese alle dinamiche di un tumulto che assume un valore peculiare e al tempo stesso paradigmatico nel panorama dei moti cinquecenteschi
FIGURE 10. Callinectes ornatus Ordway, 1863 in Juvenile development of Callinectes ornatus Ordway, 1863 (Crustacea: Decapoda: Portunidae), from megalopae obtained in the neuston
FIGURE 10. Callinectes ornatus Ordway, 1863. Female pleopods (Pl2 to Pl5): juvenile IX (JIX); juvenile X (JX). Scales: JIX = 0.2 mm; JX = 0.4 mm.Published as part of Júnior, Eduardo Antonio Bolla, Negreiros-Fransozo, Maria Lucia & Fransozo, Adilson, 2008, Juvenile development of Callinectes ornatus Ordway, 1863 (Crustacea: Decapoda: Portunidae), from megalopae obtained in the neuston, pp. 1-20 in Zootaxa 1788 (1) on page 15, DOI: 10.11646/zootaxa.1788.1.1, http://zenodo.org/record/512437
Cervical length after cerclage: comparison between laparoscopic and vaginal approach
PURPOSE: The aim of our study was to investigate the sonographic changes of the cervical length during pregnancy after the placement of a transvaginal cervical cerclage (TVC) or a laparoscopic abdominal cerclage (LAC) in patients with cervical insufficiency (CI).
METHODS: Between January 2008 and March 2015, a retrospective analysis of all women undergoing a prophylactic laparoscopic (LAC group) or transvaginal (TVC group) cerclage due to cervical insufficiency was conducted. Nonparametric variables were analysed with the Mann-Whitney (U) test, and categorical-type outcomes were analysed with the Fisher's exact test. A p value <0.05 was considered as significant. Data analysis was performed using Prism 5 for Mac OS X.
RESULTS: Thirty-eight patients were included. Of these, 18 and 20 underwent an LAC and a TVC, respectively. Mean gestational age at surgery in the LAC and TVC groups was 11.4 ± 1.6 and 17 ± 3 weeks, respectively (p < 0.05). The cervical length prior to surgery was similar among the two groups. After cerclage placement, the distance between the tape and the external cervical os differed significantly between the two groups (LAC: 31.5 ± 8.8 mm vs TVC: 13.5 ± 4.9 mm; p < 0.0001) (Fig. 1). During pregnancy, the cervical length in the TVC group showed a significant shortening (from 26.6 ± 7 mm before surgery to 13.2 ± 7 mm at 33 weeks; p < 0.0001), while in the LAC group, the cervical length remained unchanged.
CONCLUSIONS: In patients with CI, LAC is associated with a better preservation of the cervical length throughout pregnancy as compared to TVC
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