The expression and signalling patterns of CD180 toll like receptor in Chronic Lymphocytic Leukaemia (CLL)

Chronic lymphocytic leukaemia (CLL) is characterised by a progressive accumulation of mature CD5+CD20+CD23+ lymphocytes. Despite the remarkable progress in our understanding of the immunobiology of CLL, the aetiology of the disease remains unknown. The consensus is that CLL cells are driven by (auto)antigen(s) through the B cell receptor (BCR) and are regulated by a variety of signals received from the microenvironment, including toll-like receptors (TLR).Our group has previously shown that engagement of the CD180 orphan TLR expressed by approximately 60% of CLL cells, can re-wire the sIgM-mediated signalling from a pro-survival pathway, involving phosphatidylinositol-4,5-bisphosphate3-kinase (PI3K) and protein kinase B (AKT) to the potentially pro-apoptotic pathway through mitogen-activated protein kinase (p38MAPK). However, little is known about the function of the other BCR - sIgD in CLL and its possible interaction with CD180. Here we studied intracellular signalling and apoptosis of CLL cells following sole or sequential ligation of CD180 and sIgD. Our data indicated that following sequential ligation of CD180 and sIgD, CLL samples demonstrated enhanced p38MAPK phosphorylation leading to increased apoptosis of CLL cells indicating synergistic relationship between CD180 and sIgD. To better understand the prognostic importance of CD180 expression we sought to determine whether CD180 and other prognostic markers such as CD38 and ZAP70 displayed any correlation with the known cytogenetic aberrations:TP53 and DLEU1. Our results suggested that CLL cells with DLEU1 deletion are characterised by the negative expression of both, CD180 and CD38, and this might have a significance for CLL prognosis. To explain this correlation, we hypothesised that interaction of CLL cells with their microenvironment through TLRs leads to the expansion of leukaemic clones, in vivo, in lymph nodes. Our results indicated that CD180 is heterogeneously expressed in the paraffin tissue sections of the lymph nodes of CLL patients and its expression positively correlates with the expression of Ki-67. Our data demonstrated, that although CD180 expression and signaling might have negative prognostic importance in CLL due to the enhanced proliferation of leukaemic cells, its interaction with sIgD would re-direct leukaemic cells towards apoptosis thus opening new opportunities for the disease immunotherapy

Increasing Performance through Assessed Training (A Human Recourse Management Strategy)

This research finds out the way of increasing employee’s performance through training. There are many organizations which give their workers training but do not get any enhancement in their performance. Performances of a worker are directly correlated with his/her capabilities and know how to do the job. This study develops a strategy for improving the capabilities of workers which leads to increase their performance. The research proposes that just after an organization want to increase the performance of its workers, it must find out the area where they have weaknesses. After finding out the weaknesses, organizations have to assess how that weakness should be made solved. In the third stage they have to give specific training their weaknesses. This will enhance the capabilities of workers and their performance will be increased. Keywords: Weakness, Weakness needs Assessments, Training and Performanc

Mapping Regional Turbulent Heat Fluxes via Assimilation of MODIS Land Surface Temperature Data into an Ensemble Kalman Smoother Framework

Estimation of turbulent heat fluxes via variational data assimilation (VDA) approaches has been the subject of several studies. The VDA approaches need an adjoint model that is difficult to derive. In this study, remotely sensed land surface temperature (LST) data from the Moderate Resolution Imaging Spectroradiometer (MODIS) are assimilated into the heat diffusion equation within an ensemble Kalman smoother (EnKS) approach to estimate turbulent heat fluxes. The EnKS approach is tested in the Heihe River Basin (HRB) in northwest China. The results show that the EnKS approach can estimate turbulent heat fluxes by assimilating low temporal resolution LST data from MODIS. The findings indicate that the EnKS approach performs fairly well in various hydrological and vegetative conditions. The estimated sensible (H) and latent (LE) heat fluxes are compared with the corresponding observations from large aperture scintillometer systems at three sites (namely, Arou, Daman, and Sidaoqiao) in the HRB. The turbulent heat flux estimates from EnKS agree reasonably well with the observations, and are comparable to those of the VDA approach. The EnKS approach also provides statistical information on the H and LE estimates. It is found that the uncertainties of H and LE estimates are higher over wet and/or densely vegetated areas (grassland and forest) compared to the dry and/or slightly vegetated areas (cropland, shrubland, and barren land)

Nitrate- and silicate-competition among antarctic phytoplankton

Natural phytoplankton from antarctic waters in the Drake Passage were used for competition experiments in semicontinuous cultures. The outcome of interspecific competition for silicate and nitrate was studied at a range of Si:N ratios (from 2.6:1 to 425:1) and at three different dilution rates. For five species Monod kinetics of silicate-and nitrate-limited growth has been established. Comparison between theoretical predictions derived from Monod kinetics and the outcome of competition experiments showed only minor deviations. Contrary to literature data, considerable depletion of nitrate was found in antarctic seawater. Both the concentrations of soluble silicate and of nitrate were too low to support maximum growth rates of some of the diatom species under investigation

