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1.
The population structure of Plasmodium vivax remains elusive. The markers of choice for large-scale population genetic studies of eukaryotes, short tandem repeats known as microsatellites, have been recently reported to be less polymorphic in P. vivax. Here we investigate the microsatellite diversity and geographic structure in P. vivax, at both local and global levels, using 14 new markers consisting of tri- or tetranucleotide repeats. The local-level analysis, which involved 50 field isolates from Sri Lanka, revealed unexpectedly high diversity (average virtual heterozygosity [H(E)], 0.807) and significant multilocus linkage disequilibrium in this region of low malaria endemicity. Multiple-clone infections occurred in 60% of isolates sampled in 2005. The global-level analysis of field isolates or monkey-adapted strains identified 150 unique haplotypes among 164 parasites from four continents. Individual P. vivax isolates could not be unambiguously assigned to geographic populations. For example, we found relatively low divergence among parasites from Central America, Africa, Southeast Asia and Oceania, but substantial differentiation between parasites from the same continent (South Asia and Southeast Asia) or even from the same country (Brazil). Parasite relapses, which may extend the duration of P. vivax carriage in humans, are suggested to facilitate the spread of strains across continents, breaking down any pre-existing geographic structure.  相似文献   

2.
The second World Neglected Tropical Diseases (NTDs) Day was celebrated on 30 January 2021. To mark the occasion, the World Health Organization (WHO) launched its roadmap for NTDs for the period 2021 to 2030, which is aimed at increasing prevention and control of these too-long neglected diseases. Described here is a global overview on past achievements, current challenges, and future prospects for the WHO NTDs roadmap 2021–2030.  相似文献   

3.
One of the methods available for the measurement of surface potentials of planar lipid bilayers uses the conductance ratio between a charged and a neutral bilayer doped with ionophores to calculate the surface potential of the charged bilayer. We have devised a simplification of that method which does not require the use of an electrically neutral bilayer as control. The conductance of the charged bilayer is measured before and after the addition of divalent cations (Ba(2+)) to the bathing solution. Ba(2+) ions screen fixed surface charges, decreasing the surface potential. If the membrane is negatively charged the screening has the effect of decreasing the membrane conductance to cations. The resulting conductance ratio is used to calculate the surface potential change, which is fed into an iterative computer program. The program generates pairs of surface potential values and calculates the surface charge density for the two conditions. Since the surface charge density remains constant during this procedure, there is only one pair of surface potentials that satisfies the condition of constant charge density. Applying this method to experimental data from McLaughlin et al. [McLaughlin, S.G.A., Szabo, G. and Eisenman, G., Divalent ions and the surface potential of charged phospholipid membranes, J. Gen. Physiol., 58 (1971) 667-687.] we have found very similar results. We have also successfully used this method to determine the effect of palmitic acid on the surface potential of asolectin membranes.  相似文献   

4.
Critical molecular and cellular biological factors impacting design of licensable DNA vaccine vectors that combine high yield and integrity during bacterial production with increased expression in mammalian cells are reviewed. Food and Drug Administration (FDA), World Health Organization (WHO) and European Medical Agencies (EMEA) regulatory guidance's are discussed, as they relate to vector design and plasmid fermentation. While all new vectors will require extensive preclinical testing to validate safety and performance prior to clinical use, regulatory testing burden for follow-on products can be reduced by combining carefully designed synthetic genes with existing validated vector backbones. A flowchart for creation of new synthetic genes, combining rationale design with bioinformatics, is presented. The biology of plasmid replication is reviewed, and process engineering strategies that reduce metabolic burden discussed. Utilizing recently developed low metabolic burden seed stock and fermentation strategies, optimized vectors can now be manufactured in high yields exceeding 2 g/L, with specific plasmid yields of 5% total dry cell weight.  相似文献   

