Regulation of Notch signaling and endocytosis by the Lgl neoplastic tumor suppressor

The evolutionarily conserved neoplastic tumor suppressor protein, Lethal (2) giant larvae (Lgl), plays roles in cell polarity and tissue growth via regulation of the Hippo pathway. In our recent study, we showed that in the developing Drosophila eye epithelium, depletion of Lgl leads to increased ligand-dependent Notch signaling. lgl mutant tissue also exhibits an accumulation of early endosomes, recycling endosomes, early-multivesicular body markers and acidic vesicles. We showed that elevated Notch signaling in lgl⁻ tissue can be rescued by feeding larvae the vesicle de-acidifying drug chloroquine, revealing that Lgl attenuates Notch signaling by limiting vesicle acidification. Strikingly, chloroquine also rescued the lgl⁻ overgrowth phenotype, suggesting that the Hippo pathway defects were also rescued. In this extraview, we provide additional data on the regulation of Notch signaling and endocytosis by Lgl, and discuss possible mechanisms by which Lgl depletion contributes to signaling pathway defects and tumorigenesis.     

Mutation in MRPS34 Compromises Protein Synthesis and Causes Mitochondrial Dysfunction

The evolutionary divergence of mitochondrial ribosomes from their bacterial and cytoplasmic ancestors has resulted in reduced RNA content and the acquisition of mitochondria-specific proteins. The mitochondrial ribosomal protein of the small subunit 34 (MRPS34) is a mitochondria-specific ribosomal protein found only in chordates, whose function we investigated in mice carrying a homozygous mutation in the nuclear gene encoding this protein. The Mrps34 mutation causes a significant decrease of this protein, which we show is required for the stability of the 12S rRNA, the small ribosomal subunit and actively translating ribosomes. The synthesis of all 13 mitochondrially-encoded polypeptides is compromised in the mutant mice, resulting in reduced levels of mitochondrial proteins and complexes, which leads to decreased oxygen consumption and respiratory complex activity. The Mrps34 mutation causes tissue-specific molecular changes that result in heterogeneous pathology involving alterations in fractional shortening of the heart and pronounced liver dysfunction that is exacerbated with age. The defects in mitochondrial protein synthesis in the mutant mice are caused by destabilization of the small ribosomal subunit that affects the stability of the mitochondrial ribosome with age.     

Uptake,Accuracy, Safety,and Linkage into Care over Two Years of Promoting Annual Self-Testing for HIV in Blantyre,Malawi: A Community-Based Prospective Study

BackgroundHome-based HIV testing and counselling (HTC) achieves high uptake, but is difficult and expensive to implement and sustain. We investigated a novel alternative based on HIV self-testing (HIVST). The aim was to evaluate the uptake of testing, accuracy, linkage into care, and health outcomes when highly convenient and flexible but supported access to HIVST kits was provided to a well-defined and closely monitored population.ConclusionsCommunity-based HIVST achieved high coverage in two successive years and was safe, accurate, and acceptable. Proactive HIVST strategies, supported and monitored by communities, could substantially complement existing approaches to providing early HIV diagnosis and periodic repeat testing to adolescents and adults in high-HIV settings.     

Do not neglect surroundings in restoration of disturbed sites

We examined the influence of surroundings, i.e. proximity effects, on the course of spontaneous vegetation succession using two data sets. In the first data set, we tested the effects of surrounding vegetation (woodlands, wetlands, grasslands, and synanthropic) on succession in various disturbed habitats in the Czech Republic by comparing successional sites with more natural vegetation within 100 m and at 1 km from each site. The habitats included old fields, gravel‐sand pits, spoil heaps from black coal mining, industrially extracted peatlands, and acidic stone quarries. We found that, with the exception of wetlands, the influence of the vegetation types on seral vegetation was nearly always significant using marginal and partial Canonical Correspondence Analyses. In the second data set, which included 27 limestone quarries, we compared species lists outside (up to 100 m apart) and inside the quarries using Detrended Correspondence Analysis and the Sørensen similarity index. We found much higher species similarity between outside and inside particular limestone quarries than among the quarries themselves and among their surroundings, which also indicates that the seral vegetation is decisively influenced by the surroundings. We argue that restoration ecologists should carefully consider the nature of the surroundings of disturbed sites because of its profound impact on restoration processes. They should conduct inventories and prescribe some restoration measures not only inside a restored site, but also in its surroundings.     

Five new Lamiinae (Coleoptera,Cerambycidae) from Bolivia in honor of James E. Wappes

Five new species of Lamiinae are described from Bolivia, all named after James E. Wappes: Xenofrea wappesi (Xenofreini); Anobrium wappesi (Pteropliini); Cotycicuiara wappesi, Nesozineus wappesi, and Psapharochrus wappesi (Acanthoderini). Anobrium wappesi, Cotycicuiara wappesi, and Nesozineus wappesi are included in known keys. A short note on the name and date of Anobrium oberthueri Belon, 1903 is provided.     

