Mutations in DYNC2LI1 disrupt cilia function and cause short rib polydactyly syndrome.

The short rib polydactyly syndromes (SRPSs) are a heterogeneous group of autosomal recessive, perinatal lethal skeletal disorders characterized primarily by short, horizontal ribs, short limbs and polydactyly. Mutations in several genes affecting intraflagellar transport (IFT) cause SRPS but they do not account for all cases. Here we identify an additional SRPS gene and further unravel the functional basis for IFT. We perform whole-exome sequencing and identify mutations in a new disease-producing gene, cytoplasmic dynein-2 light intermediate chain 1, DYNC2LI1, segregating with disease in three families. Using primary fibroblasts, we show that DYNC2LI1 is essential for dynein-2 complex stability and that mutations in DYNC2LI1 result in variable length, including hyperelongated, cilia, Hedgehog pathway impairment and ciliary IFT accumulations. The findings in this study expand our understanding of SRPS locus heterogeneity and demonstrate the importance of DYNC2LI1 in dynein-2 complex stability, cilium function, Hedgehog regulation and skeletogenesis

Coulomb singularities in scattering wave functions of spin-orbit-coupled states

We report on our analysis of the Coulomb singularity problem in the frame of the coupled channel scattering theory including spin-orbit interaction. We assume that the coupling between the partial wave components involves orbital angular momenta such that $\Delta l = 0, \pm 2$. In these conditions, the two radial functions, components of a partial wave associated to two values of the angular momentum $l$, satisfy a system of two second-order ordinary differential equations. We examine the difficulties arising in the analysis of the behavior of the regular solutions near the origin because of this coupling. First, we demonstrate that for a singularity of the first kind in the potential, one of the solutions is not amenable to a power series expansion. The use of the Lippmann-Schwinger equations confirms this fact: a logarithmic divergence arises at the second iteration. To overcome this difficulty, we introduce two auxilliary functions which, together with the two radial functions, satisfy a system of four first-order differential equations. The reduction of the order of the differential system enables us to use a matrix-based approach, which generalizes the standard Frobenius method. We illustrate our analysis with numerical calculations of coupled scattering wave functions in a solid-state system

Relativistic quantum information and time machines

Relativistic quantum information combines the informational approach to understanding and using quantum mechanics systems - quantum information - with the relativistic view of the universe. In this introductory review we examine key results to emerge from this new field of research in physics and discuss future directions. A particularly active area recently has been the question of what happens when quantum systems interact with general relativistic closed timelike curves - effectively time machines. We discuss two different approaches that have been suggested for modelling such situations. It is argued that the approach based on matching the density operator of the quantum state between the future and past most consistently avoids the paradoxes usually associated with time travel.Comment: to appear in Contemporary Physic

Bostonia: The Boston University Alumni Magazine. Volume 9

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Statistical Analysis of Magnetic Field Spectra

We have calculated and statistically analyzed the magnetic-field spectrum (the ``B-spectrum'') at fixed electron Fermi energy for two quantum dot systems with classically chaotic shape. This is a new problem which arises naturally in transport measurements where the incoming electron has a fixed energy while one tunes the magnetic field to obtain resonance conductance patterns. The ``B-spectrum'', defined as the collection of values ${B_i}$ at which conductance $g(B_i)$ takes extremal values, is determined by a quadratic eigenvalue equation, in distinct difference to the usual linear eigenvalue problem satisfied by the energy levels. We found that the lower part of the ``B-spectrum'' satisfies the distribution belonging to Gaussian Unitary Ensemble, while the higher part obeys a Poisson-like behavior. We also found that the ``B-spectrum'' fluctuations of the chaotic system are consistent with the results we obtained from random matrices

The contribution of statistical physics to evolutionary biology

Evolutionary biology shares many concepts with statistical physics: both deal with populations, whether of molecules or organisms, and both seek to simplify evolution in very many dimensions. Often, methodologies have undergone parallel and independent development, as with stochastic methods in population genetics. We discuss aspects of population genetics that have embraced methods from physics: amongst others, non-equilibrium statistical mechanics, travelling waves, and Monte-Carlo methods have been used to study polygenic evolution, rates of adaptation, and range expansions. These applications indicate that evolutionary biology can further benefit from interactions with other areas of statistical physics, for example, by following the distribution of paths taken by a population through time.Comment: 18 pages, 3 figures, glossary. Accepted in Trend in Ecology and Evolution (to appear in print in August 2011

Effect of changes in plasma levels of free fatty acids on plasma glucagon, insulin, and growth hormone in man,

A regulatory role of acute changes in plasma concentration of free fatty acids on glucagon secretion has been suggested. We have studied the effect of such changes on plasma levels of glucagon, insulin, and growth hormone in man. Basal plasma levels of immunoreactive glucagon (IRG) were only slightly raised in 11 healthy subjects when the mean concentration of free fatty acids (FFA) was depressed to levels as low as 0.315 +/- 0.043 (SEM) mM by infusion of nicotinic acid. Basal levels were increased modestly when the mean FFA level was elevated to 3.027 +/- 0.184 mM by infusion of a triglyceride emulsion (Intralipid) with heparin. The plasma IRG response to intravenous arginine was unaffected by high or low levels of plasma FFA. These findings contrasted with the effects upon plasma levels of immunoreactive insulin (IRI) and growth hormone (IGH). During elevation of FFA levels, the mean basal level of plasma IRI increased by 100%, and the IRI response to arginine increased by 50%. Concomitantly, basal IGH levels and the plasma IGH response to arginine were suppressed markedly by elevation of FFA levels. The results of these studies do not offer support for a significant role of variation in plasma level of FFA as a regulator of acute changes in plasma IRG in man. An influence of changing levels of FFA on insulin secretion was found, and an effect on levels of growth hormone was confirmed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22854/1/0000416.pd

A CDC20-APC/SOX2 Signaling Axis Regulates Human Glioblastoma Stem-like Cells

SummaryGlioblastoma harbors a dynamic subpopulation of glioblastoma stem-like cells (GSCs) that can propagate tumors in vivo and is resistant to standard chemoradiation. Identification of the cell-intrinsic mechanisms governing this clinically important cell state may lead to the discovery of therapeutic strategies for this challenging malignancy. Here, we demonstrate that the mitotic E3 ubiquitin ligase CDC20-anaphase-promoting complex (CDC20-APC) drives invasiveness and self-renewal in patient tumor-derived GSCs. Moreover, CDC20 knockdown inhibited and CDC20 overexpression increased the ability of human GSCs to generate brain tumors in an orthotopic xenograft model in vivo. CDC20-APC control of GSC invasion and self-renewal operates through pluripotency-related transcription factor SOX2. Our results identify a CDC20-APC/SOX2 signaling axis that controls key biological properties of GSCs, with implications for CDC20-APC-targeted strategies in the treatment of glioblastoma

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events