The role of solar forcing upon climate change

Evidence for millennial-scale climate changes during the last 60,000 years has been found in Greenland ice cores and North Atlantic ocean cores. Until now, the cause of these climate changes remained a matter of debate. We argue that variations in solar activity may have played a significant role in forcing these climate changes. We review the coincidence of variations in cosmogenic isotopes (14C and 10Be) with climate changes during the Holocene and the upper part of the last Glacial, and present two possible mechanisms (involving the role of solar UV variations and solar wind/cosmic rays) that may explain how small variations in solar activity are amplified to cause significant climate changes. Accepting the idea of solar forcing of Holocene and Glacial climatic shifts has major implications for our view of present and future climate. It implies that the climate system is far more sensitive to small variations in solar activity than generally believed.

In vivo inhibition of c-MYC in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activities

Although tumor-associated macrophages (TAMs) are involved in tumor growth and metastasis, the mechanisms controlling their pro-tumoral activities remain largely unknown. The transcription factor c-MYC has been recently shown to regulate in vitro human macrophage polarization and be expressed in macrophages infiltrating human tumors. In this study, we exploited the predominant expression of LysM in myeloid cells to generate c-Myc(fl/fl) LysM(cre/+) mice, which lack c-Myc in macrophages, to investigate the role of macrophage c-MYC expression in cancer. Under steady-state conditions, immune system parameters in c-Myc(fl/fl) LysM(cre/+) mice appeared normal, including the abundance of different subsets of bone marrow hematopoietic stem cells, precursors and circulating cells, macrophage density, and immune organ structure. In a model of melanoma, however, TAMs lacking c-Myc displayed a delay in maturation and showed an attenuation of pro-tumoral functions (e.g., reduced expression of VEGF, MMP9, and HIF1α) that was associated with impaired tissue remodeling and angiogenesis and limited tumor growth in c-Myc(fl/fl) LysM(cre/+) mice. Macrophage c-Myc deletion also diminished fibrosarcoma growth. These data identify c-Myc as a positive regulator of the pro-tumoral program of TAMs and suggest c-Myc inactivation as an attractive target for anti-cancer therapy

Diabetes prevention and management in South Asia

Background: Globally, the number of people living with Diabetes Mellitus (DM) has increased four-fold since 1980. South Asia houses one-fifth of the world’s population living with diabetes, and it was the 8th leading cause of deaths in 2013 for South Asians.Aim: To review and discuss the context of diabetes in South Asia, with a particular focus on, a) contributing factors and impact; b) national health policies around non-communicable diseases in the region, and c) to o er recommendations for prevention and management of diabetes.Method: We assessed relevant publications using PubMed, Scopus and OvidSP. Similarly, the World health Organization (WHO) and relevant ministries of each South Asian country were searched for reports and policy documents.Results: Emerging evidence supports that the prevalence of diabetes (ranging from 3.3% in Nepal up to 8.7% in India) in South Asia follows the global trend over the past decades. Urban populations in the region demonstrate a higher prevalence of diabetes, although is also a public health concern for rural areas. Changes in the pattern and types of diet, together with increasingly sedentary, lifestyles are major causes of diabetes. The overall agenda of health promotion to prevent diabetes has not yet been established in the region, and the majority of the countries in the region are inadequately prepared for the therapeutic services for diabetes.Conclusions: The early onset of the diabetes, longevity of morbidity and early mortality may have a significant impact on people’s health expenditure and health systems, as well as on the region’s demographic composition. There is an urgent need to reduce the prevalence of diabetes in the region through evidence-based interventions ranging from prevention and early detection to appropriate treatment and care. We suggest that a multi-sectorial collaboration across all stakeholders is necessary to raise awareness about diabetes, its prevention, treatment and care in the region

