761 research outputs found
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The replicative lifespan-extending deletion of SGF73 results in altered ribosomal gene expression in yeast.
Sgf73, a core component of SAGA, is the yeast orthologue of ataxin-7, which undergoes CAG-polyglutamine repeat expansion leading to the human neurodegenerative disease spinocerebellar ataxia type 7 (SCA7). Deletion of SGF73 dramatically extends replicative lifespan (RLS) in yeast. To further define the basis for Sgf73-mediated RLS extension, we performed ChIP-Seq, identified 388 unique genomic regions occupied by Sgf73, and noted enrichment in promoters of ribosomal protein (RP)-encoding genes. Of 388 Sgf73 binding sites, 33 correspond to 5' regions of genes implicated in RLS extension, including 20 genes encoding RPs. Furthermore, half of Sgf73-occupied, RLS-linked RP genes displayed significantly reduced expression in sgf73Δ mutants, and double null strains lacking SGF73 and a Sgf73-regulated, RLS-linked RP gene exhibited no further increase in replicative lifespan. We also found that sgf73Δ mutants display altered acetylation of Ifh1, an important regulator of RP gene transcription. These findings implicate altered ribosomal protein expression in sgf73Δ yeast RLS and highlight altered acetylation as a pathway of relevance for SCA7 neurodegeneration
Altered sleep homeostasis in rev-erbα knockout mice
Study Objectives: The nuclear receptor REV-ERBα is a potent, constitutive transcriptional repressor critical for the regulation of key circadian and metabolic genes. Recently, REV-ERBα's involvement in learning, neurogenesis, mood, and dopamine turnover was demonstrated suggesting a specific role in central nervous system functioning. We have previously shown that the brain expression of several core clock genes, including Rev-erbα, is modulated by sleep loss. We here test the consequences of a loss of REV-ERBα on the homeostatic regulation of sleep.Methods: EEG/EMG signals were recorded in Rev-erbα knockout (KO) mice and their wild type (WT) littermates during baseline, sleep deprivation, and recovery. Cortical gene expression measurements after sleep deprivation were contrasted to baseline.Results: Although baseline sleep/wake duration was remarkably similar, KO mice showed an advance of the sleep/wake distribution relative to the light-dark cycle. After sleep onset in baseline and after sleep deprivation, both EEG delta power (1–4 Hz) and sleep consolidation were reduced in KO mice indicating a slower increase of homeostatic sleep need during wakefulness. This slower increase might relate to the smaller increase in theta and gamma power observed in the waking EEG prior to sleep onset under both conditions. Indeed, the increased theta activity during wakefulness predicted delta power in subsequent NREM sleep. Lack of Rev-erbα increased Bmal1, Npas2, Clock, and Fabp7 expression, confirming the direct regulation of these genes by REV-ERBα also in the brain.Conclusions: Our results add further proof to the notion that clock genes are involved in sleep homeostasis. Because accumulating evidence directly links REV-ERBα to dopamine signaling the altered homeostatic regulation of sleep reported here are discussed in that context
Phytophthora root and collar rot of Paulownia, a new disease for Europe
Paulownia species are fast growing trees native to China, which are being grown in managed plantings in several European countries for the production of wood and biomasses. In 2018, wilting, stunting, leaf yellowing, and collapse, as a consequence of root and crown rot, were observed in around 40% of trees of a 2-year-old planting of Paulownia elongata × P. fortunei in Calabria (Southern Italy). Two species of Phytophthora were consistently recovered from roots, basal stem bark, and rhizosphere soil of symptomatic trees and were identified as Ph. nicotianae and Ph. palmivora on the basis of both morphological characteristics and phylogenetic analysis of rDNA ITS sequences. Koch’s postulates were fulfilled by reproducing the symptoms on potted paulownia saplings transplanted into infested soil or stem-inoculated by wounding. Both Phytophthora species were pathogenic and caused root rot and stem cankers. Even though P. palmivora was the only species recovered from roots of naturally infected plants, in pathogenicity tests through infested soil P. nicotianae was more virulent. This is the first report of Phytophthora root and crown rot of a Paulownia species in Europe. Strategies to prevent this emerging disease include the use of healthy nursery plants, choice of well-drained soils for new plantations, and proper irrigation management
First Report of Root and Basal Stem Rot Caused by Phytophthora cryptogea and P. inundata on Dwarf Banana in Italy
In Sicily (southern Italy) local cultivars of dwarf banana (Musa acuminata) are cultivated for edible fruit and as ornamental plants. During the summer of 2015, in an ornamental nursery of Aci San Filippo (Catania province), eastern Sicily, ten out of forty mature plants of dwarf banana grown in the field showed leaf chlorosis, wilt and sudden collapse of the entire plant associated with root and basal stem rot. Two Phytophthora species (overall 24 and 22 isolates, respectively) were consistently recovered directly from rotted roots and stems on BNPRA-HMI selective medium (Masago et al. 1977). Pure cultures of both species were obtained by single-hypha isolations. The first species formed slight petaloid colonies on potato dextrose agar (PDA) and slightly fluffy colonies on V-8 juice agar (V8A). It grew between 2 and 30°C, with an optimum of 25°C. On V8A discs flooded with non-sterile soil extract this species produced persistent, ovoid to obpyriform, non-papillate, internally proliferating sporangia (35 ..
