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

Pneumococcal surface protein A of invasive Streptococcus pneumoniae isolates from Colombian children.

Pneumococcal surface protein A (PspA) elicits protection in mice against fatal bacteremia and sepsis caused by genetically diverse pneumococci and protects against carriage and lung infection. We determined the PspA families of invasive isolates of Streptococcus pneumoniae recovered from Colombian children <5 years of age. That 97.5% of Colombian isolates belong to PspA families 1 and 2 supports the hypothesis that a human PspA vaccine covering a few PspA families could be broadly effective

In vitro caloric restriction induces protective genes and functional rejuvenation in senescent SAMP8 astrocytes.

Astrocytes are key cells in brain aging, helping neurons to undertake healthy aging or otherwise letting them enter into a spiral of neurodegeneration. We aimed to characterize astrocytes cultured from senescence-accelerated prone 8 (SAMP8) mice, a mouse model of brain pathological aging, along with the effects of caloric restriction, the most effective rejuvenating treatment known so far. Analysis of the transcriptomic profiles of SAMP8 astrocytes cultured in control conditions and treated with caloric restriction serum was performed using mRNA microarrays. A decrease in mitochondrial and ribosome mRNA, which was restored by caloric restriction, confirmed the age-related profile of SAMP8 astrocytes and the benefits of caloric restriction. An amelioration of antioxidant and neurodegeneration-related pathways confirmed the brain benefits of caloric restriction. Studies of oxidative stress and mitochondrial function demonstrated a reduction of oxidative damage and partial improvement of mitochondria after caloric restriction. In summary, caloric restriction showed a significant tendency to normalize pathologically aged astrocytes through the activation of pathways that are protective against the age-related deterioration of brain physiology. © 2014 The AuthorsThis study was supported by grants SAF2009-13093, SAF2012-39852, and CSD2010-00045 from the Spanish MINECO, 2009/SGR/214 from the Generalitat of Catalonia, and the European Regional evelopment Fund (ERDF)Peer Reviewe

Oxidative phosphorylation selectively orchestrates tissue macrophage homeostasis

In vitro studies have associated oxidative phosphorylation (OXPHOS) with anti-inflammatory macrophages, whereas pro-inflammatory macrophages rely on glycolysis. However, the metabolic needs of macrophages in tissues (TMFs) to fulfill their homeostatic activities are incompletely understood. Here, we identified OXPHOS as the highest discriminating process among TMFs from different organs in homeostasis by analysis of RNA-seq data in both humans and mice. Impairing OXPHOS in TMFs via Tfam deletion differentially affected TMF populations. Tfam deletion resulted in reduction of alveolar macrophages (AMs) due to impaired lipid-handling capacity, leading to increased cholesterol content and cellular stress, causing cell-cycle arrest in vivo. In obesity, Tfam depletion selectively ablated pro-inflammatory lipid-handling white adipose tissue macrophages (WAT-MFs), thus preventing insulin resistance and hepatosteatosis. Hence, OXPHOS, rather than glycolysis, distinguishes TMF populations and is critical for the maintenance of TMFs with a high lipid-handling activity, including pro-inflammatory WAT-MFs. This could provide a selective therapeutic targeting tool.This project was supported by the “la Caixa” Foundation (ID 100010434) Postdoctoral Junior Leader Fellowship code LCF/BQ/PR20/11770008 (S.K.W.); “la Caixa” Foundation (ID 100010434) INPhINIT Fellowship code LCF/BQ/IN17/11620074 (I.H.-M.); Spanish Ministry of Education FPU fellowship code FPU20/01418 (M.G.); Ministerio de Ciencia e Innovación (MCIN) PID2019-104233RB-100/AEI/10.13039/501100011033 (S.L.); and NIH grants P01AG049665-08, RO1A148190, and P01HL154998 (N.S.C.). The J.A.E. laboratory is supported by the CNIC and a grant by Ministerio de Ciencia, Innovación y Universidades (MCNU); Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) (RTI2018-099357-B-I00); the Biomedical Research Networking Center on Frailty and Healthy Ageing (CIBERFES-ISCiii-CB16/10/00289); and the HFSP agency (RGP0016/2018). Work in the D.S. laboratory is funded by the CNIC; by the European Union’s Horizon 2020 research and innovation program under grant agreement ERC-2016-Consolidator grant 725091; by Spanish Ministerio de Ciencia e Innovación PID2019-108157RB/AEI/ and CPP2021-008310/AEI/10.13039/501100011033; by Comunidad de Madrid (P2022/BMD-7333 INMUNOVAR-CM); and by “la Caixa” Foundation (LCF/PR/HR20/00075 and LCF/PR/HR22/00253). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the MICINN, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (CEX2020-001041-S funded by MCIN/AEI/10.13039/501100011033)

