Direct bone marrow HSC transplantation enhances local engraftment at the expense of systemic engraftment in NSG mice

Direct bone marrow (BM) injection has been proposed as a strategy to bypass homing inefficiencies associated with intravenous (IV) hematopoietic stem cell (HSC) transplantation. Despite physical delivery into the BM cavity, many donor cells are rapidly redistributed by vascular perfusion, perhaps compromising efficacy. Anchoring donor cells to 3-dimensional (3D) multicellular spheroids, formed from mesenchymal stem/stromal cells (MSC) might improve direct BM transplantation. To test this hypothesis, relevant combinations of human umbilical cord blood-derived CD34(+) cells and BM-derived MSC were transplanted into NOD/SCID gamma (NSG) mice using either IV or intrafemoral (IF) routes. IF transplantation resulted in higher human CD45(+) and CD34(+) cell engraftment within injected femurs relative to distal femurs regardless of cell combination, but did not improve overall CD45(+) engraftment at 8 weeks. Analysis within individual mice revealed that despite engraftment reaching near saturation within the injected femur, engraftment at distal hematopoietic sites including peripheral blood, spleen and non-injected femur, could be poor. Our data suggest that the retention of human HSC within the BM following direct BM injection enhances local chimerism at the expense of systemic chimerism in this xenogeneic model.

Expression profiling of lymph nodes in tuberculosis patients reveal inflammatory milieu at site of infection

Extrapulmonary manifestations constitute 15 to 20% of tuberculosis cases, with lymph node tuberculosis (LNTB) as the most common form of infection. However, diagnosis and treatment advances are hindered by lack of understanding of LNTB biology. To identify host response, Mycobacterium tuberculosis infected lymph nodes from LNTB patients were studied by means of transcriptomics and quantitative proteomics analyses. The selected targets obtained by comparative analyses were validated by quantitative PCR and immunohistochemistry. This approach provided expression data for 8,728 transcripts and 102 proteins, differentially regulated in the infected human lymph node. Enhanced inflammation with upregulation of T-helper1-related genes, combined with marked dysregulation of matrix metalloproteinases, indicates tissue damage due to high immunoactivity at infected niche. This expression signature was accompanied by significant upregulation of an immunoregulatory gene, leukotriene A4 hydrolase, at both transcript and protein levels. Comparative transcriptional analyses revealed LNTB-specific perturbations. In contrast to pulmonary TB-associated increase in lipid metabolism, genes involved in fatty-acid metabolism were found to be downregulated in LNTB suggesting differential lipid metabolic signature. This study investigates the tissue molecular signature of LNTB patients for the first time and presents findings that indicate the possible mechanism of disease pathology through dysregulation of inflammatory and tissue-repair processes.

Germination biology and occurrence of pol-yembryony in two forms of cats claw creeper vine, Dolichandra unguis-cati (Bignonia-ceae): implications for its invasiveness and management

Cat’s claw creeper, Dolichandra unguis-cati (L.) Lohmann (syn. Macfadyena unguis-cati (L.) Gentry) is a major environmental weed in Australia. Two forms (‘long’ and ‘short’ pod) of the weed occur in Australia. This investigation aimed to evaluate and compare germination behavior and occurrence of polyembryony in the two forms of the weed. Seeds were germinated in growth chambers set to 10/20 °C, 15/25 °C, 20/30 °C, 30/45 °C and 25 °C. Germination and polyembryony were monitored over a period of 12 weeks. For all the treatments in this study, seeds from the short pod form exhibited significantly higher germination rates and higher occurrence of polyembryony than those from the long pod form. Seeds from the long pod form did not germinate at the lowest temperature of 10/20 °C; in contrast, those of the short pod form germinated under this condition, albeit at a lower rate. Results from this study could explain why the short pod form of D. unguis-cati is the more widely distributed form in Australia, while the long pod form is confined to a few localities. The results have implication in predicting future ranges of both forms of the invasive D. unguis-cati, as well as inform management decisions for control of the weed.

Experiences in becoming a paramedic: The professional socialization of university qualified paramedics

In this article, the professional socialization of university educated paramedics from the United Kingdom and Australia is discussed using the anticipatory, formal and post-formal phases of socialization. Participants for this research were from universities and ambulance services in Australia and the United Kingdom, and the data were collected and analyzed by qualitative methods. The anticipatory, formal and post-formal phases were deemed to be relevant to the professional socialization of university paramedics. However a fourth phase, called the post-internship phase was identified which better accounted for the paramedic training and practice model. The findings from this research led to the development of a four phase model of professional socialization to describe the experiences of university educated paramedics making the transition from university students to qualified paramedics.