The Role of Tricellulin in Epithelial Jamming and Unjamming via Segmentation of Tricellular Junctions

Collective cellular behavior in confluent monolayers supports physiological and pathological processes of epithelial development, regeneration, and carcinogenesis. Here, the attainment of a mature and static tissue configuration or the local reactivation of cell motility involve a dynamic regulation of the junctions established between neighboring cells. Tricellular junctions (tTJs), established at vertexes where three cells meet, are ideally located to control cellular shape and coordinate multicellular movements. However, their function in epithelial tissue dynamic remains poorly defined. To investigate the role of tTJs establishment and maturation in the jamming and unjamming transitions of epithelial monolayers, a semi-automatic image-processing pipeline is developed and validated enabling the unbiased and spatially resolved determination of the tTJ maturity state based on the localization of fluorescent reporters. The software resolves the variation of tTJ maturity accompanying collective transitions during tissue maturation, wound healing, and upon the adaptation to osmolarity changes. Altogether, this work establishes junctional maturity at tricellular contacts as a novel biological descriptor of collective responses in epithelial monolayers

Modular polyoxometalate-layered double hydroxides as efficient heterogeneous sulfoxidation and epoxidation catalysts

Selective sulfoxidation of sulfides and epoxidation of olefins are two types of important organic reactions and the corresponding products of sulfoxides, sulfones and epoxides are widely used as raw materials in industrial processes. The fabrication of one efficient catalyst for both reactions, remains a challenging task. In this paper, we report the preparation of a highly efficient heterogeneous catalyst of Mg3Al-ILs-La(PW11)2 using an exfoliation/assembly approach. The catalyst was characterized by FT-IR, XRD, TG/DTA, BET, XPS, 29Si CP/MAS NMR, the 27Al-MAS NMR, SEM, HRTEM, EDX etc. The designed catalyst showed high efficiency and selectivity for sulfoxidation of sulphides and epoxidation of olefins under mild conditions at a production rate of 208 mmol g-1 h-1 and 31 mmol g-1 h-1, respectively. Moreover, the Mg3Al-ILs-La(PW11)2 can be recycled and reused at least 5 times without obvious decrease of its catalytic activity. The scaled-up experiments revealed that the catalyst retained its efficiency and robustness, demonstrating the catalyts' great potential for industrial applications

A novel Big Data analytics and intelligent technique to predict driver's intent

Modern age offers a great potential for automatically predicting the driver's intent through the increasing miniaturization of computing technologies, rapid advancements in communication technologies and continuous connectivity of heterogeneous smart objects. Inside the cabin and engine of modern cars, dedicated computer systems need to possess the ability to exploit the wealth of information generated by heterogeneous data sources with different contextual and conceptual representations. Processing and utilizing this diverse and voluminous data, involves many challenges concerning the design of the computational technique used to perform this task. In this paper, we investigate the various data sources available in the car and the surrounding environment, which can be utilized as inputs in order to predict driver's intent and behavior. As part of investigating these potential data sources, we conducted experiments on e-calendars for a large number of employees, and have reviewed a number of available geo referencing systems. Through the results of a statistical analysis and by computing location recognition accuracy results, we explored in detail the potential utilization of calendar location data to detect the driver's intentions. In order to exploit the numerous diverse data inputs available in modern vehicles, we investigate the suitability of different Computational Intelligence (CI) techniques, and propose a novel fuzzy computational modelling methodology. Finally, we outline the impact of applying advanced CI and Big Data analytics techniques in modern vehicles on the driver and society in general, and discuss ethical and legal issues arising from the deployment of intelligent self-learning cars

Antidepressant Controlled Trial For Negative Symptoms In Schizophrenia (ACTIONS): a double-blind, placebo-controlled, randomised clinical trial

Background Negative symptoms of schizophrenia represent deficiencies in emotional responsiveness, motivation, socialisation, speech and movement. When persistent, they are held to account for much of the poor functional outcomes associated with schizophrenia. There are currently no approved pharmacological treatments. While the available evidence suggests that a combination of antipsychotic and antidepressant medication may be effective in treating negative symptoms, it is too limited to allow any firm conclusions. Objective To establish the clinical effectiveness and cost-effectiveness of augmentation of antipsychotic medication with the antidepressant citalopram for the management of negative symptoms in schizophrenia. Design A multicentre, double-blind, individually randomised, placebo-controlled trial with 12-month follow-up Setting Adult psychiatric services, treating people with schizophrenia. Participants Inpatients or outpatients with schizophrenia, on continuing, stable antipsychotic medication, with persistent negative symptoms at a criterion level of severity. Interventions Eligible participants were randomised 1 : 1 to treatment with either placebo (one capsule) or 20 mg of citalopram per day for 48 weeks, with the clinical option at 4 weeks to increase the daily dosage to 40 mg of citalopram or two placebo capsules for the remainder of the study. Main Outcome Measures The primary outcomes were quality of life measured at 12 and 48 weeks assessed using the Heinrich’s Quality of Life Scale, and negative symptoms at 12 weeks measured on the negative symptom subscale of the Positive and Negative Syndrome Scale. Results No therapeutic benefit in terms of improvement in quality of life or negative symptoms was detected for citalopram over 12 weeks or at 48 weeks, but secondary analysis suggested modest improvement in the negative symptom domain, avolition/amotivation, at 12 weeks (mean difference –1.3, 95% confidence interval–2.5 to–0.09). There were no statistically significant differences between the two treatment arms over 48-week follow-up in either the health economics outcomes or costs, and no differences in the frequency or severity of adverse effects, including corrected QT interval prolongation. Limitations The trial under-recruited, partly because cardiac safety concerns about citalopram were raised, with the 62 participants recruited falling well short of the target recruitment of 358. Although this was the largest sample randomised to citalopram in a randomised controlled trial of antidepressant augmentation for negative symptoms of schizophrenia and had the longest follow-up, the power of statistical analysis to detect significant differences between the active and placebo groups was limited. Conclusion Although adjunctive citalopram did not improve negative symptoms overall, there was evidence of some positive effect on avolition/amotivation, recognised as a critical barrier to psychosocial rehabilitation and achieving better social and community functional outcomes. Comprehensive assessment of side-effect burden did not identify any serious safety or tolerability issues. The addition of citalopram as a long-term prescribing strategy for the treatment of negative symptoms may merit further investigation in larger studies. Future Work Further studies of the viability of adjunctive antidepressant treatment for negative symptoms in schizophrenia should include appropriate safety monitoring and use rating scales that allow for evaluation of avolition/amotivation as a discrete negative symptom domain. Overcoming the barriers to recruiting an adequate sample size will remain a challenge.</p

