Post-Viking Microbiology: New Approaches,New Data,New Insights

In the 20 years since the Viking experiments, major advances have been made in the areas of microbial systematics, microbial metabolism, microbial survival capacity, and the definition of environments on earth, suggesting that life is more versatile and tenacious than was previously appreciated. Almost all niches on earth which have available energy, and which are compatible with the chemistry of carbon-carbon bonds, are known to be inhabited by bacteria. The oldest known bacteria on earth apparently evolved soon after the formation of the planet, and are heat loving, hydrogen and/or sulfur metabolizing forms. Among the two microbial domains (kingdoms) is a great deal of metabolic diversity, with members of these forms being able to grow on almost any known energy source, organic or inorganic, and to utilize an impressive array of electron acceptors for anaerobic respiration. Both hydrothermal environments and the deep subsurface environments have been shown to support large populations of bacteria, growing on energy supplied by geothermal energy, thus isolating these ecosystems from the rest of the global biogeochemical cycles. This knowledge, coupled with new insights into the history of the solar system, allow one to speculate on possible evolution and survival of life forms on Mars.     

Preventing and Treating Obesity in Girls and Young Women to Curb the Epidemic

Obesity and its serious comorbidities, type 2 diabetes, coronary heart disease, hypertension, and dyslipidemia, have reached epidemic proportions in adults and children. Female obesity is more prevalent and, thus, has greater epidemiological importance: Mothers transmit the disease epigenetically and genetically. Maternal obesity affects maternal health, pregnancy outcome, and fetal, neonatal, childhood, and ultimately adult morbidity and mortality. Obesity is easy to diagnose, as are most of its risk factors, yet very little progress has been made in preventing the disease. During a brief period of rapid early growth, there is imprinting of antecedents of adult obesity and obesity‐related disease. Because of the rapidity of this early growth and the relative brevity of the critical period, early recognition and prompt intervention are necessary and possibly sufficient to prevent the development of obesity. Identification of inappropriate rapid weight gain through frequent weighing should trigger immediate adjustment of energy intake, a simple intervention in bottle‐fed infants, the ones at greatest risk for becoming obese. This review presents a step‐care strategy with fail‐safe action levels starting with maternal education and diet, exercise, and behavior modification for mother and child and progressing to drug treatment and, in selected cases, laparoscopic surgery for young women of childbearing age in whom other measures have failed. This approach is predicated on the assumption that careful monitoring and responsive supplementation of potential deficiencies is easier to achieve, more cost‐effective, and safer than effectively treating manifest obesity and its comorbidities in adults.     

674例新生儿败血症病原学及耐药性分析

目的:了解新生儿败血症病原学特点和致病菌耐药酶的产生与抗生素应用的相关性,为临床及时明确病原、正确选用抗生素提供依据。方法:对12年间新生儿科5 350例发热新生儿患儿无菌采集血液进行细菌培养,同时进行药敏分析和耐药酶检测,并了解采集标本前抗生素的应用情况。结果:5 350份血液标本中检出需氧菌674株,阳性率12.6%,其中革兰阴性杆菌155株,占23.0%,革兰阳性球菌504株,占74.8%。排在前八位的菌种是表皮葡萄球菌、溶血葡萄球菌、嗜麦芽假单胞菌、人葡萄球菌、肺炎克雷伯菌、大肠埃希菌、不动杆菌、粪肠球菌。革兰阳性球菌对青霉素,哌拉西林,苯唑西林耐药性高,对万古霉素100%敏感;革兰阴性杆菌对氨苄西林、哌拉西林,头孢呋辛耐药性高,对亚胺培南、头孢三代较敏感;感染产耐药酶菌患儿在检测前使用抗生素比率高于感染但未产耐药酶菌的患儿比率(X2=6.55,P<0.05),尤其第三代头孢菌素的应用,差异更显著(X2=12.17,P<0.005)。结论:新生儿败血症病原菌以表皮葡萄球菌和非发酵菌为主,但溶血葡萄球菌有上升趋势。加强各类标本的细菌学检测,预防败血症,减少耐药菌株的产生。     

The Costs of Preventing and Treating Chagas Disease in Colombia

Background

The objective of this study is to report the costs of Chagas disease in Colombia, in terms of vector disease control programmes and the costs of providing care to chronic Chagas disease patients with cardiomyopathy.

Methods

Data were collected from Colombia in 2004. A retrospective review of costs for vector control programmes carried out in rural areas included 3,084 houses surveyed for infestation with triatomine bugs and 3,305 houses sprayed with insecticide. A total of 63 patient records from 3 different hospitals were selected for a retrospective review of resource use. Consensus methodology with local experts was used to estimate care seeking behaviour and to complement observed data on utilisation.

