Software for genetic linkage analysis

Recent developments in human genetic linkage analysis have included the appearance of new software and collections of data and program resources, accessible by means of the Internet. Many of these new programs and collections are described, including their availability, literature background, and specific technical information.     

BCG-induced chronic pulmonary inflammation and splenomegaly in mice: suppression of PHA-induced proliferation, delayed hypersensitivity to sheep erythrocytes, and chronic pulmonary inflammation by soluble factors from adherent spleen cells

C57BL/6 (B6), but not CBA, mice develop intense chronic granulomatous inflammation (CGI) in the lungs and spleen in response to an iv injection with killed BCG in an oil-in-saline emulsion (BCG-E). Concomitant with the development of CGI, these mice show diminished responsiveness to PHA and LPS, as well as suppression of antibody synthesis and production of delayed hypersensitivity (DH) to sheep erythrocytes (SRBC). Suppression results from the development of adherent, Thy-1^?, Ig^? spleen cells. The present study shows that cells from inflamed spleens of BCG-E-treated B6 mice elaborate factors in vitro which (a) inhibit PHA-induced proliferation of both normal syngeneic and allogencic cells, (b) suppress DH to SRBC in B6 mice, and (c) diminish the intensity of BCG-E-induced CGI in the lungs and spleens of B6 mice. These factors are produced by adherent Thy-1^? cells in BCG-injected mice but not in similarly treated CBA mice. These factors may be important in understanding the control of immunologically mediated chronic inflammation.     

Naegleria lovaniensis new species: Isolation and identification of six thermophilic strains of a new species found in association with Naegleria fowleri

Six Naegleria strains, isolated previously in association with N. fowleri from thermal waters, were studied to further determine their antigenic relationship to N. fowleri and other Naegleria species. Results of immunofluorescent antibody and immunoelectrophoretic studies clearly established the antigenic divergence of the variants from N. fowleri, N. gruberi, and N. jadini. The variants were further distinguished from known Naegleria species by several ultrastructural characteristics, which included the complete enclosure of their nuclei with one or several layers of rough endoplasmic reticulum (RER) and extrusion of their nuclear material. Extruded nuclear material was observed in the cytoplasm completely sequestered by cisternae of the RER. The variants were also shown to be sensitive to agglutination induced by concanavalin A but not by wheat germ agglutinin. Based on the differences in the antigenicity, morphology, and lectin sensitivity between these six variants and established Naegleria species, we proposed that they should be established as a new species.     

Subcellular localization of the heat-stable glucocerebrosidase activator substance in Gaucher spleen

The spleen in Gaucher's disease contains relatively large quantities of a heat-stable activator of the glucocerebrosidase of normal human tissues (Ho, M. W., and O'Brien, J. S. (1971) Proc. Nat. Acad. Sci. USA68, 2810–2813) that has been shown to be an 11,000 molecular weight acidic glycoprotein (Peters, S. P., et al. (1977) J. Biol. Chem.252, 563–573). In an effort to determine the subcellular location of the activator, a mannitol-sucrose homogenate of fresh, unfrozen spleen obtained from a 26-year-old patient with adult, nonneuropathic (Type 1) form of Gaucher's disease was subjected to subcellular fractionation. The tissue used in these experiments exhibited a β-glucocerebrosidase deficiency (11% of control tissue characteristic of Gaucher's disease. Mitochondrial and lysosomal fractions obtained by centrifugation of the spleen homogenate at 6900 and and 20,000g, respectively, contained greater than 80% of the recovered acid phosphatase and heat-stable glucocerebrosidase activator activities. In addition, 60% of the residual glucocerebrosidase activity was recovered in the mitochondrial and lysosomal fractions. The lysosomal and mitochondrial fractions were subjected to equilibrium sucrose density gradient centrifugation. Analysis of the sucrose gradient of the crude mitochondrial fraction demonstrated the mitochondrial marker enzyme (cytochrome oxidase) banding with a specific gravity of 1.19 g/ml, whereas the heat-stable activating factor banded in an acid phosphatase-rich fraction having a specific gravity of 1.12 g/ml. Sucrose gradient analysis of the crude lysosomal fraction obtained from differential centrifugation indicated the activating factor banding with a specific gravity of 1.12 g/ml. Coincident with the activating factor was glucocerebrosidase and acid phosphatase activity. Electron microscopic examination of fractions from each of the sucrose density gradients demonstrated that the glucocerebrosidase activating factor was located in the same acid phosphatase-rich fractions that contained the characteristic Gaucher deposits. Furthermore, when Gaucher deposits were isolated and purified independently by a sucrose gradient procedure, they were found to contain high concentrations of the heat-stable glucocerebrosidase activator. The specific activity of the glucocerebrosidase activating factor was approximately 15-fold greater in the extensively purified Gaucher deposits than in the crude extract of Gaucher spleen from which the deposits were isolated. These observations indicate that the heat-stable activator is associated with the storage deposits contained in lysosomes of the Gaucher cell.     

