541 research outputs found

    Evolution of a Novel Appendage Ground Plan in Water Striders Is Driven by Changes in the Hox Gene Ultrabithorax

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    Water striders, a group of semi-aquatic bugs adapted to life on the water surface, have evolved mid-legs (L2) that are long relative to their hind-legs (L3). This novel appendage ground plan is a derived feature among insects, where L2 function as oars and L3 as rudders. The Hox gene Ultrabithorax (Ubx) is known to increase appendage size in a variety of insects. Using gene expression and RNAi analysis, we discovered that Ubx is expressed in both L2 and L3, but Ubx functions to elongate L2 and to shorten L3 in the water strider Gerris buenoi. Therefore, within hemimetabolous insects, Ubx has evolved a new expression domain but maintained its ancestral elongating function in L2, whereas Ubx has maintained its ancestral expression domain but evolved a new shortening function in L3. These changes in Ubx expression and function may have been a key event in the evolution of the distinct appendage ground plan in water striders

    Serratia marcescens Is Able to Survive and Proliferate in Autophagic-Like Vacuoles inside Non-Phagocytic Cells

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    Serratia marcescens is an opportunistic human pathogen that represents a growing problem for public health, particularly in hospitalized or immunocompromised patients. However, little is known about factors and mechanisms that contribute to S. marcescens pathogenesis within its host. In this work, we explore the invasion process of this opportunistic pathogen to epithelial cells. We demonstrate that once internalized, Serratia is able not only to persist but also to multiply inside a large membrane-bound compartment. This structure displays autophagic-like features, acquiring LC3 and Rab7, markers described to be recruited throughout the progression of antibacterial autophagy. The majority of the autophagic-like vacuoles in which Serratia resides and proliferates are non-acidic and have no degradative properties, indicating that the bacteria are capable to either delay or prevent fusion with lysosomal compartments, altering the expected progression of autophagosome maturation. In addition, our results demonstrate that Serratia triggers a non-canonical autophagic process before internalization. These findings reveal that S. marcescens is able to manipulate the autophagic traffic, generating a suitable niche for survival and proliferation inside the host cell

    Combination antiretroviral therapy and the risk of myocardial infarction

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    A low-cost 2-D video system can accurately and reliably assess adaptive gait kinematics in healthy and low vision subjects

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    3-D gait analysis is the gold standard but many healthcare clinics and research institutes would benefit from a system that is inexpensive and simple but just as accurate. The present study examines whether a low-cost 2-D motion capture system can accurately and reliably assess adaptive gait kinematics in subjects with central vision loss, older controls, and younger controls. Subjects were requested to walk up and step over a 10 cm high obstacle that was positioned in the middle of a 4.5 m walkway. Four trials were simultaneously recorded with the Vicon motion capture system (3-D system) and a video camera that was positioned perpendicular to the obstacle (2-D system). The kinematic parameters (crossing height, crossing velocity, foot placement, single support time) were calculated offline. Strong Pearson's correlations were found between the two systems for all parameters (average r = 0.944, all p < 0.001). Bland-Altman analysis showed that the agreement between the two systems was good in all three groups after correcting for systematic biases related to the 2-D marker positions. The test-retest reliability for both systems was high (average ICC = 0.959). These results show that a low-cost 2-D video system can reliably and accurately assess adaptive gait kinematics in healthy and low vision subjects

    A Filamentous Hemagglutinin-Like Protein of Xanthomonas axonopodis pv. citri, the Phytopathogen Responsible for Citrus Canker, Is Involved in Bacterial Virulence

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    Xanthomonas axonopodis pv. citri, the phytopathogen responsible for citrus canker has a number of protein secretion systems and among them, at least one type V protein secretion system belonging to the two-partner secretion pathway. This system is mainly associated to the translocation of large proteins such as adhesins to the outer membrane of several pathogens. Xanthomonas axonopodis pv. citri possess a filamentous hemagglutinin-like protein in close vicinity to its putative transporter protein, XacFhaB and XacFhaC, respectively. Expression analysis indicated that XacFhaB was induced in planta during plant-pathogen interaction. By mutation analysis of XacFhaB and XacFhaC genes we determined that XacFhaB is involved in virulence both in epiphytic and wound inoculations, displaying more dispersed and fewer canker lesions. Unexpectedly, the XacFhaC mutant in the transporter protein produced an intermediate virulence phenotype resembling wild type infection, suggesting that XacFhaB could be secreted by another partner different from XacFhaC. Moreover, XacFhaB mutants showed a general lack of adhesion and were affected in leaf surface attachment and biofilm formation. In agreement with the in planta phenotype, adhesin lacking cells moved faster in swarming plates. Since no hyperflagellation phenotype was observed in this bacteria, the faster movement may be attributed to the lack of cell-to-cell aggregation. Moreover, XacFhaB mutants secreted more exopolysaccharide that in turn may facilitate its motility. Our results suggest that this hemagglutinin-like protein is required for tissue colonization being mainly involved in surface attachment and biofilm formation, and that plant tissue attachment and cell-to-cell aggregation are dependent on the coordinated action of adhesin molecules and exopolysaccharides

