Assaying locomotor activity to study circadian rhythms and sleep parameters in Drosophila.

Most life forms exhibit daily rhythms in cellular, physiological and behavioral phenomena that are driven by endogenous circadian (≡24 hr) pacemakers or clocks. Malfunctions in the human circadian system are associated with numerous diseases or disorders. Much progress towards our understanding of the mechanisms underlying circadian rhythms has emerged from genetic screens whereby an easily measured behavioral rhythm is used as a read-out of clock function. Studies using Drosophila have made seminal contributions to our understanding of the cellular and biochemical bases underlying circadian rhythms. The standard circadian behavioral read-out measured in Drosophila is locomotor activity. In general, the monitoring system involves specially designed devices that can measure the locomotor movement of Drosophila. These devices are housed in environmentally controlled incubators located in a darkroom and are based on using the interruption of a beam of infrared light to record the locomotor activity of individual flies contained inside small tubes. When measured over many days, Drosophila exhibit daily cycles of activity and inactivity, a behavioral rhythm that is governed by the animal's endogenous circadian system. The overall procedure has been simplified with the advent of commercially available locomotor activity monitoring devices and the development of software programs for data analysis. We use the system from Trikinetics Inc., which is the procedure described here and is currently the most popular system used worldwide. More recently, the same monitoring devices have been used to study sleep behavior in Drosophila. Because the daily wake-sleep cycles of many flies can be measured simultaneously and only 1 to 2 weeks worth of continuous locomotor activity data is usually sufficient, this system is ideal for large-scale screens to identify Drosophila manifesting altered circadian or sleep properties

The Catalytic and Non-catalytic Functions of the Brahma Chromatin-Remodeling Protein Collaborate to Fine-Tune Circadian Transcription in Drosophila.

Daily rhythms in gene expression play a critical role in the progression of circadian clocks, and are under regulation by transcription factor binding, histone modifications, RNA polymerase II (RNAPII) recruitment and elongation, and post-transcriptional mechanisms. Although previous studies have shown that clock-controlled genes exhibit rhythmic chromatin modifications, less is known about the functions performed by chromatin remodelers in animal clockwork. Here we have identified the Brahma (Brm) complex as a regulator of the Drosophila clock. In Drosophila, CLOCK (CLK) is the master transcriptional activator driving cyclical gene expression by participating in an auto-inhibitory feedback loop that involves stimulating the expression of the main negative regulators, period (per) and timeless (tim). BRM functions catalytically to increase nucleosome density at the promoters of per and tim, creating an overall restrictive chromatin landscape to limit transcriptional output during the active phase of cycling gene expression. In addition, the non-catalytic function of BRM regulates the level and binding of CLK to target promoters and maintains transient RNAPII stalling at the per promoter, likely by recruiting repressive and pausing factors. By disentangling its catalytic versus non-catalytic functions at the promoters of CLK target genes, we uncovered a multi-leveled mechanism in which BRM fine-tunes circadian transcription

Perceptions of social media challenges and benefits during the Covid-19 pandemic: Qualitative findings from a cross sectional international survey

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.Since the beginning of the Covid-19 pandemic in January 2020 the need for rapid information spread grew and social media became the ultimate platform for information exchange as well as a tool for connection and entertainment. With the rapid information spread along came the various public misconceptions and misinformation which consequently influenced perceptions and behaviors of the public towards the coronavirus pandemic. Thus, there was a need for identification and collation of public perceptions information to address future public health initiatives. This cross-national study aimed to examine the challenges and benefits of using social media during the Covid-19 pandemic outbreak. This study was a content analysis of the open-ended questions from a wider cross-sectional online survey conducted in Norway, UK, USA, and Australia during October/November 2020. 2368 participants out of 3474 respondents to the survey provided the open text responses included in the qualitative analysis. Thematic analysis was conducted independently by two researchers. All statements were coded to positive and negative sentiments. Three overarching themes were identified: 1. Mental health and emotional exhaustion 2. Information and misinformation; 3. Learning and inspiration.While providing a powerful mode of connection during the pandemic, social media also led to negative impact on public perceptions, including mistrust and confusion. Clarity in communications by institutions and education about credible information sources should be considered in the future. Further research is required in exploring and documenting social media narratives around COVID-19 in this and any subsequent incidents of pandemic restrictions. Understanding the public perceptions and their social narratives can support the designing of appropriate support and services for people in the future, while acknowledging the uncertainty and overwhelming impact of the pandemic that may have skewed the experiences of social media.publishedVersio

Smart Home Security System

The Home Attender is a scalable security system which integrates various components into a more complete product. It will include components as accelerometers, a thermal and optical camera module, networking, a storage for recorded data, and a phone application to alert the user of criminal activity and fires.  Benefits of the Home Attender include convenience, allowing the owner to setup an alert system and receive information about dangers from wherever they are. The system will use thermal cameras for increased accuracy in detecting intruders and fires, greatly reducing the chance of a false alarm. The Home Attender is also designed to be a scalable system and can be extended to protect large facilities such as farms or shopping centers. The scalability factor will also allow additional security features to be developed added to the Home Attender in the future

Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis

Toll receptors in Drosophila melanogaster function in morphogenesis and host defense. Mammalian orthologues of Toll, the Toll-like receptors (TLRs), have been studied extensively for their essential functions in controlling innate and adaptive immune responses. We report that TLR8 is dynamically expressed during mouse brain development and localizes to neurons and axons. Agonist stimulation of TLR8 in cultured cortical neurons causes inhibition of neurite outgrowth and induces apoptosis in a dissociable manner. Our evidence indicates that such TLR8-mediated neuronal responses do not involve the canonical TLR–NF-κB signaling pathway. These findings reveal novel functions for TLR8 in the mammalian nervous system that are distinct from the classical role of TLRs in immunity