Content Delivery Policies in Replicated Web Services: Client-Side vs. Server-Side

Replication of Web Services has an important role among techniques that have been developed in order to meet the demand for faster and more efficient access to the Internet. Replication can be addressed both by a cluster of servers, and by servers geographically distributed in the Internet. In this paper, we focus on geographical replication. Two approaches are commonly used for geographical replication: server-side and client-side. In the client-side approach, the client has a significant role in the policy used to exploit Web Service Replication. In the server-side approach, the client transparently exploits a Replicated Web Service. Both server-side and client-side approaches provide various strategies that can be adopted. An analysis of these strategies, and an overall classification, is presented here. Finally, client-side and server-side approaches are compared, identifying their pros and cons in order to propose the features of an eventual complete approach.     

Molecular expressions: exploring the world of optics and microscopy. http://microscopy.fsu.edu

Our knowledge of the structure, dynamics and physiology of a cell has increased significantly in the last ten years through the emergence of new optical imaging modalities such as optical sectioning microscopy, computer- enhanced video microscopy and laser-scanning microscopy. These techniques together with the use of genetically engineered fluorophores have helped scientists visualize the 3-dimensional dynamic processes of living cells. However as powerful as these imaging tools are, they can often be difficult to understand and fully utilize. Below I will discuss my favorite website: The Molecular Expressions Web Site that endeavors to present the power of microscopy to its visitors. The Molecular Expressions group does a remarkable job of not only clearly presenting the principles behind these techniques in a manner approachable by lay and scientific audiences alike but also provides representative data from each as well.     

Foraging at the thermal limit: burrowing spiders (Seothyra,Eresidae) in the Namib desert dunes

Summary In the Namib Desert dunes, the web of Seothyra sp. (Eresidae) comprises sticky silk lining the edges of a horizontal mat on the sand surface. The spider sits in a silk-lined burrow attached to the mat. Arthropods become entangled in the sticky silk of the mat and are attacked and pulled into the burrow by the spider. We investigated the influence of sand surface temperature on the activity of spiders during the summer. We determined the range of thermal conditions encountered by spiders, their temperature tolerance and the influence of temperature on foraging activity and prey handling behavior. The environmental temperatures available to Seothyra vary from 17–33° C at the coolest time of day to 33–73° C at the hottest. When prevented from retreating into burrows, spiders showed signs of thermal stress at about 49° C, whereas unrestrained spiders continued to forage at web temperatures above 65° C by moving between the hot surface mat and the cooler burrow. Spiders responded quicker to prey stimuli during the hot hours of the day and completed prey capture sequences in significantly less time at surface temperatures above 49° C than below. Furthermore, captured arthropods succumbed more quickly at high surface temperatures. Our study supports the hypothesis that web design and thermoregulatory behaviors enable Seothyra to hunt under extreme thermal conditions.     

Introducing accessibility analysis in mapping cultural ecosystem services

In recent years, there has been an increasing interest in the study of the spatial link between service providing areas (SPA) and service benefiting areas (SBA). Understanding the spatial link between SPAs and SBAs is essential when studying the ecosystem service delivery and the fulfilment of ecosystem service demand. However, far too little attention has been paid to the user movement related ecosystem services and where people should be geographically situated in order to benefit from these services. In the movement related services, benefiting areas are equal to providing areas and the spatial link from residential area to SPA is important. The spatial link is addressed through the concept of accessibility which determines the opportunity to move from the area where beneficiaries are located to areas where ecosystem services are produced.This study presents an accessibility approach to the ecosystem services research. Accessibility analyses offer an opportunity to identify the gap between the ecosystems’ potential to produce services and the actual usage possibilities of such services. We demonstrate the suitability of the method by using outdoor recreation and cultural heritage as examples of cultural ecosystem services that people actively want to reach. Accessibility was calculated using a geographical information system-based least-cost path analysis, which measures travel time by car between residential location and the nearest SPA via road network.The examples highlight that accessibility varies according to the ecosystem service and depends mostly on population distribution and travel possibilities. Our results demonstrate that the density of the analysed ecosystem service opportunities is higher near urban areas than elsewhere. The accessibility of different ecosystem services also depends on how much time people are willing to spend for reaching these services. Our study emphasised that, from a population perspective, accessibility analyses provide a powerful tool for illustrating the utilisation possibilities of spatially distributed ecosystem services. The accessibility approach offers great potential to assess the potential use of SPAs and respond to the need to develop a practical tool for ecosystem service research. It effectively shows, for example, the areas where the risk of overuse of ecosystem services is increased. Knowing about the regional differences in ecosystem service usage also gives background information for the decision-makers for drawing conclusions about how much and where it is sensible to invest in the maintenance of ecosystem services.     

