Star formation histories of dwarf galaxies in the FIRE simulations: dependence on mass and Local Group environment

We study star formation histories (SFHs) of $\simeq500$ dwarf galaxies (stellar mass $M_\ast = 10^5 - 10^9\,M_\odot$) from FIRE-2 cosmological zoom-in simulations. We compare dwarfs around individual Milky Way (MW)-mass galaxies, dwarfs in Local Group (LG)-like environments, and true field (i.e. isolated) dwarf galaxies. We reproduce observed trends wherein higher-mass dwarfs quench later (if at all), regardless of environment. We also identify differences between the environments, both in terms of "satellite vs. central" and "LG vs. individual MWvs. isolated dwarf central." Around the individual MW-mass hosts, we recover the result expected from environmental quenching: central galaxies in the "near field" have more extended SFHs than their satellite counterparts, with the former more closely resemble isolated ("true field") dwarfs (though near-field centrals are still somewhat earlier forming). However, this difference is muted in the LG-like environments, where both near-field centrals and satellites have similar SFHs, which resemble satellites of single MW-mass hosts. This distinction is strongest for $M_\ast = 10^6 - 10^7\,M_\odot$ but exists at other masses. Our results suggest that the paired halo nature of the LG may regulate star formation in dwarf galaxies even beyond the virial radii of the MW and Andromeda. Caution is needed when comparing zoom-in simulations targeting isolated dwarf galaxies against observed dwarf galaxies in the LG.Comment: Main text: 11 pages, 8 figures; appendices: 4 pages, 4 figures. Submitted to MNRAS; comments welcom

Modification of an aggressive model of Alport Syndrome reveals early differences in disease pathogenesis due to genetic background

The link between mutations in collagen genes and the development of Alport Syndrome has been clearly established and a number of animal models, including knock-out mouse lines, have been developed that mirror disease observed in patients. However, it is clear from both patients and animal models that the progression of disease can vary greatly and can be modifed genetically. We have identifed a point mutation in Col4a4 in mice where disease is modifed by strain background, providing further evidence of the genetic modifcation of disease symptoms. Our results indicate that C57BL/6J is a protective background and postpones end stage renal failure from 7 weeks, as seen on a C3H background, to several months. We have identifed early diferences in disease progression, including expression of podocyte-specifc genes and podocyte morphology. In C57BL/6J mice podocyte efacement is delayed, prolonging normal renal function. The slower disease progression has allowed us to begin dissecting the pathogenesis of murine Alport Syndrome in detail. We fnd that there is evidence of diferential gene expression during disease on the two genetic backgrounds, and that disease diverges by 4 weeks of age. We also show that an infammatory response with increasing MCP-1 and KIM-1 levels precedes loss of renal function

Star formation histories of dwarf galaxies in the FIRE simulations: dependence on mass and Local Group environment

We study star formation histories (SFHs) of 500 dwarf galaxies (stellar mass M∗=10⁵−10⁹M⊙⁠) from FIRE-2 cosmological zoom-in simulations. We compare dwarfs around individual Milky Way (MW)-mass galaxies, dwarfs in Local Group (LG)-like environments, and true field (i.e. isolated) dwarf galaxies. We reproduce observed trends wherein higher mass dwarfs quench later (if at all), regardless of environment. We also identify differences between the environments, both in terms of ‘satellite versus central’ and ‘LG versus individual MW versus isolated dwarf central.’ Around the individual MW-mass hosts, we recover the result expected from environmental quenching: central galaxies in the ‘near field’ have more extended SFHs than their satellite counterparts, with the former more closely resemble isolated (true field) dwarfs (though near-field centrals are still somewhat earlier forming). However, this difference is muted in the LG-like environments, where both near-field centrals and satellites have similar SFHs, which resemble satellites of single MW-mass hosts. This distinction is strongest for M* = 10⁶–10⁷M⊙ but exists at other masses. Our results suggest that the paired halo nature of the LG may regulate star formation in dwarf galaxies even beyond the virial radii of the MW and Andromeda. Caution is needed when comparing zoom-in simulations targeting isolated dwarf galaxies against observed dwarf galaxies in the LG

Update on the global epidemiology of intussusception: a systematic review of incidence rates, age distributions and case-fatality ratios among children aged <5 years, before the introduction of rotavirus vaccination.

