50 research outputs found
Intrinsic Disorder in PRAME and Its Role in Uveal Melanoma
Introduction
The PReferentially expressed Antigen in MElanoma (PRAME) protein has been shown to be an independent biomarker for increased risk of metastasis in Class 1 uveal melanomas (UM). Intrinsically disordered proteins and regions of proteins (IDPs/IDPRs) are proteins that do not have a well-defined three-dimensional structure and have been linked to neoplastic development. Our study aimed to evaluate the presence of intrinsic disorder in PRAME and the role these structureless regions have in PRAME(â+) Class 1 UM. Methods
A bioinformatics study to characterize PRAMEâs propensity for the intrinsic disorder. We first used the AlphaFold tool to qualitatively assess the protein structure of PRAME. Then we used the Compositional Profiler and a set of per-residue intrinsic disorder predictors to quantify the intrinsic disorder. The Database of Disordered Protein Prediction (D2P2) platform, IUPred, FuzDrop, fIDPnn, AUCpred, SPOT-Disorder2, and metapredict V2 allowed us to evaluate the potential functional disorder of PRAME. Additionally, we used the Search Tool for the Retrieval of Interacting Genes (STRING) to analyze PRAME\u27s potential interactions with other proteins. Results
Our structural analysis showed that PRAME contains intrinsically disordered protein regions (IDPRs), which are structureless and flexible. We found that PRAME is significantly enriched with serine (p-valueâ\u3câ0.05), a disorder-promoting amino acid. PRAME was found to have an average disorder score of 16.49% (i.e., moderately disordered) across six per-residue intrinsic disorder predictors. Our IUPred analysis revealed the presence of disorder-to-order transition (DOT) regions in PRAME near the C-terminus of the protein (residues 475â509). The D2P2 platform predicted a region from approximately 140 and 175 to be highly concentrated with post-translational modifications (PTMs). FuzDrop predicted the PTM hot spot of PRAME to be a droplet-promoting region and an aggregation hotspot. Finally, our analysis using the STRING tool revealed that PRAME has significantly more interactions with other proteins than expected for randomly selected proteins of the same size, with the ability to interact with 84 different partners (STRING analysis result: p-valueâ\u3câ1.0âĂâ10â16; model confidence: 0.400). Conclusion
Our study revealed that PRAME has IDPRs that are possibly linked to its functionality in the context of Class 1 UM. The regions of functionality (i.e., DOT regions, PTM sites, droplet-promoting regions, and aggregation hotspots) are localized to regions of high levels of disorder. PRAME has a complex proteinâprotein interaction (PPI) network that may be secondary to the structureless features of the polypeptide. Our findings contribute to our understanding of UM and suggest that IDPRs and DOT regions in PRAME may be targeted in developing new therapies for this aggressive cancer
Viscosity and Diffusion: Crowding and Salt Effects in Protein Solutions
We report on a joint experimental-theoretical study of collective diffusion
in, and static shear viscosity of solutions of bovine serum albumin (BSA)
proteins, focusing on the dependence on protein and salt concentration. Data
obtained from dynamic light scattering and rheometric measurements are compared
to theoretical calculations based on an analytically treatable spheroid model
of BSA with isotropic screened Coulomb plus hard-sphere interactions. The only
input to the dynamics calculations is the static structure factor obtained from
a consistent theoretical fit to a concentration series of small-angle X-ray
scattering (SAXS) data. This fit is based on an integral equation scheme that
combines high accuracy with low computational cost. All experimentally probed
dynamic and static properties are reproduced theoretically with an at least
semi-quantitative accuracy. For lower protein concentration and low salinity,
both theory and experiment show a maximum in the reduced viscosity, caused by
the electrostatic repulsion of proteins. The validity range of a generalized
Stokes-Einstein (GSE) relation connecting viscosity, collective diffusion
coefficient, and osmotic compressibility, proposed by Kholodenko and Douglas
[PRE 51, 1081 (1995)] is examined. Significant violation of the GSE relation is
found, both in experimental data and in theoretical models, in semi-dilute
systems at physiological salinity, and under low-salt conditions for arbitrary
protein concentrations
Female Fertility Affects Men's Linguistic Choices
We examined the influence of female fertility on the likelihood of male participants aligning their choice of syntactic construction with those of female confederates. Men interacted with women throughout their menstrual cycle. On critical trials during the interaction, the confederate described a picture to the participant using particular syntactic constructions. Immediately thereafter, the participant described to the confederate a picture that could be described using either the same construction that was used by the confederate or an alternative form of the construction. Our data show that the likelihood of men choosing the same syntactic structure as the women was inversely related to the women's level of fertility: higher levels of fertility were associated with lower levels of linguistic matching. A follow-up study revealed that female participants do not show this same change in linguistic behavior as a function of changes in their conversation partner's fertility. We interpret these findings in the context of recent data suggesting that non-conforming behavior may be a means of men displaying their fitness as a mate to women
