Telomere Length as a Quantitative Trait: Genome-Wide Survey and Genetic Mapping of Telomere Length-Control Genes in Yeast

Telomere length-variation in deletion strains of Saccharomyces cerevisiae was used to identify genes and pathways that regulate telomere length. We found 72 genes that when deleted confer short telomeres, and 80 genes that confer long telomeres relative to those of wild-type yeast. Among identified genes, 88 have not been previously implicated in telomere length control. Genes that regulate telomere length span a variety of functions that can be broadly separated into telomerase-dependent and telomerase-independent pathways. We also found 39 genes that have an important role in telomere maintenance or cell proliferation in the absence of telomerase, including genes that participate in deoxyribonucleotide biosynthesis, sister chromatid cohesion, and vacuolar protein sorting. Given the large number of loci identified, we investigated telomere lengths in 13 wild yeast strains and found substantial natural variation in telomere length among the isolates. Furthermore, we crossed a wild isolate to a laboratory strain and analyzed telomere length in 122 progeny. Genome-wide linkage analysis among these segregants revealed two loci that account for 30%–35% of telomere length-variation between the strains. These findings support a general model of telomere length-variation in outbred populations that results from polymorphisms at a large number of loci. Furthermore, our results laid the foundation for studying genetic determinants of telomere length-variation and their roles in human disease

A public early intervention approach to first-episode psychosis: treated incidence over 7 years in the Emilia-Romagna region.

Aim: To estimate the treated incidence of individuals with first-episode psychosis (FEP) who contacted the Emilia-Romagna public mental healthcare system (Italy); to examine the variability of incidence and user characteristics across centres and years. Methods: We computed the raw treated incidence in 2013–2019, based on FEP users aged 18–35, seen within or outside the regional program for FEP. We modelled FEP incidence across 10 catchment areas and 7 years using Bayesian Poisson and Negative Binomial Generalized Linear Models of varying complexity. We explored associations between user characteristics, study centre and year comparing variables and socioclinical clusters of subjects. Results: Thousand three hundred and eighteen individuals were treated for FEP (raw incidence: 25.3 / 100.000 inhabitant year, IQR: 15.3). A Negative Binomial location-scale model with area, population density and year as predictors found that incidence and its variability changed across centres (Bologna: 36.55; 95% CrI: 30.39–43.86; Imola: 3.07; 95% CrI: 1.61–4.99) but did not follow linear temporal trends or density. Centers were associated with different user age, gender, migrant status, occupation, living conditions and cluster distribution. Year was associated negatively with HoNOS score (R = 0.09, p < .001), duration of untreated psychosis (R = 0.12, p < .001) and referral type. Conclusions: The Emilia-Romagna region presents a relatively high but variable incidence of FEP across areas, but not in time. More granular information on social, ethnic and cultural factors may increase the level of explanation and prediction of FEP incidence and characteristics, shedding light on social and healthcare factors influencing FEP

Chitotriosidase expression in monocyte-derived dendritic cells

Chitotriosidase (CHIT1) belongs to 18 glycosyl-hydrolase family, an ancient gene family that is widely expressed from prokaryotes to eukaryotes [1]. CHIT1 is a very critical enzyme to regulate the susceptibility to infection of organisms containing chitin as structural components. Conversely, during the development of acute/chronic inflammatory disorders, the enzymatic activity of CHIT1 increases significantly. The CHIT1 is expressed in activated macrophages as well in different lines monocyte-derived such as Kupffer cells and osteoclasts [2]. So far, it is unknown whether CHIT1 is expressed in other cells involved in the immune response such as monocyte-derived DCs. In this study we have investigated whether CHIT1 is produced in monocyte-derived DCs (moDCs) and the differential expression of CHIT1 during the different stage of moDCs differentiation. The presence of CHIT1 were examined by real time RT-PCR, Western Blot and Confocal Immunofluorescence, in Immature Dendritic cells (iDCs), generated from human monocytes by stimulation with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) and in mature Dendritic cells (mDCs), obtained by using lipopolysaccharide (LPS) and interferon-gamma (IFN-g). We observed that CHIT1 was expressed during the DCs differentiation and maturation process in time dependent manner. The maturation of DCs showed a significantly increased expression of CHIT1 mRNA and protein. Furthermore, the CHIT1 was evenly distributed in cytoplasm both in iDCs and in mDCs. The enzymatic activity confirmed that CHIT1 could play a role in moDCs function. Taken together, our data confirm the crucial role of CHIT1 in primary immune responses and indicate that could be correlated with the immunogenicity of DCs

