A dynamic link between H/ACA snoRNP components and cytoplasmic stress granules

Many cell stressors block protein translation, inducing formation of cytoplasmic aggregates. These aggregates, named stress granules (SGs), are composed by translationally stalled ribonucleoproteins and their assembly strongly contributes to cell survival. Composition and dynamics of SGs are thus important starting points for identifying critical factors of the stress response. In the present study we link components of the H/ACA snoRNP complexes, highly concentrated in the nucleoli and the Cajal bodies, to SG composition. H/ACA snoRNPs are composed by a core of four highly conserved proteins -dyskerin, Nhp2, Nop10 and Gar1- and are involved in several fundamental processes, including ribosome biogenesis, RNA pseudouridylation, stabilization of small nucleolar RNAs and telomere maintenance. By taking advantage of cells overexpressing a dyskerin splice variant undergoing a dynamic intracellular trafficking, we were able to show that H/ACA snoRNP components can participate in SG formation, this way contributing to the stress response and perhaps transducing signals from the nucleus to the cytoplasm. Collectively, our results show for the first time that H/ACA snoRNP proteins can have additional non-nuclear functions, either independently or interacting with each other, thus further strengthening the close relationship linking nucleolus to SG composition

Thyroid hormone enhances angiogenesis and the warburg effect in squamous cell carcinomas

Cancer angiogenesis is required to support energetic demand and metabolic stress, particu-larly during conditions of hypoxia. Coupled to neo-vasculogenesis, cancer cells rewire metabolic programs to sustain growth, survival and long-term maintenance. Thyroid hormone (TH) signaling regulates growth and differentiation in a variety of cell types and tissues, thus modulating hyper proliferative processes such as cancer. Herein, we report that TH coordinates a global program of metabolic reprogramming and induces angiogenesis through up-regulation of the VEGF-A gene, which results in the enhanced proliferation of tumor endothelial cells. In vivo conditional depletion of the TH activating enzyme in a mouse model of cutaneous squamous cell carcinoma (SCC) reduces the concentration of TH in the tumoral cells and results in impaired VEGF-A production and atten-uated angiogenesis. In addition, we found that TH induces the expression of the glycolytic genes and fosters lactate production, which are key traits of the Warburg effect. Taken together, our results reveal a TH–VEGF-A–HIF1α regulatory axis leading to enhanced angiogenesis and glycolytic flux, which may represent a target for SCC therapy

Selective inhibition of genomic and non-genomic effects of thyroid hormone regulates muscle cell differentiation and metabolic behavior

Thyroid hormones (THs) are key regulators of different biological processes. Their action involves genomic and non-genomic mechanisms, which together mediate the final effects of TH in target tissues. However, the proportion of the two processes and their contribution to the TH-mediated effects are still poorly understood. Skeletal muscle is a classical target tissue for TH, which regulates muscle strength and contraction, as well as energetic metabolism of myofibers. Here we address the different contribution of genomic and non-genomic action of TH in skeletal muscle cells by specifically silencing the deiodinase Dio2 or the β3-Integrin expression via CRISPR/Cas9 technology. We found that myoblast proliferation is inversely regulated by integrin signal and the D2-dependent TH activation. Similarly, inhibition of the nuclear receptor action reduced myoblast proliferation, confirming that genomic action of TH attenuates proliferative rates. Contrarily, genomic and non-genomic signals promote muscle differentiation and the regulation of the redox state. Taken together, our data reveal that integration of genomic and non-genomic signal pathways finely regulates skeletal muscle physiology. These findings not only contribute to the understanding of the mechanisms involved in TH modulation of muscle physiology but also add insight into the interplay between different mechanisms of action of TH in muscle cells

The NANOG transcription factor induces type 2 deiodinase expression and regulates the intracellular activation of thyroid hormone in keratinocyte carcinomas

Type 2 deiodinase (D2), the principal activator of thyroid hormone (TH) signaling in target tissues, is expressed in cutaneous squamous cell carcinomas (SCCs) during late tumorigenesis, and its repression attenuates the invasiveness and metastatic spread of SCC. Although D2 plays multiple roles in cancer progression, nothing is known about the mechanisms regulating D2 in cancer. To address this issue, we investigated putative upstream regulators of D2 in keratinocyte carcinomas. We found that the expression of D2 in SCC cells is positively regulated by the NANOG transcription factor, whose expression, besides being causally linked to embryonic stemness, is associated with many human cancers. We also found that NANOG binds to the D2 promoter and enhances D2 transcription. Notably, blockage of D2 activity reduced NANOG-induced cell migration as well as the expression of key genes involved in epithelial–mesenchymal transition in SCC cells. In conclusion, our study reveals a link among endogenous endocrine regulators of cancer, thyroid hormone and its activating enzyme, and the NANOG regulator of cancer biology. These findings could provide the basis for the development of TH inhibitors as context-dependent anti-tumor agents

"I have got something positive out of this situation": psychological benefits of caregiving in relatives of young people with muscular dystrophy.