5.
The basic reproductive ratio, R0, is a central quantity in the investigation and management of infectious pathogens. The standard model for describing stochastic epidemics is the continuous time epidemic birth-and-death process. The incidence data used to fit this model tend to be collected in discrete units (days, weeks, etc.), which makes model fitting, and estimation of R0 difficult. Discrete time epidemic models better match the time scale of data collection but make simplistic assumptions about the stochastic epidemic process. By investigating the nature of the assumptions of a discrete time epidemic model, we derive a bias corrected maximum likelihood estimate of R0 based on the chain binomial model. The resulting 'removal' estimators provide estimates of R0 and the initial susceptible population size from time series of infectious case counts. We illustrate the performance of the estimators on both simulated data and real epidemics. Lastly, we discuss methods to address data collected with observation error.  相似文献   

6.
Transmission of an infectious agent can be quantified from experimental data using the transient-state (TS) algorithm. The TS algorithm is based on the stochastic SIR model and provides a time-dependent probability distribution over the number of infected individuals during an epidemic, with no need for the experiment to end in final-size (e.g., where no more infections can occur). Because of numerical limitations, the application of the TS algorithm is limited to populations with only a few individuals. We investigated the error of using the easily applicable, time-independent final-size (FS) algorithm knowing that the FS situation was not reached. We conclude that the methods based on the FS algorithm: (i) underestimate R(0), (ii) are liberal when testing H(0):R(0)1 against H(1):R(0)<1, (iii) are conservative when testing H(0):R(0)1 against H(1):R(0)>1, and (iv) are conservative when testing H(0):R(control)=R(treatment) against H(1):R(control)>R(treatment). Furthermore, a new method is presented to find a difference in transmission between two treatment groups (MaxDiff test). The MaxDiff test is compared to tests based on FS and TS algorithms. The TS test and the MaxDiff test were most powerful (approximately equally powerful) in finding a difference, whereas the FS test was less powerful (especially, when both R(control) and R(treatment) are >1).  相似文献   

7.
Two new compounds isolated from an extract of a Central Asian lichen [Umbilicaria proboscidea (L.) Schrader=Syn.: Gyrophora proboscidea (L.) Ach.] are glucosides with mono- and di-prenylated xanthones as the aglycones and a saccharide moiety from two glucoses linked at C-7. The structures were elucidated on the basis of extensive spectroscopic analysis (1D and 2D NMR, MS, IR and UV) and by hydrolysis.  相似文献   

8.
An important issue in theoretical epidemiology is the epidemic thresholdphenomenon, which specify the conditions for an epidemic to grow or die out.In standard (mean-field-like) compartmental models the concept of the basic reproductive number, R 0, has been systematically employed as apredictor for epidemic spread and as an analytical tool to study thethreshold conditions. Despite the importance of this quantity, there are nogeneral formulation of R 0 when one considers the spread of a disease ina generic finite population, involving, for instance, arbitrary topology ofinter-individual interactions and heterogeneous mixing of susceptible andimmune individuals. The goal of this work is to study this concept in ageneralized stochastic system described in terms of global and localvariables. In particular, the dependence of R 0 on the space ofparameters that define the model is investigated; it is found that near ofthe `classical' epidemic threshold transition the uncertainty about thestrength of the epidemic process still is significantly large. Theforecasting attributes of R 0 for a discrete finite system is discussedand generalized; in particular, it is shown that, for a discrete finitesystem, the pretentious predictive power of R 0 is significantlyreduced.  相似文献   

9.
猴痘(monkeypox)是由猴痘病毒感染所致的人兽共患病,主要发生在非洲中部、西部地区。猴痘病毒可感染多种哺乳类动物,主要在动物中流行,人接触感染动物后可被传染。猴痘的临床表现与天花相似(发热、皮疹等),但症状较轻。天花疫苗接种可提供预防猴痘的免疫保护力。然而,因全球天花被消灭而停止接种天花疫苗后,猴痘成为最可能威胁人类的正痘病毒性疾病。近期,其散发病例在欧洲多地出现。2022年5月7日英国报道了猴痘疫情。随后,欧洲报道猴痘确诊和疑似病例超过100例。猴痘主要传播途径包括接触感染动物、与患者直接接触或间接接触。2022年5月20日,世界卫生组织就此次猴痘疫情召开了紧急会议,旨在提高对猴痘的认识,做好防范应对准备。世界卫生组织、美国疾病预防控制中心、英国卫生部门报告了相关疫情并制定了相应的防控措施。截至2022年5月28日我国尚无输入性猴痘报道,但因国际交往频繁等仍须提高警惕。本文介绍了猴痘流行现状及有关防控信息,以供借鉴。  相似文献   

