Genetic deletion of skeletal muscle iPLA2γ results in mitochondrial dysfunction, muscle atrophy and alterations in whole-body energy metabolism

Skeletal muscle is the major site of glucose utilization in mammals integrating serum glucose clearance with mitochondrial respiration. To mechanistically elucidate the roles of iPL

Adherence to the 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations and cancer risk: A systematic review and meta‐analysis

Background: The World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations are lifestyle‐based guidelines that aim to reduce cancer risk. A systematic review and meta‐analysis of studies investigating associations between a score for adherence to the 2018 Cancer Prevention Recommendations and cancer risk was conducted. Methods: MEDLINE, Embase, Web of Science, and Scopus were searched for studies published to November 28, 2022. In meta‐analysis, the estimated risk ratios and 95% CIs for adherence score as a continuous (per 1‐point increment) and categorical (highest vs. lowest score category) variable using random‐effects models were estimated. Results: Eighteen studies (11 cohort; seven case‐control) were included investigating incidence of breast (n = 7), colorectal (n = 5), prostate (n = 2), lung (n = 2), pancreatic (n = 1), endometrial (n = 1), unknown primary cancer (n = 1), chronic lymphocytic leukemia (n = 1), and overall (any) cancer (n = 1). The summary risk ratio per 1‐point increment in adherence score was 0.89 (95% CI, 0.85–0.93; I2 = 76.5%; n = 7) for breast cancer, 0.88 (95% CI, 0.84–0.91; I2 = 26.2%; n = 4) for colorectal cancer, and 0.92 (95% CI, 0.86–0.98, I2 = 66.0%; n = 2) for lung cancer. There were no significant associations with prostate or other cancers. Meta‐analysis results using categorical adherence score variables were consistent with these findings. Conclusions: Greater adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations was associated with lower risk of breast, colorectal, and lung cancers. Future studies investigating associations with risk of other forms of cancer are warranted. PROSPERO registration number: CRD42022313327

Allelic Variation on Murine Chromosome 11 Modifies Host Inflammatory Responses and Resistance to Bacillus anthracis

Anthrax is a potentially fatal disease resulting from infection with Bacillus anthracis. The outcome of infection is influenced by pathogen-encoded virulence factors such as lethal toxin (LT), as well as by genetic variation within the host. To identify host genes controlling susceptibility to anthrax, a library of congenic mice consisting of strains with homozygous chromosomal segments from the LT-responsive CAST/Ei strain introgressed on a LT-resistant C57BL/6 (B6) background was screened for response to LT. Three congenic strains containing CAST/Ei regions of chromosome 11 were identified that displayed a rapid inflammatory response to LT similar to, but more severe than that driven by a LT-responsive allele of the inflammasome constituent NRLP1B. Importantly, increased response to LT in congenic mice correlated with greater resistance to infection by the Sterne strain of B. anthracis. The genomic region controlling the inflammatory response to LT was mapped to 66.36–74.67 Mb on chromosome 11, a region that encodes the LT-responsive CAST/Ei allele of Nlrp1b. However, known downstream effects of NLRP1B activation, including macrophage pyroptosis, cytokine release, and leukocyte infiltration could not fully explain the response to LT or the resistance to B. anthracis Sterne in congenic mice. Further, the exacerbated response in congenic mice is inherited in a recessive manner while the Nlrp1b-mediated response to LT is dominant. Finally, congenic mice displayed increased responsiveness in a model of sepsis compared with B6 mice. In total, these data suggest that allelic variation of one or more chromosome 11 genes in addition to Nlrp1b controls the severity of host response to multiple inflammatory stimuli and contributes to resistance to B. anthracis Sterne. Expression quantitative trait locus analysis revealed 25 genes within this region as high priority candidates for contributing to the host response to LT

Halo mass - concentration relation from weak lensing

We perform a statistical weak lensing analysis of dark matter profiles around tracers of halo mass from galactic- to cluster-size halos. In this analysis we use 170,640 isolated ~L* galaxies split into ellipticals and spirals, 38,236 groups traced by isolated spectroscopic Luminous Red Galaxies (LRGs) and 13,823 MaxBCG clusters from the Sloan Digital Sky Survey (SDSS) covering a wide range of richness. Together these three samples allow a determination of the density profiles of dark matter halos over three orders of magnitude in mass, from 10^{12} M_{sun} to 10^{15} M_{sun}. The resulting lensing signal is consistent with an NFW or Einasto profile on scales outside the central region. We find that the NFW concentration parameter c_{200b} decreases with halo mass, from around 10 for galactic halos to 4 for cluster halos. Assuming its dependence on halo mass in the form of c_{200b} = c_0 [M/(10^{14}M_{sun}/h)]^{\beta}, we find c_0=4.6 +/- 0.7 (at z=0.22) and \beta=0.13 +/- 0.07, with very similar results for the Einasto profile. The slope (\beta) is in agreement with theoretical predictions, while the amplitude is about two standard deviations below the predictions for this mass and redshift, but we note that the published values in the literature differ at a level of 10-20% and that for a proper comparison our analysis should be repeated in simulations. We discuss the implications of our results for the baryonic effects on the shear power spectrum: since these are expected to increase the halo concentration, the fact that we see no evidence of high concentrations on scales above 20% of the virial radius suggests that baryonic effects are limited to small scales, and are not a significant source of uncertainty for the current weak lensing measurements of the dark matter power spectrum. [ABRIDGED]Comment: 17 pages, 5 figures, accepted to JCAP pending minor revisions that are included in v2 here on arXi

A human MAP kinase interactome.

