The paradigms of Industry 4.0 and Industrial Internet of Things (IIoT) require functional architectures to deploy and organize hardware and software taking advantage of modern digital technologies in industrial systems. In this sense, a lot of the literature proposes and describes this type of architecture with a conceptual angle, without providing experimental validation or with scarce details about the involved equipment under real operation.
View Article and Find Full Text PDFAnimals optimize behavior by integrating sensory input with motor actions. We hypothe-sized that coupling thermosensory information with motor output enhances the brain's capacity to process temperature changes, leading to more precise and adaptive behaviors. To test this, we developed a virtual "thermal plaid" environment where zebrafish either actively controlled temperature changes (sensorimotor feedback) or passively experienced the same thermal fluctuations.
View Article and Find Full Text PDFCRISPR-based gene activation (CRISPRa) is a strategy for upregulating gene expression by targeting promoters or enhancers in a tissue/cell-type specific manner. Here, we describe an experimental framework that combines highly multiplexed perturbations with single-cell RNA sequencing (sc-RNA-seq) to identify cell-type-specific, CRISPRa-responsive cis-regulatory elements and the gene(s) they regulate. Random combinations of many gRNAs are introduced to each of many cells, which are then profiled and partitioned into test and control groups to test for effect(s) of CRISPRa perturbations of both enhancers and promoters on the expression of neighboring genes.
View Article and Find Full Text PDFBackground: Hypofractionated radiotherapy in the treatment of prostate cancer has been widely studied. However, in the postoperative setting it has been less explored. The objective of this prospective study is to evaluate the safety and efficacy of hypofractionated radiotherapy in postoperative prostate cancer.
View Article and Find Full Text PDFSurvival for children with cancer has primarily improved over the past decades due to refinements in surgery, radiation and chemotherapy. Although these general therapies are sometimes curative, the cancer often recurs, resulting in poor outcomes for patients. Fusion-driven pediatric soft tissue sarcomas are genetically defined by chromosomal translocations that create a chimeric oncogene.
View Article and Find Full Text PDFThe inability to scalably and precisely measure the activity of developmental cis-regulatory elements (CREs) in multicellular systems is a bottleneck in genomics. Here we develop a dual RNA cassette that decouples the detection and quantification tasks inherent to multiplex single-cell reporter assays. The resulting measurement of reporter expression is accurate over multiple orders of magnitude, with a precision approaching the limit set by Poisson counting noise.
View Article and Find Full Text PDFWe set out to exhaustively characterize the impact of the cis-chromatin environment on prime editing, a precise genome engineering tool. Using a highly sensitive method for mapping the genomic locations of randomly integrated reporters, we discover massive position effects, exemplified by editing efficiencies ranging from ∼0% to 94% for an identical target site and edit. Position effects on prime editing efficiency are well predicted by chromatin marks, e.
View Article and Find Full Text PDFObjective: To assess the mental health status and associated factors of Peruvian medical students during the COVID-19 pandemic.
Methods: Descriptive, multicentre, correlational study that used the "Patient Health Questionnaire-9 (PHQ-9)", the "Generalized Anxiety Disorder-7 (GAD-7)" and the "Impact of Event Scale-Revised (IES-R)" questionnaires to evaluate mental health problems.
Results: A total of 1,238 students from 8 Peruvian medical schools participated in the study.
Alcohol consumption activates the neuroimmune system of the brain, a system in which brain astrocytes and microglia play dominant roles. These glial cells normally produce low levels of neuroimmune factors, which are important signaling factors and regulators of brain function. Alcohol activation of the neuroimmune system is known to dysregulate the production of neuroimmune factors, such as the cytokine IL-6, thereby changing the neuroimmune status of the brain, which could impact the actions of alcohol.
View Article and Find Full Text PDFClinical sequencing efforts continue to identify novel putative oncogenes with limited strategies to perform functional validation in vivo and study their role in tumorigenesis. Here, we present a pipeline for fusion-driven rhabdomyosarcoma (RMS) in vivo modeling using transgenic zebrafish systems. This strategy originates with novel fusion-oncogenes identified from patient samples that require functional validation in vertebrate systems, integrating these genes into the zebrafish genome, and then characterizing that they indeed drive rhabdomyosarcoma tumor formation.