10.
Given the magnitude of the HIV pandemic, development of new prevention means is necessary. Male circumcision reduces HIV transmission from female to male by 57 % [95 % Confident Interval (CI): 42-68 %]. Its generalization in sub-Saharan Africa could avert, among men and women, from 1 to 4 millions new HIV infections over the next ten years. Acceptability of this new prevention mean is high in countries which could benefit the most from male circumcision, that means located in southern Africa, a region where in majority men are uncircumcised and where HIV prevalence is high. Male circumcision is a cost-effective prevention strategy. Actual prevention means (condoms, sexual abstinence and fidelity) are not used enough to curb the HIV epidemic. Research is ongoing on other prevention means (vaccine, pre- and post-exposition prophylaxis, microbicides, diaphragm) but their efficiency has not been demonstrated yet. Nevertheless, generalization of circumcision in southern Africa is responsible for contestations in part due to the fact that this prevention mean protects only partially from HIV infection. Moreover, for now, only a few countries integrated circumcision in their HIV prevention program in spite of WHO (World Health Organization) recommendations supporting male circumcision acknowledgement as an additional, important strategy for the prevention of heterosexually acquired HIV infection in men. Significant available funding should allow the situation to evolve quickly. At the same time, research goes on in order to know more about the effects and to facilitate the generalization of this prevention mean which is a great hope for southern Africa.  相似文献   

11.
We find that Rad50S mutations in yeast and mammals exhibit constitutive PIKK (PI3-kinase like kinase)-dependent signaling [T. Usui, H. Ogawa, J.H. Petrini, A DNA damage response pathway controlled by Tel1 and the Mre11 complex. Mol. Cell 7 (2001) 1255-1266.; M. Morales, J.W. Theunissen, C.F. Kim, R. Kitagawa, M.B. Kastan, J.H. Petrini, The Rad50S allele promotes ATM-dependent DNA damage responses and suppresses ATM deficiency: implications for the Mre11 complex as a DNA damage sensor. Genes Dev. 19 (2005) 3043-4354.]. The signaling depends on Mre11 complex functions, consistent with its role as a DNA damage sensor. Rad50S is distinct from hypomorphic mutations of Mre11 and Nbs1 in mammals [M. Morales, J.W. Theunissen, C.F. Kim, R. Kitagawa, M.B. Kastan, J.H. Petrini, The Rad50S allele promotes ATM-dependent DNA damage responses and suppresses ATM deficiency: implications for the Mre11 complex as a DNA damage sensor. Genes Dev. 19 (2005) 3043-3054.; J.P. Carney, R.S. Maser, H. Olivares, E.M. Davis, Le M. Beau, J.R. Yates, III, L. Hays, W.F. Morgan, J.H. Petrini, The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93 (1998) 477-486.; G.S. Stewart, R.S. Maser, T. Stankovic, D.A. Bressan, M.I. Kaplan, N.G. Jaspers, A. Raams, P.J. Byrd, J.H. Petrini, A.M. Taylor, The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell 99 (1999) 577-587.; B.R. Williams, O.K. Mirzoeva, W.F. Morgan, J. Lin, W. Dunnick, J.H. Petrini, A murine model of nijmegen breakage syndrome. Curr. Biol. 12 (2002) 648-653.; J.W. Theunissen, M.I. Kaplan, P.A. Hunt, B.R. Williams, D.O. Ferguson, F.W. Alt, J.H. Petrini, Checkpoint failure and chromosomal instability without lymphomagenesis in Mre11(ATLD1/ATLD1) mice. Mol. Cell 12 (2003) 1511-1523.] and the Mre11 complex deficiency in yeast [T. Usui, H. Ogawa, J.H. Petrini, A DNA damage response pathway controlled by Tel1 and the Mre11 complex. Mol. Cell 7 (2001) 1255-1266.; D'D. Amours, S.P. Jackson, The yeast Xrs2 complex functions in S phase checkpoint regulation. Genes Dev. 15 (2001) 2238-49. ; M. Grenon, C. Gilbert, N.F. Lowndes, Checkpoint activation in response to double-strand breaks requires the Mre11/Rad50/Xrs2 complex. Nat. Cell Biol. 3 (2001) 844-847. ] where the signaling is compromised. Herein, we describe evidence for chronic signaling by Rad50S and discuss possible mechanisms.  相似文献   

