HIV preferentially infects HIV-specific CD4+ T cells

HIV infection is associated with the progressive loss of CD4(+) T cells through their destruction or decreased production. A central, yet unresolved issue of HIV disease is the mechanism for this loss, and in particular whether HIV-specific CD4(+) T cells are preferentially affected. Here we show that HIV-specific memory CD4(+) T cells in infected individuals contain more HIV viral DNA than other memory CD4(+) T cells, at all stages of HIV disease. Additionally, following viral rebound during interruption of antiretroviral therapy, the frequency of HIV viral DNA in the HIV-specific pool of memory CD4(+) T cells increases to a greater extent than in memory CD4(+) T cells of other specificities. These findings show that HIV-specific CD4(+) T cells are preferentially infected by HIV in vivo. This provides a potential mechanism to explain the loss of HIV-specific CD4(+) T-cell responses, and consequently the loss of immunological control of HIV replication. Furthermore, the phenomenon of HIV specifically infecting the very cells that respond to it adds a cautionary note to the practice of structured therapy interruption.     

Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation

During immune responses, antibodies are selected for their ability to bind to foreign antigens with high affinity, in part by their ability to undergo homotypic bivalent binding. However, this type of binding is not always possible. For example, the small number of gp140 glycoprotein spikes displayed on the surface of the human immunodeficiency virus (HIV) disfavours homotypic bivalent antibody binding. Here we show that during the human antibody response to HIV, somatic mutations that increase antibody affinity also increase breadth and neutralizing potency. Surprisingly, the responding naive and memory B cells produce polyreactive antibodies, which are capable of bivalent heteroligation between one high-affinity anti-HIV-gp140 combining site and a second low-affinity site on another molecular structure on HIV. Although cross-reactivity to self-antigens or polyreactivity is strongly selected against during B-cell development, it is a common serologic feature of certain infections in humans, including HIV, Epstein-Barr virus and hepatitis C virus. Seventy-five per cent of the 134 monoclonal anti-HIV-gp140 antibodies cloned from six patients with high titres of neutralizing antibodies are polyreactive. Despite the low affinity of the polyreactive combining site, heteroligation demonstrably increases the apparent affinity of polyreactive antibodies to HIV.     

Testing for unreliable estimators and insignificant forecasts in combined forecasts

The reliability and precision of the weights used in combining individual forecasts, irrespective of the method of combination, is important in evaluating a combined forecast. The objective of this study is not to suggest the ‘best’ method of combining individual forecasts, but rather to propose exploratory procedures, that make use of all available sample information contained in the covariance matrix of individual forecast errors, to (1) detect if the weights used in combining forecasts are ‘reliable’ (and ‘stable’ if it is known that the covariance matrix of forecast errors is stationary over time) and (2) test for ‘insignificant’ individual forecasts used in forming a combined forecast. We present empirical applications using two-year sales and individual forecast data provided by a major consumer durables manufacturer to illustrate the feasibility of our proposed procedures.     

束参数对离子束溅射法所淀积非晶硅电特性的影响

本文论述了用离子束溅射淀积非晶硅(a-Si)和氢化非晶硅(a-Si:H)的方法,提供了加速电压和衬底位置改变对薄膜暗电阻率的影响结果,通过有关淀积工艺条件的研究,得出了一些有用的结论。     

Homeotic transformation of the occipital bones of the skull by ectopic expression of a homeobox gene.

Murine Hox genes have been postulated to play a role in patterning of the embryonic body plan. Gene disruption studies have suggested that for a given Hox complex, patterning of cell identity along the antero-posterior axis is directed by the more 'posterior' (having a more posterior rostral boundary of expression) Hox proteins expressed in a given cell. This supports the 'posterior prevalence' model, which also predicts that ectopic expression of a given Hox gene would result in altered structure only in regions anterior to its normal domain of expression. To test this model further, we have expressed the Hox-4.2 gene more rostrally than its normal mesoderm anterior boundary of expression, which is at the level of the first cervical somites. This ectopic expression results in a homeotic transformation of the occipital bones towards a more posterior phenotype into structures that resemble cervical vertebrae, whereas it has no effect in regions that normally express Hox-4.2. These results are similar to the homeotic posteriorization phenomenon generated in Drosophila by ectopic expression of genes of the homeotic complex HOM-C (refs 7-10; reviewed in ref. 3).     

Rab protein evolution and the history of the eukaryotic endomembrane system

Spectacular increases in the quantity of sequence data genome have facilitated major advances in eukaryotic comparative genomics. By exploiting homology with classical model organisms, this makes possible predictions of pathways and cellular functions currently impossible to address in intractable organisms. Echoing realization that core metabolic processes were established very early following evolution of life on earth, it is now emerging that many eukaryotic cellular features, including the endomembrane system, are ancient and organized around near-universal principles. Rab proteins are key mediators of vesicle transport and specificity, and via the presence of multiple paralogues, alterations in interaction specificity and modification of pathways, contribute greatly to the evolution of complexity of membrane transport. Understanding system-level contributions of Rab proteins to evolutionary history provides insight into the multiple processes sculpting cellular transport pathways and the exciting challenges that we face in delving further into the origins of membrane trafficking specificity.     

Long‐Term Forecasting of Global Carbon Dioxide Emissions: Reducing Uncertainties Using a Per Capita Approach

Global CO₂ emission forecasts span such a wide range as to yield little guidance for climate policy and analysis. But global per capita emissions appear to be better constrained than total emissions, which we argue has an economic justification. Trend stationarity of per capita emissions may provide a means of characterizing the relative likelihood of global forecasts. On data spanning 1950 to 2009 a unit root hypothesis allowing for endogenous structural breaks is rejected, but adding in the 2010 observation pushes the p‐value slightly over 0.1. Since structural breaks cannot be detected at the end of sample this may simply indicate a power problem. Using Monte Carlo simulations we conclude that the lower half of a well‐known suite of IPCC emission scenarios is more likely to occur than the upper half, and the top quartile is particularly difficult to justify. Copyright © 2013 John Wiley & Sons, Ltd.     

Conservation status of threatened fishes in Warner Basin, Oregon

Two federally listed fishes, the Foskett speckled dace and Warner sucker, are endemic to Warner Basin in south central Oregon. The Foskett speckled dace is native only to a single spring in Coleman Valley. A nearby spring was stocked with dace in 1979 and 1980, and now provides a second population. The present numbers of dace probably are at their highest levels since settlement of the region. The Warner sucker historically occurred throughout much of the Warner Valley, but its distribution and abundance have been reduced by construction of reservoirs and irrigation dams and the introduction of predatory game fishes. Lentic habitats have become dominated by introduced fishes, particularly white crappie, black crappie, and brown bullhead. The largest remaining population of Warner suckers occurs in Hart Lake, where successful reproduction was documented but there is no evidence of recruitment to the adult population.