bluuebunny/crossref_metadata_2025_split huggingface dataset:
Class I and IIa HDACs Mediate HIF-1α Stability Through PHD2-Dependent Mechanism, While HDAC6, a Class IIb Member, Promotes HIF-1α Transcriptional Activity in Nucleus Pulposus Cells of the Intervertebral Disc
Authors: Schoepflin Zachary R , Shapiro Irving M , Risbud Makarand V 
Published: January 2016

ABSTRACT

The objective of this study was to determine the role of histone deacetylases (HDACs) in regulating HIF-1α protein stability and activity in nucleus pulposus (NP) cells. Treatment of NP cells with pan-HDAC inhibitor TSA resulted in decreased HIF-1α levels under both normoxia and hypoxia in a dose-dependent fashion. TSA-mediated HIF-1α degradation was rescued by concomitant inhibition of not only the 26S proteasome but also PHD2 function. Moreover, TSA treatment of PHD2−/− cells had little effect on HIF-1α levels, supporting the notion that inhibition of PHD2 function by HDACs contributed to HIF-1α stabilization. Surprisingly, class-specific HDAC inhibitors did not affect HIF-1α protein stability, indicating that multiple HDACs controlled HIF-1α stability by regulating HIF-1α-PHD2 interaction in NP cells. Interestingly, lower-dose TSA that did not affect HIF-1α stability decreased its activity and target gene expression. Likewise, rescue of TSA-mediated HIF-1α protein degradation by blocking proteasomal or PHD activity did not restore HIF-1 activity, suggesting that HDACs independently regulate HIF-1α stability and activity. Noteworthy, selective inhibition of HDAC6 and not of class I and IIa HDACs decreased HIF-1-mediated transcription under hypoxia to a similar extent as lower-dose TSA, contrasting the reported role of HDAC6 as a transcriptional repressor in other cell types. Moreover, HDAC6 inhibition completely blocked TSA effects on HIF-1 activity. HDAC6 associated with and deacetylated HSP90, an important cofactor for HIF-1 function in NP cells, and HDAC6 inhibition decreased p300 transactivation in NP cells. Taken together, these results suggest that although multiple class I and class IIa HDACs control HIF-1 stability, HDAC6, a class IIb HDAC, is a novel mediator of HIF-1 activity in NP cells possibly through promoting action of critical HIF-1 cofactors. © 2016 American Society for Bone and Mineral Research.
Ameloblastin, an Extracellular Matrix Protein, Affects Long Bone Growth and Mineralization
Authors: Lu Xuanyu , Fukumoto Satoshi , Yamada Yoshihiko , Evans Carla A , Diekwisch Thomas GH , Luan Xianghong 
Published: January 2016

ABSTRACT

Matrix molecules such as the enamel-related calcium-binding phosphoprotein ameloblastin (AMBN) are expressed in multiple tissues, including teeth, bones, and cartilage. Here we have asked whether AMBN is of functional importance for timely long bone development and, if so, how it exerts its function related to osteogenesis. Adolescent AMBN-deficient mice (AMBNΔ5–6) suffered from a 33% to 38% reduction in femur length and an 8.4% shorter trunk spinal column when compared with WT controls, whereas there was no difference between adult animals. On a cellular level, AMBN truncation resulted in a shortened growth plate and a 41% to 49% reduction in the number of proliferating tibia chondrocytes and osteoblasts. Bone marrow stromal cells (BMSCs) isolated from AMBN mutant mice displayed defects in proliferation and differentiation potential as well as cytoskeleton organization. Osteogenesis-related growth factors, such as insulin-like growth factor 1 (IGF1) and BMP7, were also significantly (46% to 73%) reduced in AMBN-deficient BMSCs. Addition of exogenous AMBN restored cytoskeleton structures in AMBN mutant BMSCs and resulted in a dramatic 400% to 600% increase in BMP2, BMP7, and Col1A expression. Block of RhoA diminished the effect of AMBN on osteogenic growth factor and matrix protein gene expression. Addition of exogenous BMP7 and IGF1 rescued the proliferation and differentiation potential of AMBN-deficient BMSCs. Confirming the effects of AMBN on long bone growth, back-crossing of mutant mice with full-length AMBN overexpressors resulted in a complete rescue of AMBNΔ5–6 bone defects. Together, these data indicate that AMBN affects extracellular matrix production and cell adhesion properties in the long bone growth plate, resulting in altered cytoskeletal dynamics, increased osteogenesis-related gene expression, as well as osteoblast and chondrocyte proliferation. We propose that AMBN facilitates rapid long bone growth and an important growth spurt during the skeletogenesis of adolescent tooth-bearing vertebrates. © 2016 American Society for Bone and Mineral Research.
Regulation of Sclerostin Expression in Multiple Myeloma by Dkk-1: A Potential Therapeutic Strategy for Myeloma Bone Disease
Authors: Eda Homare , Santo Loredana , Wein Marc N , Hu Dorothy Z , Cirstea Diana D , Nemani Neeharika , Tai Yu-Tzu , Raines Sarah E , Kuhstoss Stuart Allen , Munshi Nikhil C , Kronenberg Henry M , Raje Noopur S 
Published: January 2016