Findings

The mean cost per house per entomological survey was $4.4 (in US$ of 2004), whereas the mean cost of spraying a house with insecticide was $27. The main cost driver of spraying was the price of the insecticide, which varied greatly. Treatment of a chronic Chagas disease patient costs between $46.4 and $7,981 per year in Colombia, depending on severity and the level of care used. Combining cost and utilisation estimates the expected cost of treatment per patient-year is $1,028, whereas lifetime costs averaged $11,619 per patient. Chronic Chagas disease patients have limited access to healthcare, with an estimated 22% of patients never seeking care.

Conclusion

Chagas disease is a preventable condition that affects mostly poor populations living in rural areas. The mean costs of surveying houses for infestation and spraying infested houses were low in comparison to other studies and in line with treatment costs. Care seeking behaviour and the type of insurance affiliation seem to play a role in the facilities and type of care that patients use, thus raising concerns about equitable access to care. Preventing Chagas disease in Colombia would be cost-effective and could contribute to prevent inequalities in health and healthcare.     

New Approaches to Principal Component Analysis for Trees

Object Oriented Data Analysis is a new area in statistics that studies populations of general data objects. In this article we consider populations of tree-structured objects as our focus of interest. We develop improved analysis tools for data lying in a binary tree space analogous to classical Principal Component Analysis methods in Euclidean space. Our extensions of PCA are analogs of one dimensional subspaces that best fit the data. Previous work was based on the notion of tree-lines.     

New Approaches to Enzymatic Oligosaccharide Synthesis: Glycosynthases and Thioglycoligases

Abstract

An overview of the applications of engineered glycosynthases and thioglycoligases for the enzymatic synthesis of O- and S-glycosidic linkages in oligosaccharides is presented. Glycosynthases lack the catalytic nucleophile of retaining glycosidases and use glycosyl fluorides with inverted anomeric stereochemistry as glycosyl donors. To date, nine enzymes from seven different glycosyl hydrolase families have been engineered to perform the glycosynthase reaction. Thioglycoligases lack the catalytic acid/base residue of retaining glycosidases and use dinitrophenyl glycosides as donors and deoxy-thiosugars as acceptors. The regioselectivity of the transglycosylation reaction is entirely controlled by the position of the thiol in the acceptor. To date, two retaining exo glycosidases and one endo glycanase, all from different glycosyl hydrolase families, have been engineered in this fashion.     

New Technologies, Tools and Approaches for Improving Crop Breeding

Introduction Most crops were first domesticated about 13 000 to 11 000 years ago.Humans are dependent on crops for survival,and from the beginnings of agriculture have been energetically involved in developing crops that better serve their needs     

Mechanistic Approaches to Community Ecology: A New Reductionism

Mechanistic approaches to community ecology are those whichemploy individual— ecological concepts—those ofbehavioral ecology, physiological ecology, and ecomorphology—as theoretical bases for understanding community patterns. Suchapproaches, which began explicitly about a decade ago, are justnow coming into prominence. They stand in contrast to more traditionalapproaches, such as MacArthur and Levins (1967),which interpretcommunity ecology almost strictly in terms of "megaparameters.". Mechanistic approaches can be divided into those which use populationdynamics as a major component of the theory and those whichdo not; examples of the two are about equally common. The firstapproach sacrifices a highly detailed representation of individual—ecological processes; the second sacrifices an explicit representationof the abundance and persistence of populations. Three subdisciplines of ecology—individual, populationand community ecology—form a "perfect" hierarchy in Beckner's(1974) sense. Two other subdisciplines—ecosystem ecologyand evolutionary ecology—lie somewhat laterally to thishierarchy. The modelling of community phenomena using sets ofpopulation-dynamical equations is argued as an attempt at explanationvia the reduction of community to population ecology. Much ofthe debate involving Florida State ecologists is over whetheror not such a relationship is additive (or conjunctive), a verystrong form of reduction. I argue that reduction of communityto individual ecology is plausible via a reduction of populationecology to individual ecology. Approaches that derive the population-dynamicalequations used in population and community ecology from individual-ecologicalconsiderations, and which provide a decomposition of megaparametersinto behavioral and physiological parameters, are cited as illustratinghow the reduction might be done. I argue that "sufficient parameters"generally will not enhance theoretical understanding in communityecology. A major advantage of the mechanistic approach is that variationin population and community patterns can be understood as variationin individual-ecological conditions. In addition to enrichingthe theory, this allows the best functional form to be chosenfor modeling higher-level phenomena, where "best" is definedas biologically most appropriate rather than mathematicallymost convenient. Disadvantages of the mechanistic approach arethat it may portend an overly complex, massive and special theory,and that it naturally tends to avoid many-species phenomenasuch as indirect effects. The paper ends with a scenario fora mechanistic-ecological utopia.     

