Characterisation of GLUT4 trafficking in HeLa cells: Comparable kinetics and orthologous trafficking mechanisms to 3T3-L1 adipocytes

Insulin-stimulated glucose transport is a characteristic property of adipocytes and muscle cells and involves the regulated delivery of glucose transporter (GLUT4)- containing vesicles from intracellular stores to the cell surface. Fusion of these vesicles results in increased numbers of GLUT4 molecules at the cell surface. In an attempt to overcome some of the limitations associated with both primary and cultured adipocytes, we expressed an epitope- and GFP-tagged version of GLUT4 (HA–GLUT4–GFP) in HeLa cells. Here we report the characterisation of this system compared to 3T3-L1 adipocytes. We show that insulin promotes translocation of HA–GLUT4–GFP to the surface of both cell types with similar kinetics using orthologous trafficking machinery. While the magnitude of the insulin-stimulated translocation of GLUT4 is smaller than mouse 3T3-L1 adipocytes, HeLa cells offer a useful, experimentally tractable, human model system. Here, we exemplify their utility through a small-scale siRNA screen to identify GOSR1 and YKT6 as potential novel regulators of GLUT4 trafficking in human cells

Restriction semigroups and λ -Zappa-Szép products

The aim of this paper is to study λ-semidirect and λ-Zappa-Szép products of restriction semigroups. The former concept was introduced for inverse semigroups by Billhardt, and has been extended to some classes of left restriction semigroups. The latter was introduced, again in the inverse case, by Gilbert and Wazzan. We unify these concepts by considering what we name the scaffold of a Zappa-Szép product S⋈ T where S and T are restriction. Under certain conditions this scaffold becomes a category. If one action is trivial, or if S is a semilattice and T a monoid, the scaffold may be ordered so that it becomes an inductive category. A standard technique, developed by Lawson and based on the Ehresmann-Schein-Nambooripad result for inverse semigroups, allows us to define a product on our category. We thus obtain restriction semigroups that are λ-semidirect products and λ-Zappa-Szép products, extending the work of Billhardt and of Gilbert and Wazzan. Finally, we explicate the internal structure of λ-semidirect products

Screening of depression in adolescents through the Internet: Sensitivity and specificity of two screening questionnaires.

.001). The scores on both instruments were significantly increased in all subjects with a mood disorder, whether current or lifetime, except for lifetime minor depression. In the ROC analyses, high areas under the curve were found for the MDI (0.89) and CESD (0.90). The best cut-off point for the MDI was 19 (sensitivity: 90.48; specificity: 71.53), and for the CES-D it was 22 (sensitivity: 90.48; specificity: 74.31). We conclude that the MDI and CES-D are reliable and valid instruments that can be used for this screening

Super Resolution Microscopy Reveals that Caveolin-1 Is Required for Spatial Organization of CRFB1 and Subsequent Antiviral Signaling in Zebrafish

10.1371/journal.pone.0068759PLoS ONE87-POLN

A Naturally Occurring Plant Cysteine Protease Possesses Remarkable Toxicity against Insect Pests and Synergizes Bacillus thuringiensis Toxin

When caterpillars feed on maize (Zea maize L.) lines with native resistance to several Lepidopteran pests, a defensive cysteine protease, Mir1-CP, rapidly accumulates at the wound site. Mir1-CP has been shown to inhibit caterpillar growth in vivo by attacking and permeabilizing the insect's peritrophic matrix (PM), a structure that surrounds the food bolus, assists in digestion and protects the midgut from microbes and toxins. PM permeabilization weakens the caterpillar defenses by facilitating the movement of other insecticidal proteins in the diet to the midgut microvilli and thereby enhancing their toxicity. To directly determine the toxicity of Mir1-CP, the purified recombinant enzyme was directly tested against four economically significant Lepidopteran pests in bioassays. Mir1-CP LC50 values were 1.8, 3.6, 0.6, and 8.0 ppm for corn earworm, tobacco budworm, fall armyworm and southwestern corn borer, respectively. These values were the same order of magnitude as those determined for the Bacillus thuringiensis toxin Bt-CryIIA. In addition to being directly toxic to the larvae, 60 ppb Mir1-CP synergized sublethal concentrations of Bt-CryIIA in all four species. Permeabilization of the PM by Mir1-CP probably provides ready access to Bt-binding sites on the midgut microvilli and increases its activity. Consequently, Mir1-CP could be used for controlling caterpillar pests in maize using non-transgenic approaches and potentially could be used in other crops either singly or in combination with Bt-toxins

Quantification of Epithelial Cell Differentiation in Mammary Glands and Carcinomas from DMBA- and MNU-Exposed Rats