Cation Substitution of Solution‐Processed Cu2ZnSnS4 Thin Film Solar Cell with over 9% Efficiency

To alleviate the limitations of pure sulfide Cu₂ZnSnS₄ (CZTS) thin film, such as band gaps adjustment, antisite defects, secondary phase and microstructure, Cadmium is introduced into CZTS thin film to replace Zn partially to form Cu₂Zn_1?xCd_xSnS₄ (CZCTS) thin film by low‐cost sol–gel method. It is demonstrated that the band gaps and crystal structure of CZCTS thin films are affected by the change in Zn/Cd ratio. In addition, the ZnS secondary phase can be decreased and the grain sizes can be improved to some degree by partial replacement of Zn with Cd in CZCTS thin film. The power conversion efficiency of CZTS solar cell device is enhanced significantly from 5.30% to 9.24% (active area efficiency 9.82%) with appropriate ratio of Zn/Cd. The variation of device parameter as a function of Zn/Cd ratio may be attributed to the change in electronic structure of the bulk CZCTS thin film (i.e., phase change from kesterite to stannite), which in turn affects the band alignment at the CZCTS/buffer interface and the charge separation at this interface.     

Contrasting patterns of diversity and population differentiation at the innate immunity gene toll-like receptor 2 (TLR2) in two sympatric rodent species

Comparing patterns of diversity and divergence between populations at immune genes and neutral markers can give insights into the nature and geographic scale of parasite-mediated selection. To date, studies investigating such patterns of selection in vertebrates have primarily focused on the acquired branch of the immune system, whereas it remains largely unknown how parasite-mediated selection shapes innate immune genes both within and across vertebrate populations. Here, we present a study on the diversity and population differentiation at the innate immune gene Toll-like receptor 2 (TLR2) across nine populations of yellow-necked mice (Apodemus flavicollis) and bank voles (Myodes glareolus) in southern Sweden. In yellow-necked mice, TLR2 diversity was very low, as was TLR2 population differentiation compared to neutral loci. In contrast, several TLR2 haplotypes co-occurred at intermediate frequencies within and across bank vole populations, and pronounced isolation by distance between populations was observed. The diversity and differentiation at neutral loci was similar in the two species. These results indicate that parasite-mediated selection has been acting in dramatically different ways on a given immune gene in ecologically similar and sympatric species. Furthermore, the finding of TLR2 population differentiation at a small geographical scale in bank voles highlights that vertebrate innate immune defense may be evolutionarily more dynamic than has previously been appreciated.     

Olfactomedin III expression contributes to anoikis-resistance in clonal variants of a human lung squamous carcinoma cell line

Three clonal subpopulations of DLKP, a poorly differentiated squamous lung carcinoma cell line, display striking differences in ability to survive in suspension (anoikis resistance). DLKP-SQ is anoikis resistant (7.5% anoikis at 24 h). In contrast, DLKP-M and DLKP-I are sensitive to anoikis (49.2% and 42.6% respectively). DLKP-I shows increased apoptosis consistently over all time points tested while DLKP-M appear to slow down metabolically and perhaps delays onset of anoikis by undergoing autophagy. Expression microarray analysis identified pronounced differential expression of Olfactomedin 3 (OLFM3) between the clones. High expression of OLFM3 was confirmed at the RNA level by qRT-PCR in DLKP-SQ and at the protein level by Western blotting (within the cell and secreted). Little or no OLFM3 was detected in the other two clones (DLKP-M and DLKP-I). Following siRNA knockdown of OLFM3 in DLKP-SQ, anoikis was increased 2.8-fold to 21% which was intermediate between the anoikis levels in DLKP-SQ and DLKP-M or DLKP-I. This knockdown correlated with increased apoptosis in suspension but not in attached culture conditions. Addition of recombinant OLFM3 reduced anoikis in DLKP-I. This is the first instance of OLFM3 being linked with anoikis resistance in a human cancer cell line.     

An update to modern taxonomy (2011) of freshwater planktic heterocytous cyanobacteria

It is essential for the modern taxonomic classification of cyanobacteria to be continually updated in accordance with revisions based on molecular sequence comparisons and combined with morphological features, ecophysiological characters and other biochemical and molecular markers (“polyphasic approach”). Several genera, which are characterized by their planktic life form and contain indicator species important for the evaluation of aquatic biocenoses in majority of water bodies are recognized in the monophyletic group of heterocytous cyanobacteria. Current taxonomic revisions (and nomenclatoric consequences) of the specific contents of these heterocytous cyanobacterial generic units are covered by this article. Among these genera, 12 contain only planktic species, three remaining genera contain both planktic and non-planktic species. Comments and suggestions for future research are stressed especially in the ecologically distinct genera, which includes species dominating in the plankton of various reservoir types.