216 research outputs found
Recommended from our members
Can the sustainable development goals reduce the burden of nutrition-related non-communicable diseases without truly addressing major food system reforms?
While the Millennium Development Goals (MDGs; 2000–2015) focused primarily on poverty reduction, hunger and infectious diseases, the proposed Sustainable Development Goals (SDGs) and targets pay more attention to nutrition and non-communicable diseases (NCDs). One of the 169 proposed targets of the SDGs is to reduce premature deaths from NCDs by one third; another is to end malnutrition in all its forms. Nutrition-related NCDs (NR-NCDs) stand at the intersection between malnutrition and NCDs. Driven in large part by remarkable transformations of food systems, they are rapidly increasing in most low and middle income countries (LMICs). The transformation to modern food systems began in the period following World War II with policies designed to meet a very different set of nutritional and food needs, and continued with globalization in the 1990s onwards. Another type of food systems transformation will be needed to shift towards a healthier and more sustainable diet – as will meeting many of the other SDGs. The process will be complex but is necessary. Communities concerned with NCDs and with malnutrition need to work more closely together to demand food systems change
Genetics and the Sociology of Identity.
notes: PMCID: PMC4025619types: JOURNAL ARTICLEN/AThe editorial work for this Special Issue was funded by the ESRC grants to CESAGEN (RES-145-
28-0003), EGENIS (RES-145-28-0001), the Genomics Forum (RES-145-28-0005), and
INNOGEN (RES-145-28-0002)
Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.
Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies
Feminist health psychology and abortion : towards a politics of transversal relations of commonality
In 1992 Speckhard and Rue argued in the Journal of Social Issues for the recognition of a diagnostic category, post-abortion syndrome (PAS). This term was first used in 1981 by Vincent Rue in testimony to the American Congress, but was only formalised in a published paper a decade later. Speckhard and Rue (1992) posit that abortion is a psychosocial stressor that may cause mild distress through to severe trauma, creating the need for a continuum of categories, these being post-abortion distress, post-abortion syndrome and post-abortion psychosis. PAS, which is the main focus of their paper, and which has taken root in some professional language as well as lay anti-abortion discourse, is described as a type of post-traumatic stress disorder
Ethnic Residential Segregation: A Multilevel, Multigroup, Multiscale Approach Exemplified by London in 2011
Immuno-transcriptomic profiling of extracranial pediatric solid malignancies.
We perform an immunogenomics analysis utilizing whole-transcriptome sequencing of 657 pediatric extracranial solid cancer samples representing 14 diagnoses, and additionally utilize transcriptomes of 131 pediatric cancer cell lines and 147 normal tissue samples for comparison. We describe patterns of infiltrating immune cells, T cell receptor (TCR) clonal expansion, and translationally relevant immune checkpoints. We find that tumor-infiltrating lymphocytes and TCR counts vary widely across cancer types and within each diagnosis, and notably are significantly predictive of survival in osteosarcoma patients. We identify potential cancer-specific immunotherapeutic targets for adoptive cell therapies including cell-surface proteins, tumor germline antigens, and lineage-specific transcription factors. Using an orthogonal immunopeptidomics approach, we find several potential immunotherapeutic targets in osteosarcoma and Ewing sarcoma and validated PRAME as a bona fide multi-pediatric cancer target. Importantly, this work provides a critical framework for immune targeting of extracranial solid tumors using parallel immuno-transcriptomic and -peptidomic approaches
Kinetic Pathway of Pyrophosphorolysis by a Retrotransposon Reverse Transcriptase
DNA and RNA polymerases use a common phosphoryl transfer mechanism for base addition that requires two or three acidic amino acid residues at their active sites. We previously showed, for the reverse transcriptase (RT) encoded by the yeast retrotransposon Ty1, that one of the three conserved active site aspartates (D211) can be substituted by asparagine and still retain in vitro polymerase activity, although in vivo transposition is lost. Transposition is partially restored by second site suppressor mutations in the RNAse H domain. The novel properties of this amino acid substitution led us to express the WT and D211N mutant enzymes, and study their pre-steady state kinetic parameters. We found that the kpol was reduced by a factor of 223 in the mutant, although the Kd for nucleotide binding was unaltered. Further, the