Chromosome phylogeny of the subfamily Pitheciinae (Platyrrhini,Primates) by classic cytogenetics and chromosome painting

Background  

The New World monkey (Platyrrhini) subfamily Pitheciinae is represented by the genera Pithecia, Chiropotes and Cacajao. In this work we studied the karyotypes of Pithecia irrorata (2n = 48) and Cacajao calvus rubicundus (2n = 45 in males and 2n = 46 in females) by G- and C-banding, NOR staining and chromosome painting using human and Saguinus oedipus whole chromosome probes. The karyotypes of both species were compared with each other and with Chiropotes utahicki (2n = 54) from the literature.     

<Emphasis Type="Italic">MLPAinter for MLPA interpretation:</Emphasis> an integrated approach for the analysis,visualisation and data management of Multiplex Ligation-dependent Probe Amplification

Background  

Multiplex Ligation-Dependent Probe Amplification (MLPA) is an application that can be used for the detection of multiple chromosomal aberrations in a single experiment. In one reaction, up to 50 different genomic sequences can be analysed. For a reliable work-flow, tools are needed for administrative support, data management, normalisation, visualisation, reporting and interpretation.     

The role of indoleamine 2, 3 dioxygenase in regulating host immunity to leishmania infection

Pathogen persistence in immune-competent hosts represents an immunological paradox. Increasing evidence suggests that some pathogens, such as, Leishmania major (L. major) have evolved strategies and mechanisms that actively suppress host adaptive immunity. If this notion is correct conventional vaccination therapies may be ineffective in enhancing host immunity, unless natural processes that suppress host immunity are also targeted therapeutically. The key problem is that the basis of pathogen persistence in immune-competent individuals is unknown, despite decades of intense research. This fact, coupled with poor health care and a dearth of effective treatments means that these diseases will remain a scourge on humans unless a better understanding of why the immune system tolerates such infections emerges from research. Indoleamine 2,3-dioxygenase (IDO) has been shown to act as a molecular switch regulating host responses, and IDO inhibitor drugs shown to possess potential in enhancing host immunity to established leishmania infections. It is hoped that this review will help stimulate and help generate critical new knowledge pertaining to the IDO mechanism and how to exploit it to suppress T cell mediated immunity, thus offer an innovative approach to studying the basis of chronic leishmania infection in mice.     

Production of stable bispecific IgG1 by controlled Fab-arm exchange

The manufacturing of bispecific antibodies can be challenging for a variety of reasons. For example, protein expression problems, stability issues, or the use of non-standard approaches for manufacturing can result in poor yield or poor facility fit. In this paper, we demonstrate the use of standard antibody platforms for large-scale manufacturing of bispecific IgG1 by controlled Fab-arm exchange. Two parental antibodies that each contain a single matched point mutation in the CH3 region were separately expressed in Chinese hamster ovary cells and manufactured at 1000 L scale using a platform fed-batch and purification process that was designed for standard antibody production. The bispecific antibody was generated by mixing the two parental molecules under controlled reducing conditions, resulting in efficient Fab-arm exchange of >95% at kg scale. The reductant was removed via diafiltration, resulting in spontaneous reoxidation of interchain disulfide bonds. Aside from the bispecific nature of the molecule, extensive characterization demonstrated that the IgG1 structural integrity was maintained, including function and stability. These results demonstrate the suitability of this bispecific IgG1 format for commercial-scale manufacturing using standard antibody manufacturing techniques.     

Developmental Responses to Drought and Abscisic Acid in Sunflower Roots: 2. MITOTIC ACTIVITY

Mitotic activity was studied in the root apices of aeroponicallygrown sunflower seedlings (Helianthus annum L. var. RussianGiant) which were draughted or treated with abscisic acid (ABA)over a 7 d period. Labelling index (LI) and mitotic index (MI)were scored from autoradiographs of median longitudinal sectionsof [³H] methyl-thymidine treated root apices. Both drought stressand ABA-treatment (at a concentration of 10^–2 mol m^–3inhibited DNA synthesis and mitosis within the first 6 h oftreatment. The depression of mitotic activity was first evidentin the proximal regions of the meristem (1000–1500 µmfrom the cap junction). This was followed by a general depressionof mitotic activity throughout the meristem which was, in turn,followed by a partial recovery of mitotic activity in the distalregions of the meristem. The beginning of this partial recoverywas concurrent with the activation of the quiescent centre (QC).Treatment with lower concentrations of ABA (10^–3 mol m^–3and 10^–4 mol m^–3) also inhibited mitotic activity.Exogenous supplements of sucrose to the plant did not alleviatethe inhibition of mitotic activity by drought or ABA. Thesefindings support the hypothesis that ABA mediates drought-inducedchanges in the primary development of sunflower roots. Key words: Abscisic acid, drought, mitotic activity     

KAP1 regulates endogenous retroviruses in adult human cells and contributes to innate immune control

Endogenous retroviruses (ERVs) have accumulated in vertebrate genomes and contribute to the complexity of gene regulation. KAP1 represses ERVs during development by its recruitment to their repetitive sequences through KRAB zinc‐finger proteins (KZNFs), but little is known about the regulation of ERVs in adult tissues. We observed that KAP1 repression of HERVK14C was conserved in differentiated human cells and performed KAP1 knockout to obtain an overview of KAP1 function. Our results show that KAP1 represses ERVs (including HERV‐T and HERV‐S) and ZNF genes, both of which overlap with KAP1 binding sites and H3K9me3 in multiple cell types. Furthermore, this pathway is functionally conserved in adult human peripheral blood mononuclear cells. Cytosine methylation that acts on KAP1 regulated loci is necessary to prevent an interferon response, and KAP1‐depletion leads to activation of some interferon‐stimulated genes. Finally, loss of KAP1 leads to a decrease in H3K9me3 enrichment at ERVs and ZNF genes and an RNA‐sensing response mediated through MAVS signaling. These data indicate that the KAP1‐KZNF pathway contributes to genome stability and innate immune control in adult human cells.     

HEALTH AS FREEDOM: ADDRESSING SOCIAL DETERMINANTS OF GLOBAL HEALTH INEQUITIES THROUGH THE HUMAN RIGHT TO DEVELOPMENT

In spite of vast global improvements in living standards, health, and well-being, the persistence of absolute poverty and its attendant maladies remains an unsettling fact of life for billions around the world and constitutes the primary cause for the failure of developing states to improve the health of their peoples. While economic development in developing countries is necessary to provide for underlying determinants of health – most prominently, poverty reduction and the building of comprehensive primary health systems – inequalities in power within the international economic order and the spread of neoliberal development policy limit the ability of developing states to develop economically and realize public goods for health. With neoliberal development policies impacting entire societies, the collective right to development, as compared with an individual rights-based approach to development, offers a framework by which to restructure this system to realize social determinants of health. The right to development, working through a vector of rights, can address social determinants of health, obligating states and the international community to support public health systems while reducing inequities in health through poverty-reducing economic growth. At an international level, where the ability of states to develop economically and to realize public goods through public health systems is constrained by international financial institutions, the implementation of the right to development enables a restructuring of international institutions and foreign-aid programs, allowing states to enter development debates with a right to cooperation from other states, not simply a cry for charity.