ABSTRACT

Sclerostin is a potent inhibitor of osteoblastogenesis. Interestingly, newly diagnosed multiple myeloma (MM) patients have high levels of circulating sclerostin that correlate with disease stage and fractures. However, the source and impact of sclerostin in MM remains to be defined. Our goal was to determine the role of sclerostin in the biology of MM and its bone microenvironment as well as investigate the effect of targeting sclerostin with a neutralizing antibody (scl-Ab) in MM bone disease. Here we confirm increased sclerostin levels in MM compared with precursor disease states like monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM. Furthermore, we found that a humanized MM xenograft mouse model bearing human MM cells (NOD-SCID.CB17 male mice injected intravenously with 2.5 million of MM1.S-Luc-GFP cells) demonstrated significantly higher concentrations of mouse-derived sclerostin, suggesting a microenvironmental source of sclerostin. Associated with the increased sclerostin levels, activated β-catenin expression levels were lower than normal in MM mouse bone marrow. Importantly, a high-affinity grade scl-Ab reversed osteolytic bone disease in this animal model. Because scl-Ab did not demonstrate significant in vitro anti-MM activity, we combined it with the proteasome inhibitor carfilzomib. Our data demonstrated that this combination therapy significantly inhibited tumor burden and improved bone disease in our in vivo MM mouse model. In agreement with our in vivo data, sclerostin expression was noted in marrow stromal cells and osteoblasts of MM patient bone marrow samples. Moreover, MM cells stimulated sclerostin expression in immature osteoblasts while inhibiting osteoblast differentiation in vitro. This was in part regulated by Dkk-1 secreted by MM cells and is a potential mechanism contributing to the osteoblast dysfunction noted in MM. Our data confirm the role of sclerostin as a potential therapeutic target in MM bone disease and provides the rationale for studying scl-Ab combined with proteasome inhibitors in MM. © 2016 American Society for Bone and Mineral Research.
Investigation of the Effect of Some Optically Active Imine Compounds on the Enzyme Activities of hCA‐I and hCA‐II under In Vitro Conditions: An Experimental and Theoretical Study
Authors: Tektas Osman , Akkemik Ebru , Baykara Haci 
Published: January 2016

ABSTRACTInhibitors of carbonic anhydrase (hCA; EC 4.2.1.1) are used as medicines for many diseases. Therefore, they are very important. In this study, a known series of Schiff bases were synthesized and their effects on the activities of hCA‐I and hCA‐II, which are cytosolic isoenzymes of carbonic anhydrase, were investigated under in vitro conditions. The synthesized compounds (H1, H2, H3, and H4) were found to cause inhibition on enzyme activities of hCA‐1 and hCA‐II. IC50 values of H1, H2, H3, and H4 compounds were 140, 88, 201, and 271 μM for hCA‐I enzyme activity and 134, 251, 79, and 604 μM for hCA‐II enzyme activity, respectively. The synthesized Schiff bases were characterized by several methods, including 1H NMR, FT‐IR, elemental analysis, and polarimetric measurements. Correlation coefficient square values (R2) of comparison of the theoretical and experimental 1H NMR shifts for H1, H2, H3, and H4 compounds were found as 0.9781, 0.9814, 0.9758, and 0.8635, respectively.
Venous access for hematopoietic progenitor cell collection: An international survey by the ASFA HPC donor subcommittee
Authors: O'Leary Mandy Flannery , Dunbar Nancy M. , Kim Haewon C. , Draper Nicole L. , Linenberger Michael , Schwartz Joseph , Miller Yvette , Murtaugh Ally , West F. Bernadette , Fernando Leonor P. , Park Yara A. 
Published: January 2016

