Molecular epidemiology of infections caused by methicillin-resistant staphylococci

The review deals with the periodicity of the spread of methicillin-resistant S. aureus (MRSA) strains during the last 40 years, the mechanism of their resistance to methicillin and other beta-lactamic antibiotics, the genetic control of methicillin resistance, the genome organization of mec DNA and its possible cause, as well as the organization of epidemiological surveillance on MSRA in hospitals. The problem of changes in the epidemiology of staphylococcal infections due to the appearance of MRSA in the absence of contacts with carriers, treatment with antibiotics or stay in a hospital is discussed. The concern of public health authorities in connection with the emergence of MRSA strains, moderately resistant or resistant to vancomycin, is also discussed. The most promising programs of the MRSA study, as well as the optimum programs introduced in economically developed counties for the control of hospital infections caused by MRSA, are considered.     

Mutagenesis by transient misalignment

Based upon a consideration of two mutational hot spots produced during DNA synthesis by a eukaryotic DNA repair polymerase, we suggested that certain base substitution errors result not from direct miscoding but from correct coding by a transiently misaligned template-primer (Kunkel, T. A., and Alexander, P. S. (1986) J. Biol. Chem. 261, 160-166). This model, which we called dislocation mutagenesis, has been directly tested. Introducing a single, phenotypically silent G----A base change into the template switches the base substitution specificity at the immediately adjacent hot spot, a T residue, from T----G transversions to T----A transversions. The cumulative change in frequency, represented by the disappearance of the T----G events and the appearance of the T----A events, is greater than 300-fold. These data demonstrate that during DNA synthesis in vitro, a base at one position can code a mutation at another position. This mechanism can operate over greater distances to produce complex mutations as well. We present one example in which a 123-base deletion containing three base changes at one end of the deletion can be precisely explained by transient misalignment. It remains to be established whether mutagenesis by dislocation operates in vivo to produce biologically significant changes in genetic information.     

Measurement error in heat tolerance assays

Biological measurements inherently involve some measurement error (ME), which is a major concern because measurement accuracy (how closely a measurement reproduces the true value of the attribute being measured) and statistical power steadily decrease with increasing ME. However, ME has been largely overlooked in the thermal biology literature, which can be explained by the fact that thermotolerance estimates often involve the collapse or death of the tested individuals and measurements cannot be repeated in vivo with the same specimen under identical conditions. Here we assess inter- and intra-researcher (test-retest) reliability of heat tolerance measured as knockdown time from digital recordings of Drosophila subobscura flies individually assayed in vials with a dynamic method. We provide a summary of various estimators used to compute measurement reliability (the degree to which the measurement is affected by ME) together with their statistical properties. Our results indicate that the estimation of heat knockdown time has poor reliability: intra-researcher ME=29% and inter-researcher ME=34%. This difference is attributed to lack of ‘accurateness’ (the difference in the marginal distributions of the measurements taken by the two researchers) because measurement imprecision was essentially the same in both estimates (27%). In view of our results we conclude that thermal biologists should report the reliability of thermotolerance estimates and, when necessary, adopt some straightforward guidelines suggested here to improve measurement reliability.     

Changing spatial epidemiology of pertussis in continental USA

Prediction and control of the geographical spread of emerging pathogens has become a central public health issue. Because these infectious diseases are by definition novel, there are few data to characterize their dynamics. One possible solution to this problem is to apply lessons learnt from analyses of historical data on familiar and epidemiologically similar pathogens. However, the portability of the spatial ecology of an infectious disease in a different epoch to other infections remains unexamined. Here, we study this issue by taking advantage of the recent re-emergence of pertussis in the United States to compare its spatial transmission dynamics throughout the 1950s with the past decade. We report 4-year waves, sweeping across the continent in the 1950s. These waves are shown to emanate from highly synchronous foci in the northwest and northeast coasts. In contrast, the recent resurgence of the disease is characterized by 5.5-year epidemics with no particular spatial structure. We interpret this to be the result of dramatic changes in patterns of human movement over the second half of the last century, together with changing age distribution of pertussis. We conclude that extrapolation regarding the spatial spread of contemporaneous pathogens based on analyses of historical incidence may be potentially very misleading.     

