A Peroxygenase-Alcohol Dehydrogenase Cascade Reaction to Transform Ethylbenzene Derivatives into Enantioenriched Phenylethanols.

In this study, we developed a new bienzymatic reaction to produce enantioenriched phenylethanols. In a first step, the recombinant, unspecific peroxygenase from Agrocybe aegerita (rAaeUPO) was used to oxidise ethylbenzene and its derivatives to the corresponding ketones (prochiral intermediates) followed by enantioselective reduction into the desired (R)- or (S)-phenylethanols using the (R)-selective alcohol dehydrogenase (ADH) from Lactobacillus kefir (LkADH) or the (S)-selective ADH from Rhodococcus ruber (ADH-A). In a one-pot two-step cascade, 11 ethylbenzene derivatives were converted into the corresponding chiral alcohols at acceptable yields and often excellent enantioselectivity.

99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: symbionts and immunopathology in chronic diseases: insights from evolution.

Immunological aetiologies of disease are not generally well understood, but have been attributed to intrinsic immunological imbalances, infectious triggers or persistent infections. Evolutionary considerations lead to the formulation of three feasible categories of immunopathology for common diseases. One category of hypotheses presumes that the immune system is exposed to environmental conditions to which the individual is not well adapted. One hypothesis within this category, often referred to as the hygiene hypothesis, proposes that new more hygienic environmental conditions have generated compositions of symbionts that differ from those to which humans have been adapted. A second category of hypotheses proposes that infectious agents act as triggers of immunopathology by shifting the immune system into a self-destructive state. A third category proposes that infectious agents keep the immune in a self-destructive state by causing persistent infections. To evaluate disease causation rigorously and to determine the appropriate interventions, these three categories of causation need to considered for every disease that involves immunopathology. Assessment of the progress in understanding oncogenesis and other chronic diseases emphasizes the value of such integrated assessments.

Sulfadiazine-resistant group A Neisseria meningitidis.

A meningitis epidemic due to Group A meningococci was unusual in that most of the strains isolated from patients were generally resistant to sulfadiazine. This is the first report of sulfonamide resistance in an epidemic strain of Neisseria meningitidis Group A.

Malignant and unclear histological findings in incidentalomas.

BACKGROUND: The management of incidentalomas with tumor size 3 cm and larger is still under controversial discussion. STUDY DESIGN: Clinical charts of 65 patients who underwent adrenalectomy for an incidentaloma were reviewed. RESULTS: Sixty-five patients were operated. There were 28 men and 37 women with a median age of 56.9 years. Median size of all resected lesions was 4.1 cm. Indications for surgery were tumor size equal and larger than 3 cm, recurrent pain, hormone status and patients' fear of malignancy. In 45 patients, the adenomas did not meet the defined criteria of malignancy. There were 9 cases of adrenal hyperplasia, and two cysts and two hematomas were found in 4 patients. Moreover, 1 schwannoma and 1 myelolipoma were removed. In 3 patients, a primary adrenocortical carcinoma of 3.4, 4.0, and 5.0 cm in diameter, respectively, was identified. In 1 patient, an adrenal cortical carcinoma of 10.0 cm in diameter was operated. In 1 patient, the status (size: 4.5 cm) could not be determined conclusively. CONCLUSION: Hormonal activity should be determined independent of the size, and lesions with hormonal activity should be resected; in the presence of hormonally inactive masses, removal of tumors of 3 cm and larger in size is recommended.

Transmission modes and evolution of the parasitism-mutualism continuum.

An analysis of fitness costs and benefits associated with pathogenicity suggests that modes of transmission are key determinants of evolution toward severely pathogenic, benign, or mutualistic symbioses. Specifically, this approach suggests that symbionts with mobile life history stages should evolve toward extremely severe parasitism, vector-borne symbionts should evolve toward severe parasitism in vertebrate hosts and benign parasitism in the vectors, waterborne symbionts should evolve toward severe parasitism, symbionts transmitted by predation should evolve toward severe parasitism in prey hosts and benign parasitism in predator hosts, and vertically transmitted symbionts should evolve toward benign parasitism and mutualism. Detailed reviews of the literature on human diseases support the hypothesized severity of vector-borne and waterborne transmission. Evaluation of the other associations is less detailed, but each association appears to be present. This framework draws attention to the need for detailed reviews of relationships between transmission modes and the nature of symbiotic interactions, and experimental manipulations of transmission.

