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Nadia A Akawi, Salma Ben-Salem, Jozef Hertecant, Anne John, Thachillath Pramathan, Praseetha Kizhakkedath, Bassam R Ali, Lihadh Al-Gazali
BACKGROUND: The group of ELAC2-related encephalomyopathies is a recent addition to the rapidly growing heterogeneous mitochondrial disorders. RESULTS: We describe a highly inbred consanguineous Pakistani family with multiple affected children in 2 branches exhibiting moderately severe global developmental delay. Using homozygosity mapping, we mapped the phenotype in this family to a single locus on chromosome 17. In addition, whole-exome sequencing identified a homozygous splicing mutation (c...
October 21, 2016: Orphanet Journal of Rare Diseases
Ryan C Shelstad, Justin G Reeves, Katsuhiro Yamanaka, T Brett Reece
We review the operative techniques of aortic arch replacement. Aortic arch replacement presents several formidable challenges, as it requires arresting the circulation to the body and replacement of the brachiocephalic vessels with special consideration for protecting the central nervous system. Perfusion strategies, selective antegrade cerebral perfusion, and operative graft selection are key elements in aortic arch replacement surgery. Standard approaches include the island technique, the branched graft technique, and the "Spielvogel" trifurcated graft technique-each having its own advantages...
October 7, 2016: Seminars in Cardiothoracic and Vascular Anesthesia
T A Tomsick, J Carrozzella, L Foster, M D Hill, R von Kummer, M Goyal, A M Demchuk, P Khatri, Y Palesch, J P Broderick, S D Yeatts, D S Liebeskind
BACKGROUND AND PURPOSE: Uncertainty persists regarding the safety and efficacy of endovascular therapy of M2 occlusions following IV tPA. We reviewed the impact of revascularization on clinical outcomes in 83 patients with M2 occlusions in the Interventional Management of Stroke III trial according to specific M1-M2 segment anatomic features. MATERIALS AND METHODS: Perfusion of any M2 branch distinguished M2-versus-M1 occlusion. Prespecified modified TICI and arterial occlusive lesion revascularization and clinical mRS 0-2 end points at 90 days for endovascular therapy-treated M2 occlusions were analyzed...
October 20, 2016: AJNR. American Journal of Neuroradiology
Lucas C Wheeler, Micah T Donor, James S Prell, Michael J Harms
The S100 proteins are a large family of signaling proteins that play critical roles in biology and disease. Many S100 proteins bind Zn2+, Cu2+, and/or Mn2+ as part of their biological functions; however, the evolutionary origins of binding remain obscure. One key question is whether divalent transition metal binding is ancestral, or instead arose independently on multiple lineages. To tackle this question, we combined phylogenetics with biophysical characterization of modern S100 proteins. We demonstrate an earlier origin for established S100 subfamilies than previously believed, and reveal that transition metal binding is widely distributed across the tree...
2016: PloS One
L Kostka, T Etrych
In this work, design and synthesis of high-molecular-weight N-(2-hydroxypropyl)methacrylamide-based polymer drug delivery systems tailored for cancer therapy is summarized. Moreover, the influence of their architecture on tumor accumulation and in vivo anti-cancer efficacy is discussed. Mainly, the high-molecular-weight delivery systems, such as branched, grafted, multi-block, star-like or micellar systems, with molecular weights greater than the renal threshold are discussed and reviewed in detail.
