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Following several decades of research, there is not yet a convincing vaccine against shigellosis. It is still difficult, in spite of the breadth of strategies (i.e. live attenuated oral, killed oral, subunit parenteral) to select an optimal option. Two approaches are clearly emerging: (i) live attenuated deletion mutants based on rational selection of genes that are key in the pathogenic process, and (ii) conjugated detoxified polysaccharide parenteral vaccines, or more recently conjugated synthetic carbohydrates. Some of these approaches have already undergone phase I and II clinical trials with promising results, but important issues have also emerged, particularly the discrepancy between colonization and immunogenic potential of live attenuated vaccine candidates depending upon the population concerned (i.e. non endemic vs. endemic areas). Efforts are needed to definitely establish the proof of concept of these approaches, and thus the need for clinical trials which should also soon explore the possibility to associate different serotypes, in response to serotype specific protection against shigellosis. More basic research is also required to improve what we can still consider as first-generation vaccines, and to explore possible new paradigms including the search for cross-protective antigens.  相似文献   

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The burgeoning global problem of malaria is largely due to the emergence of parasite resistance to our limited armamentarium of antimalarial drugs. The recognition of this impending disaster at the international level and the engagement of the pharmaceutical industry promise a more optimistic future for antimalarial drug development. This is particularly exciting when considering the advances in our understanding of parasite biology, which are currently being fuelled by the malaria genome project. This article discusses recent developments in the area of antimalarial drug discovery and evaluation. New advances, based on traditional antimalarial drug classes including the quinolines, peroxides and antifolates (‘back to the future’), are discussed, followed by a presentation of some novel targets (‘young guns’) that have been shown to be good candidates for chemotherapeutic attack.  相似文献   

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Tissue injury, mediated by pathologically elevated production and action of various serine- and matrix metalloproteinases (MMPs), is a hallmark of chronic inflammatory airway diseases (CIAD). CIAD includes such diseases as bronchial asthma, bronchiectasis, and chronic obstructive pulmonary disease. Tissue injury, as a consequence of chronic inflammation, can disturb the relevant repair mechanisms and also result in irreversible alteration of lung architecture. By use of proteomic methods, we analyzed proteinase cascades as an initiator of tissue destruction in CIAD. The present results revealed that elevated levels of MMP-8, -13, -14, and -2, mainly in active forms, can also be detected in CIAD BALFs. Enhanced levels of different active MMPs evidently reflect ongoing tissue-destructive inflammation and airway remodeling occurring in CIAD lung. An inverse correlation between BALF MMP-8 levels and activation degree and airflow obstruction in bronchial asthma tissue injury was shown for the first time. This strongly indicates that chronic peri-inflammatory tissue injury is a main cause of decline of lung functional capacity. Together, these data suggest that the serine and MMP proteinase network is an important feature in predicting clinical worsening of airway obstruction in CIAD. Activation of elevated MMPs seems to have a common profile for all studied CIAD, but different lung disorders react differently to ICS treatment.  相似文献   

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Chelle M 《The New phytologist》2005,166(3):781-790
This review introduces the emergence of a new research topic, phylloclimate, located at the crossroads between ecophysiology and canopy microclimate research. Phylloclimate corresponds to the physical environment actually perceived by each individual aerial organ of a plant population, and is described by physical variables such as spectral irradiance, temperature, on-leaf water and features of around-organ air (wind speed, temperature, humidity, etc.). Knowing the actual climate in which plant organs grow may enable advances in the understanding of plant-environment interactions, as knowing surface temperature instead of air temperature enabled advances in the study of canopy development. Characterizing phylloclimate variables, using experimental work or modeling, raises many questions such as the choice of suitable space- and time-scale as well as the ability to individualize plant organs within a canopy. This is of particular importance when aiming to link phylloclimate and function-structure plant models. Finally, recent trends and challenging questions in phylloclimate research are discussed, as well as the possible applications of phylloclimate results.  相似文献   

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Natural product substances have historically served as the most significant source of new leads for pharmaceutical development. However, with the advent of robotics, bioinformatics, high throughput screening (HTS), molecular biology-biotechnology, combinatorial chemistry, in silico (molecular modeling) and other methodologies, the pharmaceutical industry has largely moved away from plant derived natural products as a source for leads and prospective drug candidates. Can, or will, natural products ever recapture the preeminent position they once held as a foundation for drug discovery and development? The challenges associated with development of natural products as pharmaceuticals are illustrated by the Taxol® story. Several misconceptions, which constrain utilization of plant natural products, for discovery and development of pharmaceuticals, are addressed to return natural products to the forefront.  相似文献   

