Misdiagnosis of hereditary amyloidosis as AL (Primary) amyloidosis

Background: Hereditary, autosomal dominant amyloidosis, caused by mutations in the genes encoding transthyretin, fibrinogen A -chain, lysozyme, or apolipoprotein A-I, is thought to be extremely rare and is not routinely included in the differential diagnosis of systemic amyloidosis unless there is a family history. Methods: We studied 350 patients with systemic amyloidosis, in whom a diagnosis of the light-chain (AL) type of the disorder had been suggested by clinical and laboratory findings and by the absence of a family history, to assess whether they had amyloidogenic mutations. Results: Amyloidogenic mutations were present in 34 of the 350 patients (9.7 percent), most often in the genes encoding fibrinogen A -chain (18 patients) and transthyretin (13 patients). In all 34 of these patients, the diagnosis of hereditary amyloidosis was confirmed by additional investigations. A low-grade monoclonal gammopathy was detected in 8 of the 34 patients (24 percent). Conclusions: A genetic cause should be sought in all patients with amyloidosis that is not the reactive systemic amyloid A type and in whom confirmation of the AL type cannot be obtained

A rim-and-spoke hypothesis to explain the biomechanical roles for cytoplasmic intermediate filament networks

Textbook images of keratin intermediate filament (IF) networks in epithelial cells and the functional compromization of the epidermis by keratin mutations promulgate a mechanical role for this important cytoskeletal component. In stratified epithelia, keratin filaments form prominent radial spokes that are focused onto cell-cell contact sites, i.e. the desmosomes. In this Hypothesis, we draw attention to a subset of keratin filaments that are apposed to the plasma membrane. They form a rim of filaments interconnecting the desmosomes in a circumferential network. We hypothesize that they are part of a rim-and-spoke arrangement of IFs in epithelia. From our review of the literature, we extend this functional role for the subplasmalemmal rim of IFs to any cell, in which plasma membrane support is required, provided these filaments connect directly or indirectly to the plasma membrane. Furthermore, cytoplasmic IF networks physically link the outer nuclear and plasma membranes, but their participation in mechanotransduction processes remain largely unconsidered. Therefore, we also discuss the potential biomechanical and mechanosensory role(s) of the cytoplasmic IF network in terms of such a rim (i.e. subplasmalemmal)-and-spoke arrangement for cytoplasmic IF networks

Kinetics of active surface-mediated diffusion in spherically symmetric domains

We present an exact calculation of the mean first-passage time to a target on the surface of a 2D or 3D spherical domain, for a molecule alternating phases of surface diffusion on the domain boundary and phases of bulk diffusion. We generalize the results of [J. Stat. Phys. {\bf 142}, 657 (2011)] and consider a biased diffusion in a general annulus with an arbitrary number of regularly spaced targets on a partially reflecting surface. The presented approach is based on an integral equation which can be solved analytically. Numerically validated approximation schemes, which provide more tractable expressions of the mean first-passage time are also proposed. In the framework of this minimal model of surface-mediated reactions, we show analytically that the mean reaction time can be minimized as a function of the desorption rate from the surface.Comment: Published online in J. Stat. Phy

On the Lebesgue measure of Li-Yorke pairs for interval maps

We investigate the prevalence of Li-Yorke pairs for $C^2$ and $C^3$ multimodal maps $f$ with non-flat critical points. We show that every measurable scrambled set has zero Lebesgue measure and that all strongly wandering sets have zero Lebesgue measure, as does the set of pairs of asymptotic (but not asymptotically periodic) points. If $f$ is topologically mixing and has no Cantor attractor, then typical (w.r.t. two-dimensional Lebesgue measure) pairs are Li-Yorke; if additionally $f$ admits an absolutely continuous invariant probability measure (acip), then typical pairs have a dense orbit for $f \times f$. These results make use of so-called nice neighborhoods of the critical set of general multimodal maps, and hence uniformly expanding Markov induced maps, the existence of either is proved in this paper as well. For the setting where $f$ has a Cantor attractor, we present a trichotomy explaining when the set of Li-Yorke pairs and distal pairs have positive two-dimensional Lebesgue measure.Comment: 41 pages, 3 figure

