Trade-offs and the evolution of virulence of microparasites: do details matter?

Models of the within-host dynamics of parasites have been used to consider the evolution of microparasites causing acute infections in vertebrate hosts. In this paper, we use these models to examine how the level of virulence to which a parasite evolves, depends on factors such as the relationship between parasite density and its rate of transmission from infected hosts, and the mechanism of parasite-induced pathogenesis. We show that changes in the terms describing transmissibility and pathogenesis may lead to dramatic differences in the level of virulence to which a parasite evolves. This suggests that no single factor is likely to be responsible for the differences in virulence of different parasites, and that understanding of the evolution of virulence of parasites will require a detailed quantitative understanding of the interaction between the parasite and its host.     

Theories of adaptation: what they do and don’t say

Theoretical work on adaptation has lagged behind experimental. But two classes of adaptation model have been partly explored. One is phenotypic and the other DNA sequence based. I briefly consider an example of each – Fishers geometric model and Gillespies mutational landscape model, respectively – reviewing recent results. Despite their fundamental differences, these models give rise to several strikingly similar results. I consider possible reasons for this congruence. I also emphasize what predictions do and, as important, do not follow from these models.     

Mechanosensitive channels: what can they do and how do they do it?

While mechanobiological processes employ diverse mechanisms, at their heart are force-induced perturbations in the structure and dynamics of molecules capable of triggering subsequent events. Among the best characterized force-sensing systems are bacterial mechanosensitive channels. These channels reflect an intimate coupling of protein conformation with the mechanics of the surrounding membrane; the membrane serves as an adaptable sensor that responds to an input of applied force and converts it into an output signal, interpreted for the cell by mechanosensitive channels. The cell can exploit this information in a number of ways: ensuring cellular viability in the presence of osmotic stress and perhaps also serving as a signal transducer for membrane tension or other functions. This review focuses on the bacterial mechanosensitive channels of large (MscL) and small (MscS) conductance and their eukaryotic homologs, with an emphasis on the outstanding issues surrounding the function and mechanism of this fascinating class of molecules.     

The continuity of living matter and the discontinuities of its constituents: do plankton and benthos really exist?

Plankton and benthos are popular concepts identifying two ways of life of aquatic organisms. Their spatial separation led to the development of different sampling techniques and to separate conceptualizations of the principles governing these subsets of the aquatic environment. Reciprocal connections between plankton and benthos, however, are very strong both from a functional (energy fluxes) and a structural (life cycle dynamics) point of view. A full appreciation of such links is forcing marine ecology towards a more integrated approach.     

Prophylaxis and treatment of bacterial infections: do we need new strategies?

Bacterial infections in patients with hematologic malignancies still represent a severe and life-treating problem. Several observational studies during the last decade have revealed that neutropenic patients with fever are a heterogeneous population with various differences regarding response to initial therapy, development of serious complications and mortality. The role of neutropenia as main risk factor for infections in hematologic patients and the definition of different level of risk related to neutrophils count and duration of neutropenia have been extensively studied and different categories of patients based on the risk of infection, mostly the condition of neutropenia, have been clearly defined. The strategies on antimicrobial therapy and supportive care in hematologic patients need to be continuously assessed, in fact new conditions favouring the occurrence of infectious complications in patients with hematologic malignancies have progressively emerged. The use of oral prophylactic antibiotics in neutropenic cancer patients is still a matter of debate. Before 2005, several trials showed how the prevention of infection can be extremely important in this setting of patients but none was conclusive. In 2005 two meta-analysis and two large randomized clinical trials gave new evidence that antibacterial prophylaxis can reduce in neutropenic patients several important outcomes including mortality. The use of the empiric antibacterial therapy represents the cornerstone of the antimicrobial strategies in the febrile neutropenic patients leading, over the span of 20 years, to a dramatic decrease of deaths: Actually beta-lactam monotherapy is commonly used for the empiric treatment of febrile neutropenia. Recently, large randomized clinical trials and meta-analysis showed that the addition of an aminoglycoside and/or a glycopeptides results in a more favourable outcome only in selected severe infections. The use of antibiotics should be prudent and safe also in neutropenic hematologic patients to prevent emergence of microbial resistance, to save costs, to reduce toxicity. For this reasons, according to the evidence, antibacterial prophylaxis should be restricted to high risk hematologic patients and empiric parenteral antibiotic monotherapy should be recommended in case of febrile neutropenia limiting the use of amynoglicosides and glycopeptides. In the next future, a major effort should be made to state in hematologic patients new risk factors which could more accurately define subgroups for targeted anti-infective strategies.     