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Autophagy gene haploinsufficiency drives chromosome instability, increases migration, and promotes early ovarian tumors.
Autophagy, particularly with BECN1, has paradoxically been highlighted as tumor promoting in Ras-driven cancers, but potentially tumor suppressing in breast and ovarian cancers. However, studying the specific role of BECN1 at the genetic level is complicated due to its genomic proximity to BRCA1 on both human (chromosome 17) and murine (chromosome 11) genomes. In human breast and ovarian cancers, the monoallelic deletion of these genes is often co-occurring. To investigate the potential tumor suppressor roles of two of the most commonly deleted autophagy genes in ovarian cancer, BECN1 and MAP1LC3B were knocked-down in atypical (BECN1+/+ and MAP1LC3B+/+) ovarian cancer cells. Ultra-performance liquid chromatography mass-spectrometry metabolomics revealed reduced levels of acetyl-CoA which corresponded with elevated levels of glycerophospholipids and sphingolipids. Migration rates of ovarian cancer cells were increased upon autophagy gene knockdown. Genomic instability was increased, resulting in copy-number alteration patterns which mimicked high grade serous ovarian cancer. We further investigated the causal role of Becn1 haploinsufficiency for oncogenesis in a MISIIR SV40 large T antigen driven spontaneous ovarian cancer mouse model. Tumors were evident earlier among the Becn1+/- mice, and this correlated with an increase in copy-number alterations per chromosome in the Becn1+/- tumors. The results support monoallelic loss of BECN1 as permissive for tumor initiation and potentiating for genomic instability in ovarian cancer
Non-invasive assessment of liver steatosis and fibrosis in HIV/HCV- and HCV- infected patients
Background. Conflicting data have been reported on the prevalence of liver steatosis, its risk factors and its relationship with fibrosis in patients with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection or with HCV mono-infection. Aim. The study aims were to assess steatosis prevalence and its risk factors in both HCV groups. We also evaluated whether steatosis was linked with advanced fibrosis. Sixty-eight HIV/HCV co-infected and 69 HCV mono-infected patients were consecutively enrolled. They underwent liver ultrasonography and transient elastography. Bright liver echo-pattern was used to diagnose steatosis; advanced fibrosis was defined as liver stiffness ≥ 9.5 kPa and FIB-4 values ≥ 3.25. The optimal stiffness cut-off according to FIB-4 ≥ 3.25 was evaluated by ROC analysis. Results. No significant difference was found in steatosis-prevalence between mono- and co-infected patients (46.3 vs. 51.4%). Steatosis was associated with triglycerides and impaired fasting glucose/diabetes in HCV mono-infected, with lipodystrophy, metabolic syndrome, total-cholesterol and triglycerides in co-infected patients. Stiffness ≥ 9.5 was significantly more frequent in co-infection (P < 0.003). Advanced fibrosis wasn't significantly associated with steatosis. The area under the ROC curve was 0.85 (95% CI 0.79-0.9). On multivariate analysis steatosis was associated with triglycerides in both HCV mono- and co-infected groups (P < 0.02; P < 0.03). Conclusion. Although steatosis was common in both HCV mono- and co-infected patients, it was not linked with advanced fibrosis. Triglycerides were independent predictors of steatosis in either of the HCV-groups. Dietary interventions and lifestyle changes should be proposed to prevent metabolic risk factors
Ferrous iron- and ammonium-rich diffuse vents support habitat-specific communities in a shallow hydrothermal field off the Basiluzzo Islet (Aeolian Volcanic Archipelago)
Ammonium- and Fe(II)-rich fluid flows, known from deep-sea hydrothermal systems, have been extensively studied in the last decades and are considered as sites with high microbial diversity and activity. Their shallow-submarine counterparts, despite their easier accessibility, have so far been under-investigated, and as a consequence, much less is known about microbial communities inhabiting these ecosystems. A field of shallow expulsion of hydrothermal fluids has been discovered at depths of 170-400 meters off the base of the Basiluzzo Islet (Aeolian Volcanic Archipelago, Southern Tyrrhenian Sea). This area consists predominantly of both actively diffusing and inactive 1-3 meters-high structures in the form of vertical pinnacles, steeples and mounds covered by a thick orange to brown crust deposits hosting rich benthic fauna. Integrated