bluuebunny/crossref_metadata_2025_split huggingface dataset:
Axonal Outgrowth and Dendritic Plasticity in the Cortical Peri-Infarct Area After Experimental Stroke
Authors: Ueno Yuji , Chopp Michael , Zhang Li , Buller Benjamin , Liu Zhongwu , Lehman Norman L. , Liu Xian Shuang , Zhang Yi , Roberts Cynthia , Zhang Zheng Gang 
Published: May 2012

Background and Purpose—
Axonal remodeling is critical to brain repair after stroke. The present study investigated axonal outgrowth after stroke and the signaling pathways mediating axonal outgrowth in cortical neurons.

Methods—
Using a rodent model of middle cerebral artery occlusion, we examined high-molecular weight neurofilament (NFH) immunoreactive axons and myelin basic protein-positive oligodendrocytes in the peri-infarct area. In vitro, using cultured cortical neurons in a microfluidic chamber challenged by oxygen-glucose deprivation (OGD), we investigated mechanisms selectively regulating axonal outgrowth after OGD.

Results—

NFH
+
axons and MBP
+
oligodendrocytes substantially increased in the peri-infarct area during stroke recovery, concomitantly with an increase in dendrites and spines identified by Golgi-Cox staining. In vitro, cortical neurons subjected to OGD exhibited significant increases in axonal outgrowth and in phosphorylated NFH protein levels, concurrently with downregulation of phosphatase tensin homolog deleted on chromosome 10, activation of Akt, and inactivation of glycogen synthase kinase-3β in regenerated axons. Blockage of phosphoinositide 3-kinase with pharmacological inhibitors suppressed Akt activation and attenuated phosphorylation of glycogen synthase kinase-3β, which resulted in suppression of phosphorylated NFH and axonal outgrowth after OGD; whereas GSK-3 inhibitors augmented axonal regeneration and elevated phosphorylated NFH levels after OGD.

Conclusions—
Stroke induces axonal outgrowth and myelination in rodent ischemic brain during stroke recovery, and the phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3β signaling pathway mediates axonal regeneration of cortical neurons after OGD.
Apolipoprotein E Genotype Is Associated With CT Angiography Spot Sign in Lobar Intracerebral Hemorrhage
Authors: Brouwers H. Bart , Biffi Alessandro , McNamara Kristen A. , Ayres Alison M. , Valant Valerie , Schwab Kristin , Romero Javier M. , Viswanathan Anand , Greenberg Steven M. , Rosand Jonathan , Goldstein Joshua N. 
Published: May 2012

Background and Purpose—
The CT angiography (CTA) spot sign predicts hematoma expansion and poor outcome in patients with primary intracerebral hemorrhage (ICH). The biological underpinnings of the spot sign remain poorly understood; it may be that the underlying vasculopathy influences its presence. Therefore, we conducted a study to identify genetic predictors of the spot sign.

Methods—
In an ongoing prospective cohort study, we analyzed 371 patients with CTA and genetic data available. CTAs were reviewed for the spot sign by 2 experienced readers, blinded to clinical data, according to validated criteria. Analyses were stratified by ICH location.

Results—
In multivariate analysis, patients on warfarin were more likely to have a spot sign regardless of ICH location (OR, 3.85; 95% CI, 1.33–11.13 in deep ICH and OR, 2.86; 95% CI, 1.33–6.13 in lobar ICH). Apolipoprotein E ϵ2, but not ϵ4, was associated with the presence of a spot sign in lobar ICH (OR, 2.09; 95% CI, 1.05–4.19). There was no effect for ϵ2 or ϵ4 in deep ICH.

Conclusions—
Patients with ICH on warfarin are more likely to present with a spot sign regardless of ICH location. Among patients with lobar ICH, those who possess the apolipoprotein E ϵ2 allele are more likely to have a spot sign. Given the established relationship between apolipoprotein E ϵ2 and vasculopathic changes in cerebral amyloid angiopathy, our findings suggest that both hemostatic factors and vessel pathology influence spot sign presence.
Clinical Significance of Impaired Cerebrovascular Autoregulation After Severe Aneurysmal Subarachnoid Hemorrhage
Authors: Jaeger Matthias , Soehle Martin , Schuhmann Martin U. , Meixensberger Jürgen 
Published: May 2012

Background and Purpose—
The purpose of this study was to investigate the relationship between cerebrovascular autoregulation and outcome after aneurysmal subarachnoid hemorrhage.