Oxidative phosphorylation selectively orchestrates tissue macrophage homeostasis

We are grateful to N.-G. Larsson, F. Sa´ nchez-Madrid, G. Sabio, R.D. Palmiter, E. Gottlieb, C.T.Moraes, and M.A. del Pozofor sharing essential reagents.We thank S. Iborra, his team, M. Sa´ nchez-A´ lvarez, I. Nikolic, and members of the D.S. laboratory for discussions and critical reading of the manuscript. We thank the staff at the CNIC technical units; foremost the animal, cellomics, histology, metabolomics, genomics,microscopy, and bioinformaticsfacilities; and the SIdI of the Universidad Auto´ noma de Madrid for technical support. This project was supported by the ‘‘la Caixa’’ Foundation (ID 100010434) Postdoctoral Junior Leader Fellowship code LCF/BQ/PR20/11770008 (S.K.W.); ‘‘la Caixa’’ Foundation (ID 100010434) INPhINIT Fellowship code LCF/BQ/IN17/11620074 (I.H.-M.); Spanish Ministry of Education FPU fellowship code FPU20/01418 (M.G.); Ministerio de Ciencia e Innovacio´ n (MCIN) PID2019-104233RB-100/AEI/10.13039/ 501100011033 (S.L.); and NIH grants P01AG049665-08, RO1A148190, and P01HL154998 (N.S.C.). The J.A.E. laboratory is supported by the CNIC and a grant by Ministerio de Ciencia, Innovacio´ n y Universidades (MCNU); Agencia Estatal de Investigacio´ n (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) (RTI2018-099357-B-I00); the Biomedical Research Networking Center on Frailty and Healthy Ageing (CIBERFES-ISCiii-CB16/10/00289); and the HFSP agency (RGP0016/2018). Work in the D.S. laboratory is funded by the CNIC; by the European Union’s Horizon 2020 research and innovation program under grant agreement ERC-2016-Consolidator grant 725091; by Spanish Ministerio de Ciencia e Innovacio´ n PID2019-108157RB/AEI/ and CPP2021-008310/AEI/10.13039/ 501100011033; by Comunidad de Madrid (P2022/BMD-7333 INMUNOVARCM); and by ‘‘la Caixa’’ Foundation (LCF/PR/HR20/00075 and LCF/PR/HR22/ 00253). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the MICINN, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (CEX2020-001041-S funded by MCIN/AEI/10.13039/501100011033).S

Analysing decision logs to understand decision-making in serious crime investigations

Objective: To study decision-making by detectives when investigating serious crime through the examination of Decision Logs to explore hypothesis generation and evidence selection. Background: Decision logs are used to record and justify decisions made during serious crime investigations. The complexity of investigative decision-making is well documented, as are the errors associated with miscarriages of justice and inquests. The use of decision logs has not been the subject of an empirical investigation, yet they offer an important window into the nature of investigative decision-making in dynamic, time-critical environments. Method: A sample of decision logs from British police forces was analyzed qualitatively and quantitatively to explore hypothesis generation and evidence selection by police detectives. Results: Analyses revealed diversity in documentation of decisions that did not correlate with case type, and identified significant limitations of the decision log approach to supporting investigative decision-making. Differences emerged between experienced and less experienced officers’ decision log records in exploration of alternative hypotheses, generation of hypotheses, and sources of evidential enquiry opened over phase of investigation. Conclusion: The practical use of decision logs is highly constrained by their format and context of use. Despite this, decision log records suggest that experienced detectives display strategic decision-making to avoid confirmation and satisficing that affect less experienced detectives. Application: Potential applications of this research include both training in case documentation and the development of new decision log media that encourage detectives, irrespective of experience, to generate multiple hypotheses and optimize the timely selection of evidence to test them