Targeted deletion of the mouse \u3ci\u3eMitoferrin1\u3c/i\u3e gene: from anemia to protoporphyria

Mitoferrin1 is 1 of 2 homologous mitochondrial iron transporters and is required for mitochondrial iron delivery in developing erythroid cells. We show that total deletion of Mfrn1 in embryos leads to embryonic lethality. Selective deletion of Mfrn1 in adult hematopoietic tissues leads to severe anemia because of a deficit in erythroblast formation. Deletion of Mfrn1 in hepatocytes has no phenotype or biochemical effect under normal conditions. In the presence of increased porphyrin synthesis, however, deletion of Mfrn1 in hepatocytes results in a decreased ability to convert protoporphyrin IX into heme, leading to protoporphyria, cholestasis, and bridging cirrhosis. Our results show that the activity of mitoferrin1 is required to manage an increase in heme synthesis. The data also show that alterations in heme synthesis within hepatocytes can lead to protoporphyria and hepatotoxicity

A process of resection-dependent nonhomologous end joining involving the goddess Artemis

DNA double-strand breaks (DSBs) are a hazardous form of damage that can potentially cause cell death or genomic rearrangements. In mammalian G1- and G2-phase cells, DSBs are repaired with two-component kinetics. In both phases, a fast process uses canonical nonhomologous end joining (c-NHEJ) to repair the majority of DSBs. In G2, slow repair occurs by homologous recombination. The slow repair process in G1 also involves c-NHEJ proteins but additionally requires the nuclease Artemis and DNA end resection. Here, we consider the nature of slow DSB repair in G1 and evaluate factors determining whether DSBs are repaired with fast or slow kinetics. We consider limitations in our current knowledge and present a speculative model for Artemis-dependent c-NHEJ and the environment underlying its usage

Phosphorylation of a membrane curvature–sensing motif switches function of the HOPS subunit Vps41 in membrane tethering

An AP-3–binding site required for vesicle–vacuole fusion is masked when Vps41 is associated with highly curved membranes, such as endosomes, but is exposed at membranes with lower curvature, such as vacuoles, because of phosphorylation of the membrane-binding motif

Discovery and characterization of two new stem rust resistance genes in Aegilops sharonensis

Stem rust is one of the most important diseases of wheat in the world. When single stem rust resistance (Sr) genes are deployed in wheat, they are often rapidly overcome by the pathogen. To this end, we initiated a search for novel sources of resistance in diverse wheat relatives and identified the wild goat grass species Aegilops sharonesis (Sharon goatgrass) as a substantial reservoir of resistance to wheat stem rust. The objectives of this study were to discover and map novel Sr genes in Ae. sharonensis and to explore the possibility of identifying new Sr genes by genome-wide association study (GWAS). We developed two biparental populations between resistant and susceptible accessions of Ae. sharonensis and performed QTL and linkage analysis. In an F6 recombinant inbred line and an F2 population, two genes were identified that mapped to the short arm of chromosome 1Ssh, designated as Sr-1644-1Sh, and the long arm of chromosome 5Ssh, designated as Sr-1644-5Sh. The gene Sr-1644-1Sh confers a high level of resistance to race TTKSK (one of the Ug99 lineage races), while the gene Sr-1644-5Sh conditions strong resistance to TRTTF, another widely virulent race found in Yemen. Additionally, GWAS was conducted on 125 diverse Ae. sharonensis accessions for stem rust resistance. The gene Sr-1644-1Sh was detected by GWAS, while Sr-1644-5Sh was not detected, indicating that the effectiveness of GWAS might be affected by marker density, population structure, low allele frequency and other factors

Using fish models to investigate the links between microbiome and social behaviour: the next step for translational microbiome research?