Methods—
In a prospective observational study, 80 patients after severe subarachnoid hemorrhage were continuously monitored for cerebral perfusion pressure and partial pressure of brain tissue oxygen for an average of 7.9 days (range, 1.9–14.9 days). Autoregulation was assessed using the index of brain tissue oxygen pressure reactivity (ORx), a moving correlation coefficient between cerebral perfusion pressure and partial pressure of brain tissue oxygen. High ORx indicates impaired autoregulation; low ORx signifies intact autoregulation. Outcome was determined at 6 months and dichotomized into favorable (Glasgow Outcome Scale 4–5) and unfavorable outcome (Glasgow Outcome Scale 1–3).

Results—

Twenty-four patients had a favorable and 56 an unfavorable outcome. In a univariate analysis, there were significant differences in autoregulation (ORx 0.19±0.10 versus 0.37±0.11,
P
<0.001, for favorable versus unfavorable outcome, respectively), age (44.1±11.0 years versus 54.2±12.1 years,
P
=0.001), occurrence of delayed cerebral infarction (8% versus 46%,
P
<0.001), use of coiling (25% versus 54%,
P
=0.02), partial pressure of brain tissue oxygen (24.9±6.6 mm Hg versus 21.8±6.3 mm Hg,
P
=0.048), and Fisher grade (
P
=0.03). In a multivariate analysis, ORx (
P
<0.001) and age (
P
=0.003) retained an independent predictive value for outcome. ORx correlated with Glasgow Outcome Scale (
r
=−0.70,
P
<0.001).

Conclusions—
The status of cerebrovascular autoregulation might be an important pathophysiological factor in the disease process after subarachnoid hemorrhage, because impaired autoregulation was independently associated with an unfavorable outcome.
Crystal structures of protease nexin-1 in complex with heparin and thrombin suggest a 2-step recognition mechanism
Authors: Li Wei , Huntington James A. 
Published: May 2012

AbstractProtease nexin-1 (PN1) is a specific and extremely efficient inhibitor of thrombin. However, unlike other thrombin inhibitors belonging to the serpin family, PN1 is not synthesized in the liver and does not circulate in the blood. Rather, PN1 is expressed by multiple cell types, including macrophages, smooth muscle cells, and platelets, and it is on the surface of these cells, bound to glycosaminoglycans, that PN1 inhibits the signaling functions of thrombin. PN1 sets the threshold for thrombin-induced platelet activation and has been implicated in atherosclerosis. However, in spite of the emerging importance of PN1 in thrombosis and atherosclerosis, little is know about how it associates to cells and how it inhibits thrombin at rates that surpass the diffusion limit. To address these issues, we determined the crystal structures of PN1 in complex with heparin, and in complex with catalytically inert thrombin. The crystal structures suggest a unique 2-step mechanism of thrombin recognition involving rapid electrostatics-driven association to form an initial glycosaminoglycan-bridged complex, followed by a large conformational rearrangement to form the productive Michaelis complex.
Directed migration of mouse macrophages in vitro involves myristoylated alanine-rich C-kinase substrate (MARCKS) protein
Authors: Green Teresa D , Park Joungjoa , Yin Qi , Fang Shijing , Crews Anne L , Jones Samuel L , Adler Kenneth B 
Published: May 2012

Abstract
MARCKS is involved in directed migration of macrophages via a process involving its phosphorylation, cytoplasmic translocation, and interaction with actin.
A role for MARCKS protein in directed migration of macrophages toward a chemoattractant was investigated. A peptide identical to the N-terminus of MARCKS (the MANS peptide), shown previously to inhibit the function of MARCKS in various cell types, was used. We investigated whether this MARCKS-related peptide could affect migration of macrophages, using the mouse macrophage-like J774A.1 cell line and primary murine macrophages. Both of these cell types migrated in response to the chemoattractants macrophage/MCPs, MCP-1 (25–100 ng/ml) or C5a (5–20 ng/ml). Cells were preincubated (15 min) with MANS or a mis-sense control peptide (RNS), both at 50 μM, and effects on migration determined 3 h after addition of chemoattractants. The movement and interactions of MARCKS and actin also were followed visually via confocal microscopy using a fluorescently labeled antibody to MARCKS and fluorescently tagged phalloidin to identify actin. MANS, but not RNS, attenuated migration of J774A.1 cells and primary macrophages in response to MCP-1 or C5a, implicating MARCKS in the cellular mechanism of directed migration. Exposure of cells to MCP-1 resulted in rapid phosphorylation and translocation of MARCKS from plasma membrane to cytosol, whereas actin appeared to spread through the cell and into cell protrusions; there was visual and biochemical evidence of a transient interaction between MARCKS and actin during the process of migration. These results suggest that MARCKS is involved in directed migration of macrophages via a process involving its phosphorylation, cytoplasmic translocation, and interaction with actin.
Preparation of 4,7-Dibromobenzo[b]thiophene as a Versatile Building Block and Synthetic Application to a Bis(ethynylthienyl)oligoarene System
Authors: Yamamoto Takuya , Katsuta Hiroshi , Toyota Kozo , Iwamoto Takeaki , Morita Noboru 
Published: May 2012

