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Rasd2 is a striatal GTP-binding protein that modulates Akt and mTOR signaling cascades, well known to be highly vulnerable pathways in psychiatric disorders.
We investigated the association of Rasd2 and its genetic variation with a series of prefronto-striatal phenotypes related to psychosis in rodents and humans.
We want to provide evidence that Rasd2 controls the vulnerability to schizophrenia-related behavior induced by psychothomimetic drugs in mice. Moreover, we aim to find genetic variations within the Rasd2 gene that influence a series of brain schizophrenia-related phenotypes in human.
Rasd2 knockout mice were employed to evaluate schizophrenia-like behaviors induced by psychotomimetic drugs like amphetamine and phencyclidine. Furthermore, we investigated if RASD2genetic variations in humans are associated with mRNA expression in post-mortem prefrontal cortex, as well as prefrontal and striatal grey matter volume and physiology during working memory as measured with MRI in healthy subjects. Finally, we assessed RASD2mRNA expression levels in post-mortem brains of patients with schizophrenia and bipolar disorder.
We found that both psychotomimetics triggered greater vulnerability to motor stimulation and to prepulse inhibition deficits in Rasd2 mutants. In humans, we found that a genetic variation (rs6518956) within RASD2 predicts prefrontal mRNA expression as well as prefrontal grey matter volume and prefronto-striatal activity during working memory. Finally, we reported that RASD2 mRNA expression is slightly reduced in post-mortem prefrontal cortex of patients with schizophrenia.
Collectively, our data suggests that RASD2represents a gene of potential interest in psychiatric disorders for its ability to modulate prefronto-striatal phenotypes related to schizophrenia.
According to some studies, 80% of subjects suffering from post-traumatic stress disorder (PTSD) present twice the risk of developing an insanity as they age because of the high level of stress that has been induced. Indeed, the triggered trauma has a deleterious effect on the establishment of the stress’ axis (the hypothalamic pituitary adrenal axis) which is then not able to regulate itself. As a consequence, the hippocampal neurons will be attacked by an excess of cortisol. Memory's dysfunction is central in the symptomatology of PTSD, particularly in respect to encoding and recall. The hippocampus is able to transfer information to the prefrontal cortex. Actually, subjects with PTSD present less activity in the prefrontal cortex triggered by a decrease of encoding and recall capacities. EMDR therapy (eye movement desensitization and recruitment) allow for a fast relief of symptoms by a bilateral alternate stimulation (SBA). Indeed, saccadic eye movements stem affect related to the traumatic event and process the associated cognitions. During the desensitization phase in EMDR, we noticed an increase in activity of the brain's prefrontal, ventromedial, amygdala and thalamic regions. Indeed, the recall of traumatic memories goes through implicit emotional valence regions and associative areas for which the experience is already deeply integrated. After comparing cerebral activity before and after the therapy, researches on EMDR shows that a reduction of stress’ symptoms has some sensitive link to PTSD (in prevention to dementia).
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
The distribution of funerary stone structures in the Saharan landscape has been a subject of interest for the Italian-Libyan Archaeological Mission in the Tadrart Akakus and Massak since the early ’90s This archaeological evidence gave witness to an enduring human settlement, lasting at least from the Pastoral period to Proto-historical times, and played an important role in the definition of the cultural identities of the local groups, while representing a source of information about population features and dynamics. In the twentieth century, only a few excavations were carried out in cemeteries located in Fazzan. In 1997, as part of an interdisciplinary project focused on Holocene environment and human settlement until the rise of the Garamantian civilisation, our mission started a systematic survey and excavation of funerary structures in the Wadi Tanzzuft. The 2004–06 investigation of Fewet necropolis needs to be viewed in this framework.
Measurements in the infrared wavelength domain allow direct assessment of the physical state and energy balance of cool matter in space, enabling the detailed study of the processes that govern the formation and evolution of stars and planetary systems in galaxies over cosmic time. Previous infrared missions revealed a great deal about the obscured Universe, but were hampered by limited sensitivity.