Recent research has revealed surprisingly important connections between animals’ microbiome and social behaviour. Social interactions can affect the composition and function of the microbiome; conversely, the microbiome affects social communication by influencing the hosts’ central nervous system and peripheral chemical communication. These discoveries set the stage for novel research focusing on the evolution and physiology of animal social behaviour in relation to microbial transmission strategies. Here, we discuss the emerging roles of teleost fish models and their potential for advancing research fields, linked to sociality and microbial regulation. We argue that fish models, such as the zebrafish (Danio rerio, Cyprinidae), sticklebacks (‎Gasterosteidae), guppies (Poeciliidae) and cleaner–client dyads (e.g., obligate cleaner fish from the Labridae and Gobiidae families and their visiting clientele), will provide valuable insights into the roles of microbiome in shaping social behaviour and vice versa, while also being of direct relevance to the food and ornamental fish trades. The diversity of fish behaviour warrants more interdisciplinary research, including microbiome studies, which should have a strong ecological (field‐derived) approach, together with laboratory‐based cognitive and neurobiological experimentation. The implications of such integrated approaches may be of translational relevance, opening new avenues for future investigation using fish models

PhD

dissertationA number of studies have outlined general features of the endocytic pathway. Specific details are lacking regarding the factors that regulate the rates of movement of receptors and ligands within the endocytic pathway, as well as the organelles which constitute the pathway. These studies demonstrated that the rates of internalization of different receptor-ligand complexes, in a single cell type, are different, and that the specific internalization rate of a receptor-ligand complex was unaffected by either the degree of receptor occupancy or the simultaneous internalization of different receptor-ligand complexes in alveolar macrophages. Different receptor-ligand complexes were shown to be internalized into the same endosomes. After internalization, the degradation of different ligands was initiated at the same time, suggesting that ligands that move to the degradative compartment move at the same rate regardless of whether ligands were internalized by receptor-mediated or fluid-phase pinocytosis. Different receptors move back to the cell surface at the same rate, regardless of whether they were initially unoccupied or occupied. The fusion of sequentially internalized vesicles was examined in alveolar macrophages and HeLa cells. The results demonstrated that most ligands internalized at different times mixed within early endosomes, thus demonstrating fusion of sequentially internalized vesicles. The fusion of early endosomes appeared to involve a long lived fusion competent vesicle in which receptor and ligand sorting occurred. Transferrin molecules were shown to move into and out of this sorting compartment very rapidly such that sequentially internalized transferrin molecules did not mix in early endosomes. Additionally, sequentially internalized transferrin molecules did not mix in recycling endosomes. Ligands destined for the lysosome appeared to move rapidly into and out of fusion competent early endosomes. Within the late endocytic pathway sequentially internalized vesicles were capable of fusing prior to the lysosome. This later fusion compartment was defined as a late endosome based on the absence of transferrin-transferrin receptors and classic lysosomal markers, such as acid glycosidases. Ligand degradation occurred in this compartment, indicating the presence of proteases. The ability of late endosomes to fuse with demonstrated using lowered temperatures and/or a methodology that inhibited late endosome-lysosome fusion, the substitution of K+ for Na+ in incubation buffers. It was determined that the substitution of K+ for Na+ buffers prevented endosome-lysosome fusion in a number of different cell types. These studies also included an investigation of the mechanisms(s) by which iso-K+ solutions inhibited endosome movement. A number of potential agents or molecules were ruled out as being causal to the inhibition of endosome-lysosome fusion including: pH changes, alteration in microtubules, and increases in intracellular cyclic-AMP or Ca[2+]. Studies using ion substitution, or sucrose addition, identified changes in cell volume as being causal to derangements in late endosome movement

Processing and Marketing Cottonseed Cooperatively

Excerpt from the report: An estimated 50,000 cotton growers of this country are increasing their returns from cottonseed by owning and operating their own cottonseed oil mills on a cooperative basis. In some cases individual farmers have set up the cooperative mill. In others cooperative cotton gins, made up of individual growers, have formed the organization. Still others have both individual producers and cooperative gins as members. This report will give in some detail information on the organization, services, operating methods, and policies of these organizations and the technical processes involved in crushing cottonseed