Effect of floral orifice width and shape on hummingbird-flower interactions.

Nectar guides are common among insect-pollinated plants, yet are thought to be rare or absent among hummingbird-pollinated plants. We hypothesize that the lower lips and trumpet-shaped orifices of many hummingbird flowers act as nectar guides to direct hummingbirds to the flowers' nectar and orient the birds for pollination. To test this hypothesis we conducted laboratory experiments using flowers of Monarda didyma (bee balm) and M. fistulosa (wild bergamot), which have orifice widths of about 4 mm and 2 mm, respectively, and latex flowers with orifice widths of 4 mm and 2 mm and three orifice shapes (trumpet, lipped, and lipless). Rubythroated hummingbirds (Archilochus colubris) made fewer errors during bill insertion and spent a smaller proportion of their feeding visit in error at M. didyma flowers than at M. fistulosa flowers, and at unaltered flowers of both species than at flowers with lower lips removed. Handling times were longer at both lipped and lipless flowers of M. didyma than at those of M. fistulosa, and at lipped than at lipless flowers of M. didyma. The average duration of contact between a hummingbird and a flower's anthers and stigma was longer at M. didyma than at M. fistulosa for both lipped and lipless flowers, and at lipped than at lipless M. didyma flowers. Hummingbirds missed the openings of latex flowers with their bills more frequently and spent a greater percentage of their total feeding visit in error at (i) 2-mm than at 4-mm flowers of all three shapes, (ii) lipless flowers than at trumpet or lipped flowers, and (iii) lipped flowers than at trumpet flowers of both widths. The duration of hummingbird/anther contact was longer at (i) 2-mm than at 4-mm flowers of all shapes, (ii) lipped than at trumpet or lipless flowers, and (iii) lipless than at trumpet flowers for both widths. No significant differences in handling times of hummingbirds were observed among any of the latex flower shapes or widths. Our results demonstrate that orifice shapes can act as guides by reducing the frequency of feeding errors by visiting hummingbirds, and that effects of orifice shape on pollination must be considered in conjunction with flower widths and locations of anthers and stigmas.

Transmission modes and the evolution of virulence : With special reference to cholera, influenza, and AIDS.

Application of evolutionary principles to epidemiological problems indicates that cultural characteristics influence the evolution of parasite virulence by influencing the success of disease transmission from immobilized, infected hosts. This hypothesis is supported by positive correlations between virulence and transmission by biological vectors, water, and institutional attendants. The general evolutionary argument is then applied to the causes and consequences of increased virulence for three diseases: cholera, influenza and AIDS.

Vesicular glutamate transporter 1 immunoreactivity in extrinsic and intrinsic innervation of the rat esophagus.

Encouraged by the recent finding of vesicular glutamate transporter 2 (VGLUT2) immunoreactivity (-ir) in intraganglionic laminar endings (IGLEs) of the rat esophagus, we investigated also the distribution and co-localization patterns of VGLUT1. Confocal imaging revealed substantial co-localization of VGLUT1-ir with selective markers of IGLEs, i.e., calretinin and VGLUT2, indicating that IGLEs contain both VGLUT1 and VGLUT2 within their synaptic vesicles. Besides IGLEs, we found VGLUT1-ir in both cholinergic and nitrergic myenteric neuronal cell bodies, in fibers of the muscularis mucosae, and in esophageal motor endplates. Skeletal neuromuscular junctions, in contrast, showed no VGLUT1-ir. We also tested for probable co-localization of VGLUT1-ir with markers of extrinsic and intrinsic esophageal innervation and glia. Within the myenteric neuropil we found, besides co-localization of VGLUT1 and substance P, no further co-localization of VGLUT1-ir with any of these markers. In the muscularis mucosae some VGLUT1-ir fibers were shown to contain neuronal nitric oxide synthase (nNOS)-ir. VGLUT1-ir in esophageal motor endplates was partly co-localized with vesicular acetylcholine transporter (VAChT)/choline acetyltransferase (ChAT)-ir, but VGLUT1-ir was also demonstrated in separately terminating fibers at motor endplates co-localized neither with ChAT/VAChT-ir nor with nNOS-ir, suggesting a hitherto unknown glutamatergic enteric co-innervation. Thus, VGLUT1-ir was found in extrinsic as well as intrinsic innervation of the rat esophagus.

