Id1 Restrains p21 Expression to Control Endothelial Progenitor Cell Formation

Loss of Id1 in the bone marrow (BM) severely impairs tumor angiogenesis resulting in significant inhibition of tumor growth. This phenotype has been associated with the absence of circulating endothelial progenitor cells (EPCs) in the peripheral blood of Id1 mutant mice. However, the manner in which Id1 loss in the BM controls EPC generation or mobilization is largely unknown. Using genetically modified mouse models we demonstrate here that the generation of EPCs in the BM depends on the ability of Id1 to restrain the expression of its target gene p21. Through a series of cellular and functional studies we show that the increased myeloid commitment of BM stem cells and the absence of EPCs in Id1 knockout mice are associated with elevated p21 expression. Genetic ablation of p21 rescues the EPC population in the Id1 null animals, re-establishing functional BM-derived angiogenesis and restoring normal tumor growth. These results demonstrate that the restraint of p21 expression by Id1 is one key element of its activity in facilitating the generation of EPCs in the BM and highlight the critical role these cells play in tumor angiogenesis

DEVELOPMENT AND OPTIMIZATION OF CARVEDILOL FORMULATION USING EXPERIMENTAL DESIGN

The aim of this paper was to develop and optimize the carvedilol tablets formulation using the full factorial design. The content of binder (PVP K30), content of disintegrant (crospovidone) and main compression force were used as the independent variables. Tablets were prepared by wet granulation. The percentage of released carvedilol from prepared formulation after 10 minutes was defined as the response. It has been found that formulation with the low content of binding agents (4.8%), high content of disintegrant (4.5%) and compression force of 50 N has the best profile of drug. The optimal formulation was defined based on implementation of pharmaceuticaltechnological tests (testing strength, friability, disintegrating, contents of drug substance, drug release profiles). The stability of the optimal formulation with carvedilol was estimated using the aging tests

Dynamics of wet flue gas desulphurization in spray absorber

A concise one dimensional thermal-hydraulic two-fluid model is presented for the numerical prediction of sulphur dioxide absorption from the flue gas onto drops of the water-limestone slurry in the vertical spray tower absorber. The model is based on mass, momentum and energy balance equations for each phase separately, i.e. downward falling droplets of water-limestone slurry and upward flowing flue gas. The sulphur dioxide content in the flue gas is predicted by a balance equation of the sulphur dioxide mass fraction in the flue gas. Interface transfer processes between the flue gas and the droplets are determined by closure laws. The obtained steady-state balance equations are transformed in a form suitable for a direct application of the numerical integration method for the system of ordinary differential equations. The developed thermal-hydraulic model is validated by comparing numerical results with available measured data at the large utility absorber. The presented results clearly show the dynamics of flue gas and droplets thermal-hydraulic processes and their influence on the absorption process

Signaling via interleukin-4, receptor alpha chain is required for successful vaccination against schistosomiasis in BALB/c mice

Radiation-attenuated (RA) schistosome larvae are potent stimulators of innate immune responses at the skin site of exposure (pinna) that are likely to be important factors in the development of Th1-mediated protective immunity. In addition to causing an influx of neutrophils, macrophages, and dendritic cells (DCs) into the dermis, RA larvae induced a cascade of chemokine and cytokine secretion following in vitro culture of pinna biopsy samples. While macrophage inflammatory protein 1 and interleukin-1 (IL-1) were produced transiently within the first few days, the Th1-promoting cytokines IL-12 and IL-18 were secreted at high levels until at least day 14. Assay of C3H/HeJ mice confirmed that IL-12 secretion was not due to lipopolysaccharide contaminants binding Toll-like receptor 4. Significantly, IL-12 p40 secretion was sustained in pinnae from vaccinated mice but not in those from nonprotected infected mice. In contrast, IL-10 was produced from both vaccinated and infected mice. This cytokine regulates IL-12-associated dermal inflammation, since in vaccinated IL-10/ mice, pinna thickness was greatly increased concurrent with elevated levels of IL-12 p40. A significant number of IL-12 p40 cells were detected as emigrants from in vitro-cultured pinnae, and most were within a population of rare large granular cells that were Ia, consistent with their being antigen-presenting cells. Labeling of IL-12 cells for CD11c, CD205, CD8, CD11b, and F4/80 indicated that the majority were myeloid DCs, although a proportion were CD11c F4/80, suggesting that macrophages were an additional source of IL-12 in the skin

Graph theory analysis of resting-state functional magnetic resonance imaging in essential tremor.

Essential tremor (ET) is a neurological disease with both motor and non-motor manifestations; however, little is known about its underlying brain basis. Furthermore, the overall organization of the brain network in ET remains largely unexplored. We investigated the topological properties of brain functional network, derived from resting-state functional MRI data, in 23 ET patients vs. 23 healthy controls. Graph theory analysis was used to assess the functional network organization. At the global level, the functional network of ET patients was characterized by lower small-world values than healthy controls - less clustered functionality of the brain. At the regional level, compared with the healthy controls, ET patients showed significantly higher values of global efficiency, cost and degree, and a shorter average path length in the left inferior frontal gyrus (pars opercularis), right inferior temporal gyrus (posterior division and temporo-occipital part), right inferior lateral occipital cortex, left paracingulate, bilateral precuneus bilaterally, left lingual gyrus, right hippocampus, left amygdala, nucleus accumbens bilaterally, and left middle temporal gyrus. In addition, ET patients showed significant higher local efficiency and clustering coefficient values in the frontal medial cortex bilaterally, subcallosal cortex, posterior cingulate, parahippocampal gyri bilaterally (posterior division), right lingual gyrus, right cerebellar flocculus, right postcentral gyrus, right inferior semilunar lobule of cerebellum and culmen of vermis. In conclusion, the efficiency of the overall brain functional network in ET is disrupted. Further, our results support the concept that ET is a disorder that disrupts widespread brain regions, including those outside of the brain regions responsible for tremor.pre-print1168 K

