Target of Rapamycin Complex 1 (TORC1), Protein Kinase A (PKA) and Cytosolic pH Regulate a Transcriptional Circuit for Lipid Droplet Formation

Lipid droplets (LDs) are ubiquitous organelles that fulfill essential roles in response to metabolic cues. The identification of several neutral lipid synthesizing and regulatory protein complexes have propelled significant advance on the mechanisms of LD biogenesis in the endoplasmic reticulum (ER). However, our understanding of signaling networks, especially transcriptional mechanisms, regulating membrane biogenesis is very limited. Here, we show that the nutrient-sensing Target of Rapamycin Complex 1 (TORC1) regulates LD formation at a transcriptional level, by targeting DGA1 expression, in a Sit4-, Mks1-, and Sfp1-dependent manner. We show that cytosolic pH (pHc), co-regulated by the plasma membrane H+-ATPase Pma1 and the vacuolar ATPase (V-ATPase), acts as a second messenger, upstream of protein kinase A (PKA), to adjust the localization and activity of the major transcription factor repressor Opi1, which in turn controls the metabolic switch between phospholipid metabolism and lipid storage. Together, this work delineates hitherto unknown molecular mechanisms that couple nutrient availability and pHc to LD formation through a transcriptional circuit regulated by major signaling transduction pathwaysThis research was funded by FCT—Fundação para a Ciência e a Tecnologia. V.T. (CEECIND/00724/2017 andCEECIND/00724/2017/CP1386/CT0006) and T.M. (SFRH/BD/136996/2018) were supported by FCT. This work was also funded by national funds through FCT, under the project UIDB/04293/2020. W.A.P is supported by the Intramural Research Program of The National Institute of Diabetes and Digestive and Kidney Diseases

Myocardial Perfusion in Rheumatoid Arthritis Patients: Associations with Traditional Risk Factors and Novel Biomarkers

Introduction. Cardiovascular (CV) diseases are a major cause of death in rheumatoid arthritis (RA) patients. Novel biomarkers [B-type natriuretic peptide (BNP); osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL) ratio; and dickkopf-1 (DKK-1)] have been used in CV risk assessment. We analysed, in established RA patients, the presence of silent myocardial ischemia and its association with clinical variables, BNP, and bone and atheroma biomarkers. Methods. From a single-center tertiary referral hospital, RA patients asymptomatic for CV disease were submitted to myocardial perfusion scintigraphy (MPS) under adenosine stress and biomarkers measurements. Logistic regression was used to estimate crude odds ratios (OR) and 95% confidence intervals (CI). Results. In 189 patients, perfusion defects were frequent (25%) and associated with BNP ≥ 100 pg/mL (OR = 5.68; 95% CI: 2.038–15.830), fourth log OPG/RANKL ratio quartile (OR = 2.88; 95% CI: 1.091–7.622), and DKK-1 ≥ 133 pmol/L (OR = 2.69; 95% CI: 1.058–6.840). Similar associations were confirmed in those with C-reactive protein > or ≤ 3 mg/L. No relationship was found with the majority of traditional CV factors nor with disease variables. Conclusions. Our results corroborated the hypothesis that MPS could reveal subclinical CV dysfunction, supported the utility of BNP measurements as a screening tool, and put in perspective the potential usefulness of complementary approaches in CV risk assessment in RA patients

Shades of red and blue: Government ideology and sustainable development

We study the effect of government ideology on sustainable development, measured as investment in genuine wealth, in a dynamic panel of 79 countries between 1981 and 2013. We find robust and statistically significant evidence that genuine investment grows faster under right-wing governments than under left-wing or center governments. In contrast, we find no indication of opportunistic cycles.Vitor Castro also wishes to thank the financial support provided by the Portuguese Foundation for Science and Technology under the research grant SFRH/BSAB/113588/2015 (partially funded by COMPTE, QREN and FEDER)

Sustaining supply chain relationships for co-operative success: the case of South Devon Organic Producers Co-operative (UK)

This is the final version. Available on open access from Wageningen Academic Publishers via the DOI in this recordCo-operatives play a vital role in supplying various goods and services in the UK, as well as in other parts of the world. In the past twenty years co-operatives have become important players in modern organic food supply chains, providing small-scale farmers with access to knowledge and markets, alongside opportunities to scale up their production. This teaching case is developed from qualitative interviews with current and former members and employees from the South Devon Organic Producers (SDOP) Co-operative, an award-winning organic vegetable grower co-operative based in South Devon (UK). The case is supplemented with interviews with key managerial personnel at the SDOP’s main stakeholder Riverford Organic Farms Limited. The case explores how the relationship between SDOP and Riverford is the key to understanding SDOP’s participation in the organic food chain.British Academ

The Mechanical Behavior of a 25Cr Super Duplex Stainless Steel at Elevated Temperature

Peer reviewedPostprin

Liposomal cytarabine as cancer therapy: From chemistry to medicine

Cancer is the second leading cause of death worldwide. The main modality to fight against cancer is surgery, radiotherapy, and chemotherapy, and more recently targeted therapy, gene therapy and immunotherapy, which play important roles in treating cancer patients. In the last decades, chemotherapy has been well developed. Nonetheless, administration of the drug is not always successful, as limited drug dosage can reach the tumor cells.. In this context, the possibility to use an encapsulated anti-cancer drug may potentially solve the problem. Liposomal cytarabine is a formulation with pronounced effectiveness in lymphomatous meningitis and reduced cardiotoxicity if compared to liposomal anthracyclines. Thus, the future liposomal cytarabine use could be extended to other diseases given its reduction in cytotoxic side effects compared to the free formulation. This review summarizes the chemistry and biology of liposomal cytarabine, with exploration of its clinical implications.N. Martins would like to thank the Portuguese Foundation for Science and Technology (FCT-Portugal) for the strategic project ref. UID/BIM/04293/2013 and "NORTE2020 - Programa Operacional Regional do Norte" (NORTE-01-0145-FEDER-000012). M. Martorell would like to thank the support offered by CONICYT PIA/APOYO CCTE AFB170007

Luminance, colour, viewpoint and border enhanced disparity energy model

The visual cortex is able to extract disparity information through the use of binocular cells. This process is reflected by the Disparity Energy Model, which describes the role and functioning of simple and complex binocular neuron populations, and how they are able to extract disparity. This model uses explicit cell parameters to mathematically determine preferred cell disparities, like spatial frequencies, orientations, binocular phases and receptive field positions. However, the brain cannot access such explicit cell parameters; it must rely on cell responses. In this article, we implemented a trained binocular neuronal population, which encodes disparity information implicitly. This allows the population to learn how to decode disparities, in a similar way to how our visual system could have developed this ability during evolution. At the same time, responses of monocular simple and complex cells can also encode line and edge information, which is useful for refining disparities at object borders. The brain should then be able, starting from a low-level disparity draft, to integrate all information, including colour and viewpoint perspective, in order to propagate better estimates to higher cortical areas.Portuguese Foundation for Science and Technology (FCT); LARSyS FCT [UID/EEA/50009/2013]; EU project NeuroDynamics [FP7-ICT-2009-6, PN: 270247]; FCT project SparseCoding [EXPL/EEI-SII/1982/2013]; FCT PhD grant [SFRH-BD-44941-2008