Expression and localization of CHI3L1 in monocyte derived dendritic cells

Chitinase-3-like-1 protein (CHI3L1) also called YKL-40, is a 40 kDa mammalian glycoprotein which is a heparin, chitin and collagen binding member of the mammalian chitinase-like proteins. Biological activities of CHI3L1 embrace regulation of cell proliferation, adhesion, angiogenesis, migration and activation. CHI3L1 is produced by variety of cells, including neutrophils, monocytes/macrophages, osteoclasts and Kupffer cells [1]. CHI3L1 secretion is induced by interferon (INF)-g and interleukin (IL)-6 and is an acute phase reactant associated with disease severity and mortality in a variety of infectious [2]. In this study, we have examined the expression and localization of CHI3L1 during the differentiation and maturation of monocyte derived dendritic cells by real time RT-PCR, Western Blot, Confocal Immunofluorescence, and Immunocytochemical assays. Potential nuclear localization signal (NLS) was determinated using the open source software cNLS Mapper and Chimera. Peripheral blood monocytes were differentiated toward immature DCs (iDC) and mature DCs (mDCs) through a combination of factors and cytokines. Our result showed, for the first time, that CHI3L1 is expressed during the process of differentiation and maturation of DCs in time dependent manner. Furthermore, CHI3L1 is evenly distributed in cytoplasm and in the nucleus of both the iDCs and mDCs. In conclusion, the discovery of CHI3L1 expression in DCs has opened new dilemma for designing DC-based cancer immunotherapeutic. In fact, on the light of these results one can’t exclude that as well as activated Tumor-associated macrophages (TAMs) also DCs infiltration could to be a significant unfavorable prognostic factor for cancer patients

Guidelines for the use and interpretation of diagnostic methods in adult food allergy

Food allergy has an increasing prevalence in the general population and in Italy concerns 8 % of people with allergies. The spectrum of its clinical manifestations ranges from mild symptoms up to potentially fatal anaphylactic shock. A number of patients can be diagnosed easily by the use of first- and second-level procedures (history, skin tests and allergen specific IgE). Patients with complex presentation, such as multiple sensitizations and pollen-food syndromes, frequently require a third-level approach including molecular diagnostics, which enables the design of a component-resolved sensitization profile for each patient. The use of such techniques involves specialists' and experts' skills on the issue to appropriately meet the diagnostic and therapeutic needs of patients. Particularly, educational programs for allergists on the use and interpretation of molecular diagnostics are needed

NEMO-SN1 Abyssal Cabled Observatory in the Western Ionian Sea

The NEutrinoMediterranean Observatory—Submarine Network 1 (NEMO-SN1) seafloor observatory is located in the central Mediterranean Sea, Western Ionian Sea, off Eastern Sicily (Southern Italy) at 2100-m water depth, 25 km from the harbor of the city of Catania. It is a prototype of a cabled deep-sea multiparameter observatory and the first one operating with real-time data transmission in Europe since 2005. NEMO-SN1 is also the first-established node of the European Multidisciplinary Seafloor Observatory (EMSO), one of the incoming European large-scale research infrastructures included in the Roadmap of the European Strategy Forum on Research Infrastructures (ESFRI) since 2006. EMSO will specifically address long-term monitoring of environmental processes related to marine ecosystems, marine mammals, climate change, and geohazards

Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder

Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed

Urban Gardening as Disruptive Design Practice

Over the past decade, there has been a steady emergence of community engagement in urban food production. This paper considers how design activism is expressed through urban gardening and how citizens seek to transform and challenge the quality of urban space through two examples. By situating urban gardening within design, the paper proposes new platforms of engagement for designers, while considering a more inclusive model of what constitutes design practice

Fibromyalgia Syndrome: A Case Report on Controlled Remission of Symptoms by a Dietary Strategy

A 34-year-old woman suffered from significant chronic pain, depression, non-restorative sleep, chronic fatigue, severe morning stiffness, leg cramps, irritable bowel syndrome, hypersensitivity to cold, concentration difficulties, and forgetfulness. Blood tests were negative for rheumatic disorders. The patient was diagnosed with Fibromyalgia syndrome (FMS). Due to the lack of effectiveness of pharmacological therapies in FMS, she approached a novel metabolic proposal for the symptomatic remission. Its core idea is supporting serotonin synthesis by allowing a proper absorption of tryptophan assumed with food, while avoiding, or at least minimizing the presence of interfering non-absorbed molecules, such as fructose and sorbitol. Such a strategy resulted in a rapid improvement of symptoms after only few days on diet, up to the remission of most symptoms in 2 months. Depression, widespread chronic pain, chronic fatigue, non-restorative sleep, morning stiffness, and the majority of the comorbidities remitted. Energy and vitality were recovered by the patient as prior to the onset of the disease, reverting the occupational and social disabilities. The patient episodically challenged herself breaking the dietary protocol leading to its negative test and to the evaluation of its benefit. These breaks correlated with the recurrence of the symptoms, supporting the correctness of the biochemical hypothesis underlying the diet design toward remission of symptoms, but not as a final cure. We propose this as a low risk and accessible therapeutic protocol for the symptomatic remission in FMS with virtually no costs other than those related to vitamin and mineral salt supplements in case of deficiencies. A pilot study is required to further ground this metabolic approach, and to finally evaluate its inclusion in the guidelines for clinical management of FMS