Tip-Enhanced Second Harmonic Generation: an Approach for Hyper-Raman Spectroscopy

Plasmonics - The near-field optical response generated at the apex of a scanning probe in tip-enhanced Raman spectroscopy (TERS) enhances and confines the interaction of light and matter to a few...     

Elastin‐like polypeptide switches: A design strategy to detect multimeric proteins

Elastin‐Like Polypeptides (ELPs) reversibly phase separate in response to changes in temperature, pressure, concentration, pH, and ionic species. While powerful triggers, biological microenvironments present a multitude of more specific biological cues, such as antibodies, cytokines, and cell‐surface receptors. To develop better biosensors and bioresponsive drug carriers, rational strategies are required to sense and respond to these target proteins. We recently reported that noncovalent association of two ELP fusion proteins to a “chemical inducer of dimerization” small molecule (1.5 kDa) induces phase separation at physiological temperatures. Having detected a small molecule, here we present the first evidence that ELP multimerization can also detect a much larger (60 kDa) protein target. To demonstrate this strategy, ELPs were biotinylated at their amino terminus and mixed with tetrameric streptavidin. At a stoichiometric ratio of [4:1], two to three biotin‐ELPs associate with streptavidin into multimeric complexes with an apparent K_d of 5 nM. The increased ELP density around a streptavidin core strongly promotes isothermal phase separation, which was tuned to occur at physiological temperature. This phase separation reverses upon saturation with excess streptavidin, which only favors [1:1] complexes. Together, these findings suggest that ELP association with multimeric biomolecules is a viable strategy to deliberately engineer ELPs that respond to multimeric protein substrates.     

The Ancient Immunoglobulin Domains of Peroxidasin Are Required to Form Sulfilimine Cross-links in Collagen IV

The collagen IV sulfilimine cross-link and its catalyzing enzyme, peroxidasin, represent a dyad critical for tissue development, which is conserved throughout the animal kingdom. Peroxidasin forms novel sulfilimine bonds between opposing methionine and hydroxylysine residues to structurally reinforce the collagen IV scaffold, a function critical for basement membrane and tissue integrity. However, the molecular mechanism underlying cross-link formation remains unclear. In this work, we demonstrate that the catalytic domain of peroxidasin and its immunoglobulin (Ig) domains are required for efficient sulfilimine bond formation. Thus, these molecular features underlie the evolutionarily conserved function of peroxidasin in tissue development and integrity and distinguish peroxidasin from other peroxidases, such as myeloperoxidase (MPO) and eosinophil peroxidase (EPO).     

人工胶林群落结构生物学效应的观测及若干生态因子变化规律的研究

采用近代仪器与传统小气候观测相结合的方法：研究了人工胶林群落结构的生物学效应；对若干生态因于变化规律进行了初步讨论。胶树体温与测试地日照强弱密切相关．西双版纳树温西南高，东北低，西向与北向最高温之差约为l℃；树表和浅层受日照影响直接而明显，随深度增加而减弱，树心比较间接，既受环境影响又受本身机体调节。冬季胶林边行热效应较明显，比林内树温高2℃左右，若加充分利用对防寒有一定意义。树温和气温有差别，气温变幅大，树温变幅小，有利于植物正常生活，建议直接测定树温观察寒害．胶林中适当种植茶树，冷季有增暖效果，能对轻度寒害起缓冲作用．涂黑树干法不是理想防寒措施，因边行增温不明显 况且密林深处有轻微降温趋势，可能导致寒害加重。     

Interaction between sympathetic nervous system and renin angiotensin system on MMPs expression in juvenile rat aorta

The aim of our present study is to investigate the interaction between angiotensin II (ANG II) and sympathetic nervous system (SNS) on matrix metalloproteinase MMP-2 and MMP-9 expression and activity in juvenile rat aorta under normal conditions. Sympathectomy with guanethidine and blockade of the ANG II receptors (AT1R) by losartan were performed alone or in combination on new-born rats. mRNA, protein expression and activity of MMP-2 and MMP-9 were examined by Q-RT-PCR, immunoblotting and zymography, respectively. MMP-2 mRNA and protein amount were decreased after sympathectomy or AT1R blockade and an additive effect was observed after combined treatment. However, MMP-9 expression was reduced to the same level in the three treated groups. There were some detectable gelatinolytic activity of the MMPs in both control and treated rats. We concluded that ANG II stimulates directly and indirectly (via sympathostimulator pathway) the MMP-2 expression but seems unable to affect MMP-9 expression through direct pathway. Combined inhibition of SNS and ANG II were more efficient than a single inhibition in reducing MMP amounts in rat vessels.     