October 20, 2016: Physiological Research
Bishoy M Faltas, Davide Prandi, Scott T Tagawa, Ana M Molina, David M Nanus, Cora Sternberg, Jonathan Rosenberg, Juan Miguel Mosquera, Brian Robinson, Olivier Elemento, Andrea Sboner, Himisha Beltran, Francesca Demichelis, Mark A Rubin
Chemotherapy-resistant urothelial carcinoma has no uniformly curative therapy. Understanding how selective pressure from chemotherapy directs the evolution of urothelial carcinoma and shapes its clonal architecture is a central biological question with clinical implications. To address this question, we performed whole-exome sequencing and clonality analysis of 72 urothelial carcinoma samples, including 16 matched sets of primary and advanced tumors prospectively collected before and after chemotherapy. Our analysis provided several insights: (i) chemotherapy-treated urothelial carcinoma is characterized by intra-patient mutational heterogeneity, and the majority of mutations are not shared; (ii) both branching evolution and metastatic spread are very early events in the natural history of urothelial carcinoma; (iii) chemotherapy-treated urothelial carcinoma is enriched with clonal mutations involving L1 cell adhesion molecule (L1CAM) and integrin signaling pathways; and (iv) APOBEC-induced mutagenesis is clonally enriched in chemotherapy-treated urothelial carcinoma and continues to shape the evolution of urothelial carcinoma throughout its lifetime...
October 17, 2016: Nature Genetics
Marlen Thiere, Stefanie Kliche, Bettina Müller, Jan Teuber, Isabell Nold, Oliver Stork
Integrin-mediated cell adhesion and signaling is of critical importance for neuronal differentiation. Recent evidence suggests that an "inside-out" activation of β1-integrin, similar to that observed in hematopoietic cells, contributes to the growth and branching of dendrites. In this study, we investigated the role of the hematopoietic adaptor protein adhesion and degranulation promoting adapter protein (ADAP) in these processes. We demonstrate the expression of ADAP in the developing and adult nervous hippocampus, and in outgrowing dendrites of primary hippocampal neurons...
2016: Frontiers in Molecular Neuroscience
Simon P Overeem, Johannes T Boersen, Richte C L Schuurmann, Erik Groot Jebbink, Cornelis H Slump, Michel M P J Reijnen, Jean-Paul P M de Vries
OBJECTIVE: Gutters can be described as the loss of continuous apposition between the main body of the endograft, the chimney stent graft, and the aortic wall. Gutters have been associated with increased risk of type IA endoleaks and are considered to be the Achilles' heel of chimney endovascular aneurysm repair (ch-EVAR). However, there is no classification yet to classify and quantify gutter types after ch-EVAR. METHODS: Different gutter types can be distinguished by their morphologic appearance in two- and three-dimensional views and reconstructed slices perpendicular to the center lumen line...
October 12, 2016: Journal of Vascular Surgery
C T Angell, R Hajima, T Shizuma, B Ludewigt, B J Quiter
In recent measurements of the scissors mode in radiative decay experiments, transition strengths were observed that were double that expected from theory and systematics well established from measurements on the radiative excitation channel, that is, using nuclear resonance fluorescence (NRF). Additional strength as measured with NRF can only be present as heretofore unobserved branching or fragmentation of the scissors mode. Such possibilities were investigated in a transmission NRF measurement on the deformed, odd-mass ^{181}Ta, using a quasimonoenergetic γ-ray beam at two beam energies...
September 30, 2016: Physical Review Letters
C G Bruno, D A Scott, M Aliotta, A Formicola, A Best, A Boeltzig, D Bemmerer, C Broggini, A Caciolli, F Cavanna, G F Ciani, P Corvisiero, T Davinson, R Depalo, A Di Leva, Z Elekes, F Ferraro, Zs Fülöp, G Gervino, A Guglielmetti, C Gustavino, Gy Gyürky, G Imbriani, M Junker, R Menegazzo, V Mossa, F R Pantaleo, D Piatti, P Prati, E Somorjai, O Straniero, F Strieder, T Szücs, M P Takács, D Trezzi
The ^{17}O(p,α)^{14}N reaction plays a key role in various astrophysical scenarios, from asymptotic giant branch stars to classical novae. It affects the synthesis of rare isotopes such as ^{17}O and ^{18}F, which can provide constraints on astrophysical models. A new direct determination of the E_{R}=64.5  keV resonance strength performed at the Laboratory for Underground Nuclear Astrophysics (LUNA) accelerator has led to the most accurate value to date ωγ=10.0±1.4_{stat}±0.7_{syst}  neV, thanks to a significant background reduction underground and generally improved experimental conditions...