SPICA takes the next step in infrared observational capability by combining a large 2.5-meter diameter telescope, cooled to below 8 K, with instruments employing ultra-sensitive detectors. A combination of passive cooling and mechanical coolers will be used to cool both the telescope and the instruments. With mechanical coolers the mission lifetime is not limited by the supply of cryogen. With the combination of low telescope background and instruments with state-of-the-art detectors SPICA provides a huge advance on the capabilities of previous missions.
SPICA instruments offer spectral resolving power ranging from R ~50 through 11 000 in the 17–230 μm domain and R ~28.000 spectroscopy between 12 and 18 μm. SPICA will provide efficient 30–37 μm broad band mapping, and small field spectroscopic and polarimetric imaging at 100, 200 and 350 μm. SPICA will provide infrared spectroscopy with an unprecedented sensitivity of ~5 × 10−20 W m−2 (5σ/1 h)—over two orders of magnitude improvement over what earlier missions. This exceptional performance leap, will open entirely new domains in infrared astronomy; galaxy evolution and metal production over cosmic time, dust formation and evolution from very early epochs onwards, the formation history of planetary systems.
7-Hydroxymatairesinol (7-HMR) is a plant lignan abundant in various concentrations in plant foods. The objective of this study was to test HMRLignan™, a purified form of 7-HMR, and the corresponding Picea abies extract (total extract P. abies; TEP) as dietary supplements on a background of a high-fat diet (HFD)-induced metabolic syndrome in mice and in the 3T3-L1 adipogenesis model. Mice, 3 weeks old, were fed a HFD for 60 d. Subgroups were treated with 3 mg/kg body weight 7-HMR (HMRLignan™) or 10 mg/kg body weight TEP by oral administration. 7-HMR and TEP limited the increase in body weight (−11 and −13 %) and fat mass (−11 and −18 %) in the HFD-fed mice. Epididymal adipocytes were 19 and −12 % smaller and the liver was less steatotic (−62 and −65 %). Serum lipids decreased in TEP-treated mice (−11 % cholesterol, −23 % LDL and −15 % TAG) and sugar metabolism was ameliorated by both lignan preparations, as shown by a more than 70 % decrease in insulin secretion and insulin resistance. The expression of several metabolic genes was modulated by the HFD with an effect that was reversed by lignan. In 3T3-L1 cells, the 7-HMR metabolites enterolactone (ENL) and enterodiol (END) showed a 40 % inhibition of cell differentiation accompanied by the inhibited expression of the adipogenic genes PPARγ, C/EBPα and aP2. Furthermore, END and ENL caused a 10 % reduction in TAG uptake in HEPA 1–6 hepatoma cells. In conclusion, 7-HMR and TEP reduce metabolic imbalances typical of the metabolic syndrome and obesity in male mice, whereas their metabolites inhibit adipogenesis and lipid uptake in vitro.
Larval trematodes are the main parasites of snails, and they play a crucial role because they usually castrate their snail hosts and can thus alter their population and community dynamics. This study involved a survey of seven gastropod species (Crepipatella dilatata, Fissurella radiosa, Nacella magellanica, Pareuthria fuscata, Siphonaria lessonii, S. lateralis and Trophon geversianus) parasitized by 12 trematode species (one hemiurid, one gymnophallid, two lepocreadiids, two microphallids, one notocotylid, two renicolids, one philophtalmid, one schistosomatid and one zoogonid) from southern Patagonia (47°S, 65°W), Argentina. Only F. radiosa was free of parasites. The study included the description of five new larvae, based on morphological and molecular information, and a comparison of the parasite diversity with that of a northern locality (42°S, 64°W), characterized by a lower mollusc diversity. Species richness and diversity of parasites were higher in the southern site. This suggests a correlation between the level of parasitism and the diversity of molluscs (first intermediate hosts), which is higher at the high-latitude site and seems to attract shorebirds, which disperse the digenean eggs and facilitate the completion of their life cycles. These results support the notion that parasitism is influenced by large-scale factors such as biogeographical patterns, and small-scale factors such as diversity or abundance of intermediate and definitive hosts.
