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1.
Phospholipid transport between membranes is a fundamental aspect of organelle biogenesis in eukaryotes; however, little is know about this process. A significant body of data demonstrates that newly synthesized phospholipids can move between membranes by routes that are independent of the vesicular traffic that carries membrane proteins. Evidence continues to accumulate in support of a system for phospholipid transport that occurs at zones of apposition and contact between donor membranes - the source of specific phospholipids - and acceptor membranes that are unable to synthesize the necessary lipids. Recent findings identify some of the lipids and proteins that must be present on membranes for inter-organelle phospholipid transport to occur between the endoplasmic reticulum and mitochondria or Golgi. These data suggest that protein and lipid assemblies on donors and acceptors promote membrane docking and facilitate lipid movement.  相似文献   

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Systems biology aims at creating mathematical models, i.e., computational reconstructions of biological systems and processes that will result in a new level of understanding—the elucidation of the basic and presumably conserved “design” and “engineering” principles of biomolecular systems. Thus, systems biology will move biology from a phenomenological to a predictive science. Mathematical modeling of biological networks and processes has already greatly improved our understanding of many cellular processes. However, given the massive amount of qualitative and quantitative data currently produced and number of burning questions in health care and biotechnology needed to be solved is still in its early phases. The field requires novel approaches for abstraction, for modeling bioprocesses that follow different biochemical and biophysical rules, and for combining different modules into larger models that still allow realistic simulation with the computational power available today. We have identified and discussed currently most prominent problems in systems biology: (1) how to bridge different scales of modeling abstraction, (2) how to bridge the gap between topological and mechanistic modeling, and (3) how to bridge the wet and dry laboratory gap. The future success of systems biology largely depends on bridging the recognized gaps.  相似文献   

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Though observations on re-colonisation of post-fire sites in the Mediterranean Basin are plentiful, there still is an ongoing debate on the interrelation of fire regimes and species traits related to fire adaptation. Most of the studies found are restricted to particular species or claim to present community attributes. Therefore they often lack information for the evaluation of evolutionary evidence and historical contingency of the local fire regime and other abiotic conditions, which may act as selective pressure for plant regeneration strategies. Indeed, knowledge about the success of regeneration mechanisms and their interrelation with ecological factors is essential for the interpretation of the high spatio-temporal variability found in post-fire species performance. Such knowledge would be necessary to assess the potential of different regeneration mechanisms to cope with ongoing land-use and climate change—a crucial scientific challenge. A summary is given of the knowledge about the limits and potential of plant regeneration mechanisms after fire in the Mediterranean Basin, along with corresponding studies conducted in other parts of the world with similar climatic conditions in order to present the fullest possible picture. Moreover, the positive or negative impacts of particular parameters of a fire regime on different regeneration strategies (post-fire seeders, resprouters, and facultative resprouters) are explained and discussed in the light of published literature. To conclude, reference is made to scientific gaps that need to be filled in order to analyse species resistance and community resilience absorbing possible climate or land use changes.  相似文献   

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Calcium concentration is strictly regulated in all cells. The inositol 1,4,5-trisphosphate receptor (IP(3)R), which forms a homotetrameric Ca2+ release channel in the endoplasmic reticulum, is one of the key molecules responsible for this regulation. The opening of this channel requires binding of two intracellular messengers, which are inositol 1,4,5-trisphosphate (IP(3)) and Ca2+. To promote the Ca2+-channel gating and release from the endoplasmic reticulum, IP(3) binds to the amino-terminal region of IP(3)R. Recently, the crystal structure of IP(3)R-binding core in complex with its ligand was presented [I. Bosanac, J.R. Alattia, T.K. Mai, J. Chan, S. Talarico, F.K. Tong, K.I. Tong, F. Yoshikawa, T. Furuichi, M. Iwai, T. Michikawa, K. Mikoshiba, M. Ikura, Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand, Nature 420 (2002) 696-700; I. Bosanac, H. Yamazaki, T. Matsu-ura, T. Michikawa, K. Mikoshiba, M. Ikura, Crystal structure of the ligand-binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor, Mol. Cell 17 (2005) 193-203]. The space positions of residues 289-301 (segment A), 320-350 (segment B), 373-386 (segment C), and 529-545 (segment D) were not determined by the X-ray crystallography. To bridge these gaps, the computer modeling of physiologically meaningful low-energy 3D structures of the segments A-D of the inositol 1,4,5-trisphosphate receptor has been carried out by using a hierarchical conformational search algorithm combining two approaches: knowledge-based homology modeling and ab initio conformational search strategy. The structure analysis suggests a Ca2+-binding site of high affinity formed by residues 296-335, several low-energy regular secondary structure units within the segment B, and a number of hinge regions within the segments A-D, important for the receptor functioning.  相似文献   

