Endoplasmic reticulum (ER) stress and apoptotic cell death play an important role in the pathogenesis and perpetuation of inflammatory bowel disease (IBD). We aimed to explore the potential of ...glutamine to reduce ER stress and apoptosis in a rat model of experimental IBD. Colitis was induced in male Wistar rats by intracolonic administration of 30 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Glutamine (25 mg/dL) was given by rectal route daily for 2 d or 7 d. Both oxidative stress (TBARS concentration and oxidised/reduced glutathione ratio) and ER stress markers (CHOP, BiP, calpain-1 and caspase-12 expression) increased significantly within 48 h of TNBS instillation, and glutamine attenuated the extent of the changes. Glutamine also inhibited the significant increases of ATF6, ATF4 and spliced XBP-1 mRNA levels induced by TNBS instillation. TNBS-colitis resulted in a significant increase in p53 and cytochrome c expression, and a reduced Bcl-xL expression and Bax/Bcl-2 ratio. These effects were significantly inhibited by glutamine. Treatment with the amino acid also resulted in significant decreases of caspase-9, caspase-8 and caspase-3 activities. Double immunofluorescence staining showed co-localization of CHOP and cleaved caspase-3 in colon sections. Phospho-JNK and PARP-1 expression was also significantly higher in TNBS-treated rats, and treatment with glutamine significantly decreased JNK phosphorylation and PARP-1 proteolysis. To directly address the effect of glutamine on ER stress and apoptosis in epithelial cells, the ER stress inducers brefeldin A and tunicamycin were added to Caco-2 cells that were treated with glutamine (5 mM and 10 mM). The significant enhancement in PERK, ATF6 phosphorylated IRE1, BiP and cleaved caspase-3 expression induced by brefeldin A and tunicamycin was partly prevented by glutamine. Data obtained indicated that modulation of ER stress signalling and anti-apoptotic effects contribute to protection by glutamine against damage in TNBS-induced colitis.
This paper presents a fiducial marker system specially appropriated for camera pose estimation in applications such as augmented reality and robot localization. Three main contributions are ...presented. First, we propose an algorithm for generating configurable marker dictionaries (in size and number of bits) following a criterion to maximize the inter-marker distance and the number of bit transitions. In the process, we derive the maximum theoretical inter-marker distance that dictionaries of square binary markers can have. Second, a method for automatically detecting the markers and correcting possible errors is proposed. Third, a solution to the occlusion problem in augmented reality applications is shown. To that aim, multiple markers are combined with an occlusion mask calculated by color segmentation. The experiments conducted show that our proposal obtains dictionaries with higher inter-marker distances and lower false negative rates than state-of-the-art systems, and provides an effective solution to the occlusion problem.
•We propose an algorithm for generating configurable marker dictionaries.•We derive the maximum theoretical inter-marker distance.•A method for automatically detecting the markers and correcting errors is proposed.•A solution to the occlusion problem in augmented reality applications is shown.
Muscle coordination studies repeatedly show low-dimensionality of muscle activations for a wide variety of motor tasks. The basis vectors of this low-dimensional subspace, termed muscle synergies, ...are hypothesized to reflect neurally-established functional muscle groupings that simplify body control. However, the muscle synergy hypothesis has been notoriously difficult to prove or falsify. We use cadaveric experiments and computational models to perform a crucial thought experiment and develop an alternative explanation of how muscle synergies could be observed without the nervous system having controlled muscles in groups. We first show that the biomechanics of the limb constrains musculotendon length changes to a low-dimensional subspace across all possible movement directions. We then show that a modest assumption--that each muscle is independently instructed to resist length change--leads to the result that electromyographic (EMG) synergies will arise without the need to conclude that they are a product of neural coupling among muscles. Finally, we show that there are dimensionality-reducing constraints in the isometric production of force in a variety of directions, but that these constraints are more easily controlled for, suggesting new experimental directions. These counter-examples to current thinking clearly show how experimenters could adequately control for the constraints described here when designing experiments to test for muscle synergies--but, to the best of our knowledge, this has not yet been done.
