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Bioinformatics Insights on the Physicochemical Properties of SCN5A Mutant Proteins Associated with the Brugada Syndrome
Background: The Brugada syndrome (BrS) is a heart rhythm condition that is commonly associated with a strong predisposition for sudden cardiac death. Malignant ventricular arrhythmias could occur secondary to the dysfunction of the cardiac sodium voltage-gated Na(v)1.5 channel (SCN5A).
Objective: This study aimed to perform a multiparametric computational analysis of the physicochemical properties of SCN5A mutants associated with BrS using a set of bioinformatics tools.
Methods: In-house algorithms were calibrated to calculate, in a double-blind test, the Polarity Index Method (PIM) profile and protein intrinsic disorder predisposition (PIDP) profile of each sequence, and computer programs specialized in the genomic analysis were used.
Results: Specific regularities in the charge/polarity and PIDP profile of the SCN5A mutant proteins enabled the re-creation of the taxonomy, allowing us to propose a bioinformatics method that takes advantage of the PIM profile to identify this group of proteins from their sequence.
Conclusion: Bioinformatics programs could reproduce characteristic PIM and PIDP profiles of the BrS-related SCN5A mutant proteins. This information can contribute to a better understanding of these altered proteins
Current Therapeutic Approaches and Promising Perspectives of Using Bioengineered Peptides in Fighting Chemoresistance in Triple-negative Breast Cancer
Breast cancer is a collation of malignancies that manifest in the mammary glands at the early stages. Among breast cancer subtypes, triple-negative breast cancer (TNBC) shows the most aggressive behavior, with apparent stemness features. Owing to the lack of response to hormone therapy and specific targeted therapies, chemotherapy remains the first line of the TNBC treatment. However, the acquisition of resistance to chemotherapeutic agents increase therapy failure, and promotes cancer recurrence and distant metastasis. Invasive primary tumors are the birthplace of cancer burden, though metastasis is a key attribute of TNBC-associated morbidity and mortality. Targeting the chemoresistant metastases-initiating cells via specific therapeutic agents with affinity to the upregulated molecular targets is a promising step in the TNBC clinical management. Exploring the capacity of peptides as biocompatible entities with the specificity of action, low immunogenicity, and robust efficacy provides a principle for designing peptide-based drugs capable of increasing the efficacy of current chemotherapy agents for selective targeting of the drug-tolerant TNBC cells. Here, we first focus on the resistance mechanisms that TNBC cells acquire to evade the effect of chemotherapeutic agents. Next, the novel therapeutic approaches employing tumor-targeting peptides to exploit the mechanisms of drug resistance in chemorefractory TNBC are described
GNSI Decision Brief: Who Will Rebuild Ukraine\u27s Public Health and Disease Research Laboratories?
Amid the devastating war in Ukraine, a parallel battle rages on – that against infectious diseases. The COVID-19 pandemic starkly underlined the vital importance of global health surveillance for emerging and re-emerging human and animal pathogens. This challenge has become even more acute in war-torn regions like Ukraine, where healthcare infrastructure is under siege. For viruses with pandemic potential, such as the influenza virus, worldwide surveillance initiatives are essential in tracking the virus’s movement and spread among both animals and humans. Such monitoring serves dual purposes. Firstly, it guides the formulation of the yearly vaccine, ensuring it remains effective against prevailing strains. Secondly, it alerts livestock farmers in advance, enabling the timely rollout of mitigation measures. Moreover, discerning whether a disease outbreak is of natural origin, or an intentional release becomes critical. To achieve this, the global community must share transparent and timely information through a robust network of laboratories with cutting-edge biotechnological capabilities. The war’s ramifications have severely impacted these efforts. Yet, the stakes are too high to let these facilities fade away. This situation leads to the ultimate question: Who will step up to rebuild Ukraine’s public health and disease research laboratories?https://digitalcommons.usf.edu/gnsi_decision_briefs/1007/thumbnail.jp
Evaluation of a Story-telling Approach to Educate Minority Populations About Inherited Cancer
Utilization of hereditary cancer genetic counseling and testing services is substantially lower among minority populations compared to white populations due, in part, to lower levels of awareness and knowledge. To help improve awareness, we designed a 7-minute video that uses storytelling to translate knowledge of genetic testing and hereditary cancer to individuals who have a personal history or family history of cancer. Consented participants were asked baseline questions about hereditary cancer and genetic testing, reviewed the video, and provided feedback on its content, understandability, and visual appeal during semi-structured interviews. Data were coded and analyzed to identify themes and determine whether the educational materials addressed some of the perceived obstacles to genetic testing that were raised by participants. Analysis of 13 coded interview transcripts suggest the video may improve self-efficacy to access genetic testing because it addressed some barriers related to cost of genetic testing and the information was easy to understand. After viewing the video, a majority of participants indicated that pursuing genetic testing would be useful. Multiple participants appreciated the logical, concise flow of the video, stated that it increased their knowledge on genetic testing for hereditary cancer, and asked for more information on possible next steps. Most participants reported needing more information about whether their personal insurance plans would cover genetic testing and about the logistics of obtaining the DNA sample before they would take action to pursue genetic counseling or testing. Based on constructive feedback, we added links to more information and listed possible next steps people could take to learn more or to obtain genetic counseling and testing
Robotic Arm Manipulator Control for SG5-UT
This paper presents a complete forward and inverse kinematics solution for SG5-UT, 5 DOF robotic arm. The solution is intended to be implemented on a microprocessor to control the arm in any environment. The control presented in the paper makes it possible to manipulate the arm to any reachable position. The algorithm derived in this paper has been successfully tested on the arm. This arm is analyzed for the purposes of being mounted on a humanoid robot, called Gnuman
The sounds of travel: video ethnography in multisensory tourism research
While the analysis of the tourist experience often relies on the visual representations, recent research also increasingly calls for a multisensory understanding of tourism research. Soundscapes are an emerging type of tourism attraction that contributes to the protection and promotion of the sense of place. Departing from the use of video in ethnographic practice, this research notes illustrates the features of soundscapes in nature-based tourism research based on video auto-ethnography. Results show that the sounds of water, animals and gastronomy are evocative of people, places and practices in nature-based tourism experiences
Blood and Concrete: 21st Century Conflict in Urban Centers and Megacities. Edited by Dave Dilegge, Robert J. Bunker, John P. Sullivan, and Alma Keshavarz. Bloomington, IN: Xlibris, 2019.