Methods of molecular epidemiology of infections caused by group B streptococci

In this review the comparative analysis of advantages and disadvantages of the known methods for the immunological diagnostics of streptococcal infections (serotyping, phage typing), as well as the methods of molecular epidemiology (PCR typing with the use of "disseminated" priming, ribotyping, electrophoresis in the pulsing electric field, etc.), is presented. Essentially new approaches, capable of being used in future for the control of epidemically topical clones of group B streptococci, are discussed.     

Measurement error in racial and ethnic statistics

In the United States, the racial and ethnic statistics published by the National Center for Health Statistics (NCHS) assume that each member of the U.S. population has a race and ethnicity and that if a member is black or white with respect to his risk of one disease, he is the same race with respect to his risk of another. Such an assumption is mistaken. Race and ethnicity are taken by the NCHS to be an intrinsic property of members of a population, when they should be taken to depend on interest. The actual or underlying race or ethnicity of members of a population depends on the risk whose variation within the population we wish to describe or explain.

The epidemiology of the infection caused by the human immunodeficiency virus in the USSR

The existing system of the epidemiological surveillance of HIV infection in the USSR makes it possible to evaluate the present situation as the beginning of epidemic. The main routes of the transfer of HIV infection as per data for April 1989: 50% by the sexual route, 25.8% by parenteral manipulations.     

植物对环境应力刺激的生物学效应

植物生长在自然环境中由于其“不动性”而不可避免地要受到各种环境应力的刺激,应力－生长关系一直是生物学家和物理学家所关心的课题,是生物力学的灵魂。很多研究已经表明外界应力作用对植物的生长发育有着重要的影响。本综述了国内外关于应力对植物组织所引起的生物学效应,首先论述了环境应力所引起的宏观生物学效应,随后重点论述了环境应力所引起的生物学效应在细胞和分子水平上的研究,其中包括单个细胞的加载、电磁场、微     

Novel method for chase analysis of oligosaccharide metabolic error caused by xenobiotics

Saccharide primers, such as dodecyl β-lactoside (Lac-C12), are unique artificial precursors of glycolipid synthesis. In culture media supplemented with saccharide primers, they are taken up by the cells in the culture media and glycosylated by cellular glycosyltransferases in the Golgi apparatus to form pseudo-glycolipids. In this study, we examine the effects of various xenobiotics on glycolipid synthesis by implementing a novel method to analyze pseudo-glycolipids, mainly gangliosides, produced by ONS-76 medulloblastoma cells in a culture medium containing various xenobiotics. The ganglioside group of pseudo-glycolipids was effectively purified by using strong anion-exchange cartridges. The production of pseudo-gangliosides was stimulated by N-(n-butyl)deoxygalactonojirimycin (NB-DGJ), but was inhibited by castanospermine, 2-deoxy-2-fluoro-d-galactose, tunicamycin, and brefeldin A. Because the cells in the culture medium are exposed to the saccharide primers and xenobiotics at the same time, and are secreted in the culture medium in their glycosylated form, our method can be used to effectively analyze the direct effects of xenobiotics on ganglioside synthesis.     

Variation in vegetative and flowering phenology in a forest herb caused by environmental heterogeneity

Timing of seasonal plant development can affect biotic interactions and plant fitness. Phenology is governed largely by temperature and may therefore be affected by global climate warming, making this an important area of research. Several factors in addition to temperature may cause differences in phenology. We studied the influence of local environment, plant size, and reproductive effort on shoot emergence and flowering time of 290 individuals of Actaea spicata (Ranunculaceae), distributed among 25 plots in four populations. We used multiple regression and structural equation models (SEM) to study causal relationships. Among plots, soil temperature and canopy cover explained 63% of the variation in shoot emergence. Soil temperature, slope, and canopy cover together explained 83% of the variation in flowering time. Within plots, small plants on steep south-facing slopes with high soil potassium concentrations emerged earlier in the year. Plants emerging earlier flowered earlier, but no environmental factors affected flowering time directly. We found no effects of reproductive effort. Our results support the view that flowering time of temperate forest herbs is constrained by several environmental factors acting indirectly through effects on shoot emergence time.     

