Psoriasis patients are enriched for genetic variants that protect against HIV-1 disease

An important paradigm in evolutionary genetics is that of a delicate balance between genetic variants that favorably boost host control of infection but which may unfavorably increase susceptibility to autoimmune disease. Here, we investigated whether patients with psoriasis, a common immune-mediated disease of the skin, are enriched for genetic variants that limit the ability of HIV-1 virus to replicate after infection. We analyzed the HLA class I and class II alleles of 1,727 Caucasian psoriasis cases and 3,581 controls and found that psoriasis patients are significantly more likely than controls to have gene variants that are protective against HIV-1 disease. This includes several HLA class I alleles associated with HIV-1 control; amino acid residues at HLA-B positions 67, 70, and 97 that mediate HIV-1 peptide binding; and the deletion polymorphism rs67384697 associated with high surface expression of HLA-C. We also found that the compound genotype KIR3DS1 plus HLA-B Bw4-80I, which respectively encode a natural killer cell activating receptor and its putative ligand, significantly increased psoriasis susceptibility. This compound genotype has also been associated with delay of progression to AIDS. Together, our results suggest that genetic variants that contribute to anti-viral immunity may predispose to the development of psoriasis.     

Colmation and Depth Filtration within Streambeds: Retention of Particles in Hyporheic Interstices

Colmation refers to the retention processes that can lead to the clogging of the top layer of channel sediments and decolmation refers to the resuspension of deposited fine particles. Internal colmation, clogging of the interstices directly below the armor layer, may form a thin seal that disconnects surface water from hyporheic water by inhibiting exchange processes. The settling of particles under low flow conditions can cause external colmation. Colmated channel sediments are characterized by reduced porosity and hydraulic conductivity as well as by a consolidated texture. The term ‘depth filtration’ refers to the transport and storage of fine matrix sediments in interstitial layers. Depth filtration is of significance for the transport of colloidal and fine particulate inorganic as well as organic matter within the hyporheic interstices and into the alluvial aquifer. The role of depth filtration is assessed for the content (given in mg per liter) of matrix fine particles retained in the coarse framework sediment of a gravel-bed river in Switzerland. Sediment samples were taken by freeze-coring with liquid nitrogen down to 70 cm depth and by piezometers down to 150 cm depth. Seventy-two percent of the mobile matrix fine particles were smaller than 0.1 mm and 50% were smaller than 0.03 mm. The content of fines tended to increase with depth, although higher accumulations were found at intermediate depths in sediments influenced by exfiltrating ground water. Interstitial detrital particles >90 μm showed vertical distribution patterns opposing those of total particles. These relationships revealed a differential significance of import, storage, and transport within three types of hydrological exchange zones (infiltration, horizontal advection, exfiltration) in the cross-section of the stream.     

Wnt8 is required for growth-zone establishment and development of opisthosomal segments in a spider

The Wnt genes encode secreted glycoprotein ligands that regulate many developmental processes from axis formation to tissue regeneration [1]. In bilaterians, there are at least 12 subfamilies of Wnt genes [2]. Wnt3 and Wnt8 are required for somitogenesis in vertebrates [3-7] and are thought to be involved in posterior specification in deuterostomes in general [8]. Although TCF and beta-catenin have been implicated in the posterior patterning of some short-germ insects [9, 10], the specific Wnt ligands required for posterior specification in insects and other protostomes remained unknown. Here we investigated the function of Wnt8 in a chelicerate, the common house spider Achaearanea tepidariorum[11]. Knockdown of Wnt8 in Achaearanea via parental RNAi caused misregulation of Delta, hairy, twist, and caudal and resulted in failure to properly establish a posterior growth zone and truncation of the opisthosoma (abdomen). In embryos with the most severe phenotypes, the entire opisthosoma was missing. Our results suggest that in the spider, Wnt8 is required for posterior development through the specification and maintenance of growth-zone cells. Furthermore, we propose that Wnt8, caudal, and Delta/Notch may be parts of an ancient genetic regulatory network that could have been required for posterior specification in the last common ancestor of protostomes and deuterostomes.     

A new class of carriers that transport selective cargo from the trans Golgi network to the cell surface

We have isolated a membrane fraction enriched in a class of transport carriers that form at the trans Golgi network (TGN) and are destined for the cell surface in HeLa cells. Protein kinase D (PKD) is required for the biogenesis of these carriers that contain myosin II, Rab6a, Rab8a, and synaptotagmin II, as well as a number of secretory and plasma membrane‐specific cargoes. Our findings reveal a requirement for myosin II in the migration of these transport carriers but not in their biogenesis per se. Based on the cargo secreted by these carriers we have named them CARTS for CAR riers of the T GN to the cell S urface. Surprisingly, CARTS are distinct from the carriers that transport vesicular stomatitis virus (VSV)‐G protein and collagen I from the TGN to the cell surface. Altogether, the identification of CARTS provides a valuable means to understand TGN to cell surface traffic.     