Waterborne transmission and the evolution of virulence among gastrointestinal bacteria.

Diarrhoeal diseases are primary contributors to millions of deaths annually. Yet, little is known about the evolutionary reasons for the differences in virulence among gastrointestinal pathogens. Applying the comparative, cost/benefit approach of evolutionary biology this paper proposes that waterborne transmission should favour evolution towards high virulence. This hypothesis is supported by a cross-specific test, which shows that waterborne transmission is strongly correlated with the virulence of bacterial gastrointestinal pathogens of humans. Alternative explanations of this correlation are not supported by available data. These findings bear on public health policy because they draw attention to a previously unrecognized long-range benefit gained from purification of water supplies; diarrhoeal pathogens may evolve to lower levels of virulence.

Evolution of mutation rate and virulence among human retroviruses.

High mutation rates are generally considered to be detrimental to the fitness of multicellular organisms because mutations untune finely tuned biological machinery. However, high mutation rates may be favoured by a need to evade an immune system that has been strongly stimulated to recognize those variants that reproduced earlier during the infection. HIV infections conform to this situation because they are characterized by large numbers of viruses that are continually breaking latency and large numbers that are actively replicating throughout a long period of infection. To be transmitted, HIVs are thus generally exposed to an immune system that has been activated to destroy them in response to prior viral replication in the individual. Increases in sexual contact should contribute to this predicament by favouring evolution toward relatively high rates of replication early during infection. Because rapid replication and high mutation rate probably contribute to rapid progression of infections to AIDS, the interplay of sexual activity, replication rate, and mutation rate helps explain why HIV-1 has only recently caused a lethal pandemic, even though molecular data suggest that it may have been present in humans for more than a century. This interplay also offers an explanation for geographic differences in progression to cancer found among infections due to the other major group of human retroviruses, human T-cell lymphotropic viruses (HTLV). Finally, it suggests ways in which we can use natural selection as a tool to control the AIDS pandemic and prevent similar pandemics from arising in the future.

Guarding against the most dangerous emerging pathogens.

Control of emerging infectious diseases will be difficult because of the large number of disease-causing organisms that are emerging or could emerge and the great diversity of geographic areas in which emergence can occur. The modern view of the evolution of pathogen virulence--specifically its focus on the tradeoff between costs and benefits to the pathogen from increased host exploitation--allows control programs to identify and focus on the most dangerous pathogens (those that can be established with high virulence in human populations).

The evolution of virulence and emerging diseases.

Insights into the evolution of virulence may aid efforts to control or even prevent emerging diseases. Specifically, dangerous pathogens can be distinguished from those that pose relatively little threat by identifying characteristics that favor intense exploitation of hosts by pathogens, hence causing high virulence. Studies to date have implicated several such characteristics, including transmission by vectors, attendants, water, and durable propagules. These insights may improve the return on investments in disease control by directing effort and resources to the most-dangerous emerging pathogens. The approach also should help us to identify those control measures that will guard against the future emergence of dangerous pathogens, even those that have not yet been identified.

Chlamydia pneumoniae and cardiovascular disease: an evolutionary perspective on infectious causation and antibiotic treatment.

Evolutionary considerations implicate infectious causation of atherosclerosis and help to resolve different risk factors as parts of an overall process of disease causation. An evolutionary approach also provides insight for the timing of research efforts to provide better control of pathogen evolution. In particular, evolutionary considerations emphasize the need to understand the transmissibility of Chlamydia pneumoniae from systemic infections in order to control the evolution of antibiotic resistance.