Abstract
Benzo[b]thiophene, 4,7-dibromobenzo[b]thiophene, thieno[3,2-b]thiophene, and 3-bromothieno[3,2-b]thiophene were prepared by AuCl-catalyzed cyclization of (t-butylsulfanyl)(ethynyl)benzenes or (t-butylsulfanyl)(ethynyl)thiophenes. Several reactions of 4,7-dibromobenzo[b]thiophene were investigated, including metallation and cross coupling reactions.
Modeling Transport Properties of N2–Noble Gas Mixtures at Low and Moderate Densities
Authors: Mohammad-Aghaie Delara , Papari Mohammad Mehdi , Zargari Farshid 
Published: May 2012

Abstract
In the present paper, the unlike interaction potential energies of some nitrogen-based mixtures were determined via the inversion of reduced viscosity collision integrals and fitted to obtain analytical potential energy forms. The potentials were then applied to Schreiber et al.’s and Chapman–Enskog’s theories to calculate, respectively, the low-density thermal conductivity and other remaining transport properties of the studied mixtures. Further the calculated potential energies were applied to the Vesovic–Wakeham (VW) scheme to predict viscosity of aforementioned mixtures at moderate density. Our estimated average absolute deviation (AAD) for dilute transport properties calculated from the Chapman–Enskog (CE) method is at most to within ±1.5% for the viscosity, ±5% for the diffusion coefficient and ±25% for the thermal diffusion factor. Further, the AAD associated with the dilute thermal conductivity is of the order of ±7% using the Schreiber et al. method. As mentioned above, the calculated unlike interaction energies as well as the low-density interaction viscosity values, were employed then to predict high density viscosities using the VW scheme. The Peng–Robinson equation of state was chosen to calculate the mixture densities required by the Vesovic–Wakeham method. The obtained viscosities in the dense regime deviate from the literature data to within ±2%.
Stability of Amino Acids and Related Compounds in Simulated Submarine Hydrothermal Systems
Authors: Kurihara Hironari , Takano Yoshinori , Kaneko Takeo , Obayashi Yumiko , Kobayashi Kensei 
Published: May 2012

Abstract
Submarine hydrothermal systems (SHSs) have been thought of as a suitable environment for the origin of life subsequent to the abiotic synthesis of organic molecules. However, it has been pointed out that bioorganic molecules, such as amino acids, are easily degraded at a high temperature, and thus not likely to survive for the next step of chemical evolution in a SHS environment. On the other hand, it has been suggested that the main compounds generated abiotically at the first stage of chemical evolution are not “free” amino acid monomers but amino acid precursors with high molecular weights, i.e., complex combined amino acids. In this study, we tested the stability of complex combined amino acids, which were abiotically synthesized from a simulated primitive Earth atmosphere with proton irradiation, in a high-temperature and high-pressure environment compared with that of monomeric amino acids. Complex combined amino acids preserved more amino acids (including amino acid precursors that give amino acids after acid hydrolysis) than free amino acids after heating in simulated SHS environments. Our results suggest the possibility that complex organics prebiotically synthesized by cosmic rays could serve as primitive materials of chemical evolution at hydrothermal systems on primitive Earth.
The Role of Amide Groups in Vinyl Monomers Containing Siloxane Groups for Highly Oxygen Permeable Hydrogels
Authors: Yokota Mitsuru , Ajiro Hiroharu , Akashi Mitsuru 
Published: May 2012