mutant enzyme had a marked preference for Mn2+ over Mg2+. To better understand the functions of this residue within the Ty1 RT active site, we have now examined the in vitro properties of WT and D211N mutant Ty1 RTs in carrying out pyrophosphorolysis, the reverse reaction to polymerization, where pyrophosphate is the substrate and dNTPs are the product. We find that pyrophosphorolysis is efficient only when the base-paired primer template region is >14 bases, and that activity increases when the primer end is blunt-ended or recessed by only a few bases. Using pre-steady state kinetic analysis, we find that the rate of pyrophosphorolysis (kpyro) in the D211N mutant is nearly 320 fold lower than the WT enzyme, and that the mutant enzyme has an ∼170 fold lower apparent Kd for pyrophosphate. These findings indicate that subtle substrate differences can strongly affect the enzyme's ability to properly position the primer-end to carry out pyrophosphorolysis. Further the kinetic data suggests that the D211 residue has a role in pyrophosphate binding and release, which could affect polymerase translocation, and help explain the D211N mutant's transposition defect
Communication for Peaceful Social Change and Global Citizenry
The adoption of the 17 Sustainable Development Goals (SDGs) by the United Nations (UN) in 2015
represents a universal call to action involving multiple international actors for the purpose of eradicating
poverty, improving living conditions and promoting peace. This entry provides a theoretical overview of
the contributions of scholars and practitioners who highlight the importance of a transformative,
educational and emancipatory communication by different social actors to establish the main lines of
action for the 2030 Agenda for Sustainable Development. This communicative model involves the
coordination of actors and strategies, both short- and long-term, cross-cutting actions and discourses to
build social, cultural and political settings based on the criteria of peace, equality, social justice and
human rights. Specifically, this entails a contribution to the objectives set out in SDG 16, “Peace, Justice
and Strong Institutions”, given that the proposed theoretical framework is grounded in Communication for
Peace and Communication for Social Change, and includes a systematization of different strategies and
experiences from a variety of social issuers, mainly institutions, non-governmental organizations (NGOs)
or social movements, aimed at promoting peaceful and inclusive societies. Specifically, communication
for peaceful social change and global citizenry contributes to the achievement of specific SDG 16
objectives, particularly 16.1: Significantly reduce all forms of violence... [...
Genomic research, publics and experts in Latin America: Nation, race and body
The articles in this issue highlight contributions that studies of Latin America can make to wider debates about the effects of genomic science on public ideas about race and nation. We argue that current ideas about the power of genomics to transfigure and transform existing ways of thinking about human diversity are often overstated. If a range of social contexts are examined, the effects are uneven. Our data show that genomic knowledge can unsettle and reinforce ideas of nation and race; it can be both banal and highly politicized. In this introduction, we outline concepts of genetic knowledge in society; theories of genetics, nation and race; approaches to public understandings of science; and the Latin American contexts of transnational ideas of nation and race
Building the genomic nation: ‘Homo Brasilis’ and the ‘Genoma Mexicano’ in comparative cultural perspective
This article explores the relationship between genetic research, nationalism and the construction of collective social identities in Latin America. It makes a comparative analysis of two research projects – the ‘Genoma Mexicano’ and the ‘Homo Brasilis’ – both of which sought to establish national and genetic profiles. Both have reproduced and strengthened the idea of their respective nations of focus, incorporating biological elements into debates on social identities. Also, both have placed the unifying figure of the mestizo/mestiço at the heart of national identity constructions, and in so doing have displaced alternative identity categories, such as those based on race. However, having been developed in different national contexts, these projects have had distinct scientific and social trajectories: in Mexico, the genomic mestizo is mobilized mainly in relation to health, while in Brazil the key arena is that of race. We show the importance of the nation as a frame for mobilizing genetic data in public policy debates, and demonstrate how race comes in and out of focus in different Latin American national contexts of genomic research, while never completely disappearing
- …
