The Ovicidal,Larvacidal and Adulticidal Properties of 5,5′-Dimethyl-2,2′-Bipyridyl against Drosophila melanogaster

Insecticide resistance has limited the number of available chemical options for insect pest control. Hence there is a need for new chemistries with novel modes of action. Here we investigate the mode of action for an insecticide that has not yet been released for commercial use. The ovicidal, larvacidal and adulticidal effects of 5,5′-dimethyl -2, 2′-dipyridyl (termed Ha44), which is being developed as a treatment for head lice, were evaluated in the Drosophila melanogaster model system. Ha44 demonstrated significant activity against embryos and was capable of arresting development at a number of stages of embryogenesis. The effects of Ha44 on embryos was shown to be reversible following the addition of the metal ions Fe(II) and Fe(III), Cu and Zn. When larvae were exposed to Ha44, lethality was recorded at similar concentrations to those observed for embryos. Using an eYFP reporter system it was shown that Ha44 was able to reduce the levels of both copper and zinc in the digestive tract, confirming the binding of Ha44 to these metals in vivo. Ha44 has further been shown to inhibit a zinc containing metalloproteinase in vitro. Exposure of adult flies to Ha44 resulted in lethality, but at higher concentrations than those observed for embryos and larvae. The median lethal dose in adult flies was shown to be associated with the type of exposure, with an LD-50 of 1.57 mM being recorded following the direct contact of flies with Ha44, while an LD-50 of 12.29 mM was recorded following the ingestion of the compound. The capacity of Ha44 to act on all stages of the life-cycle and potentially via a range of targets suggests that target site resistance is unlikely to evolve.     

蛇根木细胞悬浮培养进行紫杉醇的生物转化

通过理化及光谱学方法,从蛇根木(Rautwolfia serpentina(L.)Benth.et Kurz.)悬浮细胞内分离到3个紫杉醇同系物,高分辨1H-NMR和MS结构分析表明,它们分别为10-脱乙酰紫杉醇、baccatinⅢ和10-deacetylbaccatinⅢ.本实验未检测出紫杉醇的苷化或羟基化衍生物.     

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.     

People favour imperfect catching by assuming a stable world

The visual angle that is projected by an object (e.g. a ball) on the retina depends on the object's size and distance. Without further information, however, the visual angle is ambiguous with respect to size and distance, because equal visual angles can be obtained from a big ball at a longer distance and a smaller one at a correspondingly shorter distance. Failure to recover the true 3D structure of the object (e.g. a ball's physical size) causing the ambiguous retinal image can lead to a timing error when catching the ball. Two opposing views are currently prevailing on how people resolve this ambiguity when estimating time to contact. One explanation challenges any inference about what causes the retinal image (i.e. the necessity to recover this 3D structure), and instead favors a direct analysis of optic flow. In contrast, the second view suggests that action timing could be rather based on obtaining an estimate of the 3D structure of the scene. With the latter, systematic errors will be predicted if our inference of the 3D structure fails to reveal the underlying cause of the retinal image. Here we show that hand closure in catching virtual balls is triggered by visual angle, using an assumption of a constant ball size. As a consequence of this assumption, hand closure starts when the ball is at similar distance across trials. From that distance on, the remaining arrival time, therefore, depends on ball's speed. In order to time the catch successfully, closing time was coupled with ball's speed during the motor phase. This strategy led to an increased precision in catching but at the cost of committing systematic errors.     

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.