Abstract
In order to improve the hydrophilicity of silicone-containing monomers, N-2-(N′,N′-dimethylcarbamoyl)ethyl-N-[3-tris(trimethylsiloxy)silylpropyl]acrylamide (SiDAAA) and N-2-(N′,N′-dimethylcarbamoyl)ethyl-N-{3-[methylbis(trimethylsiloxy)silyl]propyl}acrylamide (SiDAAA2) were designed. Although these two monomers had complicated side chain structures, these showed similar radical polymerizability (from 2.6 × 104 to 3.8 × 104 of Mn, and from 87 to 90% of conversion) as conventional silicone-containing monomer 3-tris(trimethylsiloxy)silylpropyl methacrylate (TRIS) due to the acrylamide backbone. Moreover, the additional amide group in those monomers contributed to improved miscibility during copolymerization with N-(hydroxyethyl)acrylamide (HEAA) and 2-hydroxyethyl methacrylate (HEMA), which was determined by light transmission observation at 88% transmittance using a SiDAAA/HEAA (50/50) hydrogel. In contrast, TRIS/HEAA was not miscible, and TRIS/HEMA (60/40) gave only 26% transmittance. The glass-transition temperatures of poly(SiDAAA) and poly(SiDAAA2) were 61 and 28 °C, which were much higher than that of poly(TRIS) at 0.8 °C. The oxygen permeability of the hydrogels varied with the copolymer composition, mainly due to the siloxanyl group contents. In particular, permeability coefficients of more than 100 Barrer (1 Barrer = 10−11 (cm3 O2) cm cm−2 s−1 mmHg−1) which is sufficient oxygen permeability for corneal safety in the case of contact lens applications, can be obtained at lower than 60% water content. The biocompatibility of these hydrogels is also discussed.
Synthesis of Novel BRET/FRET Protein Probes Containing Light-Emitting Proteins and Fluorescent Nonnatural Amino Acids
Authors: Yamaguchi Atsushi , Hohsaka Takahiro 
Published: May 2012

Abstract
Novel light-emitting protein probes were designed and synthesized by incorporating fluorescent nonnatural amino acids and fusing light-emitting proteins. Gaussia luciferase was fused as a BRET donor to the C-terminus of maltose-binding protein, and BODIPY558–aminophenylalanine was incorporated into Tyr210, which is located near the maltose-binding site of maltose-binding protein in response to a four-base codon (CGGG). In addition to the luminescence of luciferase, the double-labeled protein showed the emission of BODIPY558, which was strongly quenched by a neighboring tryptophan in the absence of maltose but was recovered in the presence of maltose. The emission intensity ratio of luciferase and BODIPY558 increased 4.0-fold upon the addition of maltose. Similar ligand-dependent emission changes were observed for a translation reaction mixture expressing the double-labeled protein, indicating that the BRET protein probe was detectable in the presence of excess fluorescent molecules. BODIPY558-containing maltose-binding protein fused with GFP in place of luciferase was also synthesized and showed the FRET and maltose-dependent fluorescence of BODIPY558. Novel BRET/FRET protein probes synthesized by fusing light-emitting proteins and incorporating fluorescent nonnatural amino acids will become valuable tools for the bioimaging and diagnostic detection of specific ligands.
A Facile Synthesis of New 4-Amino-2-iminothiazoles from Unsymmetrical Thioureas
Authors: Murthy Yellajyosula Lakshmi Narasimha , Saviri Rama Mohana Rao , Ramaiah Parimi Atchuta , Nareesh Saranapu 
Published: May 2012

Abstract
An efficient methodology for the synthesis of 4-amino-2-iminothiazole derivatives has been developed. The synthesis involves the cyclization of unsymmetrical 1-aroyl-3-arylthioureas with a variety of 2-bromo-2-phenylacetonitriles bearing α-H in the presence of triethylamine and acetonitrile.
One-step Fabrication of Polystyrene–TiO2 Nanosandwich Film by Phase Separation
Authors: Mizutani Naoki , Korposh Sergiy , Selyanchyn Roman , Yang Do-Hyeon , Lee Chang-Soo , Lee Seung-Woo , Kunitake Toyoki 
Published: May 2012

Abstract
A polystyrene–TiO2 nanosandwich film was fabricated by spin-coating a mixture of PS and Ti(O-n-Bu)4. Phase separation of the two components showed various morphological changes in the film, depending on the PS concentration, and sandwich-like phase separation was achieved for the first time. Doping pyrene as a fluorescent probe was employed to confirm the configuration of PS inside the nanosandwich structure.
Synthesis and Growth Observation of Flower- and Spike-like Gold–Silver Nanoparticles
Authors: Kumagai Keisuke , Ishida Akito 
Published: May 2012