12.
In this work the interaction of Hydroxyzine, Promethazine and Thioridazine with Langmuir films of dipalmitoylphosphatidylcholine (dpPC) and dipalmitoylphosphatidic acid (dpPA), is studied. Temporal variations in lateral surface pressure (pi) were measured at different initial pi (pi(i)), subphase pH and drug-concentration. Drugs with the smallest (PRO) and largest (HYD) molecular size exhibited the lowest adsorption (k(a)) and the highest desorption (k(d)) rate constant values, respectively. The affinity binding constants (K(b)) obtained in monolayers followed the same profile (K(b,PRO) < K(b,HYD) < K(b,THI)) of the egg-PC/water partition coefficients (P) determined in bilayers. The drug concentration required to reach the half-maximal Deltapi at pi(i) = 14 mN/m (K(0.5)), was very sensitive to pH. The maximal increment in pi upon drug incorporation into the monolayer (deltapi(max)) will depend on the phospholipid collapse pressure (pi(c)), the monolayers's compressibility and drug's size, shape and charge. The higher pi(c) of dpPC lead to higher pi(cut-off) values (maximal pi allowing drug penetration), if compared with dpPA. In dpPC and dpPA pi(cut-off) decreased as a function of the molecular size of the uncharged drugs. In dpPA, protonated drugs became electrostatically trapped at the monolayer surface hence drug penetration, monolayer deformation and pi increase were impaired and the correlation between pi(cut-off) and drug molecular size was lost.  相似文献   

13.
In August 2010, the World Health Organization and the Korea Food & Drug Administration jointly organized the first implementation workshop of WHO guidelines on evaluating similar biotherapeutic products (SBPs) at the global level. The objective of the Workshop was to facilitate implementation of the newly adopted WHO Guidelines into the practice of national regulatory authorities (NRAs). WHO Guidelines were recognized by the workshop participants as a tool for harmonizing regulatory requirements worldwide. By reviewing and practicing several case studies, better understanding and consensus on the principles of clinical trial designs were reached. However, variations in terms of the national requirements for quality, safety and efficacy of these products revealed diversity in the regulatory expectations in different countries and regions. In addition, lack of terminology for the products developed as copy products (so called "me too" products) with a partial comparability to an RBP, led to a great diversity in evaluating as well as naming these products. The workshop participants proposed the following actions: a) NRAs should make efforts to build their capacities for regulation of SBPs; b) WHO should revise WHO Guidelines for assuring the quality of products prepared by recombinant DNA technology (WHO TRS 814) and continue monitoring progress with the implementation of the Guidelines on evaluating SBPs. Publication of the outcome of the Workshop was recognized as another action that WHO should coordinate.  相似文献   