Integrating environmental and spatial processes in ecological community dynamics

The processes controlling the abundances of species across multiple sites form the cornerstone of modern ecology. In these metacommunities, the relative importance of local environmental and regional spatial processes is currently hotly debated, especially in terms of the validity of neutral model. I collected 158 published data sets with information on community structure, environmental and spatial variables. I showed that approximately 50% of the variation in community composition is explained by both environmental and spatial variables. The majority of the data sets were structured by species-sorting dynamics (SS), followed by a combination of SS and mass-effect dynamics. While neutral processes were the only structuring process in 8% of the collected natural communities, disregarding neutral dispersal processes would result in missing important patterns in 37% of the studied communities. Moreover, metacommunity characteristics such as dispersal type, habitat type and spatial scale predicted part of the detected variation in metacommunity structure.     

Molecular epidemiology and spatial distribution of a waterborne cryptosporidiosis outbreak in Australia

Cryptosporidiosis is one of the most common waterborne diseases reported worldwide. Outbreaks of this gastrointestinal disease, which is caused by the Cryptosporidium parasite, are often attributed to public swimming pools and municipal water supplies. Between the months of January and April in 2009, New South Wales, Australia, experienced the largest waterborne cryptosporidiosis outbreak reported in Australia to date. Through the course of the contamination event, 1,141 individuals became infected with Cryptosporidium. Health authorities in New South Wales indicated that public swimming pool use was a contributing factor in the outbreak. To identify the Cryptosporidium species responsible for the outbreak, fecal samples from infected patients were collected from hospitals and pathology companies throughout New South Wales for genetic analyses. Genetic characterization of Cryptosporidium oocysts from the fecal samples identified the anthroponotic Cryptosporidium hominis IbA10G2 subtype as the causative parasite. Equal proportions of infections were found in males and females, and an increased susceptibility was observed in the 0- to 4-year age group. Spatiotemporal analysis indicated that the outbreak was primarily confined to the densely populated coastal cities of Sydney and Newcastle.     

Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency

Dihydrofolate reductase (DHFR) is a critical enzyme in folate metabolism and an important target of antineoplastic, antimicrobial, and antiinflammatory drugs. We describe three individuals from two families with a recessive inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency due to a germline missense mutation in DHFR, resulting in profound enzyme deficiency. We show that cerebral folate levels, anemia, and pancytopenia of DHFR deficiency can be corrected by treatment with folinic acid. The characterization of this disorder provides evidence for the link between DHFR and metabolism of cerebral tetrahydrobiopterin, which is required for the formation of dopamine, serotonin, and norepinephrine and for the hydroxylation of aromatic amino acids. Moreover, this relationship provides insight into the role of folates in neurological conditions, including depression, Alzheimer disease, and Parkinson disease.     

Phenotypic diversity caused by differential RpoS activity among environmental Escherichia coli isolates

Enteric bacteria deposited into the environment by animal hosts are subject to diverse selective pressures. These pressures may act on phenotypic differences in bacterial populations and select adaptive mutations for survival in stress. As a model to study phenotypic diversity in environmental bacteria, we examined mutations of the stress response sigma factor, RpoS, in environmental Escherichia coli isolates. A total of 2,040 isolates from urban beaches and nearby fecal pollution sources on Lake Ontario (Canada) were screened for RpoS function by examining growth on succinate and catalase activity, two RpoS-dependent phenotypes. The rpoS sequence was determined for 45 isolates, including all candidate RpoS mutants, and of these, six isolates were confirmed as mutants with the complete loss of RpoS function. Similarly to laboratory strains, the RpoS expression of these environmental isolates was stationary phase dependent. However, the expression of RpoS regulon members KatE and AppA had differing levels of expression in several environmental isolates compared to those in laboratory strains. Furthermore, after plating rpoS+ isolates on succinate, RpoS mutants could be readily selected from environmental E. coli. Naturally isolated and succinate-selected RpoS mutants had lower generation times on poor carbon sources and lower stress resistance than their rpoS+ isogenic parental strains. These results show that RpoS mutants are present in the environment (with a frequency of 0.003 among isolates) and that, similarly to laboratory and pathogenic strains, growth on poor carbon sources selects for rpoS mutations in environmental E. coli. RpoS selection may be an important determinant of phenotypic diversification and, hence, the survival of E. coli in the environment.