CAID prediction portal: A comprehensive service for predicting intrinsic disorder and binding regions in proteins

Intrinsic disorder (ID) in proteins is well-established in structural biology, with increasing evidence for its involvement in essential biological processes. As measuring dynamic ID behavior experimentally on a large scale remains difficult, scores of published ID predictors have tried to fill this gap. Unfortunately, their heterogeneity makes it difficult to compare performance, confounding biologists wanting to make an informed choice. To address this issue, the Critical Assessment of protein Intrinsic Disorder (CAID) benchmarks predictors for ID and binding regions as a community blind-test in a standardized computing environment. Here we present the CAID Prediction Portal, a web server executing all CAID methods on user-defined sequences. The server generates standardized output and facilitates comparison between methods, producing a consensus prediction highlighting high-confidence ID regions. The website contains extensive documentation explaining the meaning of different CAID statistics and providing a brief description of all methods. Predictor output is visualized in an interactive feature viewer and made available for download in a single table, with the option to recover previous sessions via a private dashboard. The CAID Prediction Portal is a valuable resource for researchers interested in studying ID in proteins. The server is available at the URL: https://caid.idpcentral.org

The repetitive structure of DNA clamps: An overlooked protein tandem repeat

Structured tandem repeats proteins (STRPs) are a specific kind of tandem repeat proteins characterized by a modular and repetitive three-dimensional structure arrangement. The majority of STRPs adopt solenoid structures, but with the increasing availability of experimental structures and high-quality predicted structural models, more STRP folds can be characterized. Here, we describe “Box repeats”, an overlooked STRP fold present in the DNA sliding clamp processivity factors, which has eluded classification although structural data has been available since the late 1990s. Each Box repeat is a β⍺βββ module of about 60 residues, which forms a class V “beads-on-a-string” type STRP. The number of repeats present in processivity factors is organism dependent. Monomers of PCNA proteins in both Archaea and Eukarya have 4 repeats, while the monomers of bacterial beta-sliding clamps have 6 repeats. This new repeat fold has been added to the RepeatsDB database, which now provides structural annotation for 66 Box repeat proteins belonging to different organisms, including viruses

Effects of the LBV Primary's Mass-loss Rate on the 3D Hydrodynamics of eta Carinae's Colliding Winds

At the heart of eta Carinae's spectacular "Homunculus" nebula lies an extremely luminous (L(sub Total) greater than approximately 5 10(exp 6) solar luminosity) colliding wind binary with a highly eccentric (e approximately 0.9), 5.54-year orbit (Figure 1). The primary of the system, a Luminous Blue Variable (LBV), is our closest (D approximately 2.3 kpc) and best example of a pre-hypernova or pre-gamma ray burst environment. The remarkably consistent and periodic RXTE X-ray light curve surprisingly showed a major change during the system's last periastron in 2009, with the X-ray minimum being approximately 50% shorter than the minima of the previous two cycles1. Between 1998 and 2011, the strengths of various broad stellar wind emission lines (e.g. Halpha, Fe II) in line-of-sight (l.o.s.) also decreased by factors of 1.5 - 3 relative to the continuum2. The current interpretation for these changes is that they are due to a gradual factor of 2 - 4 drop in the primary's mass-loss rate over the last approximately 15 years1, 2. However, while a secular change is seen for a direct view of the central source, little to no change is seen in profiles at high stellar latitudes or reflected off of the dense, circumbinary material known as the "Weigelt blobs"2, 3. Moreover, model spectra generated with CMFGEN predict that a factor of 2 - 4 drop in the primary's mass-loss rate should lead to huge changes in the observed spectrum, which thus far have not been seen. Here we present results from large- (plus or minus 1620 AU) and small- (plus or minus 162 AU) domain, full 3D smoothed particle hydrodynamics (SPH) simulations of eta Car's massive binary colliding winds for three different primary-star mass-loss rates (2.4, 4.8, and 8.5 10(exp -4) solar mass/yr). The goal is to investigate how the mass-loss rate affects the 3D geometry and dynamics of eta Car's optically-thick wind and spatially-extended wind-wind collision (WWC) regions, both of which are known sources of observed X-ray, optical, UV, and near-IR emission and absorption. We use two domain sizes in order to better understand how the primary's mass-loss rate influences the various observables that form at different length scales. The 3D simulations provide information important for helping constrain Car's recent mass-loss history and future state

