Systematic discovery of genetic modulation by Jumonji histone demethylases in Drosophila

Jumonji (JmjC) domain proteins influence gene expression and chromatin organization by way of histone demethylation, which provides a means to regulate the activity of genes across the genome. JmjC proteins have been associated with many human diseases including various cancers, developmental and neurological disorders, however, the shared biology and possible common contribution to organismal development and tissue homeostasis of all JmjC proteins remains unclear. Here, we systematically tested the function of all 13 Drosophila JmjC genes. Generation of molecularly defined null mutants revealed that loss of 8 out of 13 JmjC genes modify position effect variegation (PEV) phenotypes, consistent with their ascribed role in regulating chromatin organization. However, most JmjC genes do not critically regulate development, as 10 members are viable and fertile with no obvious developmental defects. Rather, we find that different JmjC mutants specifically alter the phenotypic outcomes in various sensitized genetic backgrounds. Our data demonstrate that, rather than controlling essential gene expression programs, Drosophila JmjC proteins generally act to “fine-tune” different biological processes

The North American Cordilleran Anatectic Belt

The North American Cordilleran Anatectic Belt (CAB) is a ~3,000 km long region in the hinterland of the Cordillera that comprises numerous exposures of Late Cretaceous to Eocene intrusive rocks and anatectic rocks associated with crustal melting. As such, it is comparable in size and volume to major anatectic provinces including the Himalayan leucogranite belt. The CAB rocks are chiefly peraluminous, muscovite-bearing leucogranite produced primarily by anatexis of Proterozoic to Archean metasedimentary rocks. The CAB rocks lack extrusive equivalents and were typically emplaced as thick sheets, laccoliths, and dike/sill complexes. The extent, location, and age of the CAB suggests that it is integral to understanding the tectonic evolution of North America, however, the belt is rarely considered as a whole. This paper reviews localities associated with crustal melting in the CAB and compiles geochemical, geochronologic, and isotopic data to evaluate the melt conditions and processes that generated these rocks. The geochemistry and partial melting temperatures (ca. 675–775 °C) support water-absent muscovite dehydration melting and/or water-deficient melting as the primary melt reactions and are generally inconsistent with water-excess melting and high-temperature (biotite to amphibole) dehydration melting. The CAB rocks are oldest in the central U.S. Cordillera and become younger towards both the north and south. At any single location, partial melting appears to have been a protracted process (≥10 Myr) and evidence for re-melting and remobilization of magmas is common. End-member hypotheses for the origin of the CAB include decompression, crustal thickening, fluid-flux melting, and increased heat flux from the mantle. Different parts of the CAB support different hypotheses and no single model may be able to explain the entirety of the anatectic event. Regardless, the CAB is a distinct component of the Cordilleran orogenic system

Drosophila CG2469 Encodes a Homolog of Human CTR9 and Is Essential for Development

Conserved from yeast to humans, the Paf1 complex participates in a number of diverse processes including transcriptional initiation and polyadenylation. This complex typically includes five proteins: Paf1, Rtf1, Cdc73, Leo1, and Ctr9. Previous efforts identified clear Drosophila homologs of Paf1, Rtf1, and Cdc73 based on sequence similarity. Further work showed that these proteins help to regulate gene expression and are required for viability. To date, a Drosophila homolog of Ctr9 has remained uncharacterized. Here, we show that the gene CG2469 encodes a functional Drosophila Ctr9 homolog. Both human and Drosophila Ctr9 localize to the nuclei of Drosophila cells and appear enriched in histone locus bodies. RNAi knockdown of Drosophila Ctr9 results in a germline stem cell loss phenotype marked by defects in the morphology of germ cell nuclei. A molecular null mutation of Drosophila Ctr9 results in lethality and a human cDNA CTR9 transgene rescues this phenotype. Clonal analysis in the ovary using this null allele reveals that loss of Drosophila Ctr9 results in a reduction of global levels of histone H3 trimethylation of lysine 4 (H3K4me3), but does not compromise the maintenance of stem cells in ovaries. Given the differences between the null mutant and RNAi knockdown phenotypes, the germ cell defects caused by RNAi likely result from the combined loss of Drosophila Ctr9 and other unidentified genes. These data provide further evidence that the function of this Paf1 complex component is conserved across species