This paper focuses on the psychological benefits of caregiving in key relatives of patients with muscular dystrophies (MD), a group of rare diseases characterized by progressive weakness and restriction of the patient's functional abilities. We describe whether relatives perceived caregiving to be a positive experience and test whether relatives' perceptions vary in relation to their view of the patient as a valued person, the degree of involvement in care, and the level of support provided by social network and professionals. The study sample included 502 key relatives of patients aged 4-25 years, suffering from Duchenne, Becker, or limb-girdle MD, in treatment for at least 6 months to one of the eight participating centers, living with at least one relative aged 18-80 years. Of key relatives, 88 % stated that they had gotten something positive out of the situation, 96 % considered their patients to be sensitive, and 94 % viewed their patients as talented. Positive aspects of caregiving were more recognized by key relatives who were more convinced that the patient was sensitive and who perceived that they received higher level of professional help and psychological social support. These results suggest that most key relatives consider that their caregiving experience has had a positive impact on their lives, despite the practical difficulties of caring for patients with MD. Professionals should help relatives to identify the benefits of caregiving without denying its difficulties. Clinicians themselves should develop positive attitudes towards family involvement in the care of patients with long-term diseases

ANALISIS MUTU FISIK DAN CITARASA BEBERAPA VARIETAS KOPI ARABIKA GAYO AKIBAT PENUNDAAN PROSES PULPING

Selama abad terakhir ini pemanasan global yang terjadi berdampak terhadap peningkatan suhu. Dengan meningkatnya suhu, masa panen kopi menjadi lebih singkat. Singkatnya masa panen kopi memiliki masalah dikalangan petani karena kapasitas pemanenan yang meningkat dalam kurun waktu panen yang semakin pendek. Untuk mencapai pemanenan yang tepat waktu, petani biasanya cenderung lebih memilih menunda proses pulping karena kapasitas tenaga kerja yang terbatas. Penelitian ini bertujuan untuk mempelajari berapa lama waktu penundaan proses pulping yang masih bisa ditoleransi sehingga tidak terlalu berdampak pada mutu fisik dan citarasa yang dihasilkan dari beberapa varietas kopi. Penelitian ini menggunakan Rancangan Acak Kelompok (RAK) dengan pola faktorial yang terdiri atas 2 faktor. Faktor pertama adalah varietas kopi yang digunakan (V) yaitu V1 = Tim-tim, V2 = Bourbon dan V3 = Ateng Super. Faktor kedua adalah lama penundaan proses pulping yang dilakukan (P) yaitu P0 = 0 hari, P1 = 1 hari, P2 = 2 hari, P3 = 3 hari, P4 = 4 hari dan P5 = 5 hari. Setiap perlakuan diulang sebanyak dua kali sehingga terdapat 36 satuan percobaan. Analisis yang dilakukan meliputi: persentase buah mengapung, suhu buah selama penundaan proses pulping, densitas kamba, kadar air, biji busuk, biji hitam dan biji berwarna coklat. Serta pengujian pH seduhan kopi.Kata kunci : Kopi Arabika Gayo, mutu fisik,citarasa,penundaan proses pulping

The influence of causal explanations and diagnostic labeling on medical students' views of schizophrenia

PURPOSE: Negative attitudes toward mental illness among medical professionals can influence the quality of medical care they provide. The authors examined the impact of causal explanations and diagnostic labeling on medical students' views of schizophrenia. METHOD: Medical students in their fifth and sixth years at the Second University of Naples (Italy) who attended lectures from April through June 2010 completed a self-report questionnaire regarding their beliefs about the mental disorder described (but not named) in a case vignette depicting a person who meets the International Classification of Diseases-10 criteria for schizophrenia. RESULTS: Of the 232 students invited, 194 (84%) completed the questionnaire. Students most frequently cited heredity as the cause (81%), followed by stress (69%), psychological traumas (45%), and misuse of street drugs (44%). Most students (82%) labeled the case "schizophrenia"; a minority (24%) believed that persons with the case vignette disorder could be well again. Both labeling the case as "schizophrenia" and naming heredity as the cause were independently associated with pessimism about the possibility of recovery and with the perception that "others" keep their distance from persons with this diagnosis. Heredity was more frequently cited by respondents who labeled the case schizophrenia and was significantly associated with students' perception that people with this diagnosis are unpredictable. CONCLUSIONS: These findings confirm that, in a sample of medical students, biogenetic causal explanations and diagnostic labeling have negative effects on beliefs about schizophrenia. They highlight the need to educate medical students about recovery from and stigma related to schizophrenia