Fragmented Hours: The biography of a devotional book printed by Thielman Kerver
As the most richly illustrated and widely-owned texts of the late medieval and early modern eras, books of hours are essential to the study of art, religion, and the history of the book. Fragmented and damaged books, while perhaps less coveted, are of particular value to researchers for what they may reveal about their owners as well as the changing meanings of devotional texts and images over more than five centuries of use. This thesis explores the compelling biography of a damaged book of hours preserved in the University of Florida Library. The book has undergone such extensive alteration prior to its acquisition in 1989 that cataloguers could not even identify its printer or edition. This ambiguity prevented the book from receiving the scholarly attention that it deserves, leaving its many removals and deletions unexplored. Informed by scholarship on the social history of books of hours, I identify this fragmented book as a possible copy of an edition produced by Thielman Kerver in Paris on April 5, 1511, and reconstruct its missing contents through comparison with relevant editions. This identification allows me to examine the layers of the book’s complex damage in the context of sixteenth-century religious reform before turning to the book’s dislocations and the spoliation of images in the context of nineteenth and twentieth-century collecting trends in the United States and Europe
Predicting Groundwater Spring Locations from Topographic and Climatic Data Using Maxent Modeling
The World Resources Institute reveals that 17 countries face extremely high levels of water stress. Moreover, with increasing population and industrialization, the gap between water supply and demand increases day by day around the world. Groundwater is a key freshwater source, and springs are important resources as they enable to access groundwater. Therefore, it is crucial to monitor, protect, and manage groundwater springs. The first step in spring management is to recognize and define freshwater resources and to determine the locations of groundwater springs that serve as natural discharge points. Traditionally, field studies have been employed to determine the locations of springs. However, in some cases, fieldwork can be difficult, expensive, or even impossible. In this study, one of the general-purpose machine learning approaches, Maxent modeling, was used to predict the locations of springs in Florida, Oklahoma, and Kentucky, U.S.A., using topographic and bioclimatic data. Elevation, slope, flow weighted slope, distance to flowlines, planform curvature, profile curvature, CaCO3, sand, silt, clay, topographic wetness index, rainfall, and terrain ruggedness index data were used to predict spring locations. The goal of the study was to both determine if Maxent modeling can accurately predict spring locations in diverse geographic areas and to identify which environmental factors are the most predictive. For Florida, Kentucky, and Oklahoma, respectively, the model yielded AUC values of 0.89, 0.72, and 0.92. Distance to the river was the most important model contributor in Florida, with clay soil in Kentucky and profile curvature in Oklahoma
Lithium and Lithium Isotope Behavior During High Temperature Solid/Fluid Exchanges: Examples from Iceland and the Izu-Bonin Forearc
The development of a method for lithium isotopic measurement was developed using a quadrupole, single-collector ICP-MS. Measured precision was ±1.00‰ 2σ over a 15-month period based on measurements of international rock standards. A 1-hour leach using cold, HCl was sufficient to remove alteration-related Li in minimally to moderately altered seafloor basalts. Measurements on the Holocene ages lavas from the neovolcanic zones of Iceland suggest no systematic Li isotopic variability among the differing Icelandic sources. Felsic samples from Hekla and Pumice contain elevated Li contents of \u3e18ug/g while the tholeiitic and alkaline basalts are \u3c8ug/g Li. Most of the island lies around MORB values of ~+3 to +5‰ with the exception of Western Volcanic Zone samples that show evidence for seawater inputs. The RN-17 drillcore, which penetrates \u3e3000m through a hydrothermal system in the Reykjanes Peninsula, shows δ7Li changes with depth. based on temperature and mineral assemblage, with no overall changes in Li abundance. Samples from \u3c800m show δ7Li up to +8.5 ‰, while deeper chlorite-epidote and epidote-actinolite facies sections preserve MORB-like values. The deepest amphibolite-facies sections of the core range to the highest observed δ7Li (up to +12 ‰). A subduction initiation volcanic sequence of forearc basalts (FABs) and boninites from the Izu-Bonin subduction system, which were sampled during IODP Expedition 352, have elevated Li/Yb ratios, suggesting subduction-related Li enrichments. δ7Li in FABs varies, from values up to +10‰ in the deepest samples to MORB-like values upsection. Boninite δ7Li signatures are mostly higher than MORBs, reaching values of +14‰, with no clear difference between older Low Silica (+8.4‰) and late-stage High Silica boninites (+8.0‰). δ7Li systematics and Li-trace element ratios point to the influence of a higher-temperature slab-derived component in boninite and FAB petrogenesis consistent with the involvement of amphibole, a finding that is to a first order consistent with observations in the altered Icelandic basalts