September 30, 2016: Physical Review Letters
Hannes Schmidt, Stefanie Peters, Katharina Frank, Lai Wen, Robert Feil, Fritz G Rathjen
A cGMP signaling pathway, comprising C-type natriuretic peptide (CNP), its guanylate cyclase receptor Npr2, and cGMP-dependent protein kinase I (cGKI), is critical for the bifurcation of dorsal root ganglion (DRG) and cranial sensory ganglion axons when entering the mouse spinal cord and the hindbrain, respectively. However, the identity and functional relevance of phosphodiesterases (PDEs) that degrade cGMP in DRG neurons are not completely understood. Here we asked whether regulation of the intracellular cGMP concentration by PDEs modulates the branching of sensory axons...
October 14, 2016: European Journal of Neuroscience
Claudia Schaarschmidt, Christof Kolb
The subcutaneous implantable defibrillator (S-ICD) has become an established tool for the prevention of sudden cardiac death. Based on its detection properties, the S‑ICD is essentially dependent on correct morphology discrimination of the QRS complex and avoidance of potential T‑wave sensing. We report on a patient who experienced multiple inappropriate S‑ICD shocks due to T‑wave oversensing in the setting of new onset of right bundle branch block. Strategies for the optimisation of the device programming are discussed...
October 13, 2016: Herzschrittmachertherapie & Elektrophysiologie
I E Chazova, T V Martynyuk
Chronic thromboembolic pulmonary hypertension (CTEPH) is precapillary pulmonary hypertension, in which chronic obstruction of large and middle branches of pulmonary arteries (PAs) and secondary changes in the lung microcirculatory bed result in a progressive increase in pulmonary vascular resistance and PA pressure with the development of severe right cardiac dysfunction and heart failure. CTEPH is a unique form of pulmonary hypertension since it is potentially curable by surgical treatment. The diagnostic criteria for CTEPH are a mean PA pressure of ≥25 mm Hg, as evidenced by right heart catheterization; a PA wedge pressure of ≤15 mm Hg; a pulmonary vascular resistance of >2 Wood units; the presence of chronic/organized thrombi/emboli in the elastic PAs (pulmonary trunk, lobular, segmental, subsegmental PAs); effective anticoagulant therapy at therapeutic dosages over at least 3 months...
2016: Terapevticheskiĭ Arkhiv
R Fernández Del Río, M E O'Hara, P Pemberton, T Whitehouse, C A Mayhew
Isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether), C3H2ClF5O, is a commonly used inhalation anaesthetic. Using a proton transfer reaction mass spectrometer (PTR-MS) we have detected isoflurane in the breath of patients several weeks following major surgery. That isoflurane is detected in the breath of patients so long after being anaesthetised raises questions about when cognitive function has fully returned to a patient. Temporal profiles of isoflurane concentrations in breath are presented for five patients (F/M 3/2, mean age 50 years, min-max 36-58 years) who had undergone liver transplant surgery...
October 12, 2016: Journal of Breath Research
Qingyong Meng, Kevin M Hickson, Kejie Shao, Jean-Christophe Loison, Dong H Zhang
The rate coefficients of the barrierless O((1)D) + CH4 reaction are determined both theoretically and experimentally at 50-296 K. For the calculations, ring polymer molecular dynamics (RPMD) simulations are performed on the basis of a new neural network potential energy surface (PES) in the reactant asymptotic part. Only the reactant asymptotic part of the PES is constructed because of its barrierless and exothermic properties. Experimentally, the reaction rate coefficients are measured using a supersonic flow reactor...
