754 research outputs found
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Ectopic expression of the HLXB9 gene is associated with an altered nuclear position in t(7;12) leukaemias
This article is available open access through the publisher’s website at the link below. Copyright @ 2009 Macmillan Publishers Ltd.No abstract available (Letter to the editor).The Leukaemia Research Fun
Multistep, sequential control of the trafficking and function of the multiple sulfatase deficiency gene product, SUMF1 by PDI, ERGIC-53 and ERp44.
Sulfatase modifying factor 1 (SUMF1) encodes for the formylglicine generating enzyme, which activates sulfatases by modifying a key cysteine residue within their catalytic domains. SUMF1 is mutated in patients affected by multiple sulfatase deficiency, a rare recessive disorder in which all sulfatase activities are impaired. Despite the absence of canonical retention/retrieval signals, SUMF1 is largely retained in the endoplasmic reticulum (ER), where it exerts its enzymatic activity on nascent sulfatases. Part of SUMF1 is secreted and paracrinally taken up by distant cells. Here we show that SUMF1 interacts with protein disulfide isomerase (PDI) and ERp44, two thioredoxin family members residing in the early secretory pathway, and with ERGIC-53, a lectin that shuttles between the ER and the Golgi. Functional assays reveal that these interactions are crucial for controlling SUMF1 traffic and function. PDI couples SUMF1 retention and activation in the ER. ERGIC-53 and ERp44 act downstream, favoring SUMF1 export from and retrieval to the ER, respectively. Silencing ERGIC-53 causes proteasomal degradation of SUMF1, while down-regulating ERp44 promotes its secretion. When over-expressed, each of three interactors favors intracellular accumulation. Our results reveal a multistep control of SUMF1 trafficking, with sequential interactions dynamically determining ER localization, activity and secretion
Random Graph-Homomorphisms and Logarithmic Degree
A graph homomorphism between two graphs is a map from the vertex set of one
graph to the vertex set of the other graph, that maps edges to edges. In this
note we study the range of a uniformly chosen homomorphism from a graph G to
the infinite line Z. It is shown that if the maximal degree of G is
`sub-logarithmic', then the range of such a homomorphism is super-constant.
Furthermore, some examples are provided, suggesting that perhaps for graphs
with super-logarithmic degree, the range of a typical homomorphism is bounded.
In particular, a sharp transition is shown for a specific family of graphs
C_{n,k} (which is the tensor product of the n-cycle and a complete graph, with
self-loops, of size k). That is, given any function psi(n) tending to infinity,
the range of a typical homomorphism of C_{n,k} is super-constant for k = 2
log(n) - psi(n), and is 3 for k = 2 log(n) + psi(n)
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Autophagy in Lysosomal Storage Disorders
Lysosomes are ubiquitous intracellular organelles that have an acidic internal pH, and play crucial roles in cellular clearance. Numerous functions depend on normal lysosomes, including the turnover of cellular constituents, cholesterol homeostasis, downregulation of surface receptors, inactivation of pathogenic organisms, repair of the plasma membrane and bone remodeling. Lysosomal storage disorders (LSDs) are characterized by progressive accumulation of undigested macromolecules within the cell due to lysosomal dysfunction. As a consequence, many tissues and organ systems are affected, including brain, viscera, bone and cartilage. The progressive nature of phenotype development is one of the hallmarks of LSDs. In recent years biochemical and cell biology studies of LSDs have revealed an ample spectrum of abnormalities in a variety of cellular functions. These include defects in signaling pathways, calcium homeostasis, lipid biosynthesis and degradation and intracellular trafficking. Lysosomes also play a fundamental role in the autophagic pathway by fusing with autophagosomes and digesting their content. Considering the highly integrated function of lysosomes and autophagosomes it was reasonable to expect that lysosomal storage in LSDs would have an impact upon autophagy. The goal of this review is to provide readers with an overview of recent findings that have been obtained through analysis of the autophagic pathway in several types of LSDs, supporting the idea that LSDs could be seen primarily as “autophagy disorders.
Mid-Infrared Plasmonic Platform Based on n-Doped Ge-on-Si: Molecular Sensing with Germanium Nano-Antennas on Si
CMOS-compatible, heavily-doped semiconductor
films are very promising for applications in mid-infrared
plasmonic devices because the real part of their dielectric
function is negative and broadly tunable in this wavelength
range. In this work we investigate n-type doped germanium
epilayers grown on Si substrates. We design and realize Ge nanoantennas
on Si substrates demonstrating the presence of localized
plasmon resonances, and exploit them for molecular sensing in
the mid-infrared
Design of a low band gap oxide ferroelectric: BiTiO
A strategy for obtaining low band gap oxide ferroelectrics based on charge
imbalance is described and illustrated by first principles studies of the
hypothetical compound BiTiO, which is an alternate stacking of
the ferroelectric BiTiO. We find that this compound is
ferroelectric, similar to BiTiO although with a reduced
polarization. Importantly, calculations of the electronic structure with the
recently developed functional of Tran and Blaha yield a much reduced band gap
of 1.83 eV for this material compared to BiTiO. Therefore,
BiTiO is predicted to be a low band gap ferroelectric material
Optical properties of highly n-doped germanium obtained by in situ doping and laser annealing
High n-type doping in germanium is essential for many electronic and optoelectronic applications especially for high performance Ohmic contacts, lasing and mid-infrared plasmonics. We report on the combination of in situ doping and excimer laser annealing to improve the activation of phosphorous in germanium. An activated n-doping concentration of 8.8 × 1019 cm−3 has been achieved starting from an incorporated phosphorous concentration of 1.1 × 1020 cm−3. Infrared reflectivity data fitted with a multi-layer Drude model indicate good uniformity over a 350 nm thick layer. Photoluminescence demonstrates clear bandgap narrowing and an increased ratio of direct to indirect bandgap emission confirming the high doping densities achieved
n-Ge on Si for Mid-Infrared Plasmonic Sensors
The detection and amplification of molecular absorption lines from a mustard gas simulant is demonstrated using plasmonic antennas fabricated from n-Ge epitaxially grown on Si. Approaches to integrated sensors will be presented along with a review of n-Ge compared to other mid-infrared plasmonic materials
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