    Adolescents with metabolic syndrome have a history of low aerobic fitness and physical activity levels

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    Abstract: Purpose: Metabolic syndrome (MS) is a clustering of cardiovascular disease risk factors that identifies individuals with the highest risk for heart disease. Two factors that may influence the MS are physical activity and aerobic fitness. This study determined if adolescent with the MS had low levels of aerobic fitness and physical activity as children. Methods: This longitudinal, exploratory study had 389 participants: 51% girls, 84% Caucasian, 12% African American, 1% Hispanic, and 3% other races, from the State of North Carolina. Habitual physical activity (PA survey), aerobic fitness (VO2max), body mass index (BMI), blood pressure, and lipids obtained at 7–10 y of age were compared to their results obtained 7 y later at ages 14–17 y. Results: Eighteen adolescents (4.6%) developed 3 or more characteristics of the MS. Logistic regression, adjusting for BMI percentile, blood pressure, and cholesterol levels, found that adolescents with the MS were 6.08 (95%CI = 1.18–60.08) times more likely to have low aerobic fitness as children and 5.16 (95%CI = 1.06–49.66) times more likely to have low PA levels. Conclusion: Low levels of childhood physical activity and aerobic fitness are associated with the presence of the metabolic syndrome in adolescents. Thus, efforts need to begin early in childhood to increase exercise

    Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

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    The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

    Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

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    The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

    Adaptable Functionality of Transcriptional Feedback in Bacterial Two-Component Systems

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    A widespread mechanism of bacterial signaling occurs through two-component systems, comprised of a sensor histidine kinase (SHK) and a transcriptional response regulator (RR). The SHK activates RR by phosphorylation. The most common two-component system structure involves expression from a single operon, the transcription of which is activated by its own phosphorylated RR. The role of this feedback is poorly understood, but it has been associated with an overshooting kinetic response and with fast recovery of previous interrupted signaling events in different systems. Mathematical models show that overshoot is only attainable with negative feedback that also improves response time. Our models also predict that fast recovery of previous interrupted signaling depends on high accumulation of SHK and RR, which is more likely in a positive feedback regime. We use Monte Carlo sampling of the parameter space to explore the range of attainable model behaviors. The model predicts that the effective feedback sign can change from negative to positive depending on the signal level. Variations in two-component system architectures and parameters may therefore have evolved to optimize responses in different bacterial lifestyles. We propose a conceptual model where low signal conditions result in a responsive system with effectively negative feedback while high signal conditions with positive feedback favor persistence of system output

    Induction of tumour-specific CD8+ cytotoxic T lymphocytes by tumour lysate-pulsed autologous dendritic cells in patients with uterine serous papillary cancer

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    Uterine serous papillary carcinoma is a highly aggressive variant of endometrial cancer histologically similar to high grade ovarian cancer. Unlike ovarian cancer, however, it is a chemoresistant disease from onset, with responses to combined cisplatinum-based chemotherapy in the order of 20% and an extremely poor prognosis. In this study, we demonstrate that tumour lysate-pulsed autologous dendritic cells can elicit a specific CD8+ cytotoxic T lymphocyte response against autologous tumour target cells in three patients with uterine serous papillary cancer. CTL from patients 1 and 2 expressed strong cytolytic activity against autologous tumour cells, did not lyse autologous lymphoblasts or autologous EBV-transformed cell lines, and were variably cytotoxic against the NK-sensitive cell line K-562. Patient 3 CD8+ T cells expressed a modest but reproducible cytotoxicity against autologous tumour cells only at the time of the first priming. Further priming attempts with PBL collected from patient 3 after tumour progression in the lumboaortic lymph nodes were unsuccesful. Cytotoxicity against autologous tumour cells could be significantly inhibited by anti-HLA class I (W6/32) and anti-LFA-1 MAbs. Highly cytotoxic CD8+ T cells from patients 1 and 2 showed a heterogeneous CD56 expression while CD56 was not expressed by non-cytotoxic CD8+ T cells from patient 3. Using two colour flow cytometric analysis of intracellular cytokine expression at the single cell level, a striking dominance of IFN-γ expressors was detectable in CTL populations of patients 1 and 2 while in patient 3 a dominant population of CD8+ T cells expressing IL-4 and IL-10 was consistently detected. Taken together, these data demonstrate that tumour lysate-pulsed DC can be an effective tool in inducing uterine serous papillary cancer-specific CD8+ CTL able to kill autologous tumour cells in vitro. However, high levels of tumour specific tolerance in some patients may impose a significant barrier to therapeutic vaccination. These results may have important implications for the treatment in the adjuvant setting of uterine serous papillary cancer patients with active or adoptive immunotherapy
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