Insights into the regulation of intrinsically disordered proteins in the human proteome by analyzing sequence and gene expression data

Background: Disordered proteins need to be expressed to carry out specified functions; however, their accumulation in the cell can potentially cause major problems through protein misfolding and aggregation. Gene expression levels, mRNA decay rates, microRNA (miRNA) targeting and ubiquitination have critical roles in the degradation and disposal of human proteins and transcripts. Here, we describe a study examining these features to gain insights into the regulation of disordered proteins. Results: In comparison with ordered proteins, disordered proteins have a greater proportion of predicted ubiquitination sites. The transcripts encoding disordered proteins also have higher proportions of predicted miRNA target sites and higher mRNA decay rates, both of which are indicative of the observed lower gene expression levels. The results suggest that the disordered proteins and their transcripts are present in the cell at low levels and/or for a short time before being targeted for disposal. Surprisingly, we find that for a significant proportion of highly disordered proteins, all four of these trends are reversed. Predicted estimates for miRNA targets, ubiquitination and mRNA decay rate are low in the highly disordered proteins that are constitutively and/or highly expressed. Conclusions: Mechanisms are in place to protect the cell from these potentially dangerous proteins. The evidence suggests that the enrichment of signals for miRNA targeting and ubiquitination may help prevent the accumulation of disordered proteins in the cell. Our data also provide evidence for a mechanism by which a significant proportion of highly disordered proteins (with high expression levels) can escape rapid degradation to allow them to successfully carry out their function

Planar Induced Subgraphs of Sparse Graphs

We show that every graph has an induced pseudoforest of at least $n-m/4.5$ vertices, an induced partial 2-tree of at least $n-m/5$ vertices, and an induced planar subgraph of at least $n-m/5.2174$ vertices. These results are constructive, implying linear-time algorithms to find the respective induced subgraphs. We also show that the size of the largest $K_h$-minor-free graph in a given graph can sometimes be at most $n-m/6+o(m)$.Comment: Accepted by Graph Drawing 2014. To appear in Journal of Graph Algorithms and Application

So far, yet so close: α-Catenin dimers help migrating cells get together

Epithelial cells in tissues use their actin cytoskeletons to stick together, whereas unattached cells make active plasma membrane protrusions to migrate. In this issue, Wood et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201612006) show that the junction component α-catenin is critical in freely moving cells to promote adhesion and migration

Surface Polymer Network Model and Effective Membrane Curvature Elasticity

A microscopic model of a surface polymer network - membrane system is introduced, with contact polymer surface interactions that can be either repulsive or attractive and sliplinks of functionality four randomly distributed over the supporting membrane surface anchoring the polymers to it. For the supporting surface perturbed from a planar configuration and a small relative number of surface sliplinks, we investigate an expansion of the free energy in terms of the local curvatures of the surface and the surface density of sliplinks, obtained through the application of the Balian - Bloch - Duplantier multiple surface scattering method. As a result, the dependence of the curvature elastic modulus, the Gaussian modulus as well as of the spontaneous curvature of the "dressed" membrane, ~{\sl i.e.} polymer network plus membrane matrix, is obtained on the mean polymer bulk end to end separation and the surface density of sliplinks.Comment: 15 pages with one included compressed uuencoded figure

Accretion, Outflows, and Winds of Magnetized Stars

Many types of stars have strong magnetic fields that can dynamically influence the flow of circumstellar matter. In stars with accretion disks, the stellar magnetic field can truncate the inner disk and determine the paths that matter can take to flow onto the star. These paths are different in stars with different magnetospheres and periods of rotation. External field lines of the magnetosphere may inflate and produce favorable conditions for outflows from the disk-magnetosphere boundary. Outflows can be particularly strong in the propeller regime, wherein a star rotates more rapidly than the inner disk. Outflows may also form at the disk-magnetosphere boundary of slowly rotating stars, if the magnetosphere is compressed by the accreting matter. In isolated, strongly magnetized stars, the magnetic field can influence formation and/or propagation of stellar wind outflows. Winds from low-mass, solar-type stars may be either thermally or magnetically driven, while winds from massive, luminous O and B type stars are radiatively driven. In all of these cases, the magnetic field influences matter flow from the stars and determines many observational properties. In this chapter we review recent studies of accretion, outflows, and winds of magnetized stars with a focus on three main topics: (1) accretion onto magnetized stars; (2) outflows from the disk-magnetosphere boundary; and (3) winds from isolated massive magnetized stars. We show results obtained from global magnetohydrodynamic simulations and, in a number of cases compare global simulations with observations.Comment: 60 pages, 44 figure