Possible origins of macroscopic left-right asymmetry in organisms

I consider the microscopic mechanisms by which a particular left-right (L/R) asymmetry is generated at the organism level from the microscopic handedness of cytoskeletal molecules. In light of a fundamental symmetry principle, the typical pattern-formation mechanisms of diffusion plus regulation cannot implement the "right-hand rule"; at the microscopic level, the cell's cytoskeleton of chiral filaments seems always to be involved, usually in collective states driven by polymerization forces or molecular motors. It seems particularly easy for handedness to emerge in a shear or rotation in the background of an effectively two-dimensional system, such as the cell membrane or a layer of cells, as this requires no pre-existing axis apart from the layer normal. I detail a scenario involving actin/myosin layers in snails and in C. elegans, and also one about the microtubule layer in plant cells. I also survey the other examples that I am aware of, such as the emergence of handedness such as the emergence of handedness in neurons, in eukaryote cell motility, and in non-flagellated bacteria.Comment: 42 pages, 6 figures, resubmitted to J. Stat. Phys. special issue. Major rewrite, rearranged sections/subsections, new Fig 3 + 6, new physics in Sec 2.4 and 3.4.1, added Sec 5 and subsections of Sec

The bowfin genome illuminates the developmental evolution of ray-finned fishes.

The bowfin (Amia calva) is a ray-finned fish that possesses a unique suite of ancestral and derived phenotypes, which are key to understanding vertebrate evolution. The phylogenetic position of bowfin as a representative of neopterygian fishes, its archetypical body plan and its unduplicated and slowly evolving genome make bowfin a central species for the genomic exploration of ray-finned fishes. Here we present a chromosome-level genome assembly for bowfin that enables gene-order analyses, settling long-debated neopterygian phylogenetic relationships. We examine chromatin accessibility and gene expression through bowfin development to investigate the evolution of immune, scale, respiratory and fin skeletal systems and identify hundreds of gene-regulatory loci conserved across vertebrates. These resources connect developmental evolution among bony fishes, further highlighting the bowfin's importance for illuminating vertebrate biology and diversity in the genomic era

The 2dF Galaxy Redshift Survey: the dependence of galaxy clustering on luminosity and spectral type

We investigate the dependence of galaxy clustering on luminosity and spectral type using the 2dF Galaxy Redshift Survey (2dFGRS). Spectral types are assigned using the principal-component analysis of Madgwick et al. We divide the sample into two broad spectral classes: galaxies with strong emission lines ('late types') and more quiescent galaxies ('early types'). We measure the clustering in real space, free from any distortion of the clustering pattern owing to peculiar velocities, for a series of volume-limited samples. The projected correlation functions of both spectral types are well described by a power law for transverse separations in the range 2<(σ/h-1 Mpc)<15, with a marginally steeper slope for early types than late types. Both early and late types have approximately the same dependence of clustering strength on luminosity, with the clustering amplitude increasing by a factor of 2.5 between L* and 4L*. At all luminosities, however, the correlation function amplitude for the early types is 50 per cent higher than that of the late types. These results support the view that luminosity, and not type, is the dominant factor in determining how the clustering strength of the whole galaxy population varies with luminosity

Non-crossing dependencies: Least effort, not grammar

The use of null hypotheses (in a statistical sense) is common in hard sciences but not in theoretical linguistics. Here the null hypothesis that the low frequency of syntactic dependency crossings is expected by an arbitrary ordering of words is rejected. It is shown that this would require star dependency structures, which are both unrealistic and too restrictive. The hypothesis of the limited resources of the human brain is revisited. Stronger null hypotheses taking into account actual dependency lengths for the likelihood of crossings are presented. Those hypotheses suggests that crossings are likely to reduce when dependencies are shortened. A hypothesis based on pressure to reduce dependency lengths is more parsimonious than a principle of minimization of crossings or a grammatical ban that is totally dissociated from the general and non-linguistic principle of economy.Postprint (author's final draft

The size of chi = arg (-Vts Vtb* Vcs* Vcb) and physics beyond the Standard Model

We analyse the allowed range of values of chi, both in the Standard Model and in models with New Physics, pointing out that a relatively large value of chi, e.g. of order lambda, is only possible in models where the unitarity of the 3x3 Cabibbo-Kobayashi-Maskawa matrix is violated through the introduction of extra Q=2/3 quarks. We study the interesting case where the extra quark is an isosinglet, determining the allowed range for chi and the effect of a large chi on various low-energy observables, such as CP asymmetries in B meson decays. We also discuss the correlated effects which would be observable at high energy colliders, like decays t -> cZ, modifications of the cross section and forward-backward asymmetry in e+ e- -> ttbar and the direct production of a new quark.Comment: LaTeX, 19 pages, 6 PS figures. Section 3 expanded. Version to be published in NP