Childhood obesity has reached epidemic levels and is a serious health concern associated with metabolic syndrome, nonalcoholic fatty liver disease, and gut microbiota alterations. Physical exercise ...is known to counteract obesity progression and modulate the gut microbiota composition. This study aims to determine the effect of a 12-week strength and endurance combined training program on gut microbiota and inflammation in obese pediatric patients. Thirty-nine obese children were assigned randomly to the control or training group. Anthropometric and biochemical parameters, muscular strength, and inflammatory signaling pathways in mononuclear cells were evaluated. Bacterial composition and functionality were determined by massive sequencing and metabolomic analysis. Exercise reduced plasma glucose levels and increased dynamic strength in the upper and lower extremities compared with the obese control group. Metagenomic analysis revealed a bacterial composition associated with obesity, showing changes at the phylum, class, and genus levels. Exercise counteracted this profile, significantly reducing the Proteobacteria phylum and Gammaproteobacteria class. Moreover, physical activity tended to increase some genera, such as Blautia, Dialister, and Roseburia, leading to a microbiota profile similar to that of healthy children. Metabolomic analysis revealed changes in short-chain fatty acids, branched-chain amino acids, and several sugars in response to exercise, in correlation with a specific microbiota profile. Finally, the training protocol significantly inhibited the activation of the obesity-associated NLRP3 signaling pathway. Our data suggest the existence of an obesity-related deleterious microbiota profile that is positively modified by physical activity intervention. Exercise training could be considered an efficient nonpharmacological therapy, reducing inflammatory signaling pathways induced by obesity in children via microbiota modulation.
Background and purpose
Specific respiratory tract infections, including COVID‐19, may cause smell and/or taste disorders (STDs) with increased frequency. The aim was to determine whether new‐onset ...STDs are more frequent amongst COVID‐19 patients than influenza patients.
Method
This was a case–control study including hospitalized patients of two tertiary care centres. Consecutive patients positive for COVID‐19 polymerase chain reaction (cases) and patients positive for influenza polymerase chain reaction (historical control sample) were assessed during specific periods, employing a self‐reported STD questionnaire.
Results
Seventy‐nine cases and 40 controls were included. No significant differences were found in basal features between the two groups. New‐onset STDs were significantly more frequent amongst cases (31, 39.2%) than in the control group (5, 12.5 %) adjusted odds ratio 21.4 (2.77–165.4, P = 0.003). COVID‐19 patients with new‐onset STDs were significantly younger than COVID‐19 patients without STDs (52.6 ± 17.2 vs. 67.4 ± 15.1, P < 0.001). Amongst COVID‐19 patients who presented STDs, 22 (70.9%) recalled an acute onset and it was an initial manifestation in 11 (35.5%). Twenty‐five (80.6%) presented smell disorders (mostly anosmia, 14, 45.2%) and 28 (90.3%) taste disorders (mostly ageusia, 14, 45.2%). Only four (12.9 %) reported concomitant nasal obstruction. The mean duration of STD was 7.5 ± 3.2 days and 12 patients (40%) manifested complete recovery after 7.4 ± 2.3 days of onset.
Conclusion
New‐onset STDs were significantly more frequent amongst COVID‐19 patients than influenza patients; they usually had an acute onset and were commonly an initial manifestation. The use of STD assessment in anamnesis as a hint for COVID‐19 and to support individuals’ self‐isolation in the current epidemic context is suggested.
The endoplasmic reticulum (ER) is a dynamic and multifunctional organelle responsible for protein biosynthesis, folding, assembly and modifications. Loss of protein folding regulation, which leads to ...unfolded or misfolded proteins accumulation inside the ER lumen, drives ER stress (ERS) and unfolded protein response (UPR) activation. During aging, there is a decline in the ability of the cell to handle protein folding, accumulation and aggregation, and the function of UPR is compromised. There is a progressive failure of the chaperoning systems and a decline in many of its components, so that the UPR activation cannot rescue the ERS. Physical activity has been proposed as a powerful tool against aged-related diseases, which are linked to ERS. Interventional studies have demonstrated that regular exercise is able to decrease oxidative stress and inflammation and reverse mitochondrial and ER dysfunctions. Exercise-induced metabolic stress could activate the UPR since muscle contraction is directly involved in its activation, mediating exercise-induced adaptation responses. In fact, regular moderate-intensity exercise-induced ERS acts as a protective mechanism against current and future stressors. However, biological responses vary according to exercise intensity and therefore induce different degrees of ERS and UPR activation. This article reviews the effects of aging and exercise on ERS and UPR, also analyzing possible changes induced by different types of exercise in elderly subjects.
Summary
COVID‐19 is an infectious disease caused by severe acute respiratory coronavirus 2 (SARS‐CoV‐2). Vesicular skin rashes have been reported as associated with COVID‐19, but there is little ...information about this cutaneous manifestation. We designed a prospective observational study of patients diagnosed with COVID‐19 who had vesicular lesions. Clinical characterization of skin findings was conducted by dermatologists. When possible, histological analysis and detection of SARS‐CoV‐2 in the content of the vesicles was performed. In total, 24 patients were included. A disseminated pattern was found in 18 patients (75%), and a localized pattern was found in 6 (25%). Median duration of the skin rash was 10 days. Of the 24 patients, 19 (79.2%) developed the skin rash after the onset of COVID‐19 symptoms. Histological examination in two patients was consistent with viral infection, SARS‐CoV‐2 was not detected in four patients. This single‐centre study shows the clinical characteristics of vesicular skin rashes in patients with COVID‐19.
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