Hydrological (in)stability in Southern Siberia during the Younger Dryas and early Holocene

Southern Siberia is currently undergoing rapid warming, inducing changes in vegetation, loss of permafrost, and impacts on the hydrodynamics of lakes and rivers. Lake sediments are key archives of environmental change and contain a record of ecosystem variability, as well as providing proxy indicators of wider environmental and climatic change. Investigating how hydrological systems have responded to past shifts in climate can provide essential context for better understanding future ecosystem changes in Siberia. Oxygen isotope ratios within lacustrine records provide fundamental information on past variability in hydrological systems. Here we present a new oxygen isotope record from diatom silica (ẟ18Odiatom) at Lake Baunt (55°11′15″N, 113°01,45″E), in the southern part of eastern Siberia, and consider how the site has responded to climate changes between the Younger Dryas and Early to Mid Holocene (ca. 12.4 to 6.2 ka cal BP). Excursions in ẟ18Odiatom are influenced by air temperature and the seasonality, quantity, and source of atmospheric precipitation. These variables are a function of the strength of the Siberian High, which controls temperature, the proportion and quantity of winter versus summer precipitation, and the relative dominance of Atlantic versus Pacific air masses. A regional comparison with other Siberian ẟ18Odiatom records, from lakes Baikal and Kotokel, suggests that ẟ18Odiatom variations in southern Siberia reflect increased continentality during the Younger Dryas, delayed Early Holocene warming in the region, and substantial climate instability between ~10.5 to ~8.2 ka cal BP. Unstable conditions during the Early Holocene thermal optimum most likely reflect localised changes from glacial melting. Taking the profiles from three very different lakes together, highlight the influence of site specific factors on the individual records, and how one site is not indicative of the region as a whole. Overall, the study documents how sensitive this important region is to both internal and external forcing

UMass Amherst Campus Master Plan Sustainability Chapter

The UMass Amherst Campus Master Plan Sustainability Chapter articulates the manner in which the Campus Master Plan 2012 principles translate into specific recommendations for campus systems development in support of future smart growth. It summarizes the current physical campus-scale planning projects that Facilities & Campus Services have completed during and after the Master Plan process, and incorporates other operational and educational initiatives that have engaged our campus community as we plan for sustainability. The CMP Chapter is organized in three major sections: i) sustainability overview; ii) campus master plan systems; iii) current initiatives; and iv) next steps. The first section provides the context for sustainability planning at UMass Amherst and summarizes key drivers, such as the Climate Action Plan of 2012 and our approach to greenhouse gas emissions accounting. The second section articulates the Campus Master Plan 2012 systems approach to sustainability and reviews other completed operational initiatives in infrastructure and facilities planning. The overview of current initiatives describes major efforts to advance sustainability across the campus community and is the basis for outlining the steps that Facilities & Campus Services and Sustainable UMass plan to take to advance the goal for a carbon neutral campus

Cashew gum (Anacardium occidentale) as a potential source for the production of tocopherol-loaded nanoparticles: formulation, release profile and cytotoxicity