View Article and Find Full Text PDFObjective: To report outcomes of the human acellular vessel (HAV) implanted for limb salvage through the Food and Drug Administration (FDA) Expanded Access Program for patients with chronic limb-threatening ischemia with no autologous conduit.
Methods: The HAV is a bioengineered vascular conduit designed with human vascular smooth muscle cells. The product is under regulatory study.
Prime editing is a powerful means of introducing precise changes to specific locations in mammalian genomes. However, the widely varying efficiency of prime editing across target sites of interest has limited its adoption in the context of both basic research and clinical settings. Here, we set out to exhaustively characterize the impact of the chromatin environment on prime editing efficiency.
View Article and Find Full Text PDFThe regulation of neurons by circadian clock genes is thought to contribute to the maintenance of neuronal functions that ultimately underlie animal behavior. However, the impact of specific circadian genes on cellular and molecular mechanisms controlling synaptic plasticity and cognitive function remains elusive. Here, we show that the expression of the circadian protein TIMELESS displays circadian rhythmicity in the mammalian hippocampus.
View Article and Find Full Text PDFCRISPR-based gene activation (CRISPRa) is a promising therapeutic approach for gene therapy, upregulating gene expression by targeting promoters or enhancers in a tissue/cell-type specific manner. Here, we describe an experimental framework that combines highly multiplexed perturbations with single-cell RNA sequencing (sc-RNA-seq) to identify cell-type-specific, CRISPRa-responsive regulatory elements and the gene(s) they regulate. Random combinations of many gRNAs are introduced to each of many cells, which are then profiled and partitioned into test and control groups to test for effect(s) of CRISPRa perturbations of both enhancers and promoters on the expression of neighboring genes.
View Article and Find Full Text PDFSilver carp (Hypophthalmichthys molitrixi) was processed by sous-vide method at different temperatures (60, 65, 70, and 75°C). Then, the microbiological quality of the processed samples was monitored during cold storage (4°C) for 21 days. The target microorganisms were Enterobacteriaceae, Lactic Acid bacteria (LAB), Pseudomonas, Psychrotrophs, and total viable count (TVC).
View Article and Find Full Text PDFHES3 is a basic helix-loop-helix transcription factor that regulates neural stem cell renewal during development. HES3 overexpression is predictive of reduced overall survival in patients with fusion-positive rhabdomyosarcoma, a pediatric cancer that resembles immature and undifferentiated skeletal muscle. However, the mechanisms of HES3 cooperation in fusion-positive rhabdomyosarcoma are unclear and are likely related to her3/HES3's role in neurogenesis.
View Article and Find Full Text PDFClinical sequencing efforts are rapidly identifying sarcoma gene fusions that lack functional validation. An example is the fusion of transcriptional coactivators, VGLL2-NCOA2, found in infantile rhabdomyosarcoma. To delineate VGLL2-NCOA2 tumorigenic mechanisms and identify therapeutic vulnerabilities, we implement a cross-species comparative oncology approach with zebrafish, mouse allograft, and patient samples.
View Article and Find Full Text PDFMultiple studies have shown that blast injury is followed by sleep disruption linked to functional sequelae. It is well established that improving sleep ameliorates such functional deficits. However, little is known about longitudinal brain activity changes after blast injury.
View Article and Find Full Text PDFCocoa (Theobroma cacao L.) is the only tree that can produce cocoa. Cocoa beans are highly sought after by chocolate makers to produce chocolate.
View Article and Find Full Text PDFObjective: To evaluate degree of metabolic control and treatment regimens in patients with type 1 diabetes mellitus (T1DM) enrolled in the DIACAM1 study, after 10 years of follow-up under routine clinical practice conditions.
Patients And Methods: A total of 1,465 patients enrolled in the DIACAM1 study, a multicentre, cross-sectional study conducted in Castilla-La Mancha in 2010, were analysed. Of these patients, 58 (4%) died during the 10-year follow-up period.
is a powerful, long-standing model for metazoan development and gene regulation. We profiled chromatin accessibility in almost 1 million and gene expression in half a million nuclei from overlapping windows spanning the entirety of embryogenesis. Leveraging developmental asynchronicity within embryo collections, we applied deep neural networks to infer the age of each nucleus, resulting in continuous, multimodal views of molecular and cellular transitions in absolute time.
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