Rat mammary carcinogenesis models have been used extensively to study breast cancer initiation, progression, prevention, and intervention. Nevertheless, quantitative molecular data on epithelial cell differentiation in mammary glands of untreated and carcinogen-exposed rats is limited. Here, we describe the characterization of rat mammary epithelial cells (RMECs) by multicolor flow cytometry using antibodies against cell surface proteins CD24, CD29, CD31, CD45, CD49f, CD61, Peanut Lectin, and Thy-1, intracellular proteins CK14, CK19, and FAK, along with phalloidin and Hoechst staining. We identified the luminal and basal/myoepithelial populations and actively dividing RMECs. In inbred rats susceptible to mammary carcinoma development, we quantified the changes in differentiation of the RMEC populations at 1, 2, and 4 weeks after exposure to mammary carcinogens DMBA and MNU. DMBA exposure did not alter the percentage of basal or luminal cells, but upregulated CD49f (Integrin α6) expression and increased cell cycle activity. MNU exposure resulted in a temporary disruption of the luminal/basal ratio and no CD49f upregulation. When comparing DMBA- or MNU-induced mammary carcinomas, the RMEC differentiation profiles are indistinguishable. The carcinomas compared with mammary glands from untreated rats, showed upregulation of CD29 (Integrin β1) and CD49f expression, increased FAK (focal adhesion kinase) activation especially in the CD29hi population, and decreased CD61 (Integrin β3) expression. This study provides quantitative insight into the protein expression phenotypes underlying RMEC differentiation. The results highlight distinct RMEC differentiation etiologies of DMBA and MNU exposure, while the resulting carcinomas have similar RMEC differentiation profiles. The methodology and data will enhance rat mammary carcinogenesis models in the study of the role of epithelial cell differentiation in breast cancer

Exploring the potential of phone call data to characterize the relationship between social network and travel behavior

[EN] Social network contacts have significant influence on individual travel behavior. However, transport models rarely consider social interaction. One of the reasons is the difficulty to properly model social influence based on the limited data available. Non-conventional, passively collected data sources, such as Twitter, Facebook or mobile phones, provide large amounts of data containing both social interaction and spatiotemporal information. The analysis of such data opens an opportunity to better understand the influence of social networks on travel behavior. The main objective of this paper is to examine the relationship between travel behavior and social networks using mobile phone data. A huge dataset containing billions of registers has been used for this study. The paper analyzes the nature of co-location events and frequent locations shared by social network contacts, aiming not only to provide understanding on why users share certain locations, but also to quantify the degree in which the different types of locations are shared. Locations have been classified as frequent (home, work and other) and non-frequent. A novel approach to identify co-location events based on the intersection of users' mobility models has been proposed. Results show that other locations different from home and work are frequently associated to social interaction. Additionally, the importance of non-frequent locations in co-location events is shown. Finally, the potential application of the data analysis results to improve activity-based transport models and assess transport policies is discussed.The authors would like to thank the anonymous reviewers for their valuable comments and suggestions to improve the quality of the paper. The research leading to these results has received funding from the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement no 318367 (EUNOIA project) and no 611307 (INSIGHT project). The work of ML has been funded under the PD/004/2013 project, from the Conselleria de Educacion, Cultura y Universidades of the Government of the Balearic Islands and from the European Social Fund through the Balearic Islands ESF operational program for 2013-2017.Picornell Tronch, M.; Ruiz Sánchez, T.; Lenormand, M.; Ramasco, JJ.; Dubernet, T.; Frías-Martínez, E. (2015). Exploring the potential of phone call data to characterize the relationship between social network and travel behavior. Transportation. 42(4):647-668. https://doi.org/10.1007/s11116-015-9594-1S647668424Ahas, R., Aasa, A., Silm, S., Tiru, M.: Daily rhythms of suburban commuters’ movements in the tallinn metropolitan area: case study with mobile positioning data. Transp. Res. 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Climate Change and the Geographic Distribution of Infectious Diseases

Our ability to predict the effects of climate change on the spread of infectious diseases is in its infancy. Numerous, and in some cases conflicting, predictions have been developed, principally based on models of biological processes or mapping of current and historical disease statistics. Current debates on whether climate change, relative to socioeconomic determinants, will be a major influence on human disease distributions are useful to help identify research needs but are probably artificially polarized. We have at least identified many of the critical geophysical constraints, transport opportunities, biotic requirements for some disease systems, and some of the socioeconomic factors that govern the process of migration and establishment of parasites and pathogens. Furthermore, we are beginning to develop a mechanistic understanding of many of these variables at specific sites. Better predictive understanding will emerge in the coming years from analyses regarding how these variables interact with each other

Mifepristone Prevents Stress-Induced Apoptosis in Newborn Neurons and Increases AMPA Receptor Expression in the Dentate Gyrus of C57/BL6 Mice

Chronic stress produces sustained elevation of corticosteroid levels, which is why it is considered one of the most potent negative regulators of adult hippocampal neurogenesis (AHN). Several mood disorders are accompanied by elevated glucocorticoid levels and have been linked to alterations in AHN, such as major depression (MD). Nevertheless, the mechanism by which acute stress affects the maturation of neural precursors in the dentate gyrus is poorly understood. We analyzed the survival and differentiation of 1 to 8 week-old cells in the dentate gyrus of female C57/BL6 mice following exposure to an acute stressor (the Porsolt or forced swimming test). Furthermore, we evaluated the effects of the glucocorticoid receptor (GR) antagonist mifepristone on the cell death induced by the Porsolt test. Forced swimming induced selective apoptotic cell death in 1 week-old cells, an effect that was abolished by pretreatment with mifepristone. Independent of its antagonism of GR, mifepristone also induced an increase in the percentage of 1 week-old cells that were AMPA+. We propose that the induction of AMPA receptor expression in immature cells may mediate the neuroprotective effects of mifepristone, in line with the proposed antidepressant effects of AMPA receptor potentiators