Examining the developing bone: What do we measure and how do we do it?

The clinical tools available to evaluate bone development in children are often ambiguous, and difficult to interpret. Unfortunately bone densitometry methods (i.e., dual energy X-ray absorptiometry, DXA) which have a relatively straightforward application in adult osteoporosis, are far more difficult to evaluate in the growing skeleton. Even with adequate "adjustment" for bone size or maturity, bone "density" (areal or volumetric) alone often gives an inaccurate assessment of bone strength--especially in children. Ideally, we would like to measure both material and geometric properties of bone to accurately estimate "strength". Mechanically meaningful measures of bone geometry (bone cross-sectional area, cortical thickness) and estimates of bending strength (section modulus, or SSI) are available with non-invasive techniques such as (p)QCT and some DXA software. With new technology it might be possible to also measure bone material properties, which will be especially important in some pediatric disorders. In children, we also need to know something about the loads imposed on a child's bone and consider not only absolute bone strength, but also the strength of bone relative to the physiologic loads. Interpreting bone strength in light of the loads imposed (particularly muscle force) is critical for an accurate diagnosis of the developing bone.     

Ingestion and incorporation of freshwater diatoms by Daphnia pulicaria: do morphology and oxylipin production matter?

In order to explain differences in the growth and reproductionof Daphnia pulicaria fed various freshwater diatoms, we measuredingestion rates and carbon incorporation for six cultured diatomspecies: the single-celled Stephanodiscus hantzschii, Stephanodiscusminutulus and Cyclotella meneghiniana, and the colony-formingAsterionella formosa, Fragilaria capucina and Fragilaria sp.Two of the colony-forming species, when damaged, produced polyunsaturatedaldehydes (oxylipins) that have been found to impair the reproductionof marine copepods. We tested two hypotheses: (i) feeding andincorporation rates are affected by diatom morphology; and (ii)polyunsaturated aldehydes act as feeding deterrents. Daphniabody length versus ingestion rate regressions differed for single-celledand colony-forming diatoms. Ingestion rates for single-celleddiatoms showed clear size dependencies and high correlationcoefficients, while the dependency was weak for colony-formingdiatoms and individual variability was high. This differencewas not observed for carbon incorporation rates, which showedlow variability for all diatoms. Asterionella formosa yieldedthe lowest incorporation rates due to low incorporation efficiency,while all other diatoms were incorporated at similar rates.Thus, morphological differences of the diatoms had no effecton carbon uptake by Daphnia. The presence or absence of polyunsaturatedaldehydes did not cause different ingestion rates; hence thealdehydes are not feeding deterrents.     

Stickleback fights: why do winners win? Influence of metabolic and morphometric parameters