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Reviews in Fish Biology and Fisheries - A correction to this paper has been published: https://doi.org/10.1007/s11160-021-09657-9  相似文献   

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The oostegites of amphipods attached to peraeopods 2–5 are of two main types — broad with relatively short marginal setae and narrow with long marginal setae. Broad oostegites are found in other peracarids and are considered the primitive type. Amphipods with broad oostegites tend to have smaller eggs than those with narrow oostegites. It is concluded that following the evolution of the major amphipod groups, the oostegites were modified as egg sizes have changed as part of the reproductive strategies of the species within these groups.  相似文献   

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The economic and environmental viability of dedicated terrestrial energy crops is in doubt. The production of large scale biomass (macroalgae) for biofuels in the marine environment was first tested in the late 1960’s. The culture attempts failed due to the engineering challenges of farming offshore. However the energy conversion via anaerobic digestion was successful as the biochemical composition of macroalgae makes it an ideal feedstock. The technology for the mass production of macroalgae has developed principally in China and Asia over the last 50 years to such a degree that it is now the single largest product of aquaculture. There has also been significant technology transfer and macroalgal cultivation is now well tried and tested in Europe and America. The inherent advantage of production of biofuel feedstock in the marine environment is that it does not compete with food production for land or fresh water. Here we revisit the idea of the large scale cultivation of macroalgae at sea for subsequent anaerobic digestion to produce biogas as a source of renewable energy, using a European case study as an example.  相似文献   

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Osteoporosis is a disease that increases skeletal fracture risk and places a significant health and economic burden on patients, families, and health systems. Many treatment options exist, but patient use is suboptimal, thus undermining the potential cost-effectiveness of treatments. In the previous issue of Arthritis Research & Therapy, Hiligsmann and colleagues expanded the findings of previous studies to report, from a sample of 257 patients with osteoporosis, the preference to trade off clinical outcomes for the amenity provided by convenient dosing regimens. This editorial critiques the strengths and limitations of the methods, discusses the potential utility of patient treatment preferences, and suggests avenues for further research.  相似文献   

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The primary objective of this study was to determine if the ventilatory (&OV0312;E) breakpoint during incremental exercise to fatigue is best represented by a single breakpoint (BP1), double breakpoint (BP2), or an exponential function (EXP) exhibiting no BP. A secondary objective was to determine if visual assessment of the BP was valid and reliable. Subjects (n = 49) were both men (n = 12) and women (n = 37) who identified either running (n = 31) or triathlon (n = 18) as their primary sport. Subjects completed a maximal oxygen test on a motor-driven treadmill according to a modified Bruce protocol. The difference in mean square error (MSE) for BP1 (4.91 ± 3.35 L) was slightly but significantly (p < 0.05) greater than in MSE for BP2 (2.75 ± 1.7 L) for VE. Mean square error for EXP (7.85 ± 5.1 L) was significantly greater (p < 0.05) than BP1 and BP2. Visual assessment of VE on scatterplots produced poor validity, with a mean of 71.7% being misclassified compared to the computer model. Both interevaluator reliability (30.6% agreement) and intraevaluator reliability (59.7% agreement) were low. From the results of this study, it is concluded that (a) VE exhibits a BP2 model rather than BP1 or EXP and (b) visual assessment of BP is both invalid and unreliable.  相似文献   

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Intraguild predation has become a major research topic in biological control. Quantification of multipredator interactions and an understanding of the consequences on target prey populations are needed, which only highlights the importance of population dynamics models in this field. However, intraguild predation models are usually based on Lotka–Volterra equations, which have been shown not to be adequate for modeling population dynamics of aphidophagous insects and their prey. Here we use a simple model developed for simulation of population dynamics of aphidophagous insects, which is based on the type of egg distribution made by predatory females, to estimate the real strength of intraguild predation in the aphidophagous insects. The model consists of two components: random egg distribution among aphid colonies, and between-season population dynamics of the predatory species. The model is used to estimate the proportion of predatory individuals that face a conflict with a heterospecific competitor at least once during their life. Based on this, predictions are made on the population dynamics of both predatory species. The predictions are confronted with our data on intraguild predation in ladybirds.  相似文献   

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