Purpose:Hematopoietic Progenitor Cell (HPC) collection by apheresis is performed in patients and donors to obtain HPCs for transplantation. Although studies have shown these procedures to be safe, successful collection cannot be performed without establishment of venous access. This project's objective was to ascertain the current practices of donor vein assessment and central venous catheter (CVC) usage. Methods: The American Society for Apheresis (ASFA) HPC subcommittee created an electronic survey about precollection vein assessment and line placement, care, and removal in autologous and allogeneic donors. It was distributed to >5,000 possible participants, with one response analyzed per institution. Results: One hundred centers performing autologous and/or allogeneic procedures provided adequate responses for analysis. Donor vein assessment is most often performed by apheresis staff more than 1 week prior to collection. For patients with questionable access, the next step performed most often is secondary assessment for autologous procedures and CVC placement for allogeneic procedures. Most centers use interventional radiology to place CVCs in jugular veins on collection day with placement verification through electronic medical records. Verbal and written postinsertion CVC care instructions are routinely provided. The apheresis team frequently provides postinsertion CVC care for autologous patients. Heparin is used most often for CVC lock. When used, tissue plasminogen activator is usually instilled for up to 60 min. Conclusion: These data summarize the largest single survey of donor vein assessment at institutions performing HPC collections by apheresis. The variations identified in donor venous access practice warrant further investigation and consensus to establish best practices. J. Clin. Apheresis 31:529–534, 2016. © 2015 Wiley Periodicals, Inc.
Switching Opioid‐Dependent Patients From Methadone to Morphine: Safety, Tolerability, and Methadone Pharmacokinetics
Authors: Glue Paul , Cape Gavin , Tunnicliff Donna , Lockhart Michelle , Lam Fred , Gray Andrew , Hung Noelyn , Hung C. Tak , Harland Sarah , Devane Jane , Howes John , Weis Holger , Friedhoff Lawrence 
Published: January 2016

AbstractThe aim of this study was to switch patients established on methadone opioid substitution therapy (OST) to morphine over 1 week. Subjects established on daily methadone OST (mean dose 60 mg/day) were switched to morphine slow‐release capsules, dosed at 4× the previous total daily methadone dose, for 6 days, then given morphine syrup dosed q3h. All 27 subjects enrolled in this study completed the switch from methadone to morphine. Opioid withdrawal symptoms (OWS) peaked within 12–24 hours of starting morphine, and 24/27 subjects required higher daily morphine doses (mean 5.2× multiple). Pharmacokinetic evaluation showed that 91% of methadone was cleared during this time, with a mean elimination half‐life of 59 hours. The most frequent treatment‐emergent non‐OWS adverse events were headache, nausea, constipation, and neck pain. The method described here appears to be a safe and acceptable approach to switch subjects from methadone to morphine.
Petersen Cores and the Oddness of Cubic Graphs
Authors: Jin Ligang , Steffen Eckhard 
Published: January 2016

AbstractLet G be a bridgeless cubic graph. Consider a list of k 1‐factors of G. Let be the set of edges contained in precisely i members of the k 1‐factors. Let be the smallest over all lists of k 1‐factors of G. We study lists by three 1‐factors, and call with a ‐core of G. If G is not 3‐edge‐colorable, then . In Steffen (J Graph Theory 78 (2015), 195–206) it is shown that if , then is an upper bound for the girth of G. We show that bounds the oddness of G as well. We prove that . If , then every ‐core has a very specific structure. We call these cores Petersen cores. We show that for any given oddness there is a cyclically 4‐edge‐connected cubic graph G with . On the other hand, the difference between and can be arbitrarily big. This is true even if we additionally fix the oddness. Furthermore, for every integer , there exists a bridgeless cubic graph G such that .
Aggregate and hospital‐level impact of national guidelines on diagnostic resource utilization for children with pneumonia at children's hospitals
Authors: Parikh Kavita , Hall Matt , Blaschke Anne J. , Grijalva Carlos G. , Brogan Thomas V. , Neuman Mark I. , Williams Derek J. , Gerber Jeffrey S. , Hersh Adam L. , Shah Samir S. 
Published: January 2016