AdipoGauge software for analysis of biological microscopic images

Obesity is a complex disease of global epidemic proportions. Adipose tissue expansion and chronic low-grade inflammation, locally and systemically, are hallmark features of obesity. Obesity is associated with several other chronic diseases, which are also characterized by inflammation. Determination of adipocyte size and macrophage content in adipose tissue is a critical step in assessing changes in this tissue with obesity. Here, we introduce a complete standalone software package, AdipoGauge, to analyse microscopic images derived from haematoxylin and eosin (H&E)-stained and immunofluorescently stained histology sections of adipose tissue. The software package is a user-friendly application that does not require a vast knowledge of computer science or costly commercial tools. AdipoGauge includes analysing tools that are capable of cell counting and colour separation. Furthermore, it can quantify the cell data in images both with and without clear boundaries around the cells. It can also remove objects from the image that are not intended for analysis, such as blood vessels or partial cells at edges of slide sections. The simple and state-of-the-art graphical user interface requires minimal time and learning

Dietary pH Enhancement Improves Metabolic Outcomes in Diet-Induced Obese Male and Female Mice: Effects of Beef vs. Casein Proteins

(1) Consumption of diets that are caloric dense but not nutrient dense have been implicated in metabolic diseases, in part through low-grade metabolic acidosis. Mitigation strategies through dietary intervention to alleviate acidosis have not been previously reported. Our objective is to determine the effects of pH enhancement (with ammonia) in high fat diet-induced obese mice that were fed beef or casein as protein sources compared to low fat diet-fed mice. (2) Methods: B6 male and female mice were randomized (n = 10) into eight diets that differ in protein source, pH enhancement of the protein, and fat content, and fed for 13 weeks: low fat (11% fat) casein (LFC), LF casein pH-enhanced (LFCN), LF lean beef (LFB), LFBN, high fat (46%) casein (HFC), HFCN, HF beef (HFB), and HFBN. Body weights and composition, and glucose tolerance tests were conducted along with terminal serum analyses. Three-way ANOVA was performed. (3) Results: A significant effect of dietary fat (LF vs. HF) was observed across all variables in both sexes (final body weight, fat mass, glucose clearance, and serum leptin). Importantly, pH enhancement significantly reduced adiposity (males only) and final body weights (females only) and significantly improved glucose clearance in both sexes. Lastly, clear sex differences were observed across all variables. (4) Conclusions: Our findings demonstrate metabolic benefits of increasing dietary pH using ammonia, while high fat intake per se (not protein source) is the major contributor to metabolic dysfunctions. Additional research is warranted to determine mechanisms underlying the beneficial effects of pH enhancement, and interactions with dietary fat content and proteins

Tart Cherry Reduces Inflammation in Adipose Tissue of Zucker Fatty Rats and Cultured 3T3-L1 Adipocytes

Obesity increases adipose tissue inflammation and secretion of pro-inflammatory adipokines, which have systemic effects on the organism’s health status. Our objective was to dissect mechanisms of anti-inflammatory effects of tart cherry (TC) in adipose tissue of Zucker fatty rats, and cultured 3T3-L1 adipocytes. Rats were fed either a control diet, or 4% TC powder diets for eight weeks. Body and epididymal fat pad weights were not significantly different between control and TC groups. However, rats fed the TC diet had significantly reduced adipose tissue inflammation (p < 0.05), as determined by reduced mRNA levels of pro-inflammatory markers including interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), interleukin-1beta (IL-1β), monocyte chemoattractant protein 1 (MCP-1), inducible nitric oxide synthase (iNOS), and CD-11b, and increased mRNA levels of type-1 arginase (Arg-1) anti-inflammatory marker. Consistent with these in vivo results, TC significantly decreased expression of IL-6 mRNA and protein levels in lipopolysaccharide (LPS) stimulated adipocytes compared to those stimulated with LPS, but no TC. Moreover, both in vivo (rat adipose tissue) and in vitro (3T3-L1 adipocytes), phosphorylation of p65-NF-κB subunit was significantly reduced by TC. Additionally, TC decreased mRNA expression of fatty acid synthase (FASN), and increased expression of peroxisome proliferator-activated receptor alpha (PPARα), master regulator of lipid oxidation, and anti-oxidant markers nuclear factor erythroid-derived 2-related factor (NRFs) in both models. In conclusion, our findings indicate that TC downregulates inflammation in part via the nuclear factor kappa B (NF-κB) pathway in adipose tissue. Thus, TC may serve as a potential intervention to reduce obesity-associated inflammation

