Flow dynamics of an accumulation basin: a case study of upper Kahiltna Glacier, Mount McKinley, Alaska

We interpreted flow dynamics of the Kahiltna Pass Basin accumulation zone on Mount McKinley, Alaska, USA, using 40, 100 and 900 MHz ground-penetrating radar profiles and GPS surface velocity measurements. We found dipping, englacial surface-conformable strata that experienced vertical thickening as the glacier flowed westward from a steep, higher-velocity (60 m a–1) region into flat terrain associated with a 908 bend in the glacier and lower velocities (15 m a–1) to the south. Stratigraphy near the western side of the basin was surface-conformable to 170 m depth and thinned as flow diverged southward, down-glacier. We found complex strata beneath the conformable stratigraphy and interpret these features as buried crevasses, avalanche debris and deformed ice caused by up-glacier events. We also suggest that basin dimensions, bed topography and the sharp bend each cause flow extension and compression, significantly contributing to conformable and complex strata thickness variations. Our findings show that surface-conformable stratigraphy continuous with depth and consistent strata thicknesses cannot be assumed in accumulation basins, because local and upglacier terrain and flow dynamics can cause structural complexities to occur under and within surfaceconformable layers

Melt regimes, internal stratigraphy, and flow dynamics of three glaciers in the Alaska Range

We used ground-penetrating radar (GPR), GPS and glaciochemistry to evaluate melt regimes and ice depths, important variables for mass-balance and ice-volume studies, of Upper Yentna Glacier, Upper Kahiltna Glacier and the Mount Hunter ice divide, Alaska. We show the wet, percolation and dry snow zones located below 2700 m a.s.l., at 2700 to 3900 m a.s.l. and above 3900 m a.s.l., respectively. We successfully imaged glacier ice depths upwards of 480 m using 40–100 MHz GPR frequencies. This depth is nearly double previous depth measurements reached using mid-frequency GPR systems on temperate glaciers. Few Holocene-length climate records are available in Alaska, hence we also assess stratigraphy and flow dynamics at each study site as a potential ice-core location. Ice layers in shallow firn cores and attenuated glaciochemical signals or lacking strata in GPR profiles collected on Upper Yentna Glacier suggest that regions below 2800 m a.s.l. are inappropriate for paleoclimate studies because of chemical diffusion, through melt. Flow complexities on Kahiltna Glacier preclude ice-core climate studies. Minimal signs of melt or deformation, and depth–age model estimates suggesting 4815 years of ice on the Mount Hunter ice divide (3912 m a.s.l.) make it a suitable Holocene-age ice-core location

Protein associated with SMAD1 (PAWS1/FAM83G) is a substrate for type I bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling

Bone morphogenetic proteins (BMPs) control multiple cellular processes in embryos and adult tissues. BMPs signal through the activation of type I BMP receptor kinases, which then phosphorylate SMADs 1/5/8. In the canonical pathway, this triggers the association of these SMADs with SMAD4 and their translocation to the nucleus, where they regulate gene expression. BMPs can also signal independently of SMAD4, but this pathway is poorly understood. Here, we report the discovery and characterization of PAWS1/FAM83G as a novel SMAD1 interactor. PAWS1 forms a complex with SMAD1 in a SMAD4-independent manner, and BMP signalling induces the phosphorylation of PAWS1 through BMPR1A. The phosphorylation of PAWS1 in response to BMP is essential for activation of the SMAD4-independent BMP target genes NEDD9 and ASNS. Our findings identify PAWS1 as the first non-SMAD substrate for type I BMP receptor kinases and as a novel player in the BMP pathway. We also demonstrate that PAWS1 regulates the expression of several non-BMP target genes, suggesting roles for PAWS1 beyond the BMP pathway

Partial-Transfer Absorption Imaging: A versatile technique for optimal imaging of ultracold gases

Partial-transfer absorption imaging is a tool that enables optimal imaging of atomic clouds for a wide range of optical depths. In contrast to standard absorption imaging, the technique can be minimally-destructive and can be used to obtain multiple successive images of the same sample. The technique involves transferring a small fraction of the sample from an initial internal atomic state to an auxiliary state and subsequently imaging that fraction absorptively on a cycling transition. The atoms remaining in the initial state are essentially unaffected. We demonstrate the technique, discuss its applicability, and compare its performance as a minimally-destructive technique to that of phase-contrast imaging.Comment: 10 pages, 5 figures, submitted to Review of Scientific Instrument

Dystrophin deficiency exacerbates skeletal muscle pathology in dysferlin-null mice