BACKGROUND: In some countries that have introduced oral rotavirus vaccines, a small but elevated risk of intussusception-a rare bowel disorder-has been reported. Updated estimates on the global epidemiology of intussusception are needed to help predict the potential number of intussusception cases that could be caused by the vaccine in different settings. METHODS: We estimated incidence rates, age distributions and case-fatality ratios (CFRs) for intussusception hospital admissions among children aged <5 years, before the introduction of rotavirus vaccines. We included all articles identified in a systematic review between January 2002 and January 2018, and contacted authors for more granular unpublished data on age distributions. RESULTS: We identified 128 articles containing 227 country datasets (61 age distributions, 71 incidence rates and 95 CFRs). The median age of intussusception ranged from 29 weeks in Africa (83% of cases in the first year of life) to 70 weeks in the Western Pacific region (35% of cases in the first year of life). The median (range) annual incidence of intussusception hospital admissions per 100 000 aged <1 year ranged from 34 (13-56) in Africa to 90 (9-380) in the Western Pacific region. We found extreme differences between the CFRs in Africa (1 death in every 10 hospital admissions) and the rest of the world (fewer than 1 death in every 100-2000 hospital admissions). CONCLUSION: Intussusception epidemiology varies by country and region. Understanding and recognizing these differences will be important when assessing the potential number of intussusception cases associated with rotavirus vaccines

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Geographic information retrieval in a mobile environment: evaluating the needs of mobile individuals

This paper describes research that aims to define the information needs of mobile individuals, to implement a mobile information system that can satisfy those needs, and finally to evaluate the performance of that system with end-users. First a review of the emerging discipline of geographic information retrieval (GIR) is presented as background to the more specific issue of mobile information retrieval. Following this, a user needs study is described evaluating the requirements of potential users of a mobile information system; the study finds that there is a strong geographic component to users' information needs. Next, four geographic post-query filters are described which attempt to represent the region of space associated with an individual's query made at some specific spatial location. These filters are spatial proximity (distance in space), temporal proximity (travel time), speed-heading prediction surfaces (likelihood of visiting locations) and visibility (locations that can be seen). Two of these filters — spatial proximity and speed-heading prediction surfaces — are implemented in a mobile information system and subsequently evaluated with users in an outdoor setting. The results of evaluation suggest that retrieved information to which post-query geographic filters have been applied is considered more relevant than unfiltered information, and that users find information sorted by spatial proximity to be more relevant than that sorted by a prediction surface of likely future locations. The paper closes with a discussion of the wider implications of these results for developers of mobile information systems and location-based services

Explaining negative kin discrimination in a cooperative mammal society

Kin selection theory predicts that, where kin discrimination is possible, animals should typically act more favorably toward closer genetic relatives and direct aggression toward less closely related individuals. Contrary to this prediction, we present data from an 18-y study of wild banded mongooses, Mungos mungo, showing that females that are more closely related to dominant individuals are specifically targeted for forcible eviction from the group, often suffering severe injury, and sometimes death, as a result. This pattern cannot be explained by inbreeding avoidance or as a response to more intense local competition among kin. Instead, we use game theory to show that such negative kin discrimination can be explained by selection for unrelated targets to invest more effort in resisting eviction. Consistent with our model, negative kin discrimination is restricted to eviction attempts of older females capable of resistance; dominants exhibit no kin discrimination when attempting to evict younger females, nor do they discriminate between more closely or less closely related young when carrying out infanticidal attacks on vulnerable infants who cannot defend themselves. We suggest that in contexts where recipients of selfish acts are capable of resistance, the usual prediction of positive kin discrimination can be reversed. Kin selection theory, as an explanation for social behavior, can benefit from much greater exploration of sequential social interactions