Misplaced Emphases in Wars on Poverty

The development of the layer-by-layer (LbL) technique has turned out to be an efficient way to physically modify the surface properties of different materials, for example to improve the adhesive interactions between fibers in paper. The main objective of the work described in this thesis was to obtain fundamental data concerning the adhesive properties of wood biopolymers and LbL films, including the mechanical properties of the thin films, in order to shed light on the molecular mechanisms responsible for the adhesion between these materials. LbLs constructed from poly(allylamine hydrochloride) (PAH)/poly(acrylic acid) (PAA), starch containing LbL films, and LbL films containing nanofibrillated cellulose (NFC) were studied with respect to their adhesive and mechanical properties. The LbL formation was studied using a combination of stagnation point adsorption reflectometry (SPAR) and quartz crystal microbalance with dissipation (QCM-D) and the adhesive properties of the different LbL films were studied in water using atomic force microscopy (AFM) colloidal probe measurements and under ambient conditions using the Johnson-Kendall-Roberts (JKR) approach. Finally the mechanical properties were investigated by mechanical buckling and the recently developed SIEBIMM technique (strain-induced elastic buckling instability for mechanical measurements). From colloidal probe AFM measurements of the wet adhesive properties of surfaces treated with PAH/PAA it was concluded that the development of strong adhesive joints is very dependent on the mobility of the polyelectrolytes and interdiffusion across the interface between the LbL treated surfaces to allow for polymer entanglements. Starch is a renewable, cost-efficient biopolymer that is already widely used in papermaking which makes it an interesting candidate for the formation of LbL films in practical systems. It was shown, using SPAR and QCM-D, that LbL films can be successfully constructed from cationic and anionic starches on silicon dioxide and on polydimethylsiloxane (PDMS) substrates. Colloidal probe AFM measurements showed that starch LbL treatment have potential for increasing the adhesive interaction between solid substrates to levels beyond those that can be reached by a single layer of cationic starch. Furthermore, it was shown by SIEBIMM measurements that the elastic properties of starch-containing LbL films can be tailored using different nanoparticles in combination with starch. LbL films containing cellulose I nanofibrils were constructed using anionic NFC in combination with cationic NFC and poly(ethylene imine) (PEI) respectively. These NFC films were used as cellulose model surfaces and colloidal probe AFM was used to measure the adhesive interactions in water. Furthermore, PDMS caps were successfully coated by LbL films containing NFC which enabled the first known JKR adhesion measurements between cellulose/cellulose, cellulose/lignin and cellulose/glucomannan. The measured adhesion and adhesion hysteresis were similar for all three systems indicating that there are no profound differences in the interaction between different wood biopolymers. Finally, the elastic properties of PEI/NFC LbL films were investigated using SIEBIMM and it was shown that the stiffness of the films was highly dependent on the relative humidity.QC 20110923</p

BRCA1-deficient mammary tumor cells are dependent on EZH2 expression and sensitive to Polycomb Repressive Complex 2-inhibitor 3-deazaneplanocin A

10.1186/bcr2354Breast Cancer Research114R6

The Global Burden of Trachoma: A Review

Trachoma is the commonest infectious cause of blindness worldwide. Recurrent infection of the ocular surface by Chlamydia trachomatis, the causative agent, leads to inturning of the eyelashes (trichiasis) and blinding corneal opacification. Trachoma is endemic in more than 50 countries. It is currently estimated that there are about 1.3 million people blind from the disease and a further 8.2 million have trichiasis. Several estimates for the burden of disease from trachoma have been made, giving quite variable results. The variation is partly because different prevalence data have been used and partly because different sequelae have been included. The most recent estimate from the WHO placed it at around 1.3 million Disability-Adjusted Life Years (DALYs). A key issue in producing a reliable estimate of the global burden of trachoma is the limited amount of reliable survey data from endemic regions

TLR2, but Not TLR4, Is Required for Effective Host Defence against Chlamydia Respiratory Tract Infection in Early Life

Chlamydia pneumoniae commonly causes respiratory tract infections in children, and epidemiological investigations strongly link infection to the pathogenesis of asthma. The immune system in early life is immature and may not respond appropriately to pathogens. Toll-like receptor (TLR)2 and 4 are regarded as the primary pattern recognition receptors that sense bacteria, however their contribution to innate and adaptive immunity in early life remains poorly defined. We investigated the role of TLR2 and 4 in the induction of immune responses to Chlamydia muridarum respiratory infection, in neonatal wild-type (Wt) or TLR2-deficient (−/−), 4−/− or 2/4−/− BALB/c mice. Wt mice had moderate disease and infection. TLR2−/− mice had more severe disease and more intense and prolonged infection compared to other groups. TLR4−/− mice were asymptomatic. TLR2/4−/− mice had severe early disease and persistent infection, which resolved thereafter consistent with the absence of symptoms in TLR4−/− mice. Wt mice mounted robust innate and adaptive responses with an influx of natural killer (NK) cells, neutrophils, myeloid (mDCs) and plasmacytoid (pDCs) dendritic cells, and activated CD4+ and CD8+ T-cells into the lungs. Wt mice also had effective production of interferon (IFN)γ in the lymph nodes and lung, and proliferation of lymph node T-cells. TLR2−/− mice had more intense and persistent innate (particularly neutrophil) and adaptive cell responses and IL-17 expression in the lung, however IFNγ responses and T-cell proliferation were reduced. TLR2/4−/− mice had reduced innate and adaptive responses. Most importantly, neutrophil phagocytosis was impaired in the absence of TLR2. Thus, TLR2 expression, particularly on neutrophils, is required for effective control of Chlamydia respiratory infection in early life. Loss of control of infection leads to enhanced but ineffective TLR4-mediated inflammatory responses that prolong disease symptoms. This indicates that TLR2 agonists may be beneficial in the treatment of early life Chlamydia infections and associated diseases

Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function

The WHO estimates around a million children contract tuberculosis (TB) annually with over 80 000 deaths from dissemination of infection outside of the lungs. The insidious onset and association with skin test anergy suggests failure of the immune system to both recognise and respond to infection. To understand the immune mechanisms, we studied genome-wide whole blood RNA expression in children with TB meningitis (TBM). Findings were validated in a second cohort of children with TBM and pulmonary TB (PTB), and functional T-cell responses studied in a third cohort of children with TBM, other extrapulmonary TB (EPTB) and PTB. The predominant RNA transcriptional response in children with TBM was decreased abundance of multiple genes, with 140/204 (68%) of all differentially regulated genes showing reduced abundance compared to healthy controls. Findings were validated in a second cohort with concordance of the direction of differential expression in both TBM (r2 = 0.78 p = 2x10-16) and PTB patients (r2 = 0.71 p = 2x10-16) when compared to a second group of healthy controls. Although the direction of expression of these significant genes was similar in the PTB patients, the magnitude of differential transcript abundance was less in PTB than in TBM. The majority of genes were involved in activation of leucocytes (p = 2.67E-11) and T-cell receptor signalling (p = 6.56E-07). Less abundant gene expression in immune cells was associated with a functional defect in T-cell proliferation that recovered after full TB treatment (p<0.0003). Multiple genes involved in T-cell activation show decreased abundance in children with acute TB, who also have impaired functional T-cell responses. Our data suggest that childhood TB is associated with an acquired immune defect, potentially resulting in failure to contain the pathogen. Elucidation of the mechanism causing the immune paresis may identify new treatment and prevention strategies