Early cost-utility analysis of tissue-engineered heart valves compared to bioprostheses in the aortic position in elderly patients

__Objectives:__ Aortic valve disease is the most frequent indication for heart valve replacement with the highest prevalence in elderly. Tissue-engineered heart valves (TEHV) are foreseen to have important advantages over currently used bioprosthetic heart valve substitutes, most importantly reducing valve degeneration with subsequent reduction of re-intervention. We performed early Health Technology Assessment of hypothetical TEHV in elderly patients (≥ 70 years) requiring surgical (SAVR) or transcatheter aortic valve implantation (TAVI) to assess the potential of TEHV and to inform future development decisions. __Methods:__ Using a patient-level simulation model, the potential cost-effectiveness of TEHV compared with bioprostheses was predicted from a societal perspective. Anticipated, but currently hypothetical improvements in performance of TEHV, divided in durability, thrombogenicity, and infection resistance, were explored in scenario analyses to estimate quality-adjusted life-year (QALY) gain, cost reduction, headroom, and budget impact. __Results:__ Durability of TEHV had the highest impact on QALY gain and costs, followed by infection resistance. Improved TEHV performance (− 50% prosthetic valve-related events) resulted in lifetime QALY gains of 0.131 and 0.043, lifetime cost reductions of €639 and €368, translating to headrooms of €3255 and €2498 per hypothetical TEHV compared to SAVR and TAVI, respectively. National savings in the first decade after implementation varied between €2.8 and €11.2 million (SAVR) and €3.2–€12.8 million (TAVI) for TEHV substitution rates of 25–100%. __Conclusions:__ Despite the relatively short life expectancy of elderly patients undergoing SAVR/TAVI, hypothetical TEHV are predicted to be cost-effective compared to bioprostheses, commercially viable and result in national cost savings when biomedical engineers succeed in realising improved durability and/or infection resistance of TEHV

Clinical Implications of High MET Gene Dosage in Non-Small Cell Lung Cancer Patients without Previous Tyrosine Kinase Inhibitor Treatment

Introduction:Recently, two studies revealed that MET amplification was associated with secondary epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC) patients. But it remains uncertain whether MET amplification could be related to primary TKI resistance in NSCLC because of limited data.Materials and Methods:MET gene dosage of the tumor tissues from 208 NSCLC patients was investigated by real time quantitative polymerase chain reaction and compared with molecular and clinical features, including EGFR mutations, KRAS mutations, EGFR gene copy numbers, and patient survivals. Three copies were used as the cutoff. Among them, 25 patients were also evaluable for EGFR TKI responsiveness.Results:The proportion of high MET gene dosage was 10.58% (22/208) with higher incidence in squamous cell carcinoma (11.86%) and smokers (16.18%), although the differences with adenocarcinoma and nonsmokers were nonsignificant. Coexisting EGFR mutations were identified, and the incidence (8.54%) was similar to wild type (12.0%). High MET gene dosage was significantly associated with higher tumor stage (stage I + II versus stage III + IV; p = 0.0254) and prior chemotherapy for stage III + IV adenocarcinoma patients (35.71% versus 7.41%; p = 0.0145) but not correlated with primary TKI resistance. Among the 155 surgically resectable patients (stage I to IIIA), high MET gene dosage was significantly associated with shorter median survival (21.0 months versus 47.1 months; p = 0.042) by univariate analysis.Conclusions:High MET gene dosage was not related to primary TKI resistance and the incidence was increased after chemotherapy, suggesting high MET gene dosage may also be related to chemotherapy resistance

Identification of the target self-antigens in reperfusion injury

Reperfusion injury (RI), a potential life-threatening disorder, represents an acute inflammatory response after periods of ischemia resulting from myocardial infarction, stroke, surgery, or trauma. The recent identification of a monoclonal natural IgM that initiates RI led to the identification of nonmuscle myosin heavy chain type II A and C as the self-targets in two different tissues. These results identify a novel pathway in which the innate response to a highly conserved self-antigen expressed as a result of hypoxic stress results in tissue destruction

Perceptions of social media challenges and benefits during the Covid-19 pandemic: Qualitative findings from a cross sectional international survey

Since the beginning of the Covid-19 pandemic in January 2020 the need for rapid information spread grew and social media became the ultimate platform for information exchange as well as a tool for connection and entertainment. With the rapid information spread along came the various public misconceptions and misinformation which consequently influenced perceptions and behaviors of the public towards the coronavirus pandemic. Thus, there was a need for identification and collation of public perceptions information to address future public health initiatives. This cross-national study aimed to examine the challenges and benefits of using social media during the Covid-19 pandemic outbreak. This study was a content analysis of the open-ended questions from a wider cross-sectional online survey conducted in Norway, UK, USA, and Australia during October/November 2020. 2368 participants out of 3474 respondents to the survey provided the open text responses included in the qualitative analysis. Thematic analysis was conducted independently by two researchers. All statements were coded to positive and negative sentiments. Three overarching themes were identified: 1. Mental health and emotional exhaustion 2. Information and misinformation; 3. Learning and inspiration.While providing a powerful mode of connection during the pandemic, social media also led to negative impact on public perceptions, including mistrust and confusion. Clarity in communications by institutions and education about credible information sources should be considered in the future. Further research is required in exploring and documenting social media narratives around COVID-19 in this and any subsequent incidents of pandemic restrictions. Understanding the public perceptions and their social narratives can support the designing of appropriate support and services for people in the future, while acknowledging the uncertainty and overwhelming impact of the pandemic that may have skewed the experiences of social media