LMW-PTP modulates glucose metabolism in cancer cells

Background

Low Molecular Weight Phosphotyrosine Protein Phosphatase (LMW-PTP) is an enzyme involved not only in tumor onset and progression but also in type 2 diabetes. A recent review shows that LMW-PTP acts on several RTK (receptor tyrosine kinase) such as PDGFR, EGFR, EphA2, Insulin receptor. It is well described also its interaction with cSrc. It is noteworthy that most of these conclusions are based on the use of cell lines expressing low levels of LMW-PTP. The aim of the present study was to discover new LMW-PTP substrates in aggressive human tumors where the over-expression of this phosphatase is a common feature.

Multiple non-catalytic ADAMs are novel integrin α4 ligands

The ADAM (a disintegrin and metalloprotease) protein family uniquely exhibits both catalytic and adhesive properties. In the well-defined process of ectodomain shedding, ADAMs transform latent, cell-bound substrates into soluble, biologically active derivatives to regulate a spectrum of normal and pathological processes. In contrast, the integrin ligand properties of ADAMs are not fully understood. Emerging models posit that ADAM–integrin interactions regulate shedding activity by localizing or sequestering the ADAM sheddase. Interestingly, 8 of the 21 human ADAMs are predicted to be catalytically inactive. Unlike their catalytically active counterparts, integrin recognition of these “dead” enzymes has not been largely reported. The present study delineates the integrin ligand properties of a group of non-catalytic ADAMs. Here we report that human ADAM11, ADAM23, and ADAM29 selectively support integrin α4-dependent cell adhesion. This is the first demonstration that the disintegrin-like domains of multiple catalytically inactive ADAMs are ligands for a select subset of integrin receptors that also recognize catalytically active ADAMs.     

Oligosaccharides containing fucose linked alpha(1-3) and alpha(1-4) to N-acetylglucosamine cause decompaction of mouse morulae

Two- to four-cell and eight-cell mouse embryos were incubated in various fucosylated and unfucosylated oligosaccharides, fucose binding protein, and fucosylated BSA. Compaction at the eight-cell stage was reversed by a mixture containing the oligosaccharides lacto-N-fucopentaose II (80-90%), in which fucose is linked alpha(1-4) to N-acetylglucosamine, and lacto-N-fucopentaose III (10-20%), in which fucose is linked alpha(1-3) to N-acetylglucosamine. Pure lacto-N-fucopentaose III (LNFP III) and 3-fucosyl lactose (containing fucose alpha(1-3)glucose) had a similar effect. All three molecules affected blastocyst formation. Various closely related fucosylated and unfucosylated oligosaccharides did not induce decompaction or inhibit blastocyst formation. The proportion of embryos incubated from the two- to four-cell stage in LNFP II/III which reached the eight-cell stage and formed blastocysts was reduced. Those which formed compact morulae subsequently decompacted. Precompact or early compacting eight-cell embryos incubated in LNFP II/III compacted normally but subsequently decompacted and failed to form blastocysts. Decompaction of eight-cell embryos in LNFP II/III occurred during a specific period of development (80-90 hr post-hCG) and was reversible up to 84-86 hr post-hCG, but not by 92 hr post-hCG. The period of sensitivity to LNFP II/III was associated with the decrease in the ability of calcium-free medium to cause decompaction. It appears that LNFP II/III interferes with a later calcium-independent phase of compaction and we propose that LNFP III and II inhibit an endogenous lectin-saccharide interaction between membranes involved in the stabilization of compaction.     

Climate-related adaptive genetic variation and population structure in natural stands of Norway spruce in the South-Eastern Alps

Forest trees dominate many Alpine landscapes that are currently exposed to changing climate. Norway spruce is one of the most important conifer species of the Italian Alps, and natural populations are found across steep environmental gradients with large differences in temperature and moisture availability. This study seeks to determine and quantify patterns of genetic diversity in natural populations toward understanding adaptive responses to changing climate. Across the Italian species range, 24 natural stands were sampled with a major focus on the Eastern Italian Alps. Sampled trees were genotyped for 384 selected single nucleotide polymorphisms (SNPs) from 285 genes. A wide array of potential candidate genes was tested for correlation with climatic parameters. To minimize false-positive association between genotype and climate, population structure was investigated. Pairwise F _ST estimates between sampled populations ranged between 0.000 and 0.075, with the highest values involving the two disjoint populations, Valdieri, on the western Italian Alps, and Campolino, the most southern population on the Apennines. Despite considerable genetic admixture among populations, both Bayesian and multivariate approach identified four genetic clusters. Selection scans revealed five F _ST outliers, and the environmental association analysis detected ten SNPs associated to one or more climatic variables. Overall, 13 potentially adaptive loci were identified, three of which have been reported in a previous study on the same species conducted on a broader geographical scale. In our study, precipitation, more than temperature, was often associated with genotype; therefore, it appears as the most important environmental variable associated with the high sensitivity of Norway spruce to soil water supply. These findings provide relevant information for understanding and quantifying climate change effects on this species and its ability to genetically adapt.     