Pairs of reproductively mature male three-spined stickleback (Gasterosteus aculeatus) were introduced into unfamiliar aquaria and observed until one male became dominant. Skin carotenoid content, morphometric indexes, and metabolic capacities of the axial and pectoral muscles were examined to establish whether morphological or physiological parameters differentiated winners and losers. Stickleback that initiated fights typically won. Quick initiation led to quick victory. Overall, winners and losers differed in few morphological or metabolic characteristics, but these properties and the differences between these attributes for losers and winners of specific fights were linked with initiation time and fight duration. Morphometric indexes of losers were the primary determinants of initiation time and fight duration, whereas for winners muscle metabolic capacities were linked to these fight characteristics. The greater the hepatosomatic index (HSI) of losers, the longer the fight initiation times. Similarly, losers with high HSI and carotenoid levels resisted defeat longer. In winners, initiation time decreased as axial muscle phosphofructokinase levels increased and citrate synthase levels decreased, whereas the metabolic capacities of the pectoral muscle were linked with time to achieve victory. When losers had greater HSI values than the winners of a specific fight, fight initiation was delayed and fights lasted longer. When losers had higher carotenoid levels than winners, fights also lasted longer. On the other hand, when losers had more visceral fat (fat body mass over somatic mass) than winners, both initiation time and combat duration were reduced. These results suggest that male stickleback assess their physiological status and that of their opponents, in particular the HSI, and adjust their combat strategies accordingly.     

Rhizosphere priming effects of soybean and cottonwood: do they vary with latitude?

Plant and Soil - Soil seed banks are an important source of seedling recruits in grassland ecosystems, particularly following large-scale disturbance. Nonetheless, the relative importance of...     

Nurse practitioners in accident and emergency departments: what do they do?

OBJECTIVE--To determine the distribution and scope of nurse practitioner schemes in accident and emergency departments in England and Wales; to describe the caseloads of doctors and nurse practitioners on two representative days; and to estimate the number of patients managed by nurse practitioners in the year to 31 March 1991. DESIGN--A postal survey of accident and emergency departments and a content analysis of case notes of new patients attending a representative sample of accident and emergency departments on two days. SETTING--All accident and emergency departments in England and Wales. PARTICIPANTS--Survey: 560 nurses in charge of accident and emergency departments. Census: case notes of 5814 patients in 37 accident and emergency departments. MAIN OUTCOME MEASURES--Survey: number of accident and emergency departments with nurse practitioner schemes. Census: demographic and clinical characteristics of new patients attending and whether nurse practitioner or doctor made diagnoses and ordered investigations, treatments, referrals, discharges. RESULTS--513 replies (92%) from 465 surveyed functioning accident and emergency departments and 48 departments recently closed. 27 (6%) departments used designated nurse practitioners and 159 (34%) "unofficial" nurse practitioners. Only 530 (9%) of the 5814 patients in the census were managed entirely or mainly by nurse practitioners, with higher proportions in ophthalmic departments (nearly 30%) and minor casualty departments (over 40%) than in major departments (3%). Most patients managed by nurse practitioners (86%) had minor trauma. In the year ending 31 March 1991 an estimated 390,000 (95% confidence interval 260,000 to 520,000) patients out of a total of 12.5 million (3.1%, 2.1% to 4.1%) were clinically managed by a nurse practitioner. CONCLUSIONS--Designated nurse practitioner schemes are rare. The volume and range of nurse practitioner work in major general accident and emergency departments is small compared with those in specialised and minor accident and emergency departments.     

Mechanobiology of cartilage: how do internal and external stresses affect mechanochemical transduction and elastic energy storage?

 Articular cartilage is a multilayered structure that lines the surfaces of all articulating joints. It contains cells, collagen fibrils, and proteoglycans with compositions that vary from the surface layer to the layer in contact with bone. It is composed of several zones that vary in structure, composition, and mechanical properties. In this paper we analyze the structure of the extracellular matrix found in articular cartilage in an effort to relate it to the ability of cartilage to store, transmit, and dissipate mechanical energy during locomotion. Energy storage and dissipation is related to possible mechanisms of mechanochemical transduction and to changes in cartilage structure and function that occur in osteoarthritis. In addition, we analyze how passive and active internal stresses affect mechanochemical transduction in cartilage, and how this may affect cartilage behavior in health and disease. Received: 8 February 2002 / Accepted: 9 July 2002