Mechanosensory interactions drive collective behaviour in Drosophila.

Collective behaviour enhances environmental sensing and decision-making in groups of animals. Experimental and theoretical investigations of schooling fish, flocking birds and human crowds have demonstrated that simple interactions between individuals can explain emergent group dynamics. These findings indicate the existence of neural circuits that support distributed behaviours, but the molecular and cellular identities of relevant sensory pathways are unknown. Here we show that Drosophila melanogaster exhibits collective responses to an aversive odour: individual flies weakly avoid the stimulus, but groups show enhanced escape reactions. Using high-resolution behavioural tracking, computational simulations, genetic perturbations, neural silencing and optogenetic activation we demonstrate that this collective odour avoidance arises from cascades of appendage touch interactions between pairs of flies. Inter-fly touch sensing and collective behaviour require the activity of distal leg mechanosensory sensilla neurons and the mechanosensory channel NOMPC. Remarkably, through these inter-fly encounters, wild-type flies can elicit avoidance behaviour in mutant animals that cannot sense the odour--a basic form of communication. Our data highlight the unexpected importance of social context in the sensory responses of a solitary species and open the door to a neural-circuit-level understanding of collective behaviour in animal groups

Attenuation of Toll-Like Receptor Expression and Function in Latent Tuberculosis by Coexistent Filarial Infection with Restoration Following Antifilarial Chemotherapy

Mycobacterium tuberculosis (Mtb) and filarial coinfection is highly prevalent, and the presence of filarial infections may regulate the Toll-like receptor (TLR)-dependent immune response needed to control Mtb infection. By analyzing the baseline and mycobacterial antigen–stimulated expression of TLR1, 2, 4, and 9 (in individuals with latent tuberculosis [TB] with or without filarial infection), we were able to demonstrate that filarial infection, coincident with Mtb, significantly diminishes both baseline and Mtb antigen-specific TLR2 and TLR9 expression. In addition, pro-inflammatory cytokine responses to TLR2 and 9 ligands are significantly diminished in filaria/TB-coinfected individuals. Definitive treatment of lymphatic filariasis significantly restores the pro-inflammatory cytokine responses in individuals with latent TB. Coincident filarial infection exerted a profound inhibitory effect on protective mycobacteria-specific TLR-mediated immune responses in latent tuberculosis and suggests a novel mechanism by which concomitant filarial infections predispose to the development of active tuberculosis in humans

Developing Literacy Learning Model Based on Multi Literacy, Integrated, and Differentiated Concept at Primary School

The main issue addressed in this research is the low writing skills of primary school students. One of the reasons for this condition is that the existing model of writing literacy learning is not appropriate. The purpose of this study is to explain MID-based literacy teaching model and the impact of the model in increasing primary school students\u27 writing skills. This study used combined methods of exploratory type. The samples were elementary school students coming from six schools with three different characteristics. Based on the data analysis, it can be concluded that the implementation of MID-based literacy learning model has proven to signi cantly contribute to the improvement of students\u27 writing skills. Taking place in all sample schools, the improvement may suggest that the model ts not only to students with high- ability but also those with low-ability. Therefore, the MID-based literacy learning model is needed to improve the ability to write various text types appropriately

Combined Inactivation of MYC and K-Ras Oncogenes Reverses Tumorigenesis in Lung Adenocarcinomas and Lymphomas

Conditional transgenic models have established that tumors require sustained oncogene activation for tumor maintenance, exhibiting the phenomenon known as "oncogene-addiction." However, most cancers are caused by multiple genetic events making it difficult to determine which oncogenes or combination of oncogenes will be the most effective targets for their treatment.To examine how the MYC and K-ras(G12D) oncogenes cooperate for the initiation and maintenance of tumorigenesis, we generated double conditional transgenic tumor models of lung adenocarcinoma and lymphoma. The ability of MYC and K-ras(G12D) to cooperate for tumorigenesis and the ability of the inactivation of these oncogenes to result in tumor regression depended upon the specific tissue context. MYC-, K-ras(G12D)- or MYC/K-ras(G12D)-induced lymphomas exhibited sustained regression upon the inactivation of either or both oncogenes. However, in marked contrast, MYC-induced lung tumors failed to regress completely upon oncogene inactivation; whereas K-ras(G12D)-induced lung tumors regressed completely. Importantly, the combined inactivation of both MYC and K-ras(G12D) resulted more frequently in complete lung tumor regression. To account for the different roles of MYC and K-ras(G12D) in maintenance of lung tumors, we found that the down-stream mediators of K-ras(G12D) signaling, Stat3 and Stat5, are dephosphorylated following conditional K-ras(G12D) but not MYC inactivation. In contrast, Stat3 becomes dephosphorylated in lymphoma cells upon inactivation of MYC and/or K-ras(G12D). Interestingly, MYC-induced lung tumors that failed to regress upon MYC inactivation were found to have persistent Stat3 and Stat5 phosphorylation.Taken together, our findings point to the importance of the K-Ras and associated down-stream Stat effector pathways in the initiation and maintenance of lymphomas and lung tumors. We suggest that combined targeting of oncogenic pathways is more likely to be effective in the treatment of lung cancers and lymphomas

