抗菌肽的研究现状和挑战

抗菌肽(AMPs)广泛存在于生物体内,可以协助机体抵御外源微生物的侵害,是生物体先天性防御系统中的重要组成成分。普遍认为,抗菌肽通过膜损伤机制,破坏微生物细胞膜或细胞壁的完整性,达到抑杀微生物的目的。然而,越来越多的证据表明抗菌肽还存在非膜损伤机制,作用于胞内靶位点杀伤细胞。由于其独特的作用机制及广谱抗菌活性,抗菌肽被应用于各行各业。但是,抗菌肽的推广应用也面临着诸多难题,如生物稳定性、抗菌活性的维持和微生物耐受性等。主要对抗菌肽的种类、作用机制、微生物对抗菌肽耐受性的产生机制及抗菌肽的应用和挑战进行综述。     

Clinical Utility of Microarrays: Current Status, Existing Challenges and Future Outlook

Microarray-based clinical tests have become powerful tools in the diagnosis and treatment of diseases. In contrast to traditional DNA-based tests that largely focus on single genes associated with rare conditions, microarray-based tests are ideal for the study of diseases with underlying complex genetic causes. Several microarray based tests have been translated into clinical practice such as MammaPrint and AmpliChip CYP450. Additional cancer-related microarray-based tests are either in the process of FDA review or under active development, including Tissue of Tumor Origin and AmpliChip p53. All diagnostic microarray testing is ordered by physicians and tested by a Clinical Laboratories Improvement Amendment-certified (CLIA) reference laboratory. Recently, companies offering consumer based microarray testing have emerged. Individuals can order tests online and service providers deliver the results directly to the clients via a password-protected secure website. Navigenics, 23andMe and deCODE Genetics represent pioneering companies in this field. Although the progress of these microarray-based tests is extremely encouraging with the potential to revolutionize the recognition and treatment of common diseases, these tests are still in their infancy and face technical, clinical and marketing challenges. In this article, we review microarray-based tests which are currently approved or under review by the FDA, as well as the consumer-based testing. We also provide a summary of the challenges and strategic solutions in the development and clinical use of the microarray-based tests. Finally, we present a brief outlook for the future of microarray-based clinical applications.     

Brazilian Tapir Density in the Pantanal: A Comparison of Systematic Camera-Trapping and Line-Transect Surveys

The density of Brazilian tapirs ( Tapirus terrestris) was studied in the northeastern part of the Pantanal wetlands of Brazil using two simultaneous and independent methods: (1) systematic camera trapping combined with capture–recapture analysis, with camera traps spaced 1 km apart and distributed over 54 km²; and (2) line-transect sampling using an array of 12 linear transects, from 3.8 to 7.2 km long, covering the principal open and forest habitat types across the entire 1063 km² SESC Pantanal Reserve. The two methods yielded conservative density estimates of 0.58 ± 0.11 tapirs/km² (camera trapping) and 0.55 (95% CI 0.30–1.01) tapirs/km² (line transects). The study suggests that certain Pantanal habitats and sites can sustain relatively high population densities of tapirs when these animals are protected from hunting. Further testing of the camera-trapping methodology as applied to tapirs is required, particularly focusing on extending the survey period. As it represents a relatively rapid method for estimating population density, in comparison to line-transect surveys, and as it generates information simultaneously on multiple species that are conservation priorities, we recommend that camera-trapping surveys be applied more widely across a variety of Pantanal habitats and land-use categories in order to confirm the value of the vast 140,000 km² wilderness region for this vulnerable species.     

Penicillium marneffei Infection: Knowledge, Gaps, and Future Directions

Penicilliosis is a disease caused by Penicillium marneffei, a fungus endemic to Southeast Asia. Prior to the HIV/AIDS epidemic, infection was exceedingly rare, but penicilliosis is currently one of the most common opportunistic infections in persons with HIV/AIDS in some Asian countries. This paper describes the clinical manifestations, diagnosis, and epidemiology of this emerging opportunistic infection and will focus on some gaps in our knowledge and directions for future research.     

Amoeboid Chemotaxis: Future Challenges and Opportunities

Chemotaxis is the directed movement of a cell towards a gradient of chemicals such as chemokines or growth factors. This phenomenon can be studied in organisms ranging from bacteria to mammalian cells, and here we will focus on eukaryotic amoeboid chemotaxis. Chemotactic responses are mediated by two major classes of receptors: GPCR''s and RTK''s, with multiple pathways signaling downstream of them, certain ones functioning in parallel. In this review we address two important features of amoeboid chemotaxis that will be important for further advances in the field. First, the application of in vivo imaging will be critical for providing insight into the functional requirements for chemotactic responses. We will briefly cover a number of systems in which in vivo imaging is providing new insights. Second, due to the network-type design of signaling pathways of eukaryotic chemotaxis, more refined phenotypic analysis will be necessary, and we will discuss recent analyses of the role of the phosphoinositide 3-kinase pathway in this light. We will close with some speculations regarding future applications of more detailed in vivo analysis and mechanistic understanding of eukaryotic amoeboid chemotaxis.Key Words: chemotaxis, signaling, in vivo models, development, phospholipase, phosphoinositide 3-kinase     

Pancreatic Cancer: Current Progress and Future Challenges

Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, remains one of the highly lethal malignancies. The highly refractory nature of clinically advanced disease and lack of a reliable biomarker for early detection are major obstructions in improving patient outcome. The recent efforts, however, in understanding the pancreatic tumor biology have resulted in the recognition of novel addictions as well as vulnerabilities of tumor cells and are being assessed for their clinical potential. This special issue highlights some of the recent progress, complexity and challenges towards improving disease outcome in patients with this lethal malignancy.     

