Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population.

The composition of human immunodeficiency virus type 1 (HIV-1) clonal populations at different stages of infection and in different compartments was analyzed. Biological HIV-1 clones were obtained by primary isolation from patient peripheral blood mononuclear cells under limiting dilution conditions, with either blood donor peripheral blood lymphocytes or monocyte-derived macrophages (MDM) as target cells, and the biological phenotype of the clones was analyzed. In asymptomatic individuals, low frequencies of HIV-1 clones were observed. These clones were non-syncytium inducing and preferentially monocytotropic. In individuals progressing to disease, a 100-fold increase in frequencies of productively HIV-1-infected cells was observed as a result of a selective expansion of nonmonocytotropic clones. In a person progressing to AIDS within 19 months after infection, only syncytium-inducing clones were detected, shifting from MDM-tropic to non-MDM-tropic over time. From his virus donor, a patient with wasting syndrome, only syncytium-inducing clones, mostly non-MDM-tropic, were recovered. Parallel clonal analysis of HIV-1 populations in cells present in bronchoalveolar lavage fluid and peripheral blood from an AIDS patient revealed a qualitatively and quantitatively more monocytotropic virus population in the lung compartment than in peripheral blood at the same time point. These findings indicate that monocytotropic HIV-1 clones, probably generated in the tissues, are responsible for the persistence of HIV-1 infection and that progression of HIV-1 infection is associated with a selective increase of T-cell-tropic, nonmonocytotropic HIV-1 variants in peripheral blood.     

Molecular packing and packing defects in helical membrane proteins

The packing of helices spanning lipid bilayers is crucial for the stability and function of alpha-helical membrane proteins. Using a modified Voronoi procedure, we calculated packing densities for helix-helix contacts in membrane spanning domains. Our results show that the transmembrane helices of protein channels and transporters are significantly more loosely packed compared with helices in globular proteins. The observed packing deficiencies of these membrane proteins are also reflected by a higher amount of cavities at functionally important sites. The cavities positioned along the gated pores of membrane channels and transporters are noticeably lined by polar amino acids that should be exposed to the aqueous medium when the protein is in the open state. In contrast, nonpolar amino acids surround the cavities in those protein regions where large rearrangements are supposed to take place, as near the hinge regions of transporters or at restriction sites of protein channels. We presume that the observed deficiencies of helix-helix packing are essential for the helical mobility that sustains the function of many membrane protein channels and transporters.     

Tumor progression in murine leukemia virus-induced T-cell lymphomas: monitoring clonal selections with viral and cellular probes.

Clonal selections occurring during the progression of Moloney murine leukemia virus (MuLV)-induced T-cell lymphomas in mice were examined in primary and transplanted tumors by monitoring various molecular markers: proviral integration patterns, MuLV insertions near c-myc and pim-1, and rearrangements of the immunoglobulin heavy chain and beta-chain T-cell receptor genes. The results were as follows. Moloney MuLV frequently induced oligoclonal tumors with proviral insertions near c-myc or pim-1 in the independent clones. Moloney MuLV acted as a highly efficient insertional mutagen, able to activate different (putative) oncogenes in one cell lineage. Clonal selections during tumor progression were frequently marked by the acquisition of new proviral integrations. Independent tumor cell clones exhibited a homing preference upon transplantation in syngeneic hosts and were differently affected by the route of transplantation.     

Selenium status inCharadriiformes

The distribution of selenium in a marine wader, the Oystercatcher (Haematopus ostralegus) is given by the levels in 15 tissues and plasma. Red blood cells (RBC) contain the highest level (23 mg/kg dry wt) followed by liver, lung, and kidney (17–19 mg/kg). Most other tissues range from 3–10 mg/kg. The average kidney and liver concentrations of the Oystercatcher belong to the concentrations characteristic in birds. However, the Oystercatcher's tissue selenium concentrations are in general four-to fivefold mammalian levels, but in liver and lung, 11- to 13-fold and in the RBC, 12- to 33-fold. The selenium plasma and RBC levels of the Oystercatcher vary during the year from 280 to 410 μg/L and 13 to 30 mg/kg dry wt, respectively; the plasma concentrations are positively correlated with the RBC selenium concentrations. An overview of literature data shows that the selenium kidney and liver concentrations of birds do not vary with geographical latitude and size (length) of the birds. In species of the ordersCharadriiformes andProcellariiformes, high selenium kidney, and to a lesser extent liver, concentrations may occur. A function of selenium in antioxidation is suggested.     

Homonyms and synonyms in the Dictionary of Interfaces in Proteins (DIP)

MOTIVATION: Should reports on molecular mimicry in particular cases, e.g. responsible for cross-reactivity, be considered as accidental or as a general principle in protein evolution? To answer this question, two types of similarity have to be considered: those in homologues (synonyms) and resemblance between patches from unrelated proteins (homonyms). RESULTS: All interfaces from known protein structures were collected in a comprehensive data bank [Dictionary of Interfaces in Proteins (DIP)]. A fast, sequence-independent, three-dimensional superposition procedure was developed to search automatically for geometrically similar surface areas. Surprisingly, we found a large number of structurally similar interfaces on the surface of unrelated proteins. Even patches from different types of secondary structure were found resembling each other. The putative functional meaning of homonyms is demonstrated with striking examples.     