14.
The seeds of 36 pigeonpea [Cajanus cajan (L) Millsp.] cultivars, resistant and susceptible to pests and pathogens and 17 of its wild relatives were analysed for inhibitors of trypsin, chymotrypsin, and insect gut proteinases to identify potential inhibitors of insect (Helicoverpa armigera) gut enzymes. Proteinase inhibitors (PIs) of pigeonpea cultivars showed total inhibition of trypsin and chymotrypsin, and moderate inhibition potential towards H. armigera proteinases (HGP). PIs of wild relatives exhibited stronger inhibition of HGP, which was up to 87% by Rhynchosia PIs. Electrophoretic detection of HGPI proteins and inhibition of HGP isoforms by few pigeonpea wild relative PIs supported our enzyme inhibitor assay results. Present results indicate that PIs exhibit wide range of genetic diversity in the wild relatives of pigeonpea whereas pigeonpea cultivars (resistant as well as susceptible to pests and pathogens) are homogeneous. The potent HGPIs identified in this study need further exploration for their use in strengthening pigeonpea defence against H. armigera.  相似文献   

15.
In 1996, the World Health Assembly declared violence a major public health issue. To follow up on this resolution, on October 3 this year, WHO released the first World Report on Violence and Health. The report analyses different types of violence including child abuse and neglect, youth violence, intimate partner violence, sexual violence, elder abuse, self-directed violence, and collective violence. For all these types of violence, the report explores the magnitude of the health and social effects, the risk and protective factors, and the types of prevention efforts that have been initiated. The launch of the report will be followed by a 1-year Global Campaign on Violence Prevention, focusing on implementation of the recommendations. This article summarises some of the main points of the world report.  相似文献   

16.
OBJECTIVE: To investigate whether statistical classification tools can infer the correct World Health Organization (WHO) grade from standardized histologic features in astrocytomas and how these tools compare with GRADO-IGL, an earlier computer-assisted method. STUDY DESIGN: A total of 794 human brain astrocytomas were studied between January 1976 and June 2005. The presence of 50 histologic features was rated in 4 categories from 0 (not present) to 3 (abundant) by visual inspection of the sections under a microscope. All tumors were also classified with the corresponding WHO grade between I and IV. We tested the prediction performance of several statistical classification tools (learning vector quantization [LVQ], supervised relevance neural gas [SRNG], support vector machines [SVM], and generalized regression neural network [GRNN]) for this data set. RESULTS: The WHO grade was predicted correctly from histologic features in close to 80% of the cases by 2 modern classifiers (SRNG and SVM), and GRADO-IGL was predicted correctly in > 84% of the cases by a GRNN. CONCLUSION: A standardized report, based the 50 histologic features, can be used in conjunction with modern classification tools as an objective and reproducible method for histologic grading of astrocytomas.  相似文献   

17.
Brassinin is a phytoalexin produced by plants from the family Brassicaceae that displays antifungal activity against a number of pathogens of Brassica species, including Leptosphaeria maculans (Desm.) Ces. et de Not. [asexual stage Phoma lingam (Tode ex Fr.) Desm.] and L. biglobosa. The interaction of a group of isolates of L. maculans virulent on brown mustard (Brassica juncea) with brassinin was investigated. The metabolic pathway for degradation of brassinin, the substrate selectivity of the putative detoxifying hydrolase, as well as the antifungal activity of metabolites and analogs of brassinin are reported. Brassinin hydrolase activity was detectable only in cell-free homogenates resulting from cultures induced with brassinin, N'-methylbrassinin, or camalexin. The phytoalexin camalexin was a substantially stronger inhibitor of these isolates than brassinin, causing complete growth inhibition at 0.5mM.  相似文献   

18.
In the New World, visceral leishmaniasis (VL), which is a progressive disease and frequently fatal, is caused by Leishmania (Leishmania) infantum/chagasi. It is endemic in many regions of Brazil and occasionally occurs in non-endemic regions when dogs from an endemic area are introduced. The aim of the present study is to compare different skin infection patterns of dogs from two leishmaniasis endemic areas. A histological analysis of dogs from Campo Grande, Mato Grosso do Sul state, a region where epidemic episodes are currently taking place, showed dermic inflammatory infiltrates, composed of numerous vacuolated parasitized macrophages, few lymphocytes, plasma cells and many degranulated mast cells. In the other region of the study, São Luís, Maranhão state, the skin of dogs presented a remarkable inflammatory reaction composed mainly of plasma cells, lymphocytes and very few parasites. We concluded that there is a difference in the skin lesion patterns of dogs with leishmaniasis that is directly related to the endemic area where the animals live.  相似文献   