<p>Abstract</p> <p>Background</p> <p>Mutations in the genes coding for either dystrophin or dysferlin cause distinct forms of muscular dystrophy. Dystrophin links the cytoskeleton to the sarcolemma through direct interaction with β-dystroglycan. This link extends to the extracellular matrix by β-dystroglycan's interaction with α-dystroglycan, which binds extracellular matrix proteins, including laminin α2, agrin and perlecan, that possess laminin globular domains. The absence of dystrophin disrupts this link, leading to compromised muscle sarcolemmal integrity. Dysferlin, on the other hand, plays an important role in the Ca²⁺-dependent membrane repair of damaged sarcolemma in skeletal muscle. Because dysferlin and dystrophin play different roles in maintaining muscle cell integrity, we hypothesized that disrupting sarcolemmal integrity with dystrophin deficiency would exacerbate the pathology in dysferlin-null mice and allow further characterization of the role of dysferlin in skeletal muscle.</p> <p>Methods</p> <p>To test our hypothesis, we generated dystrophin/dysferlin double-knockout (DKO) mice by breeding <it>mdx </it>mice with dysferlin-null mice and analyzed the effects of a combined deficiency of dysferlin and dystrophin on muscle pathology and sarcolemmal integrity.</p> <p>Results</p> <p>The DKO mice exhibited more severe muscle pathology than either <it>mdx </it>mice or dysferlin-null mice, and, importantly, the onset of the muscle pathology occurred much earlier than it did in dysferlin-deficient mice. The DKO mice showed muscle pathology of various skeletal muscles, including the mandible muscles, as well as a greater number of regenerating muscle fibers, higher serum creatine kinase levels and elevated Evans blue dye uptake into skeletal muscles. Lengthening contractions caused similar force deficits, regardless of dysferlin expression. However, the rate of force recovery within 45 minutes following lengthening contractions was hampered in DKO muscles compared to <it>mdx </it>muscles or dysferlin-null muscles, suggesting that dysferlin is required for the initial recovery from lengthening contraction-induced muscle injury of the dystrophin-glycoprotein complex-compromised muscles.</p> <p>Conclusions</p> <p>The results of our study suggest that dysferlin-mediated membrane repair helps to limit the dystrophic changes in dystrophin-deficient skeletal muscle. Dystrophin deficiency unmasks the function of dysferlin in membrane repair during lengthening contractions. Dystrophin/dysferlin-deficient mice provide a very useful model with which to evaluate the effectiveness of therapies designed to treat dysferlin deficiency.</p

Identification of critical amino acids involved in α1-β interaction in voltage-dependent Ca2+ channels

AbstractIn voltage-dependent Ca2+ channels, the α1 and β subunits interact via two cytoplasmic regions defined as the Alpha Interaction Domain (AID) and Beta Interaction Domain (BID). Several novel amino acids for that interaction have now been mapped in both domains by point mutations. It was found that three of the nine amino acids in AID and four of the eight BID amino acids tested were essential for the interaction. Whereas the important AID amino acids were clustered around five residues, the important BID residues were more widely distributed within a larger 16 amino acid sequence. The affinity of the AIDA GST fusion protein for the four interacting β1b BID mutants was not significantly altered compared with the wild-type β1b despite the close localization of mutated residues to disruptive BID amino acids. Expression of these interactive β mutants with the full-length α1A subunit only slightly modified the stimulation efficiency when compared with the wild-type β1b subunit. Our data suggest that non-disruptive BID sequence alterations do not dramatically affect the β subunit-induced current stimulation

Dystroglycan Overexpression in Vivo Alters Acetylcholine Receptor Aggregation at the Neuromuscular Junction

AbstractDystroglycan is a member of the transmembrane dystrophin glycoprotein complex in muscle that binds to the synapse-organizing molecule agrin. Dystroglycan binding and AChR aggregation are mediated by two separate domains of agrin. To test whether dystroglycan plays a role in receptor aggregation at the neuromuscular junction, we overexpressed it by injecting rabbit dystroglycan RNA into one- or two-celled Xenopus embryos. We measured AChR aggregation in myotomes by labeling them with rhodamine–α-bungarotoxin followed by confocal microscopy and image analysis. Dystroglycan overexpression decreased AChR aggregation at the neuromuscular junction. This result is consistent with dystroglycan competition for agrin without signaling AChR aggregation. It also supports the hypothesis that dystroglycan is not the myotube-associated specificity component, (MASC) a putative coreceptor needed for agrin to activate muscle-specific kinase (MuSK) and signal AChR aggregation. Dystroglycan was distributed along the surface of muscle membranes, but was concentrated at the ends of myotomes, where AChRs normally aggregate at synapses. Overexpressed dystroglycan altered AChR aggregation in a rostral–caudal gradient, consistent with the sequential development of neuromuscular synapses along the embryo. Increasing concentrations of dystroglycan RNA did not further decrease AChR aggregation, but decreased embryo survival. Development often stopped during gastrulation, suggesting an essential, nonsynaptic role of dystroglycan during this early period of development

Structural Analysis of the Voltage-Dependent Calcium Channel β Subunit Functional Core and Its Complex with the α1 Interaction Domain

AbstractVoltage-dependent calcium channels (VDCC) are multiprotein assemblies that regulate the entry of extracellular calcium into electrically excitable cells and serve as signal transduction centers. The α1 subunit forms the membrane pore while the intracellular β subunit is responsible for trafficking of the channel to the plasma membrane and modulation of its electrophysiological properties. Crystallographic analyses of a β subunit functional core alone and in complex with a α1 interaction domain (AID) peptide, the primary binding site of β to the α1 subunit, reveal that β represents a novel member of the MAGUK protein family. The findings illustrate how the guanylate kinase fold has been fashioned into a protein-protein interaction module by alteration of one of its substrate sites. Combined results indicate that the AID peptide undergoes a helical transition in binding to β. We outline the mechanistic implications for understanding the β subunit's broad regulatory role of the VDCC, particularly via the AID

Affinity Purification of Antibodies Specific for 1,4-Dihydropyridine Ca 2+ Channel Blockers

High-affinity antibodies specific for the 1,4-dihydropyridine Ca 2+ channel blockers have been produced in sheep and affinity purified using a dihydropyridine-Sepharose affinity column. Dihydropyridine-Sepharose affinity matrix was synthesized by reaction of aminohexyl-Sepharose with an affinity analogue of nifedipine, dimethyl l,4-dihydro-2,6-dimethyl-4-(2-isothiocyanatophenyl)-3,5-pyridinedicarboxylate. Residual amine groups were then blocked by carbodiimide-catalyzed acetylation. channels is important in mediation of contraction in cardiac and smooth muscle