Physical activity (PA) and exercise are among the most important determinants of health. However, PA is a complex and heterogeneous behavior and the biological mechanisms through which it impacts ...individuals and populations in different ways are not well understood. Genetics and environment likely play pivotal roles but further work is needed to understand their relative contributions and how they may be mediated. Metabolomics offers a promising approach to explore these relationships.
In this review, we provide a comprehensive appraisal of the PA-metabolomics literature to date. This overwhelmingly supports the hypothesis of a metabolomic response to PA, which can differ between groups and individuals. It also suggests a biological gradient in this response based on PA intensity, with some evidence for global longer-term changes in the metabolome of highly active individuals. However, many questions remain and we conclude by highlighting future critical research avenues to help elucidate the role of PA in the maintenance of health and the development of disease.
•Physical inactivity is a strong disease risk factor, but mechanisms are elusive.•Metabolomics is ideally suited to explore the physical activity-health relationship.•Literature supports metabolomic response to physical activity and exercise that can differ between individuals.•Volume of physical activity and exercise may be the biggest drivers of the metabolomic adaptions.•Branched chain amino acids, Tricarboxylic Acid (TCA) cycle, oxidative stress and fatty acid mobilization are key.
Abstract Objective To demonstrate that six common errors made in attempts to change behaviour have prevented the implementation of the scientific evidence base derived from psychology and sociology; ...to suggest a new approach which incorporates recent developments in the behavioural sciences. Study design The role of health behaviours in the origin of the current epidemic of non-communicable disease is observed to have driven attempts to change behaviour. It is noted that most efforts to change health behaviours have had limited success. This paper suggests that in policy-making, discussions about behaviour change are subject to six common errors and that these errors have made the business of health-related behaviour change much more difficult than it needs to be. Methods Overview of policy and practice attempts to change health-related behaviour. Results The reasons why knowledge and learning about behaviour have made so little progress in alcohol, dietary and physical inactivity-related disease prevention are considered, and an alternative way of thinking about the behaviours involved is suggested. This model harnesses recent developments in the behavioural sciences. Conclusion It is important to understand the conditions preceding behaviour psychologically and sociologically and to combine psychological ideas about the automatic and reflective systems with sociological ideas about social practice.
Metastasis is the leading cause of cancer-related deaths, and greater knowledge of the metastatic microenvironment is necessary to effectively target this process. Microenvironmental changes occur at ...distant sites prior to clinically detectable metastatic disease; however, the key niche regulatory signals during metastatic progression remain poorly characterized. Here, we identify a core immune suppression gene signature in pre-metastatic niche formation that is expressed predominantly by myeloid cells. We target this immune suppression program by utilizing genetically engineered myeloid cells (GEMys) to deliver IL-12 to modulate the metastatic microenvironment. Our data demonstrate that IL12-GEMy treatment reverses immune suppression in the pre-metastatic niche by activating antigen presentation and T cell activation, resulting in reduced metastatic and primary tumor burden and improved survival of tumor-bearing mice. We demonstrate that IL12-GEMys can functionally modulate the core program of immune suppression in the pre-metastatic niche to successfully rebalance the dysregulated metastatic microenvironment in cancer.
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•A myeloid-rich, T-cell-poor immunosuppressive microenvironment promotes metastasis•Genetically engineered myeloid cells (GEMys) deliver IL-12 to metastatic sites•IL12-GEMys reverse immune suppression and activate anti-tumor immunity•Chemotherapy with IL12-GEMy treatment achieves durable cures in pre-clinical models
Genetically engineered myeloid cells expressing IL-12 can reverse the immunosuppressive environment developed during metastatic progression by augmenting T cell responses and reducing metastatic burden in preclinical models.
End-of-life care policy has a focus on enabling patients to die in their preferred place; this is believed for most to be home. This review assesses patient preferences for place of death examining: ...the extent of unreported preferences, the importance of patient factors (place of care and health diagnosis) and who reports preferences.
Systematic literature review of 7 electronic databases, grey literature, backwards citations from included studies and Palliative Medicine hand search. Included studies published between 2000-2015, reporting original, quantifiable results of adult UK preferences for place of death. Of 10826 articles reviewed, 61 met the inclusion criteria. Summary charts present preferences for place of death by health diagnosis, where patients were asked and who reported the preference. These charts are recalculated to include 'missing data,' the views of those whose preferences were not asked, expressed or reported or absent in studies. Missing data were common. Across all health conditions when missing data were excluded the majority preference was for home: when missing data were included, it was not known what proportion of patients with cancer, non-cancer or multiple conditions preferred home. Patients, family proxies and public all expressed a majority preference for home when missing data were excluded: when included, it was not known what proportion of patients or family proxies preferred home. Where patients wished to die was related to where they were asked their preference. Missing data calculations are limited to 'reported' data.
It is unknown what proportion of patients prefers to die at home or elsewhere. Reported preferences for place of death often exclude the views of those with no preference or not asked: when 'missing data' are included, they supress the proportion of preferences for all locations. Caution should be exercised if asserting that most patients prefer to die at home.