BACKGROUNDNational guidelines for the management of community‐acquired pneumonia (CAP) in children were published in 2011. These guidelines discourage most diagnostic testing for outpatients, as well as repeat testing for hospitalized patients who are improving. We sought to evaluate the temporal trends in diagnostic testing associated with guideline implementation among children with CAP.METHODSChildren 1 to 18 years old who were discharged with pneumonia after emergency department (ED) evaluation or hospitalization from January 1, 2008 to June 30, 2014 at any of 32 children's hospitals participating in the Pediatric Health Information System were included. We excluded children with complex chronic conditions and those requiring intensive care or who underwent early pleural drainage. We compared use of diagnostic testing (blood culture, complete blood count [CBC], C‐reactive protein [CRP], and chest radiography [CXR]) before and after release of the guidelines, and assessed for temporal trends using interrupted time series analysis. We also calculated the cost impact of these changes on diagnostic utilization and evaluated the variability of the guideline's impact across hospitals.RESULTSOverall, 220,539 patients were included; 53% were male and the median age was 4 years (interquartile range, 2–7). For patients discharged from the ED with CAP, diagnostic utilization rates for blood culture, CBC, CRP, and CXR were higher after guideline publication compared with expected utilization rates without guidelines. In contrast, initial testing and repeat testing among patients hospitalized with CAP was lower after guideline publication. There were modest reductions in estimated costs associated with these changes. However, wide variability was observed in the impact of the guidelines across hospitals.CONCLUSIONSPublication of national pneumonia guidelines in 2011 was associated with modest changes in diagnostic testing for children with CAP. However, the changes varied across hospitals, and the financial impact was modest. Local implementation efforts are warranted to ensure widespread guideline adherence. Journal of Hospital Medicine 2016;11:317–323. © 2016 Society of Hospital Medicine
An assessment of ancient DNA preservation in Holocene–Pleistocene fossil bone excavated from the world heritage Naracoorte Caves, South Australia
Authors: Grealy Alicia , Macken Amy , Allentoft Morten E. , Rawlence Nicolas J. , Reed Elizabeth , Bunce Michael 
Published: January 2016

ABSTRACTAlthough there is a long history of research into the fossil deposits of the Naracoorte Caves (South Australia), ancient DNA (aDNA) has not been integrated into any palaeontological study from this World Heritage site. Here, we provide the first evidence of aDNA preservation in Holocene‐ and Pleistocene‐aged fossil bone from a deposit inside Robertson Cave. Using a combination of metabarcoding and shotgun next‐generation sequencing approaches, we demonstrate that aDNA from diverse taxa can be retrieved from bulk bone as old as 18 600 cal a BP. However, the DNA is highly degraded and contains a lower relative proportion of endogenous sequences in bone older than 8400 cal a BP. Furthermore, modelling of DNA degradation suggests that the decay rate is rapid, and predicts a very low probability of obtaining informative aDNA sequences from extinct megafaunal bones from Naracoorte (ca. 50 000 cal a BP). We also provide new information regarding the past faunal biodiversity of Robertson Cave, including families that have not been formerly described in the fossil record from here before. Collectively, these data demonstrate the potential for future aDNA studies to be conducted on material from Naracoorte, which will aid in the understanding of faunal turnover in southern Australia.
The onset of ultrashort pulse‐induced nanogratings
Authors: Zimmermann Felix , Plech Anton , Richter Sören , Tünnermann Andreas , Nolte Stefan 
Published: January 2016

The fundamental formation process of nanogratings induced by focused ultrashort laser pulses inside the bulk of transparent materials is still object of intense debate. In particular the initial evolutionary steps, including the formation of anisotropic pores, alignment and arrangement in highly periodic grating planes could not been clarified up to now. To this end we have performed a comprehensive investigation of this process by optical retardance measurements, small‐angle X‐ray scattering, and focused ion beam milling in combination with scanning electron microscopy. The results show that the formation of nanogratings starts with isotropic, deterministic voids after the first incident laser pulse which start to elongate perpendicular to the laser scan direction with further illumination and the appearance of cracks along the scan direction. For increasing pulse overlap these cracks as well as randomly aligned voids build the template for the subsequent pore growth perpendicular to the laser polarization. The process of grating formation and subsequent period reduction occurs via increasing number of sheets and mutual realignment forming a more porous glass matrix.
image
A New Generation Co‐Assembled Small Molecular Gel with Polyaniline: Exciting Mechanical, Electronic and Photovoltaic Properties
Authors: Chakraborty Priyadarshi , Bairi Partha , Nandi Arun K. 
Published: January 2016