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Cancer in children is a major concern in many countries. An important question is whether these childhood cancers are caused by something, or are just tragic random events. Causation of at least some children's cancers is suggested by direct and indirect evidence, including epidemiological data, and animal studies that predict early life sensitivity of humans to carcinogenic effects. Candidate risk factors include genotoxic agents (chemicals and radiation), but also diet/nutrition, and infectious agents/immune responses. With regard to likelihood of risks posed by genotoxicants, there are pros and cons. The biological properties of fetuses and infants are consistent with sensitivity to preneoplastic genotoxic damage. Recent studies of genetic polymorphisms in carcinogen-metabolizing enzymes confirm a role for chemicals. On the other hand, in numerous epidemiological studies, associations between childhood cancers and exposure to genotoxicants, including tobacco smoke, have been weak and hard to reproduce. Possibly, sensitive genetic or ontogenetic subpopulations, and/or co-exposure situations need to be discovered to allow identification of susceptible individuals and their risk factors. Among the critical knowledge gaps needing to be bridged to aid in this effort include detailed tissue and cellular ontogeny of carcinogen metabolism and DNA repair enzymes, and associations of polymorphisms in DNA repair enzymes with childhood cancers. Perinatal bioassays in animals of specific environmental candidates, for example, benzene, could help guide epidemiology. Genetically engineered animal models could be useful for identification of chemical effects on specific genes. Investigations of interactions between factors may be key to understanding risk. Finally, fathers and newborn infants should receive more attention as especially sensitive targets.  相似文献   

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大学生的创新能力培养对于培育创新型人才具有极其重要的意义。本文旨在通过讲述指导学生参与课外实验的体会,探索一种高效合理的大学生创新型人才培养模式,为提高大学生综合素质、培养创新型人才提供探索经验。  相似文献   

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Background  

Lymnaeidae snails play a prominent role in the transmission of helminths, mainly trematodes of medical and veterinary importance (e.g., Fasciola liver flukes). As this family exhibits a great diversity in shell morphology but extremely homogeneous anatomical traits, the systematics of Lymnaeidae has long been controversial. Using the most complete dataset to date, we examined phylogenetic relationships among 50 taxa of this family using a supermatrix approach (concatenation of the 16 S, ITS-1 and ITS-2 genes, representing 5054 base pairs) involving both Maximum Likelihood and Bayesian Inference.  相似文献   

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Background

Many international statements have urged researchers, policy-makers and health care providers to collaborate in efforts to bridge the gaps between research, policy and practice in low- and middle-income countries. We surveyed researchers in 10 countries about their involvement in such efforts.

Methods

We surveyed 308 researchers who conducted research on one of four clinical areas relevant to the Millennium Development Goals (prevention of malaria, care of women seeking contraception, care of children with diarrhea and care of patients with tuberculosis) in each of 10 low- and middle-income countries (China, Ghana, India, Iran, Kazakhstan, Laos, Mexico, Pakistan, Senegal and Tanzania). We focused on their engagement in three promising bridging activities and examined system-level, organizational and individual correlates of these activities.

Results

Less than half of the researchers surveyed reported that they engaged in one or more of the three promising bridging activities: 27% provided systematic reviews of the research literature to their target audiences, 40% provided access to a searchable database of research products on their topic, and 43% established or maintained long-term partnerships related to their topic with representatives of the target audience. Three factors emerged as statistically significant predictors of respondents’ engagement in these activities: the existence of structures and processes to link researchers and their target audiences predicted both the provision of access to a database (odds ratio [OR] 2.62, 95% CI 1.30–5.27) and the establishment or maintenance of partnerships (OR 2.65, 95% CI 1.25–5.64); stability in their contacts predicted the provision of systematic reviews (OR 2.88, 95% CI 1.35–6.13); and having managers and public (government) policy-makers among their target audiences predicted the provision of both systematic reviews (OR 4.57, 95% CI 1.78–11.72) and access to a database (OR 2.55, 95% CI 1.20–5.43).

