Type 1 diabetes in mice is linked to the interleukin-1 receptor and Lsh/Ity/Bcg genes on chromosome 1.

Human type 1 (insulin-dependent) diabetes is a common auto-immune disease of the insulin-producing beta cells of the pancreas which is caused by both genetic and environmental factors. Several features of the genetics and immunopathology of diabetes in nonobese diabetic (NOD) mice are shared with the human disease. Of the three diabetes-susceptibility genes, Idd-1 -3 and -4 that have been mapped in mice to date, only in the case of Idd-1 is there any evidence for the identity of the gene product: allelic variation within the murine immune response I-A beta gene and its human homologue HLA-DQB1 correlates with susceptibility, implying that I-A beta is a component of Idd-1. We report here the mapping of Idd-5 to the proximal region of mouse chromosome 1. This region contains at least two candidate susceptibility genes, the interleukin-1 receptor gene and Lsh/Ity/Bcg, which encodes resistance to bacterial and parasitic infections and affects the function of macrophages.     

HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus

Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8+ T-cell responses. The declining CD8+ T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8+ T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development.     

Capacity limit of visual short-term memory in human posterior parietal cortex

At any instant, our visual system allows us to perceive a rich and detailed visual world. Yet our internal, explicit representation of this visual world is extremely sparse: we can only hold in mind a minute fraction of the visual scene. These mental representations are stored in visual short-term memory (VSTM). Even though VSTM is essential for the execution of a wide array of perceptual and cognitive functions, and is supported by an extensive network of brain regions, its storage capacity is severely limited. With the use of functional magnetic resonance imaging, we show here that this capacity limit is neurally reflected in one node of this network: activity in the posterior parietal cortex is tightly correlated with the limited amount of scene information that can be stored in VSTM. These results suggest that the posterior parietal cortex is a key neural locus of our impoverished mental representation of the visual world.     

Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA

The extreme polymorphism in the human leukocyte antigen (HLA) class I region of the human genome is suggested to provide an advantage in pathogen defence mediated by CD8+ T cells. HLA class I molecules present pathogen-derived peptides on the surface of infected cells for recognition by CD8+ T cells. However, the relative contributions of HLA-A and -B alleles have not been evaluated. We performed a comprehensive analysis of the class I restricted CD8+ T-cell responses against human immunodeficiency virus (HIV-1), immune control of which is dependent upon virus-specific CD8+ T-cell activity. In 375 HIV-1-infected study subjects from southern Africa, a significantly greater number of CD8+ T-cell responses are HLA-B-restricted, compared to HLA-A (2.5-fold; P = 0.0033). Here we show that variation in viral set-point, in absolute CD4 count and, by inference, in rate of disease progression in the cohort, is strongly associated with particular HLA-B but not HLA-A allele expression (P < 0.0001 and P = 0.91, respectively). Moreover, substantially greater selection pressure is imposed on HIV-1 by HLA-B alleles than by HLA-A (4.4-fold, P = 0.0003). These data indicate that the principal focus of HIV-specific activity is at the HLA-B locus. Furthermore, HLA-B gene frequencies in the population are those likely to be most influenced by HIV disease, consistent with the observation that B alleles evolve more rapidly than A alleles. The dominant involvement of HLA-B in influencing HIV disease outcome is of specific relevance to the direction of HIV research and to vaccine design.     

Breeding ecology of White-faced Ibis ( Pleagadis chihi ) in the Upper Klamath Basin, California

The White-faced Ibis ( Plegadis chihi ) is a California state and U.S. Fish and Wildlife Service species of special management concern. We studied White-faced Ibis breeding ecology from May through July 1995 on Lower Klamath National Wildlife Refuge (NWR) in the upper Klamath Basin of California. A total of 2029 pairs nested in 3 colonies exclusively in early-successional hardstem bulrush ( Scirpus acutus ). Nest initiation dates ranged from 10 May to 12 June, and mean clutch size was 3.16. Reproductive success averaged 87% apparent nest success ( n = 115), 82% hatchability, 97% whole and partial brood survival, and 2.39 fledglings per successful nest. Mayfield estimates of nest survival were 79.1% during the laying and incubation period and 95% during the nestling period. Overall nest success as estimated by the Mayfield method was 75.4%. Our estimates of nest success are some of the highest reported anywhere in the literature for White-faced Ibis. Therefore, Lower Klamath NWR may maintain preferred White-faced Ibis breeding habitats in years of otherwise poor habitat conditions across the Intermountain West.     

Postoperative hypoxia after extracorporeal circulation: A possible graft against host reaction (preliminary communication)

Zusammenfassung Bei Patienten, bei welchen ein extrakorporaler Blutkreislauf durchgeführt wurde, fanden sich in den Lungen grosse Mengen von Plasmazellen. Bei Benützung von frischem homologem Blut für die Ingangsetzung des extrakorporalen Kreislaufes scheinen die Plasmazellen des Spenderblutes in den Lungen schädigend zu wirken. Sie können möglicherweise für Kapillarschädigungen und Störungen des normalen Gasaustausches verantwortlich gemacht werden.