Deer feeding selectivity for invasive plants

Native generalist herbivores might limit plant invasion by consuming invading plants or enhance plant invasion by selectively avoiding them. The role of herbivores in plant invasion has been investigated in relation to plant native/introduced status, however, a knowledge gap exists about whether food selection occurs according to native/introduced status or to species. We tested preference of the native herbivore white-tailed deer (Odocoileus virginianus) for widespread and frequently occurring invasive introduced and native plants in the northeastern United States. Multiple-choice deer preference trials were conducted for the species and relative preference was determined using biomass consumption and feeding behavior. While more native than introduced plant biomass was consumed overall, deer food selection varied strongly by plant species. Results show consistent deer avoidance of several invasive introduced plants (Alliaria petiolata, Berberis thunbergii, and Microstegium vimineum) and a native plant (Dennstaedtia punctilobula). Other invasive introduced plants (Celastrus orbiculatus, Ligustrum vulgare, and Lonicera morrowii) and a native plant (Acer rubrum) were highly preferred. These results provide evidence that herbivore impacts on plant invaders depend on plant species palatability. Consequently, herbivore selectivity likely plays an important role in the invasion process. To the extent that herbivory impacts population demographics, these results suggest that native generalist herbivores promote enemy release of some plant invaders by avoiding them and contribute to biotic resistance of others by consuming them.     

Abundance estimates to inform butterfly management: double-observer versus distance sampling

Abundance estimates are used to establish baselines, set recovery targets, and assess management actions, all of which are essential aspects of evidence-based natural resource management. For many rare butterflies, these estimates do not exist, and conservation decisions rely instead on expert opinion. Using Bartram’s scrub-hairstreak (Strymon acis bartrami, US Endangered) as a case study, we present a novel comparison of two methods that permit the incorporation of detection probabilities into abundance estimates, distance sampling and double-observer surveys. Additionally we provide a framework for establishing a systematic sampling scheme for monitoring very rare butterflies. We surveyed butterflies monthly in 2013, increasing intensity to weekly when butterflies were detected. We conducted 19 complete, island-wide surveys on Big Pine Key in the Florida Keys, detecting a total of 59 Bartram’s scrub-hairstreaks across all surveys. Peak daily abundances were similar as estimated with distance sampling, 156 butterflies (95 % CI 65–247), and double-observer, 169 butterflies (95 % CI 65–269). Selecting a method for estimating abundance of rare species involves evaluating trade-offs between methods. Distance sampling requires at least 40 detections, but only one observer, while double-observer requires only 10 detections, but two observers. Double-observer abundance estimates agreed with distance sampling estimates, which suggests that double-observer is a reasonable alternative method to use for estimating detection probability and abundance for rare species that cannot be surveyed with other, more commonly used methods.     

The Effects of Ivermectin on Brugia malayi Females In Vitro: A Transcriptomic Approach

BackgroundLymphatic filariasis and onchocerciasis are disabling and disfiguring neglected tropical diseases of major importance in developing countries. Ivermectin is the drug of choice for mass drug administration programs for the control of onchocerciasis and lymphatic filariasis in areas where the diseases are co-endemic. Although ivermectin paralyzes somatic and pharyngeal muscles in many nematodes, these actions are poorly characterized in adult filariae. We hypothesize that paralysis of pharyngeal pumping by ivermectin in filariae could result in deprivation of essential nutrients, especially iron, inducing a wide range of responses evidenced by altered gene expression, changes in metabolic pathways, and altered developmental states in embryos. Previous studies have shown that ivermectin treatment significantly reduces microfilariae release from females within four days of exposure in vivo, while not markedly affecting adult worms. However, the mechanisms responsible for reduced production of microfilariae are poorly understood.Conclusion/SignificanceThese changes provide insight into the mechanisms involved in ivermectin-induced reduction in microfilaria output and impaired fertility, embryogenesis, and larval development.