NOEMA maps the CO J=2−1J = 2-1 environment of the red supergiant μ\mu Cep

Red supergiant stars are surrounded by a gaseous and dusty circumstellar environment created by their mass loss which spreads heavy elements into the interstellar medium. The structure and the dynamics of this envelope are crucial to understand the processes driving the red supergiant mass loss and the shaping of the pre-supernova ejecta. We have observed the emission from the CO $J = 2-1$ line from the red supergiant star $\mu$~Cep with the NOEMA interferometer. In the line the synthesized beam was $0.92 \times 0.72$~arcsec ($590 \times 462$~au at 641~pc). The continuum map shows only the unresolved contribution of the free-free emission of the star chromosphere. The continuum-subtracted channel maps reveal a very inhomogeneous and clumpy circumstellar environment. In particular, we detected a bright CO clump, as bright as the central source in the line, at 1.80~arcsec south-west from the star, in the blue channel maps. After a deprojection of the radial velocity assuming two different constant wind velocities, the observations were modelled using the 3D radiative transfer code \textsc{lime} to derive the characteristics of the different structures. We determine that the gaseous clumps observed around $\mu$~Cep are responsible for a mass loss rate of $(4.9 \pm 1.0) \times 10^{-7}~{\rm M}_\odot\,{\rm yr}^{-1}$, in addition to a spatially unresolved wind component with an estimated mass-loss rate of $2.0 \times 10^{-6}~{\rm M}_\odot\,{\rm yr}^{-1}$. Therefore, the clumps have a significant role in $\mu$~Cep's mass loss ($\ge 25 \%$). We cannot exclude that the unresolved central outflow may be made of smaller unresolved clumps.Comment: 15 pages, 4 tables, 9 figures. 2nd version : one co-author removed and acknowledgement updated (consistent with erratum https://doi.org/10.1093/mnras/stz1006

Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation

A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281–1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of ‘large’ arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the ‘smaller’ arteries and veins of radii ≥ 50 μ m. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung

Nuclear Transparency to Intermediate-Energy Protons

Nuclear transparency in the (e,e'p) reaction for 135 < Tp < 800 MeV is investigated using the distorted wave approximation. Calculations using density-dependent effective interactions are compared with phenomenological optical potentials. Nuclear transparency is well correlated with proton absorption and neutron total cross sections. For Tp < 300 MeV there is considerable sensitivity to the choice of optical model, with the empirical effective interaction providing the best agreement with transparency data. For Tp > 300 MeV there is much less difference between optical models, but the calculations substantially underpredict transparency data and the discrepancy increases with A. The differences between Glauber and optical model calculations are related to their respective definitions of the semi-inclusive cross section. By using a more inclusive summation over final states the Glauber model emphasizes nucleon-nucleon inelasticity, whereas with a more restrictive summation the optical model emphasizes nucleon-nucleus inelasticity; experimental definitions of the semi-inclusive cross section lie between these extremes.Comment: uuencoded gz-compressed tar file containing revtex and bbl files and 5 postscript figures, totalling 31 pages. Uses psfi

Flow Residence Time and Regions of Intraluminal Thrombus Deposition in Intracranial Aneurysms

Thrombus formation in intracranial aneurysms, while sometimes stabilizing lesion growth, can present additional risk of thrombo-embolism. The role of hemodynamics in the progression of aneurysmal disease can be elucidated by patient-specific computational modeling. In our previous work, patient-specific computational fluid dynamics (CFD) models were constructed from MRI data for three patients who had fusiform basilar aneurysms that were thrombus-free and then proceeded to develop intraluminal thrombus. In this study, we investigated the effect of increased flow residence time (RT) by modeling passive scalar advection in the same aneurysmal geometries. Non-Newtonian pulsatile flow simulations were carried out in base-line geometries and a new postprocessing technique, referred to as “virtual ink” and based on the passive scalar distribution maps, was used to visualize the flow and estimate the flow RT. The virtual ink technique clearly depicted regions of flow separation. The flow RT at different locations adjacent to aneurysmal walls was calculated as the time the virtual ink scalar remained above a threshold value. The RT values obtained in different areas were then correlated with the location of intra-aneurysmal thrombus observed at a follow-up MR study. For each patient, the wall shear stress (WSS) distribution was also obtained from CFD simulations and correlated with thrombus location. The correlation analysis determined a significant relationship between regions where CFD predicted either an increased RT or low WSS and the regions where thrombus deposition was observed to occur in vivo. A model including both low WSS and increased RT predicted thrombus-prone regions significantly better than the models with RT or WSS alone