Every year, more than thirty thousand tons of Cashew gum (Anacardium occidentale, family: Anacardiaceae) are produced in Brazil; however, only a small amount is used for different applications in foodstuff and in pharmaceutical industries. As a raw material for the production of drug delivery systems, cashew gum is still regarded as an innovative compound worth to be exploited. In this work, cashew gum was extracted from the crude exudate of cashew tree employing four methodologies resulting in a light brown powder in different yields (40.61% to 58.40%). The total ashes (0.34% to 1.05%) and moisture (12.90% to 14.81%) were also dependent on the purification approach. FTIR spectra showed the typical bands of purified cashew gum samples, confirming their suitability for the development of a pharmaceutical product. Cashew gum nanoparticles were produced by nanoprecipitation resulting in particles of low polydispersity (<0.2) and an average size depending on the percentage of the oil. The zeta potential of nanoparticles was found to be below 20 mV, which promotes electrostatic stability. Encapsulation efficiencies were above 99.9%, while loading capacity increased with the increase of the percentage of the oil content of particles. The release of the oil from the nanoparticles followed the KorsmeyerPeppas kinetics model, while particles did not show any signs of toxicity when tested in three distinct cell lines (LLC-MK2, HepG2, and THP-1). Our study highlights the potential added value of using a protein-, lignans-, and nucleic acids-enriched resin obtained from crude extract as a new raw material for the production of drug delivery systems.This research received funding from the Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES), Fundação de Ámparo à Pesquisa do Estado de Sergipe (FAPITEC) (PROCESSO: 88887.159533/2017-00 extração, encapsulação e caracterização de bioativos para o interesse biotecnologico) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 301964/2019-0 Chamada 06/2019, and Chamada CNPq nº 01/2019), from Portuguese Foundation for Science and Technology (FCT/MEC) through national funds, and co-financed by FEDER, under the Partnership Agreement PT2020 for the project UIDB/04469/2020.info:eu-repo/semantics/publishedVersio

Metabolism within the tumor microenvironment and its implication on cancer progression: an ongoing therapeutic target

Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment. Metabolic features of these cells are being studied in deep in order to find relationships between metabolism within the tumor microenvironment and tumor progression. Moreover, it cannot be forgotten that tumor growth is able to modulate host metabolism and homeostasis, so that tumor microenvironment is not the whole story. Importantly, the metabolic switch in cancer is just a consequence of the flexibility and adaptability of metabolism and should not be surprising. Treatments of cancer patients with combined therapies including anti-tumor agents with those targeting stromal cell metabolism, anti-angiogenic drugs and/or immunotherapy are being developed as promising therapeutics.Mª Carmen Ocaña is recipient of a predoctoral FPU grant from the Spanish Ministry of Education, Culture and Sport. Supported by grants BIO2014-56092-R (MINECO and FEDER), P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript

Empirical studies on informal patient payments for health care services: a systematic and critical review of research methods and instruments

<p>Abstract</p> <p>Background</p> <p>Empirical evidence demonstrates that informal patient payments are an important feature of many health care systems. However, the study of these payments is a challenging task because of their potentially illegal and sensitive nature. The aim of this paper is to provide a systematic review and analysis of key methodological difficulties in measuring informal patient payments.</p> <p>Methods</p> <p>The systematic review was based on the following eligibility criteria: English language publications that reported on empirical studies measuring informal patient payments. There were no limitations with regard to the year of publication. The content of the publications was analysed qualitatively and the results were organised in the form of tables. Data sources were Econlit, Econpapers, Medline, PubMed, ScienceDirect, SocINDEX.</p> <p>Results</p> <p>Informal payments for health care services are most often investigated in studies involving patients or the general public, but providers and officials are also sample units in some studies. The majority of the studies apply a single mode of data collection that involves either face-to-face interviews or group discussions.</p> <p>One of the main methodological difficulties reported in the publication concerns the inability of some respondents to distinguish between official and unofficial payments. Another complication is associated with the refusal of some respondents to answer questions on informal patient payments.</p> <p>We do not exclude the possibility that we have missed studies that reported in non-English language journals as well as very recent studies that are not yet published.</p> <p>Conclusions</p> <p>Given the recent evidence from research on survey methods, a self-administrated questionnaire during a face-to-face interview could be a suitable mode of collecting sensitive data, such as data on informal patient payments.</p

The population history of northeastern Siberia since the Pleistocene.