The generalized theory of terawatt laser pulse interaction with a low-dense porous substance of light chemical elements including laser light absorption and energy transfer in a wide region of parameter variation is developed on the base of the model of laser-supported hydrothermal wave in a partially homogenized plasma. Laser light absorption, hydrodynamic motion, and electron thermal conductivity are implemented in the hydrodynamic code, according to the degree of laser-driven homogenization of the laser-produced plasma. The results of numerical simulations obtained by using the hydrodynamic code are presented. The features of laser-supported hydrothermal wave in both possible cases of a porous substance with a density smaller and larger than critical plasma density are discussed along with the comparison with the experiments. The results are addressed to the development of design of laser thermonuclear target as well as and powerful neutron and X-ray sources.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
Larval stages of the trematodes Maritrema madrynense and Hemiuroidea fam. gen. et sp. differentially parasitized Siphonaria lessonii and S. lateralis, two sympatric pulmonate snail species on the rocky intertidal shore at Puerto Deseado, south-western Atlantic coast of Patagonia, Argentina. Snail specimens were collected at two sampling sites with contrasting physical–chemical characteristics. One site, in the upper intertidal, was exposed to sewage from fish-processing plants, greater hydrodynamic forcing and desiccation, a wider temperature range, longer exposure to ultraviolet radiation and higher abundance of birds. The second site, in the lower intertidal, was generally characterized by less stressful environmental conditions. At both sites, S. lateralis showed a markedly higher density than S. lessonii (55.13 vs. 5.87 snails/m2, respectively). Despite this, the prevalence of both digeneans was higher in S. lessonii (17.37% and 3.52% for M. madrynense and Hemiuroidea, respectively) than in S. lateralis (0.09% and 0% for M. madrynense and Hemiuroidea, respectively). This study demonstrates high parasite specificity for the host. Low densities of S. lessonii are attributed to castration of parasitized hosts and reduction of their physiological condition. The prevalence and intensity of infection of both digenean parasites were higher at the more stressful, upper intertidal site, thus suggesting that a higher abundance of birds and exposure to sewage pollution may promote the transmission of trematodes.
A 25 m-thick outcrop section exposed at Torre Mucchia, on the sea-cliff north of Ortona, eastern central Italy, comprises a rare Middle Pleistocene succession of shallow-water and paralic sediments along the western Adriatic Sea. An integrated study of the section, including facies and microfacies analyses, and characterization of paleobiological associations (mollusks, fishes, ostracods, foraminifers and pollen), enable a detailed reconstruction of the paleoenvironmental and paleoclimatic conditions during deposition. The shallow-water deposits include a transgressive, deepening- and fining-upward shoreface to offshore-transition facies succession overlain by a regressive shoreface-foreshore sandstone body with an erosive base and a rooted and pedogenically altered horizon at the top that imply deposition during sea-level fall. This forced regressive unit is overlain by paralic strata forming a transgressive succession comprising palustrine carbonates and back-barrier lagoonal mudstones. The palustrine carbonates exhibit some of the typical features encountered in palustrine limestones deposited within seasonal freshwater wetlands (marl prairies). Following the sea-level rising trend, the freshwater marshes were abruptly replaced by a barrier-lagoon system that allowed deposition of the overlying mud-rich unit. Within these deposits, the faunal assemblages are consistent with a low-energy brackish environment characterized by a relatively high degree of confinement. The pollen record documents the development of open forest vegetation dominated by Pinus and accompanied by a number of mesophilous and thermophilous tree taxa, whose composition supports a tentative correlation with Marine Oxygen Isotope Stage 17. The new pollen record from Torre Mucchia improves our understanding of the vegetation development in the Italian Peninsula during the Middle Pleistocene and sheds new light on the role played by the most marked glacial periods in determining the history of tree taxa.
