Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs

Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs. We further characterized the early dynamics of LILRB2 and MHC-I expression by showing that SIVmac251 infection of macaques promotes coordinated up-regulation of LILRB2 and MHC-I on cDCs and monocytes/macrophages, from blood and lymph nodes. Orientation towards the LILRB2/MHC-I inhibitory axis starts from the first days of infection and is transiently induced in the entire cDC population in acute phase. Analysis of the factors involved indicates that HIV-1 replication, TLR7/8 triggering, and treatment by IL-10 or type I IFNs increase LILRB2 expression. Finally, enhancement of the LILRB2/MHC-I inhibitory axis is specific to HIV-1 and SIVmac251 infections, as expression of LILRB2 on cDCs decreased in naturally controlled chikungunya virus infection of macaques. Altogether, our data reveal a unique up-regulation of LILRB2 and its MHC-I ligands on cDCs in the early phase of SIV/HIV infection, which may account for immune dysregulation at a critical stage of the anti-viral response.     

Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy

Host genetics has an important role in leprosy, and variants in the shared promoter region of PARK2 and PACRG were the first major susceptibility factors identified by positional cloning. Here we report the linkage disequilibrium mapping of the second linkage peak of our previous genome-wide scan, located close to the HLA complex. In both a Vietnamese familial sample and an Indian case-control sample, the low-producing lymphotoxin-alpha (LTA)+80 A allele was significantly associated with an increase in leprosy risk (P = 0.007 and P = 0.01, respectively). Analysis of an additional case-control sample from Brazil and an additional familial sample from Vietnam showed that the LTA+80 effect was much stronger in young individuals. In the combined sample of 298 Vietnamese familial trios, the odds ratio of leprosy for LTA+80 AA/AC versus CC subjects was 2.11 (P = 0.000024), which increased to 5.63 (P = 0.0000004) in the subsample of 121 trios of affected individuals diagnosed before 16 years of age. In addition to identifying LTA as a major gene associated with early-onset leprosy, our study highlights the critical role of case- and population-specific factors in the dissection of susceptibility variants in complex diseases.     

DETERMINATION OF KRAFT LIGNIN CONCENTRATIONS BY FTIR

A fast and accurate method based on FTIR is developed for determining the lignin content and its characteristic bands in alkali solutions. The work consisted of two main parts: 1) establishing a predictive model and 2) determination of the accuracy of the model. The model was derived by applying the partial least squares algorithm for multivariate analyses to a set of spectrum data obtained from selected IR absorption regions in the range of 1600 - 900 cm-1. The model was tested with spent liquors obtained from commercial pulp mills.The accuracy of the predictive model is extremely high suitable for commercial applications,particularly for monitoring the dynamic response of modern kraft pulping processes.     

Natural variation for sulfate content in Arabidopsis thaliana is highly controlled by APR2

Most agronomic traits of importance, whether physiological (such as nutrient use efficiency) or developmental (such as flowering time), are controlled simultaneously by multiple genes and their interactions with the environment. Here, we show that variation in sulfate content between wild Arabidopsis thaliana accessions Bay-0 and Shahdara is controlled by a major quantitative trait locus that results in a strong interaction with nitrogen availability in the soil. Combining genetic and biochemical results and using a candidate gene approach, we have cloned the underlying gene, showing how a single-amino acid substitution in a key enzyme of the assimilatory sulfate reduction pathway, adenosine 5'-phosphosulfate reductase, is responsible for a decrease in enzyme activity, leading to sulfate accumulation in the plant. This work illustrates the potential of natural variation as a source of new alleles of known genes, which can aid in the study of gene function and metabolic pathway regulation. Our new insights on sulfate assimilation may have an impact on sulfur fertilizer use and stress defense improvement.     

Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy

Centronuclear myopathies are characterized by muscle weakness and abnormal centralization of nuclei in muscle fibers not secondary to regeneration. The severe neonatal X-linked form (myotubular myopathy) is due to mutations in the phosphoinositide phosphatase myotubularin (MTM1), whereas mutations in dynamin 2 (DNM2) have been found in some autosomal dominant cases. By direct sequencing of functional candidate genes, we identified homozygous mutations in amphiphysin 2 (BIN1) in three families with autosomal recessive inheritance. Two missense mutations affecting the BAR (Bin1/amphiphysin/RVS167) domain disrupt its membrane tubulation properties in transfected cells, and a partial truncation of the C-terminal SH3 domain abrogates the interaction with DNM2 and its recruitment to the membrane tubules. Our results suggest that mutations in BIN1 cause centronuclear myopathy by interfering with remodeling of T tubules and/or endocytic membranes, and that the functional interaction between BIN1 and DNM2 is necessary for normal muscle function and positioning of nuclei.     

半群Q(k)的极大正则子半带

设T(X)和O(X)分别是X上的全变换半群和保序全变换半群,Y是X的非空子集,令F(X,Y)={α∈T(X):Xα?Yα?Y},OF(X,Y)=O(X)∩F(X,Y).当Y=n≥4时,对任意的2≤k≤n-2,考虑半群Q(k)={α∈OF(X,Y):Im(α)≤k}的极大正则子半带的结构,利用Miller-Clifford定理,证明了半群Q(k)的极大正则子半带有且仅有两类:A(α)=Q(k-1)∪(J(k)\L_α),α∈J(k);B(β)=Q(k-1)∪(J(k)\R_β),β∈N(k).     

Systemic Indicators for Rural Communities in Developing Economies: Bringing the Shared Vision into Being

Community indicators have been a frequent focus of the scholarly literature. There has been little exploration, however, in relation to rural communities, especially in developing countries. This reflects the special challenges associated with the complexity of rural systems, and the difficulties involved in developing appropriate and systemic indicators for rural communities. Identifying indicators that help the community to monitor progress towards sustainable outcomes requires a framework that is both practical and holistic. This paper introduces a participatory systemic framework for identifying community indicators, which respects the principles of complexity and honours the sense of ownership present in the communities. This framework is an iterative, sharing, co-learning engagement process that extends from creating a shared vision and extracting its core messages, to identifying indicators of progress and determining what actions to try. Importantly, this framework enables us to rank the indicators identified by communities with reference to ‘leverage points’, the best places to intervene in the social-environmental system for transformational change. This framework provides a potential pathway for sustainable rural development and perhaps also for organisations and urban communities.     

Progressive field-state collapse and quantum non-demolition photon counting

The irreversible evolution of a microscopic system under measurement is a central feature of quantum theory. From an initial state generally exhibiting quantum uncertainty in the measured observable, the system is projected into a state in which this observable becomes precisely known. Its value is random, with a probability determined by the initial system's state. The evolution induced by measurement (known as 'state collapse') can be progressive, accumulating the effects of elementary state changes. Here we report the observation of such a step-by-step collapse by non-destructively measuring the photon number of a field stored in a cavity. Atoms behaving as microscopic clocks cross the cavity successively. By measuring the light-induced alterations of the clock rate, information is progressively extracted, until the initially uncertain photon number converges to an integer. The suppression of the photon number spread is demonstrated by correlations between repeated measurements. The procedure illustrates all the postulates of quantum measurement (state collapse, statistical results and repeatability) and should facilitate studies of non-classical fields trapped in cavities.