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Cellular lineage tracking provides a means to observe population makeup at the clonal level, allowing exploration of heterogeneity, evolutionary and developmental processes and individual clones' relative fitness. It has thus contributed significantly to understanding microbial evolution, organ differentiation and cancer heterogeneity, among others. Its use, however, is limited because existing methods are highly specific, expensive, labour-intensive, and, critically, do not allow the repetition of experiments. To address these issues, we developed gUMI-BEAR (genomic Unique Molecular Identifier Barcoded Enriched Associated Regions), a modular, cost-effective method for tracking populations at high resolution. We first demonstrate the system's application and resolution by applying it to track tens of thousands of Saccharomyces cerevisiae lineages growing together under varying environmental conditions applied across multiple generations, revealing fitness differences and lineage-specific adaptations. Then, we demonstrate how gUMI-BEAR can be used to perform parallel screening of a huge number of randomly generated variants of the Hsp82 gene. We further show how our method allows isolation of variants, even if their frequency in the population is low, thus enabling unsupervised identification of modifications that lead to a behaviour of interest.

Information theoretic approaches are ubiquitous and effective in a wide variety of bioinformatics applications. In comparative genomics, alignment-free methods, based on short DNA words, or k-mers, are particularly powerful. We evaluated the utility of varying k-mer lengths for genome comparisons by analyzing their sequence space coverage of 5805 genomes in the KEGG GENOME database. In subsequent analyses on four k-mer lengths spanning the relevant range (11, 21, 31, 41), hierarchical clustering of 1634 genus-level representative genomes using pairwise 21- and 31-mer Jaccard similarities best recapitulated a phylogenetic/taxonomic tree of life with clear boundaries for superkingdom domains and high subtree similarity for named taxons at lower levels (family through phylum). By analyzing ~14.2M prokaryotic genome comparisons by their lowest-common-ancestor taxon levels, we detected many potential misclassification errors in a curated database, further demonstrating the need for wide-scale adoption of quantitative taxonomic classifications based on whole-genome similarity.

Differential signaling of the type I interferon receptor (IFNAR) has been correlated with the ability of its subunit, IFNAR1, to differentially recognize a large spectrum of different ligands, which involves intricate conformational re-arrangements of multiple interacting domains. To shed light onto the structural determinants governing ligand recognition, we compared the force-induced unfolding of the IFNAR1 ectodomain when bound to interferon and when free, using the atomic force microscope and steered molecular dynamics simulations. Unexpectedly, we find that IFNAR1 is easier to mechanically unfold when bound to interferon than when free. Analysis of the structures indicated that the origin of the reduction in unfolding forces is a conformational change in IFNAR1 induced by ligand binding.

More than 30 years after the first outbreak of Marburg virus disease in Germany and Yugoslavia and 20 years after Ebola hemorrhagic fever first occurred in central Africa, the natural history of filoviruses remains unknown. In 1979 and 1980, animals in the Democratic Republic of the Congo and Cameroon were collected during the dry season near the site of the 1976 Ebola hemorrhagic fever epidemic. The study objectives were to identify local animals and search for evidence of Ebola virus in their tissues. A total of 1664 animals representing 117 species was collected, including >400 bats and 500 rodents. Vero and CV-1 cells and IFA and RIA were used for virus and antibody detection, respectively. No evidence of Ebola virus infection was found. This study was limited in time and animal collections and excluded insects and plants. Long-term, prospective, multidisciplinary comparative studies will yield more information than will repeat short forays on the ecology of filoviruses.

Household members of 46 patients with confirmed acquired immunodeficiency syndrome (AIDS) and 43 human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV)-seronegative controls from Kinshasa, Zaire, were identified and sought for serologic testing for evidence of HTLV-III/LAV infection. Twenty (9.8%) of 204 case-household members and three (1.9%) of 155 control-household members were HTLV-III/LAV seropositive (relative risk = 5.1; 95% confidence interval, 1.7 to 15.2). Eleven (61.1%) of 18 spouses of patients with AIDS were HTLV-III/LAV seropositive, compared with one (3.7%) of 27 control spouses (relative risk = 16.5; 95% confidence interval, 3.7 to 75.0). Except for spouses, the rate of HTLV-III/LAV seropositivity did not differ significantly between case and control households. Furthermore, for adults in case households who were not spouses, the number seropositive for HTLV-III/LAV was identical to that predicted from sex- and age-specific HTLV-III/LAV seroprevalence rates. These data from Zaire confirm the results of US and European studies of household contacts of infected hemophiliacs and pediatric patients with AIDS.