In the current data-driven science era, it is needed that data analysis techniques has to quickly evolve to face with data whose dimensions has increased up to the Petabyte scale. In particular, being modern astrophysics based on multi-wavelength data organized into large catalogues, it is crucial that the astronomical catalog cross-matching methods, strongly dependant from the catalogues size, must ensure efficiency, reliability and scalability. Furthermore, multi-band data are archived and reduced in different ways, so that the resulting catalogues may differ each other in formats, resolution, data structure, etc, thus requiring the highest generality of cross-matching features. We present C3 (Command-line Catalogue Cross-match), a multi-platform application designed to efficiently cross-match massive catalogues from modern surveys. Conceived as a stand-alone command-line process or a module within generic data reduction/analysis pipeline, it provides the maximum flexibility, in terms of portability, configuration, coordinates and cross-matching types, ensuring high performance capabilities by using a multi-core parallel processing paradigm and a sky partitioning algorithm.
This work presents the experimental validation and updating of a flexible multibody model ideated for taking into account installation conditions of industrial serial planar manipulators without resorting to cumbersome modeling. The flexibility of the frame, the manipulator is fixed, is modeled over the flexibility of joints, which is introduced as lumped stiffness. In particular, the flexible frame is included in the model by using the Component Mode Synthesis methodology, in which only the natural modes of vibration and the static constrain modes are accounted. The flexible multibody model has been developed because these commercial machines are mainly used to perform low-speed tasks, and they are designed by taking into account their flexibility at most in the joints. Unfortunately, there are particular installation conditions in which even low-speed tasks can generate low-frequency vibrations that highly interfere with the task. This aspect is considered here, and how to manage this problem is explained by using the developed multibody model. The model is validated through experimental measurements. The experimental tests consist of several modal analyses, together with acceleration and laser Doppler measurements in operational conditions. This methodology takes into account the installation conditions through the model of flexible frame, and gives a tool for studying ad hoc solutions which prevent the occurrence of unwanted low-frequency vibrations.
Abnormalities in hippocampal–parahippocampal (H-PH) function are prominent features of schizophrenia and have been associated with deficits in episodic memory. However, it remains unclear whether these abnormalities represent a phenotype related to genetic risk for schizophrenia or whether they are related to disease state.
We investigated H-PH-mediated behavior and physiology, using blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI), during episodic memory in a sample of patients with schizophrenia, clinically unaffected siblings and healthy subjects.
Patients with schizophrenia and unaffected siblings displayed abnormalities in episodic memory performance. During an fMRI memory encoding task, both patients and siblings demonstrated a similar pattern of reduced H-PH engagement compared with healthy subjects.
Our findings suggest that the pathophysiological mechanism underlying the inability of patients with schizophrenia to properly engage the H-PH during episodic memory is related to genetic risk for the disorder. Therefore, H-PH dysfunction can be assumed as a schizophrenia susceptibility-related phenotype.
Two different topologies of radio frequency micro-electro-mechanical system (RF MEMS) series ohmic switches (cantilever and clamped–clamped beams) in coplanar waveguide (CPW) configuration have been characterized by means of DC, environmental, and RF measurements. In particular, on-wafer checks have been followed by RF test after vibration, thermal shocks, and temperature cycles. The devices have been manufactured on high resistivity silicon substrates, as building blocks to be implemented in different single-pole 4-throw (SP4 T), double-pole double-throw (DPDT) configurations, and then integrated in Low Temperature Co-fired Ceramics (LTCC) technology for the realization of large-order Clos 3D networks.
Emotion dysregulation is a key feature of schizophrenia, a brain disorder strongly associated with genetic risk and aberrant dopamine signalling. Dopamine is inactivated by catechol-O-methyltransferase (COMT), whose gene contains a functional polymorphism (COMT Val158Met) associated with differential activity of the enzyme and with brain physiology of emotion processing. The aim of the present study was to investigate whether genetic risk for schizophrenia and COMT Val158Met genotype interact on brain activity during implicit and explicit emotion processing.