Interpretation

Our findings suggest potential areas for improvement in light of the bridging strategies targeted at health care providers that have been found to be effective in some contexts and the factors that appear to increase the prospects for using research in policy-making.The need to bridge the gaps between research, policy and practice appears to be a global phenomenon. Three recent, highly visible resolutions — the Mexico Action Statement on Health Research in 2004 (58 countries),1 the related World Health Assembly resolution in 2005 (193 countries)2 and the Bamako Call to Action on Research for Health in 2008 (53 countries) 3 — urged researchers, policy-makers and health care providers to collaborate in efforts to bridge these gaps. These efforts can range from bringing research-based evidence to the attention of those who could use it, to making research-based evidence available so that it can be readily retrieved when needed.We are not aware of a survey having been conducted in a range of low- and middle-income countries about researchers’ bridging activities related to specific high-priority health topics. Researchers and research organizations have been surveyed about their bridging activities in single high-income countries such as Canada.46 Guideline-producing organizations and health technology assessment agencies have also been surveyed about their bridging activities;7 only in one case was the focus on bridging activities in low- and middle-income countries.8 Select research funding agencies have been studied in low- and middle-income countries.9 Yet the Millennium Development Goals and the goals of many countries call for topic-focused efforts to bridge the gaps between research, policy and practice.We studied efforts to bridge the gaps between research, policy and practice in 10 low- and middle-income countries (China, Ghana, India, Iran, Kazakhstan, Laos, Mexico, Pakistan, Senegal and Tanzania). In this article, we describe the findings from a survey of researchers in these countries who conducted research in one of four clinical areas relevant to the Millennium Development Goals: prevention of malaria (Ghana, Laos, Senegal and Tanzania), care of women seeking contraception (China, Kazakhstan, Laos and Mexico), care of children with diarrhea (Ghana, India, Pakistan and Senegal) and care of patients with tuberculosis (China, India, Iran and Mexico). In a related article, we describe the findings from a survey of health care providers in these countries who were practising in one of these clinical areas about their awareness of, access to and use of research-based evidence in these clinical areas and the influence of such evidence on their professional practice.10The challenges associated with documenting such efforts include cross-country differences in the capacity to conduct surveys of researchers; the visibility of researchers depending on their alignment with priorities of government, development agencies, research funding agencies and industry (and hence their likelihood of being identified to participate in these surveys); and researchers’ familiarity with and attitudes toward the bridging activities asked about in these surveys.  相似文献   

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Syntheses of knowledge are important to reveal trends, biases and gaps in the scientific literature, indicating main data shortfalls and research needs. In this regard, the authors conducted a broad systematic review on the literature about freshwater fish eggs and larvae to investigate (a) temporal trends in the global scientific production, (b) the scope and habitat types, (c) the spatial distribution of studies, (d) the fish species contemplated and their respective conservation status and (e) the factors associated with the spatial distribution of studies. They analysed 654 studies published between 1950 and 2020. The number of studies has increased over time, but with a weak trend. Most studies investigated basic questions about biology and ecology and were carried out chiefly in rivers and lakes. These studies covered 95 freshwater ecoregions (22.3% of all ecoregions) and recorded 871 fish species (4.8% of all freshwater fish currently described). Most species were assessed by the IUCN and classified into six threat categories, but approximately 35% were not evaluated. The main drivers affecting the spatial distribution of studies were ecoregion area, road density, river volume and the number of hydroelectric plants. Results point to significant biases and gaps in the global scientific literature on fish eggs and larvae, especially associated with habitat type, spatial distribution and target species, emphasizing the need to address specific topics. Such biases and gaps indicate the existence of important data shortfalls, which compromise management and conservation planning, as information on fish eggs and larvae is basic and critical for the assessment of fish recruitment and population dynamics.  相似文献   

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Hydrobiologia - Despite the socio-environmental importance of ichthyofauna, global fish biodiversity has decreased, and the damming of rivers is one anthropogenic activity that causes this...  相似文献   

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Primary schools constitute a key risk group for the transmission of infectious diseases, concentrating great numbers of immunologically naive individuals at high densities. Despite this, very little is known about the social patterns of mixing within a school, which are likely to contribute to disease transmission. In this study, we present a novel approach where scientific engagement was used as a tool to access school populations and measure social networks between young (4-11 years) children. By embedding our research project within enrichment activities to older secondary school (13-15) children, we could exploit the existing links between schools to achieve a high response rate for our study population (around 90% in most schools). Social contacts of primary school children were measured through self-reporting based on a questionnaire design, and analysed using the techniques of social network analysis. We find evidence of marked social structure and gender assortativity within and between classrooms in the same school. These patterns have been previously reported in smaller studies, but to our knowledge no study has attempted to exhaustively sample entire school populations. Our innovative approach facilitates access to a vitally important (but difficult to sample) epidemiological sub-group. It provides a model whereby scientific communication can be used to enhance, rather than merely complement, the outcomes of research.  相似文献   

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