Identifying Electroencephalography Biomarkers in Individuals at Clinical High Risk for Psychosis in an International Multi-Site Study

Background: The clinical high-risk for psychosis (CHR-P) paradigm was introduced to detect individuals at risk of developing psychosis and to establish preventive strategies. While current prediction of outcomes in the CHR-P state is based mostly on the clinical assessment of presenting features, several emerging biomarkers have been investigated in an attempt to stratify CHR-P individuals according to their individual trajectories and refine the diagnostic process. However, heterogeneity across subgroups is a key challenge that has limited the impact of the CHR-P prediction strategies, as the clinical validity of the current research is limited by a lack of external validation across sites and modalities. Despite these challenges, electroencephalography (EEG) biomarkers have been studied in this field and evidence suggests that EEG used in combination with clinical assessments may be a key measure for improving diagnostic and prognostic accuracy in the CHR-P state. The PSYSCAN EEG study is an international, multi-site, multimodal longitudinal project that aims to advance knowledge in this field. Methods: Participants at 6 international sites take part in an EEG protocol including EEG recording, cognitive and clinical assessments. CHR-P participants will be followed up after 2 years and subcategorised depending on their illness progression regarding transition to psychosis. Differences will be sought between CHR-P individuals and healthy controls and between CHR-P individuals who transition and those who do not transition to psychosis using data driven computational analyses. Discussion: This protocol addresses the challenges faced by previous studies of this kind to enable valid identification of predictive EEG biomarkers which will be combined with other biomarkers across sites to develop a prognostic tool in CHR-P. The PSYSCAN EEG study aims to pave the way for incorporating EEG biomarkers in the assessment of CHR-P individuals, to refine the diagnostic process and help to stratify CHR-P subjects according to risk of transition. This may improve our understanding of the CHR-P state and therefore aid the development of more personalized treatment strategies. Keywords: CHR-P; EEG; biomarkers; multi-site; psychosis predictio

DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity

Surfactant protein D inhibits HIV-1 infection of target cells via interference with gp120-CD4 interaction and modulates pro-inflammatory cytokine production

© 2014 Pandit et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Surfactant Protein SP-D, a member of the collectin family, is a pattern recognition protein, secreted by mucosal epithelial cells and has an important role in innate immunity against various pathogens. In this study, we confirm that native human SP-D and a recombinant fragment of human SP-D (rhSP-D) bind to gp120 of HIV-1 and significantly inhibit viral replication in vitro in a calcium and dose-dependent manner. We show, for the first time, that SP-D and rhSP-D act as potent inhibitors of HIV-1 entry in to target cells and block the interaction between CD4 and gp120 in a dose-dependent manner. The rhSP-D-mediated inhibition of viral replication was examined using three clinical isolates of HIV-1 and three target cells: Jurkat T cells, U937 monocytic cells and PBMCs. HIV-1 induced cytokine storm in the three target cells was significantly suppressed by rhSP-D. Phosphorylation of key kinases p38, Erk1/2 and AKT, which contribute to HIV-1 induced immune activation, was significantly reduced in vitro in the presence of rhSP-D. Notably, anti-HIV-1 activity of rhSP-D was retained in the presence of biological fluids such as cervico-vaginal lavage and seminal plasma. Our study illustrates the multi-faceted role of human SPD against HIV-1 and potential of rhSP-D for immunotherapy to inhibit viral entry and immune activation in acute HIV infection. © 2014 Pandit et al.The work (Project no. 2011-16850) was supported by Medical Innovation Fund of Indian Council of Medical Research, New Delhi, India (www.icmr.nic.in/)

Ultra-stable optical clock with two cold-atom ensembles

Atomic clocks based on optical transitions are the most stable, and therefore precise, timekeepers available. These clocks operate by alternating intervals of atomic interrogation with dead time required for quantum state preparation and readout. This non-continuous interrogation of the atom system results in the Dick effect, an aliasing of frequency noise of the laser interrogating the atomic transition. Despite recent advances in optical clock stability achieved by improving laser coherence, the Dick effect has continually limited optical clock performance. Here we implement a robust solution to overcome this limitation: a zero-dead-time optical clock based on the interleaved interrogation of two cold-atom ensembles. This clock exhibits vanishingly small Dick noise, thereby achieving an unprecedented fractional frequency instability of $6 \times 10^{-17} / \sqrt{\tau}$ for an averaging time $\tau$ in seconds. We also consider alternate dual-atom-ensemble schemes to extend laser coherence and reduce the standard quantum limit of clock stability, achieving a spectroscopy line quality factor $Q> 4 \times 10^{15}$