19.
An increasing amount of evidence indicates that N can be transferred between plants. Nonetheless, a number of fundamental questions remain. A series of experiments was initiated in the field to examine N transfer between N2-fixing soybean (Glycine max [L.] Merr.) varieties and a non-nodulating soybean, and between N2-fixing peanut (Arachis hypogaea L.) or soybean and neighboring weed species. The experiments were conducted in soils with low N fertilities and used differences in N accumulation and/or 15N natural abundance to estimate N transfer. Mixtures of N2-fixing and non-nod soybean indicated that substantial inter-plant N transfer occurred. Amounts were variable, ranging from negligible levels to 48% of the N found in the non-nod at maturity. Transfer did not appear to strongly penalize the N2-fixing donor plants. But, in cases where high amounts of N were transferred, N content of donors was noticeably lowered. Differences were evident in the amount of N transferred from different N2-fixing donor genotypes. Results of experiments with N2-fixing crops and the weed species prickly sida (Sida spinosa L.) and sicklepod (Senna obtusifolia [L.] Irwin & Barneby) also indicated substantial N transfer occurred over a 60-day period, with amounts accounting for 30–80% of the N present in the weeds. Transfer of N, however, was generally very low in weed species that are known to be non-hosts for arbuscular mycorrhizae (yellow nutsedge, Cyperus esculentus L. and Palmer amaranth, Amaranthus palmeri [S.] Watson). The results are consistent with the view that N transfer occurs primarily through mycorrhizal hyphal networks, and they reveal that N transfer may be a contributing factor to weed problems in N2-fixing crops in low N fertility conditions.  相似文献   

20.
Wang X W  Ji L Z  Liu Y 《农业工程》2006,26(10):3166-3173
Changes in the concentrations of phytochemical compounds usually occur when plants are grown under elevated atmospheric CO2. CO2-induced changes in foliar chemistry tend to reduce leaf quality and may further affect insect herbivores. Increased atmospheric CO2 also has a potential influence on decomposition because it causes variations in chemical components of plant tissues. To investigate the effects of increased atmospheric CO2 on the nutritional contents of tree tissues and the activities of leaf-chewing forest insects, samples of Populus pseudo-simonii [Kitag.] grown in open-top chambers under ambient and elevated CO2 (650 μmol mol-1) conditions were collected for measuring concentrations of carbon, nitrogen, C : N ratio, soluble sugar and starch in leaves, barks, coarse roots (>2 mm in diameter) and fine roots (<2 mm in diameter). Gypsy moth (Lymantria dispar) larvae were reared on a single branch of experimental trees in a nylon bag with 1 mm 1 mm grid. The response of larval growth was observed in situ. Elevated CO2 resulted in significant reduction in nitrogen concentration and increase in C : N ratio of all poplar tissues. In all tissues, total carbon contents were not affected by CO2 treatments. Soluble sugar and nonstructural carbohydrate (TNC) in the poplar leaves significantly increased with CO2 enrichment, whereas starch concentration increased only on partial sampling dates. Carbohydrate concentration in roots and barks was generally not affected by elevated CO2, whereas soluble sugar contents in fine roots decreased in response to elevated CO2. When second instar gypsy moth larvae consuming poplars grew under elevated CO2 for the first 13 days, their body weight was 30.95% lower than that of larvae grown at ambient CO2, but no significant difference was found when larvae were fed in the same treatment for the next 11 days. Elevated atmospheric CO2 had adverse effects on the nutritional quality of Populus pseudo-simonii [Kitag.] tissues and the resultant variations in foliar chemical components had a significant but negative effect on the growth of early instar gypsy moth larvae.  相似文献   

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