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Chromosomal instability (CIN) is a hallmark of many cancers. Restricting the localization of centromeric histone H3 variant CENP-A to centromeres prevents CIN. CENP-A overexpression (OE) and mislocalization have been observed in cancers and correlate with poor prognosis; however, the molecular consequences of CENP-A OE on CIN and aneuploidy have not been defined. Here, we show that CENP-A OE leads to its mislocalization and CIN with lagging chromosomes and micronuclei in pseudodiploid DLD1 cells and xenograft mouse model. CIN is due to reduced localization of proteins to the kinetochore, resulting in defects in kinetochore integrity and unstable kinetochore-microtubule attachments. https://www.selleckchem.com/products/Mubritinib-TAK-165.html CENP-A OE contributes to reduced expression of cell adhesion genes and higher invasion of DLD1 cells. We show that CENP-A OE contributes to aneuploidy with karyotypic heterogeneity in human cells and xenograft mouse model. In summary, our results provide a molecular link between CENP-A OE and aneuploidy, and suggest that karyotypic heterogeneity may contribute to the aggressive phenotype of CENP-A-overexpressing cancers.JCB asks early career investigators to share their experience launching a lab during the COVID-19 pandemic.
Frail older persons may have an atypical presentation of coronavirus disease 2019 (COVID-19). The value of real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) testing for identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nursing homes (NHs) residents is not known.
To determine whether (i) atypical symptoms may predict rRT-PCR results and (ii) rRT-PCR results may predict immunisation against SARS-CoV-2 in NH residents.
A retrospective longitudinal study.
Eight NHs with at least 10 rRT-PCR-positive residents.
A total of 456 residents.
Typical and atypical symptoms recorded in residents' files during the 14days before and after rRT-PCR testing were analysed. Residents underwent blood testing for IgG-SARS-CoV-2 nucleocapsid protein 6 to 8 weeks after testing. Univariate and multivariate analyses compared symptoms and immunisation rates in rRT-PCR-positive and negative residents.
A total of 161 residents had a positive rRT-PCR (35.3%), 17.4% of whom were asympto strategy based on (i) testing residents with typical or unexplained atypical symptoms for an early identification of the first SARS-CoV-2 cases, (ii) rT-PCR testing for identifying COVID-19 residents, (iii) repeated wide-facility testing (including asymptomatic cases) as soon as a resident is tested positive for SARS-CoV-2 and (iv) implementing SARS-CoV-2 infection control measures in rRT-PCR-negative residents when they have unexplained typical or atypical symptoms.Visual translation tolerance refers to our capacity to recognize objects over a wide range of different retinal locations. Although translation is perhaps the simplest spatial transform that the visual system needs to cope with, the extent to which the human visual system can identify objects at previously unseen locations is unclear, with some studies reporting near complete invariance over 10 degrees and other reporting zero invariance at 4 degrees of visual angle. Similarly, there is confusion regarding the extent of translation tolerance in computational models of vision, as well as the degree of match between human and model performance. Here, we report a series of eye-tracking studies (total N = 70) demonstrating that novel objects trained at one retinal location can be recognized at high accuracy rates following translations up to 18 degrees. We also show that standard deep convolutional neural networks (DCNNs) support our findings when pretrained to classify another set of stimuli across a range of locations, or when a global average pooling (GAP) layer is added to produce larger receptive fields. Our findings provide a strong constraint for theories of human vision and help explain inconsistent findings previously reported with convolutional neural networks (CNNs).The visual system can predict visual features across saccades based on learned transsaccadic associations between peripheral and foveal input. This has been shown for simple visual features such as shape, size, and spatial frequency. The present study investigated whether transsaccadic predictions are also made for more complex visual stimuli. In an acquisition phase, new transsaccadic associations were established. In the first experiment, pictures of real-world objects changed category during the saccade (fruits were changed into balls or vice versa). In the second experiment, the gender of faces was manipulated during the saccade (faces changed from male to female or vice versa). In the following test phase, the stimuli were briefly presented in the periphery, and participants had to indicate which object or face, respectively, they had perceived. In both experiments, peripheral perception was biased toward the acquired associated foveal input. These results demonstrate that transsaccadic predictions are not limited to a small set of simple visual features but can also be made for more complex and realistic stimuli. Multiple new associations can be learned within a short time frame, and the resulting predictions appear to be object specific.
Major adverse cardiac events (MACE) triggered by non-cardiac surgery are prognostically important perioperative complications. However, due to often asymptomatic presentation, the incidence and timing of postoperative MACE are incompletely understood.
We conducted a prospective observational study implementing a perioperative screening for postoperative MACE [cardiovascular death (CVD), acute heart failure (AHF), haemodynamically relevant arrhythmias, spontaneous myocardial infarction (MI), and perioperative myocardial infarction/injury (PMI)] in patients at increased cardiovascular risk (≥65 years OR ≥45 years with history of cardiovascular disease) undergoing non-cardiac surgery at a tertiary hospital. All patients received serial measurements of cardiac troponin to detect asymptomatic MACE. Among 2265 patients (mean age 73 years, 43.4% women), the incidence of MACE was 15.2% within 30 days, and 20.6% within 365 days. CVD occurred in 1.2% [95% confidence interval (CI) 0.9-1.8] and in 3.7% (95% CI 3.0-4.
Homepage: https://www.selleckchem.com/products/Mubritinib-TAK-165.html
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