The Analyticity of a Generalized Ruelle's Operator

In this work we propose a generalization of the concept of Ruelle operator for one dimensional lattices used in thermodynamic formalism and ergodic optimization, which we call generalized Ruelle operator, that generalizes both the Ruelle operator proposed in [BCLMS] and the Perron Frobenius operator defined in [Bowen]. We suppose the alphabet is given by a compact metric space, and consider a general a-priori measure to define the operator. We also consider the case where the set of symbols that can follow a given symbol of the alphabet depends on such symbol, which is an extension of the original concept of transition matrices from the theory of subshifts of finite type. We prove the analyticity of the Ruelle operator and present some examples

Association mapping and genetic dissection of drought-induced canopy temperature differences in rice

Drought-stressed plants display reduced stomatal conductance, which results in increased leaf temperature by limiting transpiration. In this study, thermal imaging was used to quantify the differences in canopy temperature under drought in a rice diversity panel consisting of 293 indica accessions. The population was grown under paddy field conditions and drought stress was imposed for 2 weeks at flowering. The canopy temperature of the accessions during stress negatively correlated with grain yield (r= –0.48) and positively with plant height (r=0.56). Temperature values were used to perform a genome-wide association (GWA) analysis using a 45K single nucleotide polynmorphism (SNP) map. A quantitative trait locus (QTL) for canopy temperature under drought was detected on chromosome 3 and fine-mapped using a high-density imputed SNP map. The candidate genes underlying the QTL point towards differences in the regulation of guard cell solute intake for stomatal opening as the possible source of temperature variation. Genetic variation for the significant markers of the QTL was present only within the tall, low-yielding landraces adapted to drought-prone environments. The absence of variation in the shorter genotypes, which showed lower leaf temperature and higher grain yield, suggests that breeding for high grain yield in rice under paddy conditions has reduced genetic variation for stomatal response under drought

The Role of Rab3a in Secretory Vesicle Docking Requires Association/Dissociation of Guanidine Phosphates and Munc18-1

Rab3a is a small GTPase that binds selectively to secretory vesicles and switches between active, GTP-bound and inactive, GDP-bound conformations. In yeast, Rab and SM-genes interact genetically to promote vesicle targeting/fusion. We tested different Rab3a conformations and genetic interactions with the SM-gene munc18-1 on the docking function of Rab3a in mammalian chromaffin cells. We expressed Rab3a mutants locked in the GTP- or GDP-bound form in wild-type and munc18-1 null mutant cells and analyzed secretory vesicle distribution. We confirmed that wild-type Rab3a promotes vesicle docking in wild-type cells. Unexpectedly, both GTP- and GDP-locked Rab3a mutants did not promote docking. Furthermore, wild-type Rab3a did not promote docking in munc18-1 null cells and GTP- and GDP-Rab3a both decreased the amount of docked vesicles. The results show that GTP- and GDP-locked conformations do not support a Munc18-1 dependent role of Rab3a in docking. This suggests that nucleotide cycling is required to support docking and that this action of Rab3a is upstream of Munc18-1

Exploring the Free Energy Landscape: From Dynamics to Networks and Back

The knowledge of the Free Energy Landscape topology is the essential key to understand many biochemical processes. The determination of the conformers of a protein and their basins of attraction takes a central role for studying molecular isomerization reactions. In this work, we present a novel framework to unveil the features of a Free Energy Landscape answering questions such as how many meta-stable conformers are, how the hierarchical relationship among them is, or what the structure and kinetics of the transition paths are. Exploring the landscape by molecular dynamics simulations, the microscopic data of the trajectory are encoded into a Conformational Markov Network. The structure of this graph reveals the regions of the conformational space corresponding to the basins of attraction. In addition, handling the Conformational Markov Network, relevant kinetic magnitudes as dwell times or rate constants, and the hierarchical relationship among basins, complete the global picture of the landscape. We show the power of the analysis studying a toy model of a funnel-like potential and computing efficiently the conformers of a short peptide, the dialanine, paving the way to a systematic study of the Free Energy Landscape in large peptides.Comment: PLoS Computational Biology (in press