Loss of leptin-induced modulation of hippocampal synaptic trasmission and signal transduction in high-fat diet-fed mice

Hippocampal plasticity is triggered by a variety of stimuli including sensory inputs, neurotrophins and inflammation. Leptin, whose primary function is to regulate food intake and energy expenditure, has been recently shown to affect hippocampal neurogenesis and plasticity. Interestingly, mice fed a high-fat diet (HFD) exhibit impaired hippocampal function, but the underlying mechanisms are poorly understood. To address this issue, we compared leptin responsiveness of hippocampal neurons in control and HFD-fed mice by combining single-cell electrophysiology and biochemical assays. We found that leptin modulated spontaneous and evoked synaptic transmission in control, but not HFD, mice. This functional impairment was paralleled by blunted activation of STAT-3, one of the key signal transduction pathways controlled by the fully functional isoform of the leptin receptor, ObRb. In addition, SOCS-3 expression was non-responsive to leptin, indicating that modulation of negative feedback impinging on ObRb was also altered. Our results advance the understanding of leptin action on hippocampal plasticity and, more importantly, suggest that leptin resistance is a key determinant of hippocampal dysfunction associated with hypercaloric diet

PhosTryp: a phosphorylation site predictor specific for parasitic protozoa of the family trypanosomatidae

<p>Abstract</p> <p>Background</p> <p>Protein phosphorylation modulates protein function in organisms at all levels of complexity. Parasites of the <it>Leishmania </it>genus undergo various developmental transitions in their life cycle triggered by changes in the environment. The molecular mechanisms that these organisms use to process and integrate these external cues are largely unknown. However <it>Leishmania </it>lacks transcription factors, therefore most regulatory processes may occur at a post-translational level and phosphorylation has recently been demonstrated to be an important player in this process. Experimental identification of phosphorylation sites is a time-consuming task. Moreover some sites could be missed due to the highly dynamic nature of this process or to difficulties in phospho-peptide enrichment.</p> <p>Results</p> <p>Here we present PhosTryp, a phosphorylation site predictor specific for trypansomatids. This method uses an SVM-based approach and has been trained with recent <it>Leishmania </it>phosphosproteomics data. PhosTryp achieved a 17% improvement in prediction performance compared with Netphos, a non organism-specific predictor. The analysis of the peptides correctly predicted by our method but missed by Netphos demonstrates that PhosTryp captures <it>Leishmania</it>-specific phosphorylation features. More specifically our results show that <it>Leishmania </it>kinases have sequence specificities which are different from their counterparts in higher eukaryotes. Consequently we were able to propose two possible <it>Leishmania</it>-specific phosphorylation motifs.</p> <p>We further demonstrate that this improvement in performance extends to the related trypanosomatids <it>Trypanosoma brucei </it>and <it>Trypanosoma cruzi</it>. Finally, in order to maximize the usefulness of PhosTryp, we trained a predictor combining all the peptides from <it>L. infantum, T. brucei and T. cruzi</it>.</p> <p>Conclusions</p> <p>Our work demonstrates that training on organism-specific data results in an improvement that extends to related species. PhosTryp is freely available at <url>http://phostryp.bio.uniroma2.it</url></p

Prospective validation of the CLIP score: a new prognostic system for patient with cirrhosis and hepatocellular carcinoma

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage, As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with RCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection

Betting on ESGs Impacts Long-Term Market Value. The Case of European Energy Firms During COVID-19 and Ukraine Armed Conflicts

The present study evaluates how environmental, social and governance (ESG) as well as corporate social responsibility (CSR) contribute to firms’ resiliency and ability to overcome crises. Taking as a standing point the triple bottom line theory, the analysis is focused on Germany and Spain, two of the most affected nations considering COVID-19 pandemic and Ukraine armed conflicts. In this context, the companies studied operate in the energy industry, being an essential economic activity and one of the hardest hit by both crises. Following a quantitative -shareprice evolution- and qualitative -ESG adoption by companiesanalysis, main findings show that sustainable business models and an adequate ESG Management, help companies to be more resilient in a scenario of crisis. Findings contribute to re-evaluate the post-modernWorld economy together with filling some research gaps. Future recommended researchwould include analyzing other combinations of crisis-country-sector analysis.Sin financiaciónSPI 2022UE

Facing a global crisis - how sustainable business models helped firms overcome COVID

Purpose The purpose of this study is to analyse how implementation of corporate social responsibility (CSR) policies following United Nations’ Global Compact (UNGC) guidelines can contribute to firm’s performance during a global crisis, such as the case of COVID-19. Based on the triple bottom line theoretical framework, this work explores the relation between the creation of value and sustainable business models with long-term strategies and strong policy commitments, and their performance in the stock market years later during a crisis. By doing so, new insights on strategic management to create value and consolidate sustainable business models are provided. Design/methodology/approach The present study analyses firms within the context of the European Union, considering the involvement of the region in achieving sustainable development. In particular, the long-term impact in the usage of the UNGC management model and the firm's sustainability performance based on the results during COVID-19 crisis. To achieve this goal, energy firms operating in Spain and subscribing to UNGC were evaluated, specifically those publicly listed in the IBEX35, benchmark index of Spain's Stock Market Interconnection System. In addition, firms were also considered regarding the strong impact within their industries not only nationally but also worldwide. Findings Findings show long-term CSR strategies and a strong commitment to sustainable development contribute to firm’s overcoming periods of economic crisis. In addition, considering the environmental impact of the firms’ actions, transition to sustainable business and widening portfolio in the case of energy firms proved to have a positive impact in overcoming a hard context such as COVID-19. The virtuous cycle can be created by honouring the social contract, yet the tools and management models shall be further tailored to ensure an effective win-win situation. Originality/value This study evaluates a company's strategic involvement in sustainability, considering the UNGC 10 principles and SDG and the effects of these strategies in the long-term. Specifically, the role of UNGC management model is evaluated in designing effective policies that can help firms better overcome a context of crisis such as COVID-19. Consequently, researchers studying business strategy can incorporate the findings in strategic planning. Practitioners can learn the implications of CSR strategic planning in the long-term. Moreover, work illustrates corporate results in sustainability matters after the first decade of the UNGC management model and the impact of a crisis context.Sin financiaciónNo data JCR 20210.847 Q1 SJR 2021No data IDR 2021UE

La riabilitazione della disfagia: presupposti valutativi

The aspiration of part of the bolus in the airways is the element to define as subject as dysphagic, but the knowledge of this data does not allow to plan a correct rehabilitation program