Peripheral blood mononuclear cells immunophenotyping in pulmonary tuberculosis patients before and after treatment

Tuberculosis (TB) is a lung disease caused by Mycobacterium tuberculosis. The interaction between the bacillus and the host may lead to a protective cellular immune response. In the present study, we propose the "in vitro" evaluation of this cellular immune response in patients with tuberculosis before and after chemotherapic treatment. Eleven patients with TB and 9 asymptomatic subjects with tuberculin skin test negative (TST-) (purified protein derivative (PPD) 相似文献   

Air pollution and the lung: epidemiological approach

Epidemiological evidence has concurred with clinical and experimental evidence to correlate current levels of ambient air pollution, both indoors and outdoors, with respiratory effects. In this respect, the use of specific epidemiological methods has been crucial. Common outdoor pollutants are particulate matter, nitrogen dioxide, carbon monoxide, volatile organic compounds and ozone. Short-term effects of outdoor air pollution include changes in lung function, respiratory symptoms and mortality due to respiratory causes. Increase in the use of health care resources has also been associated with short-term effects of air pollution. Long-term effects of cumulated exposure to urban air pollution include lung growth impairment, chronic obstructive pulmonary disease (COPD), lung cancer, and probably the development of asthma and allergies. Lung cancer and COPD have been related to a shorter life expectancy. Common indoor pollutants are environmental tobacco smoke, particulate matter, nitrogen dioxide, carbon monoxide, volatile organic compounds and biological allergens. Concentrations of these pollutants can be many times higher indoors than outdoors. Indoor air pollution may increase the risk of irritation phenomena, allergic sensitisation, acute and chronic respiratory disorders and lung function impairment. Recent conservative estimates have shown that 1.5-2 million deaths per year worldwide could be attributed to indoor air pollution. Further epidemiological research is necessary to better evaluate the respiratory health effects of air pollution and to implement protective programmes for public health.     

Cost-effectiveness of magnetic resonance imaging with a new contrast agent for the early diagnosis of Alzheimer's disease

Background

Used as contrast agents for brain magnetic resonance imaging (MRI), markers for beta-amyloid deposits might allow early diagnosis of Alzheimer''s disease (AD). We evaluated the cost-effectiveness of such a diagnostic test, MRI+CLP (contrastophore-linker-pharmacophore), should it become clinically available.

Methodology/Principal Findings

We compared the cost-effectiveness of MRI+CLP to that of standard diagnosis using currently available cognition tests and of standard MRI, and investigated the impact of a hypothetical treatment efficient in early AD. The primary analysis was based on the current French context for 70-year-old patients with Mild Cognitive Impairment (MCI). In alternative “screen and treat” scenarios, we analyzed the consequences of systematic screenings of over-60 individuals (either population-wide or restricted to the ApoE4 genotype population). We used a Markov model of AD progression; model parameters, as well as incurred costs and quality-of-life weights in France were taken from the literature. We performed univariate and probabilistic multivariate sensitivity analyses.The base-case preferred strategy was the standard MRI diagnosis strategy. In the primary analysis however, MRI+CLP could become the preferred strategy under a wide array of scenarios involving lower cost and/or higher sensitivity or specificity. By contrast, in the “screen and treat” analyses, the probability of MRI+CLP becoming the preferred strategy remained lower than 5%.

Conclusions/Significance

It is thought that anti-beta-amyloid compounds might halt the development of dementia in early stage patients. This study suggests that, even should such treatments become available, systematically screening the over-60 population for AD would only become cost-effective with highly specific tests able to diagnose early stages of the disease. However, offering a new diagnostic test based on beta-amyloid markers to elderly patients with MCI might prove cost-effective.