A split-mouth randomized controlled trial to compare the rate of canine retraction after a soft tissue procedure compared against a corticotomy procedure for accelerated tooth movement

Background and Aim: Various methods to accelerate the orthodontic tooth movement have been used, among which corticotomy is considered to be the most common one. The suggested reasoning for such acceleration was the regional acceleratory phenomenon (RAP). Since the RAP is a property of both the hard and soft tissues, we designed a soft tissue flap procedure to compare the effects with the conventional corticotomy procedure. A split-mouth study was conducted where the two procedures were assessed in a single participant. Patients and Methods: The total sample size was calculated to be 40 with 20 participants in each group. The rate of tooth movement was the primary outcome measure, and the secondary outcomes were dentoalveolar changes, which were studied in both the conventional corticotomy and the flap-only procedure based on a cone-beam computed tomography (CBCT) wherein the alveolar bone density (BD) around canines, tipping, and rotational changes in canines, premolars, and molars were assessed. Results: Corticotomy resulted in greater canine angulation, lesser canine rotation and premolar rotation, and greater molar rotation compared with flap elevation, but these differences were statistically insignificant. Conclusion: Though the corticotomy resulted in higher BD, the differences were statistically insignificant. There was no significant difference in the rate of space closure assessed by the two techniques compared

Von Hippel-Lindau protein in the RPE is essential for normal ocular growth and vascular development

Molecular oxygen is essential for the development, growth and survival of multicellular organisms. Hypoxic microenvironments and oxygen gradients are generated physiologically during embryogenesis and organogenesis. In the eye, oxygen plays a crucial role in both physiological vascular development and common blinding diseases. The retinal pigment epithelium (RPE) is a monolayer of cells essential for normal ocular development and in the mature retina provides support for overlying photoreceptors and their vascular supply. Hypoxia at the level of the RPE is closely implicated in pathogenesis of age-related macular degeneration. Adaptive tissue responses to hypoxia are orchestrated by sophisticated oxygen sensing mechanisms. In particular, the von Hippel-Lindau tumour suppressor protein (pVhl) controls hypoxia-inducible transcription factor (HIF)-mediated adaptation. However, the role of Vhl/Hif1a in the RPE in the development of the eye and its vasculature is unknown. In this study we explored the function of Vhl and Hif1a in the developing RPE using a tissue-specific conditional-knockout approach. We found that deletion of Vhl in the RPE results in RPE apoptosis, aniridia and microphthalmia. Increased levels of Hif1a, Hif2a, Epo and Vegf are associated with a highly disorganised retinal vasculature, chorioretinal anastomoses and the persistence of embryonic vascular structures into adulthood. Additional inactivation of Hif1a in the RPE rescues the RPE morphology, aniridia, microphthalmia and anterior vasoproliferation, but does not rescue retinal vasoproliferation. These data demonstrate that Vhl-dependent regulation of Hif1a in the RPE is essential for normal RPE and iris development, ocular growth and vascular development in the anterior chamber, whereas Vhl-dependent regulation of other downstream pathways is crucial for normal development and maintenance of the retinal vasculature

The Effect of Statin Therapy on the Incidence of Infections: A Retrospective Cohort Analysis

Statins have been postulated to prevent infection through immunomodulatory effects

Poverty moderates the association between gender and school dropout in South African adolescents

This study examined prospective associations between poverty, gender, and school dropout in a large community sample of South African adolescents (baseline: n = 3515, follow-up: n = 3401, 57% female, age range at baseline: 10–17 years, mean age at baseline = 13.45). School dropout was defined as being enrolled in school at baseline assessment but no longer enrolled in school at follow-up assessment. Poverty was measured at baseline assessment using an index of access to the eight highest socially perceived necessities for South African children and adolescents. Demographic characteristics including child gender and age, province, and urban versus rural location were recorded at baseline assessment and controlled for in the analysis. As predicted, higher poverty scores (AOR = 2.01, p < .001) were associated with increased odds of school dropout 1 year later. Gender was not a significant predictor of school dropout (AOR = 1.56, p = .07) but did interact with poverty (AOR = 0.66, p = .04) in predicting school dropout. However, our initial hypothesis that the impact of poverty on school dropout would be stronger for girls than boys was not supported. Instead, results indicated that while girls were at elevated risk of school dropout at low and mean levels of poverty, at high levels of poverty this gender difference was no longer evident. Findings suggest that vulnerable boys should not be neglected in policies to improve retention in education in contexts of extreme poverty