SuperDrug: a conformational drug database

MOTIVATION: Different resources exist for experimentally determined and computed three-dimensional (3D)-structures of low molecular weight structures but for approved drugs, no free, publicly accessible source of 3D-structures and conformers is available. Furthermore, for selection purposes or for correlation of structural similarity with medical application, the assignment of the Anatomical Therapeutic Chemical (ATC) classification codes to each structure according to the WHO-scheme would be desirable. RESULTS: The database contains approximately 2500 3D-structures of active ingredients of essential marketed drugs. To account for structural flexibility they are represented by 10(5) structural conformers. Here we present a web-query system enabling searches for drug name, synonyms, trade name, trivial name, formula, CAS-number, ATC-code etc. 2D-similarity screening (Tanimoto coefficients) and an automatic 3D-superposition procedure based on conformational representation are implemented. Drug structures above a similarity threshold as well as superimposed conformers can be retrieved in the mol- file format via a graphical interface. AVAILABILITY: For academic use the system is accessible at http://bioinf.charite.de/superdrug. The retrieval system requires the free browser-plugin 'chime' from MDL for visualization.     

Accelerating screening of 3D protein data with a graph theoretical approach

MOTIVATION: The Dictionary of Interfaces in Proteins (DIP) is a database collecting the 3D structure of interacting parts of proteins that are called patches. It serves as a repository, in which patches similar to given query patches can be found. The computation of the similarity of two patches is time consuming and traversing the entire DIP requires some hours. In this work we address the question of how the patches similar to a given query can be identified by scanning only a small part of DIP. The answer to this question requires the investigation of the distribution of the similarity of patches. RESULTS: The score values describing the similarity of two patches can roughly be divided into three ranges that correspond to different levels of spatial similarity. Interestingly, the two iso-score lines separating the three classes can be determined by two different approaches. Applying a concept of the theory of random graphs reveals significant structural properties of the data in DIP. These can be used to accelerate scanning the DIP for patches similar to a given query. Searches for very similar patches could be accelerated by a factor of more than 25. Patches with a medium similarity could be found 10 times faster than by brute-force search.     

Realized heritability and repeatability of risk-taking behaviour in relation to avian personalities

Personalities are general properties of humans and other animals. Different personality traits are phenotypically correlated, and heritabilities of personality traits have been reported in humans and various animals. In great tits, consistent heritable differences have been found in relation to exploration, which is correlated with various other personality traits. In this paper, we investigate whether or not risk-taking behaviour is part of these avian personalities. We found that (i) risk-taking behaviour is repeatable and correlated with exploratory behaviour in wild-caught hand-reared birds, (ii) in a bi-directional selection experiment on 'fast' and 'slow' early exploratory behaviour, bird lines tend to differ in risk-taking behaviour, and (iii) within-nest variation of risk-taking behaviour is smaller than between-nest variation. To show that risk-taking behaviour has a genetic component in a natural bird population, we bred great tits in the laboratory and artificially selected 'high' and 'low' risk-taking behaviour for two generations. Here, we report a realized heritability of 19.3 +/- 3.3% (s.e.m.) for risk-taking behaviour. With these results we show in several ways that risk-taking behaviour is linked to exploratory behaviour, and we therefore have evidence for the existence of avian personalities. Moreover, we prove that there is heritable variation in more than one correlated personality trait in a natural population, which demonstrates the potential for correlated evolution.     

Differential syncytium-inducing capacity of human immunodeficiency virus isolates: frequent detection of syncytium-inducing isolates in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex.

Human immunodeficiency virus isolates were studied with respect to syncytium-inducing capacity, replicative properties, and host range. Five of 10 isolates from patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex were able to induce syncytia in cultures of peripheral blood mononuclear cells (MNC). In contrast, only 2 of 12 isolates from asymptomatic individuals had syncytium-inducing capacity. Syncytium-inducing isolates were reproducibly obtained from the same MNC sample in over 90% of the cases, independent of the donor MNC used for propagation. Syncytium-inducing capacity was shown to be a stable property of an isolate, independent of viral replication rates. Evidence was obtained that the high replication rate of syncytium-inducing isolates observed during primary isolation may be due to higher infectivity of these isolates. The finding that only syncytium-inducing isolates could be transmitted to the H9 cell line is compatible with this higher infectivity. The frequent isolation of syncytium-inducing isolates from individuals with AIDS-related complex or AIDS and the apparent higher in vitro infectivity of these isolates suggest that syncytium-inducing isolates may unfavorably influence the course of human immunodeficiency virus infection.     

Feeding Habits in Soil Nematode Families and Genera—An Outline for Soil Ecologists

Because research on nematode involvement in trophic interactions, foodweb structure, and biodiversity is constrained by lack of an overview of nematode feeding habits, this outline presents a consensus of current thought on nematode feeding habits. The source of food is fundamental to trophic interactions and provides the basis for our definitions of the essential feeding types: 1) plant feeder, 2) hyphal feeder, 3) bacterial feeder, 4) substrate ingester, 5) predator of animals, 6) unicellular eucaryote feeder, 7) dispersal or infective stage of parasites, and 8) omnivore. Lists of families and genera with their presumed feeding types are given. Major gaps in knowledge of feeding in the smaller tylenchids and many dorylaims are noted.