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Stalled mRNA translation results in the production of incompletely synthesized proteins that are targeted for degradation by ribosome-associated quality control (RQC). Here we investigated the fate of defective proteins translated from stall-inducing, nonstop mRNA that escape ubiquitylation by the RQC protein LTN1. We found that nonstop protein products accumulated in nucleoli and this localization was driven by polylysine tracts produced by translation of the poly(A) tails of nonstop mRNA. Nucleolar sequestration increased the solubility of invading proteins but disrupted nucleoli, altering their dynamics, morphology, and resistance to stress in cell culture and intact flies. Our work elucidates how stalled translation may affect distal cellular processes and may inform studies on the pathology of diseases caused by failures in RQC and characterized by nucleolar stress.
Many studies about bariatric surgery have analyzed the effect of sleeve gastrectomy (SG) on glucose improvement, beta-cell mass, and islet size modification. The effects of SG on the other endocrine cells of the pancreas, such as the alpha-cell population, and their regulatory mechanisms remain less studied.
We focused our work on the changes in the alpha-cell population after SG in a healthy model of Wistar rats. We measured alpha-cell mass, glucose tolerance, and insulin release after oral glucose tolerance tests and plasma glucagon secretion patterns after insulin infusion. Three Wistar rat groups were employed SG-operated, surgical control (Sham), and fasting control.
The results obtained showed significant increases in the alpha-cell population after SG. The result was an increase in beta-cell transdifferentiation; it was shown by some expressed molecules (the loss of expression of Pdx-1 and the increase in Arx and Pax6 cells/mm
of islet). The serum results were enhanced plasma glucagon secretion pattern after insulin infusion assays and normal glucose tolerance and insulin release after OGTT.
We concluded that SG leads to an expansion of the alpha-cell population, at expense of beta-cell; this expansion of alpha-cells is related to transdifferentiation. Plasma glucose level was not affected due to an increased glucagon response.
We concluded that SG leads to an expansion of the alpha-cell population, at expense of beta-cell; this expansion of alpha-cells is related to transdifferentiation. Plasma glucose level was not affected due to an increased glucagon response.
Gastrogastric fistulae (GGF) occur in 1-6% of Roux-en-Y gastric bypass (RYGB) patients. Many patients undergo abdominal computed tomography (CT) as an initial test owing to its wide availability; however, CT diagnostic accuracy for GGF is unclear. Our aim was to evaluate test characteristics of abdominal CT compared to upper gastrointestinal series (UGI) and esophagogastroduodenoscopy (EGD) for diagnosing GGF using surgery as a gold standard.
Retrospective review of RYGB patients who underwent abdominal CT with oral contrast within 1 year. Demographics, weight parameters, and symptoms were collected. Surgery within 1 year of the diagnostic tests was included as the gold standard comparison. Primary outcomes included CT sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy (DA) for GGF.
One hundred thirty-seven patients were included, where 42 (30.1%) had positive CT and 95 (69.3%) had negative CT for GGF. Compared to surgical confirmation, CT abdomen with PO contrast had sensitivity of 73.1% (59-84.4), specificity of 95.2% (88.3-98.7), PPV 90.5% (77.4-97.3), NPV of 85.1% (76.3-91.2), and DA 89.7%. UGI series had sensitivity of 58.5% (42.1-73.7), specificity of 98.8% (93.5-99.9), PPV of 96% (79.7-99.9), NPV of 82.8% (73.9-89.7), and diagnostic accuracy (DA) of 85.4%. EGD had sensitivity of 78.3% (63.6-89.1), specificity of 98.8% (93.5-99.9), PPV 97.3 (85.8-99.9), and DA 91.5%. There were no significant differences in diagnostic test characteristics among modalities.
Abdominal CT with oral contrast has similar diagnostic test characteristics to UGI and EGD at detecting GGF when using surgical diagnosis as a gold standard.
Abdominal CT with oral contrast has similar diagnostic test characteristics to UGI and EGD at detecting GGF when using surgical diagnosis as a gold standard.
To evaluate the reliability and agreement between Fully Refocused Steady-State magnetic resonance sequences (FRSS) and the IOLMaster
500 optical biometer for measuring anterior chamber depth (ACD) and axial length (AL).
In a sample of 32 healthy volunteers, separate observers measured the ACD and AL of both eyes using both techniques (inter-method) and through repeated FRSS measurements (interobserver) and by the same observer (intraobserver). We employed the Bland-Altman method to determine the agreement between FRSS and partial coherence interferometry (using the IOLMaster
) and the interobserver and intraobserver variability, providing the limits of agreement (LoA, or mean difference ± 1.96 SD). Correlation coefficients and intraclass correlation coefficients were also provided.
For ACD measurements with FRSS in pseudo-color scale, we obtained an LoA of 0.016 ± 0.266mm compared with partial coherence interferometry. For AL with FRSS in greyscale, the LoA was 0.019 ± 0.383mm. Maximum interobserver variability showed a - 0.036 ± 0.247mm LoA for ACD with FRSS in pseudo-color scale. Maximum intraobserver variability was 0.000 ± 0.157mm LoA for AL with FRSS in greyscale.
ACD and AL measurements using FRSS sequencing present high LoA and reliability when compared with partial coherence interferometry using the IOLMaster
500. The results were better for FRSS in pseudo-color scale in ACD determination and for FRSS in greyscale in AL determination. FRSS would not be recommended for IOL power calculation due to variability of AL measurement.
ACD and AL measurements using FRSS sequencing present high LoA and reliability when compared with partial coherence interferometry using the IOLMaster® 500. Oxythiaminechloride The results were better for FRSS in pseudo-color scale in ACD determination and for FRSS in greyscale in AL determination. FRSS would not be recommended for IOL power calculation due to variability of AL measurement.
Website: https://www.selleckchem.com/products/oxythiamine-chloride-hydrochloride.html
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