Adoptive T cell therapy (ACT) using ex vivo-expanded autologous tumor-infiltrating lymphocytes (TILs) can mediate complete regression of certain human cancers. The impact of TIL phenotypes on ...clinical success of TIL-ACT is currently unclear. Using high-dimensional analysis of human ACT products, we identified a memory-progenitor CD39-negative stem-like phenotype (CD39
CD69
) associated with complete cancer regression and TIL persistence and a terminally differentiated CD39-positive state (CD39
CD69
) associated with poor TIL persistence. Most antitumor neoantigen-reactive TILs were found in the differentiated CD39
state. However, ACT responders retained a pool of CD39
stem-like neoantigen-specific TILs that was lacking in ACT nonresponders. Tumor-reactive stem-like TILs were capable of self-renewal, expansion, persistence, and superior antitumor response in vivo. These data suggest that TIL subsets mediating ACT response are distinct from TIL subsets enriched for antitumor reactivity.
This article examines the interrelationship of race, space, and landed property in the historical development of racially segregated housing geographies in the United States. Using archival methods, ...I directly connect late 18th century land speculation to early 20th century suburban real estate development based on racially restrictive covenants. I investigate the city of Syracuse—a small, post‐industrial city in Upstate New York on unceded Onondaga Nation land and one of the most racially segregated cities in the US. Dispossession, speculation, and homesteading on the “Central New York Military Tract” generated a racialised, spatialised form of property that real estate capitalists later utilised to create and maintain profit‐oriented suburban segregation. This article extends the historical timeline in studies of residential segregation, provides clarity on dispossession and housing inequity in small and mid‐sized cities, and contributes to understanding how processes of racial capitalism operate through private real estate markets.
Resumen
Este artículo examina la interrelación de la raza, el espacio, y propiedad terrateniente en el desarrollo histórico de las geografías de viviendas segregadas basadas en el origen racial en los Estados Unidos. Usando métodos de investigación de archivos, conecto directamente las ocurrencias de especulación de tierras de fines del siglo XVIII con el desarrollo inmobiliario suburbano de principios del siglo XX, cuales fueron basados en convenios racialmente restrictivos. Investigo la ciudad de Syracuse, una ciudad pequeña y posindustrial en el norte del estado de Nueva York en tierras que no han sido cedidas de la Nación Onondaga, y cual es una de las ciudades más segregadas por el origen racial en los EE.UU. El despojo, la especulación y la apropiación de viviendas en la zona militar central de Nueva York “Central New York Military Tract” generaron una forma de propiedad racializada y espacializada que los inmobiliarios capitalistas después utilizaron para crear y mantener segregación suburbana orientada a las ganancias. Este artículo extiende la cronograma histórica en los estudios de segregación residencial, aclara el despojo y la inequidad de vivienda en ciudades pequeñas y medianas, y contribuye al entendimiento de cómo los procesos de capitalismo racial funcionan a través de los mercados inmobiliarios privados.
In the inner ear, cochlear and vestibular sensory epithelia utilize grossly similar cell types to transduce different stimuli: sound and acceleration. Each individual sensory epithelium is composed ...of highly heterogeneous populations of cells based on physiological and anatomical criteria. However, limited numbers of each cell type have impeded transcriptional characterization. Here we generated transcriptomes for 301 single cells from the utricular and cochlear sensory epithelia of newborn mice to circumvent this challenge. Cluster analysis indicates distinct profiles for each of the major sensory epithelial cell types, as well as less-distinct sub-populations. Asynchrony within utricles allows reconstruction of the temporal progression of cell-type-specific differentiation and suggests possible plasticity among cells at the sensory-nonsensory boundary. Comparisons of cell types from utricles and cochleae demonstrate divergence between auditory and vestibular cells, despite a common origin. These results provide significant insights into the developmental processes that form unique inner ear cell types.
Many animals use self-built structures (extended phenotypes) to enhance body functions, such as thermoregulation, prey capture or defence. Yet, it is unclear whether the evolution of animal ...constructions supplements or substitutes body functions-with disparate feedbacks on trait evolution. Here, using brown spiders (Araneae: marronoid clade), we explored if the evolutionary loss and gain of silken webs as extended prey capture devices correlates with alterations in traits known to play an important role in predatory strikes-locomotor performance (sprint speed) and leg spination (expression of capture spines on front legs). We found that in this group high locomotor performance, with running speeds of over 100 body lengths per second, evolved repeatedly-both in web-building and cursorial spiders. There was no correlation with running speed, and leg spination only poorly correlated, relative to the use of extended phenotypes, indicating that web use does not reduce selective pressures on body functions involved in prey capture and defence
. Consequently, extended prey capture devices serve as supplements rather than substitutions to body traits and may only be beneficial in conjunction with certain life-history traits, possibly explaining the rare evolution and repeated loss of trapping strategies in predatory animals.
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