October 12, 2016: Physical Chemistry Chemical Physics: PCCP
Rajiv T Sawant, Marc Y Stevens, Christian Sköld, Luke R Odell
A novel metal-free microwave-assisted branching cascades strategy for the efficient synthesis of 3,4-dihydroquinazolinone-embedded polyheterocyclic scaffolds is reported. Starting from in situ generated key N-acyliminium ion precursors, 12 distinct and skeletally diverse polycyclic frameworks were accessed in a single step/pot via adjustment of the nucleophile(s) and reaction conditions. Postcascade functionalization of these compounds was also demonstrated, proving the utility of this method in accessing structurally diverse chemical entities...
October 11, 2016: Organic Letters
Matias R Fagiani, Harald Knorke, Tim K Esser, Nadja Heine, Conrad T Wolke, Sandy Gewinner, Wieland Schöllkopf, Marie-Pierre Gaigeot, Riccardo Spezia, Mark A Johnson, Knut R Asmis
We use cryogenic ion trap vibrational spectroscopy to study the structure of the protonated water pentamer, H(+)(H2O)5, and its fully deuterated isotopologue, D(+)(D2O)5, over nearly the complete infrared spectral range (220-4000 cm(-1)) in combination with harmonic and anharmonic electronic structure calculations as well as RRKM modelling. Isomer-selective IR-IR double-resonance measurements on the H(+)(H2O)5 isotopologue establish that the spectrum is due to a single constitutional isomer, thus discounting the recent analysis of the band pattern in the context of two isomers based on AIMD simulations 〈W...
September 29, 2016: Physical Chemistry Chemical Physics: PCCP
Genki Ozawa, Shigeru Shimamura, Yoshihiro Takaki, Shin-Ichi Yokobori, Yasuhiko Ohara, Kiyotaka Takishita, Tadashi Maruyama, Katsunori Fujikura, Takao Yoshida
The mitochondrial genomes of bivalves have often been used for comparative genomics and for resolving phylogenetic relationships. More than 100 bivalve complete mitochondrial genomes have been sequenced to date. However, few mitochondrial genomes have been reported for deep-sea chemosymbiotic bivalves, which belong to the subclasses Pteriomorphia and Heterodonta. In the present study, we sequenced the mitochondrial genomes of eight deep-sea chemosymbiotic bivalve species: three species of Bathymodiolus mussels (B...
October 6, 2016: Marine Genomics
Timo H Lüdtke, Carsten Rudat, Irina Wojahn, Anna-Carina Weiss, Marc-Jens Kleppa, Jennifer Kurz, Henner F Farin, Anne Moon, Vincent M Christoffels, Andreas Kispert
Numerous signals drive the proliferative expansion of the distal endoderm and the underlying mesenchyme during lung branching morphogenesis, but little is known about how these signals are integrated. Here, we show by analysis of conditional double mutants that the two T-box transcription factor genes Tbx2 and Tbx3 act together in the lung mesenchyme to maintain branching morphogenesis. Expression of both genes depends on epithelially derived Shh signaling, with additional modulation by Bmp, Wnt, and Tgfβ signaling...
October 4, 2016: Developmental Cell
Valeria Perugini, Anna L Guildford, Joana Silva-Correia, Joaquim M Oliveira, Steven T Meikle, Rui L Reis, Matteo Santin
Damage of non-vascularised tissues such as cartilage and cornea can result in healing processes accompanied by a non-physiological angiogenesis. Peptidic aptamers have recently been reported to block the vascular endothelial growth factor (VEGF). However, the therapeutic applications of these aptamers is limited due to their short half-life in vivo. In this work, an enhanced stability and bioavailability of a known VEGF blocker aptamer sequence (WHLPFKC) was pursued through its tethering of molecular scaffolds based on hyperbranched peptides, the poly(ɛ-lysine) dendrons, bearing three branching generations...
October 8, 2016: Journal of Tissue Engineering and Regenerative Medicine
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