Wiki Surveys: Open and Quantifiable Social Data Collection

In the social sciences, there is a longstanding tension between data collection methods that facilitate quantification and those that are open to unanticipated information. Advances in technology now enable new, hybrid methods that combine some of the benefits of both approaches. Drawing inspiration from online information aggregation systems like Wikipedia and from traditional survey research, we propose a new class of research instruments called wiki surveys. Just as Wikipedia evolves over time based on contributions from participants, we envision an evolving survey driven by contributions from respondents. We develop three general principles that underlie wiki surveys: they should be greedy, collaborative, and adaptive. Building on these principles, we develop methods for data collection and data analysis for one type of wiki survey, a pairwise wiki survey. Using two proof-of-concept case studies involving our free and open-source website www.allourideas.org, we show that pairwise wiki surveys can yield insights that would be difficult to obtain with other methods.     

Assessing Coverage,Equity and Quality Gaps in Maternal and Neonatal Care in Sub-Saharan Africa: An Integrated Approach

BackgroundGaps in coverage, equity and quality of health services hinder the achievement of the Millennium Development Goals 4 and 5 in most countries of sub-Saharan Africa as well as in other high-burden countries, yet few studies attempt to assess all these dimensions as part of the situation analysis. We present the base-line data of a project aimed at simultaneously addressing coverage, equity and quality issues in maternal and neonatal health care in five districts belonging to three African countries.MethodsData were collected in cross-sectional studies with three types of tools. Coverage was assessed in three hospitals and 19 health centres (HCs) utilising emergency obstetric and newborn care needs assessment tools developed by the Averting Maternal Death and Disability program. Emergency obstetrics care (EmOC) indicators were calculated. Equity was assessed in three hospitals and 13 HCs by means of proxy wealth indices and women delivering in health facilities were compared with those in the general population to identify inequities. Quality was assessed in three hospitals using the World Health Organization’s maternal and neonatal quality of hospital care assessment tool which evaluates the whole range of aspects of obstetric and neonatal care and produces an average score for each main area of care.ResultsAll the three hospitals qualified as comprehensive EmOC facilities but none of the HCs qualified for basic EmOC. None of the districts met the minimum requisites for EmOC indicators. In two out of three hospitals, there were major quality gaps which were generally greater in neonatal care, management of emergency and complicated cases and monitoring. Higher access to care was coupled by low quality and good quality by very low access. Stark inequities in utilisation of institutional delivery care were present in all districts and across all health facilities, especially at hospital level.ConclusionOur findings confirm the existence of serious issues regarding coverage, equity and quality of health care for mothers and newborns in all study districts. Gaps in one dimension hinder the potential gains in health outcomes deriving from good performances in other dimensions, thus confirm the need for a three-dimensional profiling of health care provision as a basis for data-driven planning.     

Using Seroprevalence and Immunisation Coverage Data to Estimate the Global Burden of Congenital Rubella Syndrome, 1996-2010: A Systematic Review

Background

The burden of Congenital Rubella Syndrome (CRS) is typically underestimated in routine surveillance. Updated estimates are needed following the recent WHO position paper on rubella and recent GAVI initiatives, funding rubella vaccination in eligible countries. Previous estimates considered the year 1996 and only 78 (developing) countries.

Methods

We reviewed the literature to identify rubella seroprevalence studies conducted before countries introduced rubella-containing vaccination (RCV). These data and the estimated vaccination coverage in the routine schedule and mass campaigns were incorporated in mathematical models to estimate the CRS incidence in 1996 and 2000–2010 for each country, region and globally.

Results

The estimated CRS decreased in the three regions (Americas, Europe and Eastern Mediterranean) which had introduced widespread RCV by 2010, reaching <2 per 100,000 live births (the Americas and Europe) and 25 (95% CI 4–61) per 100,000 live births (the Eastern Mediterranean). The estimated incidence in 2010 ranged from 90 (95% CI: 46–195) in the Western Pacific, excluding China, to 116 (95% CI: 56–235) and 121 (95% CI: 31–238) per 100,000 live births in Africa and SE Asia respectively. Highest numbers of cases were predicted in Africa (39,000, 95% CI: 18,000–80,000) and SE Asia (49,000, 95% CI: 11,000–97,000). In 2010, 105,000 (95% CI: 54,000–158,000) CRS cases were estimated globally, compared to 119,000 (95% CI: 72,000–169,000) in 1996.

Conclusions

Whilst falling dramatically in the Americas, Europe and the Eastern Mediterranean after vaccination, the estimated CRS incidence remains high elsewhere. Well-conducted seroprevalence studies can help to improve the reliability of these estimates and monitor the impact of rubella vaccination.