During the course of the recently concluded smallpox eradication program, a new human orthopoxvirus infection was discovered which is caused by monkeypox virus. The disease occurs sporadically in remote villages within tropical rain forests of West and Central Africa. The disease is rare; only 155 cases having been reported from 1970 to 1983. The symptoms and signs of human monkeypox resemble those of smallpox, differing significantly only in the occurrence of lymphadenopathy with human monkeypox disease. Of 155 cases, some 80% are believed to have resulted from infection from an as yet unknown animal reservoir; the rest occurred among unvaccinated close contacts among whom a secondary attack rate of 15% was observed. Although person-to-person spread appears to have occurred in some instances, few cases were observed in the third or fourth generation of transmission and none thereafter. Since 1982, the incidence of human monkeypox infections in Zaire has increased concomitant with an intensified surveillance program. Additional reasons which might explain the increased incidence are discussed. Further surveillance and research of this primarily zoonotic infection are warranted and are in progress.

From April to June 1983, combined in vivo and in vitro studies were conducted to assess the response to chloroquine of Plasmodium falciparum in Kinshasa and Mbuji-Mayi, Zaire. A total of 109 patients were treated with chloroquine, either as a single dose of 10 mg/kg or as a full dose of 25 mg/kg. All patients rapidly cleared their asexual parasitaemia, no recurrence being noted during the subsequent 3 weeks of follow-up. In the fourth week, recurrences were noted in 3 out of 66 patients treated with the full dose of chloroquine and in 10 out of 43 patients treated with the single dose. A total of 101 in vitro tests (30 macro tests, 39 micro tests, and 32 48-hour tests) were successfully performed with blood samples collected from 51 of these patients. Full sensitivity to chloroquine was demonstrated in all but 3 of the successful in vitro tests, the results from these 3 tests being contradicted either by alternative in vitro tests or by the corresponding in vivo findings. These investigations thus failed to detect chloroquine resistance at the level reported in East Africa or eastern Zaire (in Kivu).

A study of seroprevalence of the human immunodeficiency virus involving 2384 (96%) of Mama Yemo Hospital's (Kinshasa, Zaire) 2492 personnel found 152 (6.4%) to be seropositive. Prevalence was higher among women than among men (8.1% vs 5.2%); in women peak seroprevalence (13.9%) occurred in 20- to 29-year-olds. Workers most likely to be seropositive were those who were relatively young, those who were unmarried, those reporting a blood transfusion or hospitalization during the previous ten years, and those receiving medical injections during the previous three years. Medical, administrative, and manual workers had similar seroprevalence (6.5%, 6.4%, and 6.0%, respectively), and seropositivity was not associated with any measure of patient, blood, or needle contact. These findings are consistent with other hospital-based studies indicating low risks for occupational transmission of human immunodeficiency virus.

Human tanapox, a mild disease characterized by a short febrile illness associated with one or more skin lesions, is important because of its possible confusion with smallpox. The article describes clinical and epidemiological features of 264 laboratory-confirmed tanapox cases observed in a geographically limited area in northern Zaire over the period 1979-83.

Surveillance for acquired immunodeficiency syndrome (AIDS) in Kinshasa, Zaire, was initiated in July 1984, using a modified version of the case definition developed by the Centers for Disease Control. During the first eight months, 332 patients met all clinical and laboratory criteria; surveillance information was available for 295 (89%) of these patients. Of the sera tested from these patients, 99% had antibodies to human T-cell lymphotropic virus type III/lymphadenopathy-associated virus by both enzyme-linked immunosorbent assay and Western blot procedures. The male-female case ratio was 1:1.1; the mean age of patients was 33.6 years (median, 32 years; range, 1.5 to 64 years); and men were significantly older than women (mean, 37.4 vs 30.0 years). The estimated incidence rate for adults in Kinshasa is 380 cases per 1 million people per year. Peak age-specific incidence rates for men and women occurred among the 30- to 39-year age group, although the rate for men in this age group was 24% higher than the rate for women (786 vs 601 per 1 million). A reasonable estimate of the current annual incidence of AIDS is 550 to 1,000 cases per 1 million people. Surveillance of AIDS in Zaire provides important information on transmission patterns and rates in Africa.