Inactivation of adipose Angiotensinogen reduces inflammatory adipokines and adipose tissue macrophages

Adiposerennin-angiotensin systemhasbeen linked to obesity and metabolic syndrome. Previously we showed that overexpression of Angiotensinogen(Agt) in adipose tissue increased insulin resistance, adipose and systemic inflammation in mice fed a low fat(LF)diet. To further dissect the direct role of adipose Agt in metabolic disorders,we have created an adipose specific Agt knockout (Agt-KO)mice using the Cre-LoxPsystem.Agt-KO and control(WT) littermates were fed either a low-fat (LF) or high-fat (HF) diet to assess metabolic changes. Surprisingly, most metabolic parameters (body weight and fat mass, glucose and insulin tolerance tests) were comparable between the WT and Agt-KO littermates in both diets. Analyses of adipose tissue gene expression indicated shifts in angiogenesis and insulin signaling in the Agt-KO mice fed LF diets when compared to the WT mice. MCP1 gene expression was also downregulated in adipose tissue of the Agt-KO vs. WT littermates. These changes correlated with MCP-1 and Leptin protein expression, both of which were downregulated in the Agt-KO. Moreover,targeted inactivation of adipose Agt reduced total macrophage infiltration in both the LF and HF fed Agt-KO mice. This was in contrast to the total adipocyte area,which did not change between the two genotypes. In conclusion, despite the lack of an obvious phenotype in adipose Agt deficient mice, cellular and molecular changes observed are consistent with previously reported functions of RAS in insulin resistance, and inflammation

Mesozoic to Cenozoic magmatic history of the Pamir

New geochronologic, geochemical, and isotopic data for Mesozoic to Cenozoic igneous rocks and detrital minerals from the Pamir Mountains help to distinguish major regional magmatic episodes and constrain the tectonic evolution of the Pamir orogenic system. After final accretion of the Central and South Pamir terranes during the Late Triassic to Early Jurassic, the P amir was largely amagmatic until the emplacement of the intermediate (SiO2 > 60 wt.%), talc-alkaline, and isotopically evolved (-13 to -5 zircon epsilon Hf-(t)) South Pamir batholith between 120-100 Ma, which is the most volumetrically significant magmatic complex in the Pamir and includes a high flux magmatic event at similar to 105 Ma. The South Pamir batholith is interpreted as the northern (inboard) equivalent of the Cretaceous Karakoram batholith and the along-strike equivalent of an Early Cretaceous magmatic belt in the northern Lhasa terrane in Tibet. The northern Lhasa terrane is characterized by a similar high-flux event at similar to 110 Ma. Migration of continental arc magmatism into the South Pamir terrane during the mid-Cretaceous is interpreted to reflect northward directed, low-angle to flat-slab subduction of the Neo-Tethyan oceanic lithosphere. Late Cretaceous magmatism (80-70 Ma) in the Pamir is scarce, but concentrated in the Central and northern South Pamir terranes where it is comparatively more mafic (SiO2 2500 km across the Pamir and northern Qiangtang terrane in Tibet. All of these complexes are located directly south of the Tanymas-Jinsha suture zone, an important lithospheric and rheological boundary that focused mantle lithosphere deformation after India-Asia collision. Miocene magmatism (20-10 Ma) in the Pamir includes: 1) isotopically evolved migmatite and leucogranite related to crustal anataxis and decompression melting within extensional gneiss domes, and; 2) localized intra-continental magmatism in the Dunkeldik/Taxkorgan complex. (C) 2017 Elsevier B.V. All rights reserved.NSF [EAR-1419748, EAR-1450899, EAR-1338583]; Romanian Executive Agency for Higher Education, Research, Development and Innovation [PN-III-P4-ID-PCE-2016-0127]; EarthScope Award for Geochronology Student Research24 month embargo; published online: 16 November 2017This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]