Phosphoprotein from Dentin. New Approaches to Achieve and Assess Purity

Phosphoprotein extracted from rat incisors was purified by passage through a sulfonated polystyrene column. The phosphoprotein that emerged in the void volume contained 54% phosphoserine + serine and 36% aspartic acid and, in contrast to that obtained by DEAE-cellulose chromatography, was devoid of proline, valine, isoleucine, leucine, tyrosine, phenylalanine and arginine. Gel electrophoresis of the material purified on sulfonated polystyrene columns gave one major phosphate-containing band which would not stain with Coomassie Blue. EDTA or acetic acid demineralization yielded phosphoprotein preparations with identical compositions and electrophoretic properties. These data show that purification procedures reported earlier are insufficient.     

Papillomavirus Prophylactic Vaccines: Established Successes,New Approaches

Vaccines against the human papillomaviruses (HPVs) most frequently associated with cancer of the cervix are now available. These prophylactic vaccines, based on virus-like particles (VLPs), are extremely effective, providing protection from infection in almost 100% of cases. However, the vaccines present some limitations: they are effective primarily against the HPV type present in the vaccine, are expensive to produce, and need a cold chain. Vaccines based on the minor capsid protein L2 have been very successful in animal models and have been shown to provide a good level of protection against different papillomavirus types. The potential of L2-based vaccines to protect against many types of HPVs is discussed.Papillomaviruses (PVs) make up a vast family that comprises hundreds of different viruses (30). PVs infect epithelia in humans and animals and cause benign hyperproliferative lesions, commonly called warts or papillomas, which can occasionally progress to squamous cell cancer or less commonly, adenocarcinoma (12). Cancer of the uterine cervix is caused by human papillomavirus (HPV), primarily types 16 and 18, but also a dozen other “high risk” HPV types that infect the genital mucosa. The presence of viral proteins, i.e., foreign antigens, in the cancers and precancers presents the opportunity for prevention or cure of the lesions via vaccination targeted against the viral proteins. The virus infectious cycle and the neoplastic progression from papilloma to carcinoma are broadly similar in humans and animals, and animal PVs and their hosts represent excellent model systems for HPVs, infection, and neoplastic progression (8, 13). Additionally, animal PVs have provided powerful models for antiviral vaccines (15). This is particularly true of the bovine papillomavirus types 1 and 4 (BPV), the cottontail rabbit papillomavirus (CRPV), and later of the canine oral papillomavirus (COPV).In this review, we briefly describe the virus, its structure, its genomic organization, and its proteins, review the history of the development of the current prophylactic vaccines against HPV, and discuss the requirement for new broad-spectrum prophylactic vaccines. We note that a number of preclinical vaccination studies utilizing early viral antigens (not present in a virion) protect against experimental viral challenge (9, 43). Since this presumably occurs by triggering cellular immunity that clears the virus early after the initiation of infection, prior to the induction of clinically apparent disease, we classify this approach as therapeutic vaccination. Here we focus on the late proteins, L1 and L2, key structural components of the virion, and their role in prophylactic vaccination, first in animal models and then in humans.     

Neonatal Gram Negative and Candida Sepsis Survival and Neurodevelopmental Outcome at the Corrected Age of 24 Months

Objectives

To evaluate the long term neurodevelopmental outcome of premature infants exposed to either gram- negative sepsis (GNS) or neonatal Candida sepsis (NCS), and to compare their outcome with premature infants without sepsis.

Methods

Historical cohort study in a population of infants born at <30 weeks gestation and admitted to the Neonatal Intensive Care Unit (NICU) of the Academic Medical Center in Amsterdam during the period 1997–2007. Outcome of infants exposed to GNS or NCS and 120 randomly chosen uncomplicated controls (UC) from the same NICU were compared. Clinical data during hospitalization and neurodevelopmental outcome data (clinical neurological status; Bayley –test results and vision/hearing test results) at the corrected age of 24 months were collected. An association model with sepsis as the central determinant of either good or adverse outcome (death or severe developmental delay) was made, corrected for confounders using multiple logistic regression analysis.

Results

Of 1362 patients, 55 suffered from GNS and 29 suffered from NCS; cumulative incidence 4.2% and 2.2%, respectively. During the follow-up period the mortality rate was 34% for both GNS and NCS and 5% for UC. The adjusted Odds Ratio (OR) [95% CI] for adverse outcome in the GNS group compared to the NCS group was 1.4 [0.4–4.9]. The adjusted ORs [95% CI] for adverse outcome in the GNS and NCS groups compared to the UC group were 4.8 [1.5–15.9] and 3.2 [0.7–14.7], respectively.

Conclusions

We found no statistically significant difference in outcome at the corrected age of 24 months between neonatal GNS and NCS cases. Suffering from either gram –negative or Candida sepsis increased the odds for adverse outcome compared with an uncomplicated neonatal period.