Rapid enhancer remodeling and transcription factor repurposing enable high magnitude gene induction upon acute activation of NK cells

During development, innate lymphocytes acquire defined sets of primed enhancers facilitating the rapid immune response. In this issue of Immunity, Sciumè et al. delineate the epigenetic changes occurring during acute NK cell activation, revealing the formation of de novo enhancers and repurposing of both lineage-determining and signal-regulated transcription factors

Tumor response and patient outcome after preoperative radiotherapy in locally advanced non-inflammatory breast cancer patients

Purpose: The purpose of this analysis was to assess the tumor response and long-term outcome in patients treated with preoperative radiotherapy (PRT) without systemic therapy. Methods: Between 1997 and 2000, 134 patients with non-inflammatory locally advanced breast cancer (LABC) were treated with PRT. The tumor dose was 45 Gy in 15 fractions to the breast and to regional lymph nodes over 6 weeks. Radical mastectomy was performed 6 weeks after PRT to all patients and adjuvant systemic therapy was administered as per protocol. The measures of disease outcome were overall survival (OS) and disease-free survival (DFS) which estimated using the Kaplan-Meier method. Results: Median follow-up was 74 months (range 4-216). Objective clinical tumor response after PRT was observed in 77.6% of the patients. Clinical complete tumor response (cCR) was achieved in 21.6% of the patients. Pathological CR in the breast was achieved in 15% of the patients. The 5- and 10-year OS were 55.1 and 37.8%, respectively. The 5- and 10-year DFS were 39.2 and 27%, respectively. Patients who achieved cCR had significantly longer OS in comparison with patients achieving clinical partial response (cPR) and clinical stable disease (cSD). Similarly, DFS of patients in the cCR group was longer compared with patients with cPR and cSD, yet without statistical significance. Conclusions: Our results showed that local control in LABC patients achieved by primary PRT, followed by radical mastectomy was comparable with the results reported in the literature. Complete pathologic response to PRT identified a subgroup of patients with a trend toward better DFS and OS

Experience with developing antibiotic stewardship programmes in Serbia : potential model for other Balkan countries?

Introduction: Antimicrobial resistance (AMR) and inappropriate use of antibiotics in children are important issues. Consequently, there is a need to develop comprehensive stewardship programmes even in hospitals with limited resources starting with children’s hospitals. Method: Retrospective observational analysis of antimicrobial utilization and resistance patterns over five years in a tertiary care children’s hospital in Serbia. Results: Cumulative AMR decreased but were still high, with high cumulative resistance rates among the most widely used antibiotics in the hospital. Total antibiotic use decreased from 2010 to 2014 although there was still high prescribing of reserved antibiotics. Conclusion: Concerns with inappropriate use, and high resistance rates, among some antibiotics used in the hospital are being used to develop guidance on future antibiotic use in this hospital, building on the recently introduced antibiotic stewardship programme, as well as encourage other hospitals in Serbia to review their policies

Palladium-Ceria Catalysts with Enhanced Alkaline Hydrogen Oxidation Activity for Anion Exchange Membrane Fuel Cells

International audienc

Sentinel Lymph Nodes in the Rat: Noninvasive Photoacoustic and US Imaging with a Clinical US System

Purpose: To evaluate in vivo sentinel lymph node (SLN) mapping by using photoacoustic and ultrasonographic (US) imaging with a modified clinical US imaging system. Materials and Methods: Animal protocols were approved by the Animal Studies Committee. Methylene blue dye accumulation in axillary lymph nodes of seven healthy Sprague-Dawley rats was imaged by using a photoacoustic imaging system adapted from a clinical US imaging system. To investigate clinical translation, the imaging depth was extended up to 2.5 cm by adding chicken or turkey breast on top of the rat skin surface. Three-dimensional photoacoustic images were acquired by mechanically scanning the US transducer and light delivery fiber bundle along the elevational direction. Results: Photoacoustic images of rat SLNs clearly help visualization of methylene blue accumulation, whereas coregistered photoacoustic/US images depict lymph node positions relative to surrounding anatomy. Twenty minutes following methylene blue injection, photoacoustic signals from SLN regions increased nearly 33-fold from baseline signals in preinjection images, and mean contrast between SLNs and background tissue was 76.0 ± 23.7 (standard deviation). Methylene blue accumulation in SLNs was confirmed photoacoustically by using the optical absorption spectrum of the dye. Three-dimensional photoacoustic images demonstrate dynamic accumulation of methylene blue in SLNs after traveling through lymph vessels. Conclusion: In vivo photoacoustic and US mapping of SLNs was successfully demonstrated with a modified clinical US scanner. These results raise confidence that photoacoustic and US imaging can be used clinically for accurate, noninvasive imaging of SLNs for axillary lymph node staging in breast cancer patients