Repeated long-distance dispersal and convergent evolution in hazel

Closely related species with a worldwide distribution provide an opportunity to understand evolutionary and biogeographic processes at a global scale. Hazel (Corylus) is an economically important genus of tree and shrub species found in temperate regions of Asia, North America and Europe. Here we use multiple nuclear and chloroplast loci to estimate a time-calibrated phylogenetic tree of the genus Corylus. We model the biogeographic history of this group and the evolutionary history of tree and shrub form. We estimate that multiple Corylus lineages dispersed long distances between Europe and Asia and colonised North America from Asia in multiple independent events. The geographic distribution of tree versus shrub form of species appears to be the result of 4–5 instances of convergent evolution in the past 25 million years. We find extensive discordance between our nuclear and chloroplast trees and potential evidence for chloroplast capture in species with overlapping ranges, suggestive of past introgression. The important crop species C. avellana is estimated to be closely related to C. maxima, C. heterophylla var. thunbergii and the Colurnae subsection. Our study provides a new phylogenetic hypothesis or Corylus and reveals how long-distance dispersal can shape the distribution of biodiversity in temperate plants

Skeleton of an unusual cat-sized marsupial relative (Metatheria: Marsupialiformes) from the middle Eocene (Lutetian: 44-43 million years ago) of Turkey

We describe a near-complete, three-dimensionally preserved skeleton of a metatherian (relative of modern marsupials) from the middle Eocene (Lutetian: 44–43 million years ago) Lülük member of the Uzunçarşıdere Formation, central Turkey. With an estimated body mass of 3–4 kg, about the size of a domestic cat (Felis catus) or spotted quoll (Dasyurus maculatus), it is an order of magnitude larger than the largest fossil metatherians previously known from the Cenozoic of the northern hemisphere. This new taxon is characterised by large, broad third premolars that probably represent adaptations for hard object feeding (durophagy), and its craniodental morphology suggests the capacity to generate high bite forces. Qualitative and quantitative functional analyses of its postcranial skeleton indicate that it was probably scansorial and relatively agile, perhaps broadly similar in locomotor mode to the spotted quoll, but with a greater capacity for climbing and grasping. Bayesian phylogenetic analysis of a total evidence dataset comprising 259 morphological characters and 9kb of DNA sequence data from five nuclear protein-coding genes, using both undated and “tip-and-node dating” approaches, place the new taxon outside the marsupial crown-clade, but within the clade Marsupialiformes. It demonstrates that at least one metatherian lineage evolved to occupy the small-medium, meso- or hypo-carnivore niche in the northern hemisphere during the early Cenozoic, at a time when there were numerous eutherians (placentals and their fossil relatives) filling similar niches. However, the known mammal fauna from Uzunçarşıdere Formation appears highly endemic, and geological evidence suggests that this region of Turkey was an island for at least part of the early Cenozoic, and so the new taxon may have evolved in isolation from potential eutherian competitors. Nevertheless, the new taxon reveals previously unsuspected ecomorphological disparity among northern hemisphere metatherians during the first half of the Cenozoic

NK-CD11c+ Cell Crosstalk in Diabetes Enhances IL-6-Mediated Inflammation during Mycobacterium tuberculosis Infection

In this study, we developed a mouse model of type 2 diabetes mellitus (T2DM) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis (Mtb). All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 months, whereas all control mice survived. In Mtb-infected mice, T2DM increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those in uninfected T2DM mice and infected control mice. Levels of IL-6 also increased. Anti-IL-6 monoclonal antibody treatment of Mtb-infected acute- and chronic-T2DM mice increased survival (to 100%) and reduced pro- and anti-inflammatory cytokine expression. CD11c+ cells were the major source of IL-6 in Mtb-infected T2DM mice. Pulmonary natural killer (NK) cells in Mtb-infected T2DM mice further increased IL-6 production by autologous CD11c+ cells through their activating receptors. Anti-NK1.1 antibody treatment of Mtb-infected acute-T2DM mice increased survival and reduced pro- and anti-inflammatory cytokine expression. Furthermore, IL-6 increased inflammatory cytokine production by T lymphocytes in pulmonary tuberculosis patients with T2DM. Overall, the results suggest that NK-CD11c+ cell interactions increase IL-6 production, which in turn drives the pathological immune response and mortality associated with Mtb infection in diabetic mice