Mitogen-activated protein kinase (MAPK) pathways form the backbone of signal transduction in the mammalian cell. Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. Multiple lines of evidence including conservation with yeast supported a core network of 641 interactions. Using small interfering RNA knockdowns, we observed that approximately one-third of MAPK-interacting proteins modulated MAPK-mediated signaling. We uncovered the Na-H exchanger NHE1 as a potential MAPK scaffold, found links between HSP90 chaperones and MAPK pathways and identified MUC12 as the human analog to the yeast signaling mucin Msb2. This study makes available a large resource of MAPK interactions and clone libraries, and it illustrates a methodology for probing signaling networks based on functional refinement of experimentally derived protein-interaction maps

Discovery and Use of a Natural Mutation that Results in Severe Combined Immuno Deficiency in Pigs

Piglets from the low residual feed intake (RFI) line at ISU were found to be affected with a lethal autosomal recessive mutation that causes Severe Combined Immunodeficiency (SCID). Bone marrow allotransplantation rescued the immune deficiency in four of nine attempted transfers; the other five exhibited signs of severe graft versus host disease and were euthanized. A genome wide association study identified a 5.6 Mb region that contained the causative mutation. Affected haplotypes were traced back to the founders of the RFI population, who were sourced from the purebred Yorkshire population. The SCID pigs will be useful as a biomedical model, as pigs are anatomically and genetically more similar to humans than SCID mice, which are now widely used. Development of a genetic test for the causative mutation will be valuable to the swine industry, allowing breeders to identify carriers

Defective sphingosine-1-phosphate receptor 1 (S1P1) phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation

Sphingosine-1-phosphate (S1P) signaling regulates lymphocyte egress from lymphoid organs into systemic circulation. Sphingosine phosphate receptor 1 (S1P1) agonist, FTY-720 (Gilenya™) arrests immune trafficking and prevents multiple sclerosis (MS) relapses. However, alternative mechanisms of S1P-S1P1 signaling have been reported. Phosphoproteomic analysis of MS brain lesions revealed S1P1 phosphorylation on S351, a residue crucial for receptor internalization. Mutant mice harboring a S1pr1 gene encoding phosphorylation-deficient receptors [S1P1(S5A)] developed severe experimental autoimmune encephalomyelitis (EAE) due to T helper (TH) 17-mediated autoimmunity in the peripheral immune and nervous system. S1P1 directly activated Janus-like kinase–signal transducer and activator of transcription 3 (JAK-STAT3) pathway via interleukin 6 (IL-6). Impaired S1P1 phosphorylation enhances TH17 polarization and exacerbates autoimmune neuroinflammation. These mechanisms may be pathogenic in MS

WATER2006-20008 DEVELOPMENT OF A TECHNOLOGY ROADMAP FOR THE ENERGY AND WATER NEXUS

INTRODUCTION Energy and water are critical resources that are inextricably and reciprocally linked. The production of energy requires large volumes of water, and the treatment and distribution of water depends upon readily available, low-cost energy. For example, electricity production from thermoelectric power plants can use ~140,000 million gallons of water per day for cooling-accounting for 39% of all freshwater withdrawals in the nation, second only to agriculture in the United State

Properties of Galaxies Hosting X-ray Selected Active Galactic Nuclei in the Cl1604 Supercluster at z=0.9

To investigate the role of feedback from Active Galactic Nuclei (AGN) in driving the evolution of their host galaxies, we have carried out a study of the environments and optical properties of galaxies harboring X-ray luminous AGN in the Cl1604 supercluster at z~0.9. Making use of Chandra, HST/ACS and Keck/DEIMOS observations, we examine the integrated colors, morphologies and spectral properties of nine moderate-luminosity (L_x ~ 10^43 erg s^-1) type 2 Seyferts detected in the Cl1604 complex. We find that the AGN are predominantly hosted by luminous spheroids and/or bulge dominated galaxies which have colors that place them in the valley between the blue cloud and red sequence in color-magnitude space, consistent with predictions that AGN hosts should constitute a transition population. Half of the hosts have bluer overall colors as a result of blue resolved cores in otherwise red spheroids and a majority show signs of recent or pending interactions. We also find a substantial number exhibit strong Balmer absorption features indicative of post-starburst galaxies, despite the fact that we detect narrow [OII] emission lines in all of the host spectra. If the [OII] lines are due in part to AGN emission, as we suspect, then this result implies that a significant fraction of these galaxies (44%) have experienced an enhanced level of star formation within the last ~1 Gyr which was rapidly suppressed. Overall we find that the properties of the nine host galaxies are generally consistent with a scenario in which recent interactions have triggered both increased levels of nuclear activity and an enhancement of centrally concentrated star formation, followed by a rapid truncation of the latter, possibly as a result of feedback from the AGN itself. [Abridged]Comment: 15 pages, 9 Figures, submitted to Ap