26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15â20 July 2017
This work was produced as part of the activities of FAPESP Research,\ud
Disseminations and Innovation Center for Neuromathematics (grant\ud
2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud
FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud
supported by a CNPq fellowship (grant 306251/2014-0)
Polymer-Induced Self-Assembly of Small Organic Molecules into Ultralong Microbelts with Electronic Conductivity
The principle of polymer-controlled crystallization of inorganic materials has been successfully transferred to functional aromatic organic dyes, in this instance 3,4,9,10-perylenetetracarboxylic acid potassium salt (PTCAPS), after its single-crystal structure was determined. The cationic double hydrophilic block copolymer poly(ethylene glycol)-block-branched-poly(ethyleneimine) (PEG-b-PEI) was used as the polymer additive to modify the crystallization of PTCAPS. Ultralong hierarchically structured PTCAPS microbelts with constant width and thickness of each individual belt have been fabricated. The belts are a mesocrystalline assembly of primary nanoparticles with high-energy anionic {001} faces stabilized by polymer complexation. Polarization microscopy, X-ray diffraction, optical absorption spectra, and fluorescence spectra indicate the favorable orientation of the 1D microbelts in the close-stacking direction and reveal a specific 1D superstructure fluorescence. Electrical conductivity measurements performed on a single nanobelt disclose in the doped state a remarkably high electronic conductivity and further demonstrate extended, wirelike ÏâÏ interactions along the [020] long axis of the belts. Together with the very large length of the belts and their organicâorganic hybrid nanostructure, this makes these organic wires potentially interesting for the field of nano-/micro-optoelectronics
Vertically Aligned Two-Dimensional Graphene-Metal Hydroxide Hybrid Arrays for LiâO<sub>2</sub> Batteries
Lithium oxygen batteries (LOBs) are
a very promising upcoming technology
which, however, still suffers from low lifespan and dramatic capacities
fading. Solid discharge products increase the contact resistance and
block the electrochemically active electrodes. The resulting high
oxidative potentials and formation of Li<sub>2</sub>CO<sub>3</sub> due to electrolyte and carbon electrode decomposition at the positive
electrode lead to irreversible deactivation of oxygen evolution reaction
(OER) and oxygen reduction reaction (ORR) sites. Here we demonstrate
a facile strategy for the scalable production of a new electrode structure
constituted of vertically aligned carbon nanosheets and metal hydroxide
(MÂ(OH)<sub><i>x</i></sub>@CNS) hybrid arrays, integrating
both favorable ORR and OER active materials to construct bifunctional
catalysts for LOBs. Excellent lithiumâoxygen battery properties
with high specific capacity of 5403 mAh g<sup>â1</sup> and
12123 mAh g<sup>â1</sup> referenced to the carbon and MÂ(OH)<sub><i>x</i></sub> weight, respectively, long cyclability,
and low charge potentials are achieved in the resulting MÂ(OH)<sub><i>x</i></sub>@CNS cathode architecture. The properties
are explained by improved O<sub>2</sub>/ion transport properties and
spatially limited precipitation of Li<sub>2</sub>O<sub>2</sub> nanoparticles
inside interstitial cavities resulting in high reversibility. The
strategy of creating ORR and OER bifunctional catalysts in a single
conductive hybrid component may pave the way to new cathode architectures
for metal air batteries
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Face Off: 3D-Printed Masks as a Cost-Effective and Reusable Alternative to N95 Respirators: A Feasibility Study
One of the best methods for protection against respiratory diseases is the use of an N95 mask. Supply shortages have demonstrated a significant need for effective alternatives to N95 masks. Benefits of 3D-printed respirators over N95s include reduced cost and ease of production, widespread availability, reusability/sterilizability, and customizability. 3D-printed mask designs have been downloaded thousands of times; however, there is little to no data on the efficacy of these potential alternatives.
Three of the most popular 3D-printed respirator designs were modified to allow for the Occupational Safety and Health Administration (OSHA) quantitative fit testing that disperses saline into the ambient air and determines concentrations within the mask during multiple trials. Five volunteers conducted standardized fit tests of these masks, as well as an N95 and a KN95, and the results were compared.
One of the 3D-printed respirators, low poly COVID-19 face mask respirator (mask 2), achieved a fit factor greater than 100 in every trial, representing sufficient fit according to OSHA protocols. The N95 mask achieved a sufficient fit in 60% of the trials, and none of the remaining masks provided a suitable fit factor reliably according to the OSHA fit test. Further trials showed no change in fit factor when different 3D-printable plastics are used or when a widely available high efficiency particulate air (HEPA) filter was used.
3D-printed respirators provide a possible alternative to N95 masks to protect against respiratory pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Fit testing results demonstrate that certain 3D-printed mask designs may exceed the fit of N95 masks