Northeastern Siberia has been inhabited by humans for more than 40,000 years but its deep population history remains poorly understood. Here we investigate the late Pleistocene population history of northeastern Siberia through analyses of 34 newly recovered ancient genomes that date to between 31,000 and 600 years ago. We document complex population dynamics during this period, including at least three major migration events: an initial peopling by a previously unknown Palaeolithic population of 'Ancient North Siberians' who are distantly related to early West Eurasian hunter-gatherers; the arrival of East Asian-related peoples, which gave rise to 'Ancient Palaeo-Siberians' who are closely related to contemporary communities from far-northeastern Siberia (such as the Koryaks), as well as Native Americans; and a Holocene migration of other East Asian-related peoples, who we name 'Neo-Siberians', and from whom many contemporary Siberians are descended. Each of these population expansions largely replaced the earlier inhabitants, and ultimately generated the mosaic genetic make-up of contemporary peoples who inhabit a vast area across northern Eurasia and the Americas

Global metabolomic profiling of uterine leiomyomas

Background: Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers: MED12 mutations, HMGA2 upregulation, or inactivation of FH. The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes of leiomyomas. Methods: We performed global metabolomic profiling of 25 uterine leiomyomas and 17 corresponding myometrium specimens using liquid chromatography-tandem mass spectroscopy. Results: A total of 641 metabolites were detected. All leiomyomas displayed reduced homocarnosine and haeme metabolite levels. We identified a clearly distinct metabolomic profile for leiomyomas of the FH subtype, characterised by metabolic alterations in the tricarboxylic acid cycle and pentose phosphate pathways, and increased levels of multiple lipids and amino acids. Several metabolites were uniquely elevated in leiomyomas of the FH subtype, including N6-succinyladenosine and argininosuccinate, serving as potential biomarkers for FH deficiency. In contrast, leiomyomas of the MED12 subtype displayed reduced levels of vitamin A, multiple membrane lipids and amino acids, and dysregulation of vitamin C metabolism, a finding which was also compatible with gene expression data. Conclusions: The study reveals the metabolomic heterogeneity of leiomyomas and provides the requisite framework for strategies designed to target metabolic alterations promoting the growth of these prevalent tumours.Peer reviewe

Cell Cycle- and Cancer-Associated Gene Networks Activated by Dsg2: Evidence of Cystatin A Deregulation and a Potential Role in Cell-Cell Adhesion

This work was supported by grants from the National Institutes of Health (Mahoney, R01AR056067; Riobo, RO1 GM088256). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

F4+ ETEC infection and oral immunization with F4 fimbriae elicits an IL-17-dominated immune response

Enterotoxigenic Escherichia coli (ETEC) are an important cause of post-weaning diarrhea (PWD) in piglets. Porcine-specific ETEC strains possess different fimbrial subtypes of which F4 fimbriae are the most frequently associated with ETEC-induced diarrhea in piglets. These F4 fimbriae are potent oral immunogens that induce protective F4-specific IgA antibody secreting cells at intestinal tissues. Recently, T-helper 17 (Th17) cells have been implicated in the protection of the host against extracellular pathogens. However, it remains unknown if Th17 effector responses are needed to clear ETEC infections. In the present study, we aimed to elucidate if ETEC elicits a Th17 response in piglets and if F4 fimbriae trigger a similar response. F4+ ETEC infection upregulated IL-17A, IL-17F, IL-21 and IL-23p19, but not IL-12 and IFN-γ mRNA expression in the systemic and mucosal immune system. Similarly, oral immunization with F4 fimbriae triggered a Th17 signature evidenced by an upregulated mRNA expression of IL-17F, RORγt, IL-23p19 and IL-21 in the peripheral blood mononuclear cells (PBMCs). Intriguingly, IL-17A mRNA levels were unaltered. To further evaluate this difference between systemic and mucosal immune responses, we assayed the cytokine mRNA profile of F4 fimbriae stimulated PBMCs. F4 fimbriae induced IL-17A, IL-17F, IL-22 and IL-23p19, but downregulated IL-17B mRNA expression. Altogether, these data indicate a Th17 dominated response upon oral immunization with F4 fimbriae and F4+ ETEC infection. Our work also highlights that IL-17B and IL-17F participate in the immune response to protect the host against F4+ ETEC infection and could aid in the design of future ETEC vaccines