Retention in Care of HIV-Infected Children from HIV Test to Start of Antiretroviral Therapy: Systematic Review

Background

In adults it is well documented that there are substantial losses to the programme between HIV testing and start of antiretroviral therapy (ART). The magnitude and reasons for loss to follow-up and death between HIV diagnosis and start of ART in children are not well defined.

Methods

We searched the PubMed and EMBASE databases for studies on children followed between HIV diagnosis and start of ART in low-income settings. We examined the proportion of children with a CD4 cell count/percentage after after being diagnosed with HIV infection, the number of treatment-eligible children starting ART and predictors of loss to programme. Data were extracted in duplicate.

Results

Eight studies from sub-Saharan Africa and two studies from Asia with a total of 10,741 children were included. Median age ranged from 2.2 to 6.5 years. Between 78.0 and 97.0% of HIV-infected children subsequently had a CD4 cell count/percentage measured, 63.2 to 90.7% of children with an eligibility assessment met the eligibility criteria for the particular setting and time and 39.5 to 99.4% of the eligible children started ART. Three studies reported an association between low CD4 count/percentage and ART initiation while no association was reported for gender. Only two studies reported on pre-ART mortality and found rates of 13 and 6 per 100 person-years.

Conclusion

Most children who presented for HIV care met eligibility criteria for ART. There is an urgent need for strategies to improve the access to and retention to care of HIV-infected children in resource-limited settings.     

Chlamydia pneumoniae Hides inside Apoptotic Neutrophils to Silently Infect and Propagate in Macrophages

Background

Intracellular pathogens have developed elaborate strategies for silent infection of preferred host cells. Chlamydia pneumoniae is a common pathogen in acute infections of the respiratory tract (e.g. pneumonia) and associated with chronic lung sequelae in adults and children. Within the lung, alveolar macrophages and polymorph nuclear neutrophils (PMN) are the first line of defense against bacteria, but also preferred host phagocytes of chlamydiae.

Methodology/Principal Findings

We could show that C. pneumoniae easily infect and hide inside neutrophil granulocytes until these cells become apoptotic and are subsequently taken up by macrophages. C. pneumoniae infection of macrophages via apoptotic PMN results in enhanced replicative activity of chlamydiae when compared to direct infection of macrophages, which results in persistence of the pathogen. Inhibition of the apoptotic recognition of C. pneumoniae infected PMN using PS- masking Annexin A5 significantly lowered the transmission of chlamydial infection to macrophages. Transfer of apoptotic C. pneumoniae infected PMN to macrophages resulted in an increased TGF-ß production, whereas direct infection of macrophages with chlamydiae was characterized by an enhanced TNF-α response.

Conclusions/Significance

Taken together, our data suggest that C. pneumoniae uses neutrophil granulocytes to be silently taken up by long-lived macrophages, which allows for efficient propagation and immune protection within the human host.     

Hotspots and richness pattern of grasshopper species in cultural landscapes

The success of the hotspot approach for biodiversity conservation depends on the spatial scale and the indicator species used. In this study, we investigated grasshopper species richness in Switzerland at a 1 ha resolution including a total of 111 species. We compared the representativeness of common and of endangered grasshopper species for the overall grasshopper species richness and we assessed the efficiency of the hotspot approach for grasshopper conservation. The pattern of overall grasshopper species richness was well represented by both the number of common and the number of endangered grasshopper species. For evaluating the efficiency of different hotspot approaches for conservation, we compared hotspots of common species, hotspots of endangered species (rarity hotspots), and hotspots of all grasshopper species (richness hotspots). Among these hotspot types, richness hotspots not only featured most common grasshopper species, but they even contained more endangered species than the rarity hotspots. The combination of rarity hotspots and hotspots of common species featured more species than the other combinations of hotspot types. However, the gain of combining two hotspot types compared to the single-hotspot approach was low (max. 3 species). About 24% of the species were not contained in any of the hotspots. These grasshopper species require species-specific action plans. As rarity hotspots were located in areas that are rather strongly affected by landscape change, species richness in rarity hotspots may decrease in the future. We conclude that, for grasshoppers, the hotspot approach on the 1 ha scale can be an effective way to conserve a high proportion of species richness.