SummaryFolic acid (F), Fmoc‐protected phenylalanine (FP) and 5,5′‐(1,3,5,7‐tetraoxopyrrolo[3,4‐f]isoindole‐2,6‐diyl) diisophthalic acid (PMDIG) are used to produce co‐assembled gels with polyaniline(PANI). The formation of PANI inside the gel matrices are confirmed by FTIR and UV‐vis spectroscopy. UV‐vis spectra also exhibit the polaron band transitions of the doped PANI. Both F‐PANI and PMDIG‐PANI gels exhibit fibrillar network morphogy but the branching is more in the F‐PANI gel. The FP‐PANI gel however exhibits nanotubular morphology. The dc conductivity values of F‐PANI, FP‐PANI and PMDIG‐PANI xerogels are 0.14 × 10−4, 0.12 × 10−1 and 0.3 × 10−4 S/cm, respectively. The current–voltage (I–V) curves of the F‐PANI gel shows a negative differential resistance(NDR) property both at forward and backward bias. The I–V property of the FP‐PANI xerogel resembles to the behavior of a semiconductor‐metal junction and that of PMDIG‐PANI xerogel exhibits a signature of rectification property. A dye‐sensitized solar cell is also fabricated using the PMDIG‐PANI gel with a power conversion efficiency of 0.1%.
The Role of Molecular Interactions in Controlling Methanol Diffusion in Polyimides: A Time‐Resolved FTIR Spectroscopy Investigation
Authors: Musto Pellegrino , La Manna Pietro , Pannico Marianna 
Published: January 2016

SummaryPolyimides are a well‐known class of high‐performance polymers with excellent properties and a wide range of applications, especially as membranes for gas and liquid separation. In this contribution a molecular level description of the methanol diffusion in three different polyimides is reported. Two commercial polyimides (PMDA‐ODA and Ultem 1000) and a third one synthetized ad‐hoc (6FDA‐ODA) were examined in detail by time‐resolved FTIR spectroscopy supplemented with gravimetric analysis. Complementary approaches were employed for the interpretation of the spectral data [difference spectroscopy (DS) and least‐squares curve fitting (LSCF)]. Information about the overall diffusivity, the interactions and the dynamics of the molecular species in the polymer/penetrant systems were provided.
Chiral Optical Response of Achiral and Enantiomeric Guests in Syndiotactic Polystyrene Films
Authors: Ianniello Graziella , Lepera Eugenia , Rizzo Paola 
Published: January 2016

SummaryCircular dichroism of achiral (azulene and 4‐nitro‐aniline) and non‐racemic, enantiomeric molecules (carvone), being guests of s‐PS films crystallized with a non racemic guest, have been studied. Surprisingly the chiral response of the considered achiral guests is definitely higher than for the chirality‐inducing non‐racemic guest (carvone). This clearly indicates that the origin of the chiral‐optical response is extrinsic to the site of photon absorption. As for the circular dichroism of non‐racemic, enantiomeric guest molecules, after desorption and renewed absorption in sPS films, it has been observed that chiral response does not depend on their R or S molecular chirality but essentially only on the polymer host supramolecular chirality.
Nanoporous Semicrystalline Syndiotactic Polystyrene with Sulfonated Amorphous Phase, for a Fast and Efficient Removal of VOC Pollutant Traces From Water
Authors: Daniel Christophe , Pellegrino Marina , Borriello Anna , Venditto Vincenzo 
Published: January 2016

SummarySyndiotactic polystyrene films and aerogels with nanoporous crystalline phase and sulfonated amorphous phase have been prepared and characterized. The nanoporous nature of the crystalline phase confers to these materials a high solubility of volatile organic compounds (VOCs) from aqueous solutions even at low VOC concentrations while the sulfonation of the amorphous phase enhance the VOC sorption kinetics. These combined properties make these materials particularly interesting for a potential use as a sorption medium to remove traces of pollutants from water. Different aspects relative to the preparation, the structure and the transport properties of these innovative polymeric materials are described.
Cylindromatosis—A Protective Molecule against Liver Diseases
Authors: Hellerbrand Claus , Massoumi Ramin 
Published: January 2016

AbstractCylindromatosis (CYLD) is a deubiquitination enzyme involved in the regulation of different cellular processes including inflammation, fibrosis, and cancer. The function of CYLD is via deubiquitination of specific substrates in different signaling pathways including NF‐κB, Notch, and JNK. CYLD contributes to hepatic homeostasis and restoration upon liver injury. Mutation or disruption of the activity of CYLD in animals aggravates acute as well as chronic liver injury and promotes development and progression of hepatocellular cancer. This is mediated by a shift of the balance toward pro‐inflammatory, pro‐fibrogenic, and pro‐oncogenic pathways. In this review, we will explain the liver‐associated signaling pathways that CYLD regulates in hepatocytes and nonparenchymal liver cells under physiological and pathological conditions. We will also describe the most recent findings concerning CYLD‐mediated downstream signaling in the liver in situations such as injury, infection, inflammation, and cancer. Furthermore, we will discuss the potential of novel diagnostic tools and treatment strategies utilizing CYLD and its target genes.