Constructing multimetric indices and testing ability of landscape metrics to assess condition of freshwater wetlands in the Northeastern US

Using data collected for the Environmental Protection Agency's (EPA) 2011 National Wetland Condition Assessment (NWCA), we developed separate multimetric indices (MMIs) for vegetation, soil, algae taxa, and water to assess condition of freshwater wetlands in the northeastern US. This study represents the first attempt at developing multiple biotic and abiotic MMIs of wetland condition over this large of an area, and is only possible because of the high quality data collected by the NWCA. We chose metrics that distinguished between reference and most disturbed sites, had a signal:noise ratio > 2, and were not strongly correlated with other metrics, latitude, or longitude. The vegetation and soil MMIs were the best performing indices, with good separation between reference and most disturbed sites, and included commonly used condition metrics (e.g., pH and P concentration for soil, and percent cover of exotic species for vegetation). The algae MMI was the weakest index, with considerable overlap between reference and most disturbed sites. For areas smaller than our study, algae taxa may be suitable for wetland MMIs. However, in our study area, many algae taxa followed strong latitudinal or longitudinal gradients, and could not be considered for the algae MMI. Small sample size and several metrics with a high signal:noise ratio were the major limitations of the water MMI. We also examined how well landscape (level 1) and rapid assessment (level 2) metrics predicted MMIs using random forest regression. Agricultural land use surrounding wetlands was an important predictor for all four MMIs, although the soil, algae and water MMI models performed best when intensive (level 3) vegetation metrics were also included in the random forest regression models. Based on these results, we recommend wetland assessment programs employ a combination of landscape and rapid assessment monitoring at many sites, along with level 3 monitoring at a subset of sites. We developed these MMIs to evaluate freshwater wetland condition for a long-term monitoring program in Acadia National Park. These MMIs are also applicable to a range of wetland types covering 11 states in the northeastern United States and can be calculated using a downloadable spreadsheet that calculates and rates each MMI using raw metric values.     

Exploring local consequences of two land-use alternatives for the supply of urban ecosystem services in Stockholm year 2050

Ecosystem services (ESs) are gaining ground in urban policy as a key to attaining sustainable cities. However, strategic and land-use planners need operational and accessible tools to better understand the consequences of policy and planning measures. Based on a study of the City of Stockholm and its surrounding region, we argue that spatially explicit land-use mapping is a good base for modeling and visualizing the supply of urban ESs provided by different patterns of Service Providing Units. By adding more detailed characteristics of land use through the concept of Service Providing Elements (SPEs), and by assessing synergies and trade-offs between these attributes, implications for the supply of ESs at different scale levels could be identified and discussed. Detailed land-use mapping and ES modeling were applied to two future land-use alternatives. The supply of eight urban ESs was found to vary significantly between the two alternatives depending on the ratios of different SPEs, even within identical land-use classes. One of the land-use alternatives had significantly higher potential for food and energy provision, much higher air cooling and air quality regulation capacity especially in densely built areas, showed less surface sealing, and provided better conditions for mental recreation. The exception was supply of physical recreation opportunities, where the other land-use option had an advantage. These differences became more accentuated when we zoomed in on two local urban areas. Based on these findings, our main conclusion is that, in order to provide planning and policy-making with an adequate knowledge base, it is necessary to move beyond land-use classes, as defined by European data sets like Urban Atlas, and toward tools capable of capturing more detailed aspects of land use and its relations to the supply of urban ESs. This should be made a priority, especially in early stages of planning and policy formation, and also used to support development of urban by-laws, procurement arrangements, neighborhood and building certification, etc. The approaches used in the study can serve as a valid starting point for further development of such tools and methods compatible with planners’ ordinary working modes. However, to make such progress possible, the ecosystem service research community needs to step up to the challenge of delivering locally specific and useful data on how urban land-use links to ES supply, including synergies and trade-offs between different ESs.