Thyroid hormone regulates glutamine metabolism and anaplerotic fluxes by inducing mitochondrial glutamate aminotransferase GPT2

Thyroid hormones (THs) are key metabolic regulators coordinating short- and long-term energy needs. In skeletal muscle, THs modulate energy metabolism in pathophysiological conditions. Indeed, hypo- and hyperthyroidism are leading causes of muscle weakness and strength; however, the metabolic pathways underlying these effects are still poorly understood. Using molecular, biochemical, and isotope-tracing approaches combined with mass spectrometry and denervation experiments, we find that THs regulate glutamine metabolism and anaplerotic fluxes by up-regulating the glutamate pyruvate transaminase 2 (GPT2) gene. In humans, GPT2 autosomal recessive mutations cause a neurological syndrome characterized by intellectual disability, microcephaly, and progressive motor symptoms. Here, we demonstrate a role of the TH/GPT2 axis in skeletal muscle in which it regulates muscle weight and fiber diameter in resting and atrophic conditions and results in protection from muscle loss during atrophy. These results describe an anabolic route by which THs rewire glutamine metabolism toward the maintenance of muscle mass

The hepatoprotective effect of taurisolo, a nutraceutical enriched in resveratrol and polyphenols, involves activation of mitochondrial metabolism in mice liver

Liver diseases affect millions of people worldwide. In most of the cases, severe hepatic dysfunction and liver cancer stem from mild and common clinical signs including hepatic steatosis, insulin resistance, liver inflammation, and oxidative stress, all together referred to as Nonalcoholic Fatty Liver Disease (NAFLD). Nutraceuticals endowed with antioxidant activity have been shown to reduce NAFLD risk factors and exert hepatoprotective effects. Here, we test the protective effect exerted on liver by the antioxidant Taurisolo, a nutraceutical formulation produced by grape pomace and enriched in Resveratrol and Polyphenols. We analyze the effect of Taurisolo on liver cells by profiling the metabolome of in vitro cultured hepatic HuH7 cells and of C57BL-6J mice fed a High Fat Diet and treated with the nutraceutical. Both in vitro and in vivo, we provide evidence that Taurisolo reduces risk factor markers associated with NAFLD. Taurisolo stimulates glucose uptake and reduces hepatic cholesterol and serum triglycerides. Furthermore, we give new insights into the mechanism of action of Taurisolo. The nutraceutical increases mitochondrial activity and promotes respiration and ATP production, fostering catabolic reactions like fatty acid β-oxidation and amino acid catabolism. On the contrary, Taurisolo reduces anabolic reactions like biosynthesis of cholesterol, bile acids, and plasma membrane lipids

The hepatoprotective effect of taurisolo, a nutraceutical enriched in resveratrol and polyphenols, involves activation of mitochondrial metabolism in mice liver

Liver diseases affect millions of people worldwide. In most of the cases, severe hepatic dysfunction and liver cancer stem from mild and common clinical signs including hepatic steatosis, insulin resistance, liver inflammation, and oxidative stress, all together referred to as Nonalcoholic Fatty Liver Disease (NAFLD). Nutraceuticals endowed with antioxidant activity have been shown to reduce NAFLD risk factors and exert hepatoprotective effects. Here, we test the protective effect exerted on liver by the antioxidant Taurisolo, a nutraceutical formulation produced by grape pomace and enriched in Resveratrol and Polyphenols. We analyze the effect of Taurisolo on liver cells by profiling the metabolome of in vitro cultured hepatic HuH7 cells and of C57BL-6J mice fed a High Fat Diet and treated with the nutraceutical. Both in vitro and in vivo, we provide evidence that Taurisolo reduces risk factor markers associated with NAFLD. Taurisolo stimulates glucose uptake and reduces hepatic cholesterol and serum triglycerides. Furthermore, we give new insights into the mechanism of action of Taurisolo. The nutraceutical increases mitochondrial activity and promotes respiration and ATP production, fostering catabolic reactions like fatty acid β-oxidation and amino acid catabolism. On the contrary, Taurisolo reduces anabolic reactions like biosynthesis of cholesterol, bile acids, and plasma membrane lipids