A conserved structural element in the RNA helicase UPF1 regulates its catalytic activity in an isoform-specific manner

The RNA helicase UPF1 is a key component of the nonsense mediated mRNA decay (NMD) pathway. Previous X-ray crystal structures of UPF1 elucidated the molecular mechanisms of its catalytic activity and regulation. In this study, we examine features of the UPF1 core and identify a structural element that adopts different conformations in the various nucleotide- and RNA-bound states of UPF1. We demonstrate, using biochemical and single molecule assays, that this structural element modulates UPF1 catalytic activity and thereby refer to it as the regulatory loop. Interestingly, there are two alternatively spliced isoforms of UPF1 in mammals which differ only in the lengths of their regulatory loops. The loop in isoform 1 (UPF11) is 11 residues longer than that of isoform 2. We find that this small insertion in UPF11 leads to a two-fold increase in its translocation and ATPase activities. To determine the mechanistic basis of this differential catalytic activity, we have determined the X-ray crystal structure of the helicase core of UPF11 in its apo-state. Our results point toward a novel mechanism of regulation of RNA helicases, wherein alternative splicing leads to subtle structural rearrangements within the protein that are critical to modulate enzyme movements and catalytic activity

Nb-substitution suppresses the superconducting critical temperature of pressurized MoB2_2

A recent work has demonstrated that MoB$_2$, transforming to the same structure as MgB$_2$ ($P6/mmm$), superconducts at temperatures above 30 K near 100 GPa [C. Pei $et$ $al$. Natl. Sci. Rev., nwad034 (2023)], and Nb-substitution in MoB$_2$ stabilizes the $P6/mmm$ structure down to ambient pressure [A. C. Hire $et$ $al$. Phys. Rev. B 106, 174515 (2022)]. The current work explores the high pressure superconducting behavior of Nb-substituted MoB$_2$ (Nb$_{0.25}$Mo$_{0.75}$B$_2$). High pressure x-ray diffraction measurements show that the sample remains in the ambient pressure $P6/mmm$ structure to at least 160 GPa. Electrical resistivity measurements demonstrate that from an ambient pressure $T_c$ of 8 K (confirmed by specific heat to be a bulk effect), the critical temperature is suppressed to 4 K at 50 GPa, before gradually rising to 5.5 K at 170 GPa. The critical temperature at high pressure is thus significantly lower than that found in MoB$_2$ under pressure (30 K), revealing that Nb-substitution results in a strong suppression of the superconducting critical temperature. Our calculations indeed find a reduced electron-phonon coupling in Nb$_{0.25}$Mo$_{0.75}$B$_2$, but do not account fully for the observed suppression, which may also arise from inhomogeneity and enhanced spin fluctuations.Comment: 8 pages, 5 figures, 1 tabl

Correction: Light intensity physical activity and sedentary behavior in relation to body mass index and grip strength in older adults: Cross-sectional findings from the lifestyle interventions and independence for elders (LIFE) study

[This corrects the article DOI: 10.1371/journal.pone.0116058.]

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Design and analysis of cross vaults along history

The history of cross vaults began almost 2,000 years ago with a widespread use during the Middle Ages and Renaissance, becoming nowadays one of the most diffused and fascinating structural typologies of the European building cultural heritage. However, conversely to the undeniable excellence achieved by the ancient masons, the structural behavior of these elements is still at the center of the scientific debate. In this regard, with the aim of reviewing the knowledge on this subject as a concise and valuable support for researchers involved in conservation of historical buildings, with a focus on design rules and structural analysis, the present study firstly introduces the cross vaults from a historical perspective, by describing the evolution of the main geometrical shapes together with basic practical rules used to size them. Then, the article deals with the subsequent advancements in structural analysis methods of vaults, until the development of modern limit analysis.This work was partially carried out under the program "Dipartimento di Protezione Civile - Consorzio RELUIS", signed on 2013-12-27.info:eu-repo/semantics/publishedVersio

Light Intensity Physical Activity and Sedentary Behavior in Relation to Body Mass Index and Grip Strength in Older Adults: Cross-Sectional Findings from the Lifestyle Interventions and Independence for Elders (LIFE) Study.

Background Identifying modifiable determinants of fat mass and muscle strength in older adults is important given their impact on physical functioning and health. Light intensity physical activity and sedentary behavior are potential determinants, but their relations to these outcomes are poorly understood. We evaluated associations of light intensity physical activity and sedentary time—assessed both objectively and by self-report—with body mass index (BMI) and grip strength in a large sample of older adults. Methods We used cross-sectional baseline data from 1130 participants of the Lifestyle Interventions and Independence for Elders (LIFE) study, a community-dwelling sample of relatively sedentary older adults (70-89 years) at heightened risk of mobility disability. Time spent sedentary and in light intensity activity were assessed using an accelerometer worn for 3–7 days (Actigraph GT3X) and by self-report. Associations between these exposures and measured BMI and grip strength were evaluated using linear regression. Results Greater time spent in light intensity activity and lower sedentary times were both associated with lower BMI. This was evident using objective measures of lower-light intensity, and both objective and self-reported measures of higher-light intensity activity. Time spent watching television was positively associated with BMI, while reading and computer use were not. Greater time spent in higher but not lower intensities of light activity (assessed objectively) was associated with greater grip strength in men but not women, while neither objectively assessed nor self-reported sedentary time was associated with grip strength. Conclusions In this cross-sectional study, greater time spent in light intensity activity and lower sedentary times were associated with lower BMI. These results are consistent with the hypothesis that replacing sedentary activities with light intensity activities could lead to lower BMI levels and obesity prevalence among the population of older adults. However, longitudinal and experimental studies are needed to strengthen causal inferences

Geometrically Transformed Image Retrieval with Transfer Learning

Image retrieval as per their features is an important topic since last decades. For image processing, classification and retrieval deep learning (DL) techniques utilized as state-of-the art techniques. For the images geometric transformation especially, rotation is common thing. However, Convolutional Neural Networks (CNNs) not supporting rotation invariance features due to use of anisotropic filters for convolution. So, it an important emerging field in image processing that, rotations in images should not affect on its characteristics or features. In this paper, we propose to use features pre-trained CNN model combinations, which trained for large image database containing rotated as well as scaled images for classification & similar image retrieval. This approach produces superior result of classification and retrieval for Corel dataset for original query images and comparably good results by considering rotated & scaled query images