A total of 25 patients with schizophrenia, 23 healthy siblings of patients and 24 comparison subjects genotyped for COMT Val158Met underwent functional magnetic resonance imaging during implicit and explicit processing of facial stimuli with negative emotional valence.
We found a main effect of diagnosis in the right amygdala, with decreased activity in patients and siblings compared with control subjects. Furthermore, a genotype × diagnosis interaction was found in the left middle frontal gyrus, such that the effect of genetic risk for schizophrenia was evident in the context of the Val/Val genotype only, i.e. the phenotype of reduced activity was present especially in Val/Val patients and siblings. Finally, a complete inversion of the COMT effect between patients and healthy subjects was found in the left striatum during explicit processing.
Overall, these results suggest complex interactions between genetically determined dopamine signalling and risk for schizophrenia on brain activity in the prefrontal cortex during emotion processing. On the other hand, the effects in the striatum may represent state-related epiphenomena of the disorder itself.
A growing number of studies focusing on the developmental origin of health and disease hypothesis have identified links among early nutrition, epigenetic processes and diseases also in later life. Different epigenetic mechanisms are elicited by dietary factors in early critical developmental ages that are able to affect the susceptibility to several diseases in adulthood. The studies here reviewed suggest that maternal and neonatal diet may have long-lasting effects in the development of non-communicable chronic adulthood diseases, in particular the components of the so-called metabolic syndrome, such as insulin resistance, type 2 diabetes, obesity, dyslipidaemia, hypertension, and CVD. Both maternal under- and over-nutrition may regulate the expression of genes involved in lipid and carbohydrate metabolism. Early postnatal nutrition may also represent a vital determinant of adult health by making an impact on the development and function of gut microbiota. An inadequate gut microbiota composition and function in early life seems to account for the deviant programming of later immunity and overall health status. In this regard probiotics, which have the potential to restore the intestinal microbiota balance, may be effective in preventing the development of chronic immune-mediated diseases. More recently, the epigenetic mechanisms elicited by probiotics through the production of SCFA are hypothesised to be the key to understand how they mediate their numerous health-promoting effects from the gut to the peripheral tissues.
In this work a de-embedding technique oriented to the evaluation of the load line at the intrinsic resistive core of microwave FET devices is presented. The approach combines vector high-frequency nonlinear load-pull measurements with an accurate description of the reactive nonlinearities, thus allowing one to determine the actual load line of the drain–source current generator under realistic conditions. Thanks to the proposed approach, the dispersive behavior of the resistive core and the compatibility of the voltage and current waveforms with reliability requirements can be directly monitored. Different experiments carried out on a gallium nitride HEMT sample are reported.
Catechol-O-methyltransferase (COMT) Val158Met has been associated with activity of the mesial temporal lobe during episodic memory and it may weakly increase risk for schizophrenia. However, how this variant affects parahippocampal and hippocampal physiology when dopamine transmission is perturbed is unclear. The aim of the present study was to compare the effects of the COMT Val158Met genotype on parahippocampal and hippocampal physiology during encoding of recognition memory in patients with schizophrenia and in healthy subjects.
Using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), we studied 28 patients with schizophrenia and 33 healthy subjects matched for a series of sociodemographic and genetic variables while they performed a recognition memory task.
We found that healthy subjects had greater parahippocampal and hippocampal activity during memory encoding compared to patients with schizophrenia. We also found different activity of the parahippocampal region between healthy subjects and patients with schizophrenia as a function of the COMT genotype, in that the predicted COMT Met allele dose effect had an opposite direction in controls and patients.
Our results demonstrate a COMT Val158Met genotype by diagnosis interaction in parahippocampal activity during memory encoding and may suggest that modulation of dopamine signaling interacts with other disease-related processes in determining the phenotype of parahippocampal physiology in schizophrenia.