Abstract
In this paper, we report a simple and reproducible synthesis of flower- and spike-like gold–silver (Au–Ag) nanoparticles. Reduction of aqueous solution of AgNO3 and HAuCl4 mixtures by l-ascorbic acid (AA) in the presence of poly(vinylpyrrolidone) (PVP) afforded the nanoparticles in a few minutes at room temperature. Stepwise trapping of the intermediate nanoparticles revealed the growth process of the petals of the flower-like nanoparticles from an initially formed nanoplate.
A comparison of lidocaine, ropivacaine and dexamethasone toxicity on bovine tenocytes in culture
Authors: Piper S. L. , Laron D. , Manzano G. , Pattnaik T. , Liu X. , Kim H. T. , Feeley B. T. 
Published: May 2012

Peri-tendinous injection of local anaesthetic, both alone and in combination with corticosteroids, is commonly performed in the treatment of tendinopathies. Previous studies have shown that local anaesthetics and corticosteroids are chondrotoxic, but their effect on tenocytes remains unknown. We compared the effects of lidocaine and ropivacaine, alone or combined with dexamethasone, on the viability of cultured bovine tenocytes. Tenocytes were exposed to ten different conditions: 1) normal saline; 2) 1% lidocaine; 3) 2% lidocaine; 4) 0.2% ropivacaine; 5) 0.5% ropivacaine; 6) dexamethasone (dex); 7) 1% lidocaine+dex; 8) 2% lidocaine+dex; 9) 0.2% ropivacaine+dex; and 10) 0.5% ropivacaine+dex, for 30 minutes. After a 24-hour recovery period, the viability of the tenocytes was quantified using the CellTiter-Glo viability assay and fluorescence-activated cell sorting (FACS) for live/dead cell counts. A 30-minute exposure to lidocaine alone was significantly toxic to the tenocytes in a dose-dependent manner, but a 30-minute exposure to ropivacaine or dexamethasone alone was not significantly toxic.Dexamethasone potentiated ropivacaine tenocyte toxicity at higher doses of ropivacaine, but did not potentiate lidocaine tenocyte toxicity. As seen in other cell types, lidocaine has a dose-dependent toxicity to tenocytes but ropivacaine is not significantly toxic. Although dexamethasone alone is not toxic, its combination with 0.5% ropivacaine significantly increased its toxicity to tenocytes. These findings might be relevant to clinical practice and warrant further investigation.
Eribulin: A Novel Cytotoxic Chemotherapy Agent
Authors: Preston Jessica N , Trivedi Meghana V 
Published: May 2012

OBJECTIVE: To review the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of eribulin (Halaven). DATA SOURCES: A literature search (up to December 2011) using the terms eribulin, Halaven, ER-086526, and E7389 was performed with PubMed, Google Scholar, selected Ovid bibliography searches, and the abstract search tool from the American Society of Clinical Oncology Annual Meetings and the San Antonio Breast Cancer Symposia. Additional references from the bibliographies of these articles were also assessed. DATA EXTRACTION: English-language preclinical and clinical studies on the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of eribulin were reviewed. DATA SYNTHESIS: Eribulin is a novel microtubule inhibitor with a unique mechanism of action, which involves interaction with a distinct binding site on β-tubulin leading to G2/M phase cell-cycle arrest and apoptosis. Eribulin has been approved by the Food and Drug Administration for the treatment of metastatic breast cancer in patients who have been previously treated with an anthracycline and a taxane. In a pivotal Phase 3 study conducted in patients with metastatic breast cancer, eribulin 1.4 mg/m2, administered over 2-5 minutes as an intravenous infusion on days 1 and 8 of 21-day cycles, was associated with a significantly increased median overall survival of 13.1 months compared to the median overall survival of 10.6 months in the therapy of physician's choice. Eribulin has also shown activity in Phase 2 studies in other types of cancers, such as non–small cell lung cancer, prostate cancer, urothelial cancer, soft tissue sarcomas, and platinum-susceptible ovarian, fallopian tube, or peritoneal cancers. The most severe (grade 3/4) adverse effects associated with eribulin include neutropenia, leukopenia, and peripheral neuropathy. Common toxicities include fatigue, neutropenia, alopecia, anemia, and peripheral neuropathy. CONCLUSIONS: Eribulin is a promising new cytotoxic chemotherapy agent due to its ability to treat cancers that are refractory or resistant to other drugs as well as its manageable toxicity profile.