A Study of the 't Hooft Model with the Overlap Dirac Operator

We present the results of an exploratory numerical study of two dimensional QCD with overlap fermions. We have performed extensive simulations for U(N_c) and SU(N_c) color groups with N_c=2, 3, 4 and coupling constants chosen to satisfy the 't Hooft condition g^2 N_c =const=4/3. We have computed the meson spectrum and decay constants, the topological susceptibility and the chiral condensate. For U(N_c) gauge groups, our results indicate that the Witten-Veneziano relation is satisfied within our statistical errors and that the chiral condensate for N_f=1 is compatible with a non-zero value. Our results exhibit universality in N_c and confirm once more the excellent chiral properties of the overlap-Dirac operator.Comment: 18 pages, 4 figure

Dispersive properties of quasi-phase-matched optical parametric amplifiers

The dispersive properties of non-degenerate optical parametric amplification in quasi-phase-matched (QPM) nonlinear quadratic crystals with an arbitrary grating profile are theoretically investigated in the no-pump-depletion limit. The spectral group delay curve of the amplifier is shown to be univocally determined by its spectral power gain curve through a Hilbert transform. Such a constraint has important implications on the propagation of spectrally-narrow optical pulses through the amplifier. In particular, it is shown that anomalous transit times, corresponding to superluminal or even negative group velocities, are possible near local minima of the spectral gain curve. A possible experimental observation of such effects using a QPM Lithium-Niobate crystal is suggested.Comment: submitted for publicatio

The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration

Integrin β3 is seen as a key anti-angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro- or anti-angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3-dependent adhesome. We show that depletion of β3-integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3-integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2-driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3-integrin levels are reduced

Demographics and Functional Outcome of Toe Fractures

Toe fractures are common; however, there are few data on demographics and functional outcome. We studied outcomes in 339 consecutive patients with toe fractures treated between January 2006 and September 2008. Two hundred and sixty-four patients, aged 16 to 75, were mailed an outcome questionnaire, and overall subjective satisfaction with the outcome of treatment was measured using a visual analog scale (VAS). Most frequently affected were the first (38%) and fifth (30%) toes, and most (75.6%) of the fractures were caused by stubbing or crush injury. More than 95% of the fractures were displaced less than 2 mm, and all of the fractures were treated conservatively. The questionnaire was returned by 141 (53%) patients with a median follow-up of 27 months. Respondents were female in 57.4% of cases and had a median age of 45 years. The median AOFAS score was 100 (P25, P75= 93,100) points; the median VAS was 10 (P25, P75= 8, 10) points. Univariate regression analysis revealed no statistically significant associations between outcome and the particular toe or phalanx involved, number of fractured toes, fracture type and location, articular involvement, gender, age, body mass index, smoking habits, and the presence of diabetes mellitus. Satisfaction VAS was dependent on age (P = .047) and gender (P = .049) in the multivariate analysis. The AOFAS midfoot score was not influenced by any of the covariates. This is the first epidemiological investigation using 2 outcome-scoring systems to determine function and satisfaction following treatment of toe fractures

Impact of extractive industries on malaria prevalence in the Democratic Republic of the Congo: a population-based cross-sectional study

Extraction of natural resources through mining and logging activities provides revenue and employment across sub-Saharan Africa, a region with the highest burden of malaria globally. The extent to which mining and logging influence malaria transmission in Africa remains poorly understood. Here, we evaluate associations between mining, logging, and malaria in the high transmission setting of the Democratic Republic of the Congo using population-representative malaria survey results and geographic data for environmental features and mining and logging concessions. We find elevated malaria prevalence among individuals in rural areas exposed to mining; however, we also detect significant spatial confounding among locations. Upon correction, effect estimates for mining and logging shifted toward the null and we did not find sufficient evidence to detect an association with malaria. Our findings reveal a complex interplay between mining, logging, space, and malaria prevalence. While mining concessions alone may not drive the high prevalence, unobserved features of mining-exposed areas, such as human migration, changing vector populations, or parasite genetics, may instead be responsible