morphological, mineralogical, and geochemical analyses revealed that, above all, these crusts are formed by ferrihydrite-type Fe3+ oxyhydroxides. Two cruises in 2013 allowed us to monitor and sampled this novel ecosystem, certainly interesting in terms of shallow-water iron-rich site. The main objective of this work was to characterize the composition of extant communities of iron microbial mats in relation to the environmental setting and the observed patterns of macrofaunal colonization. We demonstrated that iron-rich deposits contain complex and stratified microbial communities with a high proportion of prokaryotes akin to ammonium- and iron-oxidizing chemoautotrophs, belonging to Thaumarchaeota, Nitrospira, and Zetaproteobacteria. Colonizers of iron-rich mounds, while composed of the common macrobenthic grazers, predators, filter-feeders, and tube-dwellers with no representatives of vent endemic fauna, differed from the surrounding populations. Thus, it is very likely that reduced electron donors (Fe2+ and NH4+) are important energy sources in supporting primary production in microbial mats, which form a habitat-specific trophic base of the whole Basiluzzo hydrothermal ecosystem, including macrobenthic fauna
CLINICAL OUTCOMES OF SELF-EXPAMDABLE METALLIC STENTS IN PALLIATION OF MALIGNANT ANASTOMOTIC STRICTURES: A SINGLE CENTER EXPERIENCE
Background: self-expandable metallic stents (SEMS) are employed as the preferred non surgical palliative treatment for gastric outlet obstruction due to malignancies. Metallic stents are often employed to treat malignant anastomotic obstructions after surgicsl interventions as esophagojejunostomy, gastrojejunostomy and esophagogastrojejunostomy. Methods: this case series reports prospectively the clinical outcomes of SEMS in the palliative care of malignant anastomotic strictures caused by the recurrence gastric cancer follwing gastric surgery as oncological curative treatment, in a series of nine consecutive patients, treated between January 2009 and december 2012 in our center. Results: Nine patients (M:F=8:1) were enrolled in the study. The operation was a total gastrectomy with esophagogastrojejunostomy (n=4), subtotal gastrectomy with Bilroth-II reconstruction (n=4), subtotal gastrectomy with Billroth-II reconstruction (n=3), and subtotal gastrectomy with esophagogastrostomy (n=2). The technical success rate was 88,9%, and the clinical success rate was 88.9%. The reostruction of the stent, due to the ingrowth of the tumor, occurred in 1 patient (11,1%) within 1 month after stent placement. the migration of the stent occurred after the placement of a covered stent in 1 patient who underwent a subtotal gastrectomy (with Billroth-II reconstruction). A case o partial stent dislodgement was treated with the placement of a second stent. The median survival period was 180 days (range, 30-240 days) and the median stent patency was 45 days 8range, 30-90 days). Conclusions: Although the number of the patients treated with SEMS results, in this series, almost small to certainly judge the safety and feasibility of SEMS, we believe that the endoscopic insertion of SEMS seems to be a safe, easily feasible, and effective treatment in the palliative care of malignant anastomotic strictures caused by the recurrence of gastric cancer following gastric surgery. The technical and clinical success, and the onset of complications of this procedure are influenced by several factors, such as the type of anastomosis, the technical features of the stent, and the extent of the underlying tumor
Surface Wave Cloak from Graded Refractive Index Nanocomposites
Recently, a great deal of interest has been re-emerged on the possibility to manipulate surface waves, in particular, towards the THz and optical regime. Both concepts of Transformation Optics (TO) and metamaterials have been regarded as one of key enablers for such applications in applied electromagnetics. In this paper, we experimentally demonstrate for the first time a dielectric surface wave cloak from engineered gradient index materials to illustrate the possibility of using nanocomposites to control surface wave propagation through advanced additive manufacturing. The device is designed analytically and validated through numerical simulations and measurements, showing good agreement and performance as an effective surface wave cloak. The underlying design approach has much wider applications, which span from microwave to optics for the control of surface plasmon polaritons (SPPs) and radiation of nanoantennas
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