bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydroxyurea adherence and associated outcomes among Medicaid enrollees with sickle cell disease
Authors: Candrilli Sean D. , O'Brien Sarah H. , Ware Russell E. , Nahata Milap C. , Seiber Eric E. , Balkrishnan Rajesh
Published: December 2010

While laboratory and clinical benefits of hydroxyurea for patients with sickle cell disease (SCD) are well‐established, few data describe the extent and implications of non‐adherence. We sought to assess adherence to hydroxyurea among patients with SCD and investigate associations between adherence and clinical and economic outcomes. Insurance claims of North Carolina Medicaid enrollees (6/2000‐8/2008) with SCD were analyzed. Inclusion criteria included age <65 years, continuous Medicaid enrollment ≥12 months before and following hydroxyurea initiation, and ≥2 hydroxyurea prescriptions. Three hundred twelve patients, mean age 21 (±12.2) years, met inclusion criteria and 35% were adherent, defined as a medication possession ration (MPR) ≥ 0.80; mean MPR was 0.60. In the 12 months following hydroxyurea initiation, adherence was associated with reduced risk of SCD‐related hospitalization (hazard ratio [HR] = 0.65, p = .0351), all‐cause and SCD‐related emergency department visit (HR = 0.72, p = .0388; HR = 0.58, p =.0079, respectively), and vaso‐occlusive event (HR = 0.66, p = .0130). Adherence was associated with reductions in health care costs such as all‐cause and SCD‐related inpatient (−$5,286, p < .0001; −$4,403, p < .0001, respectively), ancillary care (−$1,336, p < .0001; −$836, p < .0001, respectively), vaso‐occlusive event‐related (−$5,793, p < .0001), and total costs (−$6,529, p < .0001; −$5,329, p <.0001, respectively). Adherence to hydroxyurea among SCD patients appears suboptimal and better adherence is associated with improved clinical and economic outcomes. Am. J. Hematol. 2011. © 2010 Wiley‐Liss, Inc.
Cerebrovasculopathy in NF1 associated with ocular and scalp defects
Authors: Smith Matt , Heran Manraj K.S. , Connolly Mary B. , Heran Harindar K. , Friedman J.M. , Jett Kimberly , Lyons Christopher J. , Steinbok Paul , Armstrong Linlea
Published: December 2010

Vascular lesions are uncommon in children with neurofibromatosis 1 (NF1) but can cause serious complications. We report on a child with NF1 who presented at 18 months of age with symptomatic stenosis of the left middle cerebral artery and its branches, and associated moyamoya disease. She also had bilateral posterior embryotoxon, left corneal opacity (Peters anomaly), and cutis aplasia of the left scalp. All of these defects may have occurred as a result of disruption of the blood supply caused by NF1 vasculopathy prenatally. This constellation of vascular anomalies has not been previously reported in a patient with NF1. © 2010 Wiley‐Liss, Inc.
Al‐Awadi–Raas‐Rothschild (limb/pelvis/uterus–hypoplasia/aplasia) syndrome and WNT7A mutations: Genetic homogeneity and nosological delineation
Authors: Garavelli Livia , Wischmeijer Anita , Rosato Simonetta , Gelmini Chiara , Reverberi Sandro , Sassi Silvia , Ferrari Adriano , Mari Francesca , Zabel Bernhard , Lausch Ekkehart , Unger Sheila , Superti‐Furga Andrea
Published: December 2010

The Al‐Awadi–Raas‐Rothschild syndrome (AARRS; OMIM 276820) and the Fuhrmann syndrome (FS; OMIM 228930) are distinct limb malformation disorders comprising different degrees of limb aplasia or hypoplasia. In 2006, Woods et al. found different recessive WNT7A mutations in one family segregating the AARRS phenotype and in a second family with FS. To explain the common genetic basis for the two clinically distinct disorders, functional studies were done showing that partial loss of WNT7A function resulted in FS, while complete loss of WNT7A function resulted in the more severe phenotype of AARRS. In spite of the elucidation of the molecular basis of AARRS, there remains to this day considerable diagnostic confusion that has culminated in the lumping of Schinzel phocomelia syndrome with AARRS; however, this phocomelic limb defect is quite different in its clinical aspect and pathogenesis from the limb findings of AARRS. Here, we report on a child with the AARRS phenotype and homozygosity for a non‐conservative E72K mutation in WNT7A, underline the homogeneity of the WNT7A‐associated AARRS phenotype, and propose differential diagnostic criteria for the AARRS reflecting the roles of WNT7A in limb development. © 2010 Wiley‐Liss, Inc.
A patient with a de novo distal 22q11.2 microdeletion and anxiety disorder
Authors: Verhoeven Willem , Egger Jos , Brunner Han , de Leeuw Nicole
Published: December 2010

We report on a young female with normal intelligence evaluated for long‐term anxiety. Her history includes prematurity, neonatal feeding problems, surgical correction of congenital heart defects, recurrent upper airway and urinary tract infections, and delayed motor and developmental milestones. Physical examination disclosed small stature and minor dysmorphisms. Chromosome analysis, 22q11.2 FISH analysis, and subtelomeric MLPA testing did not detect any abnormalities. Genome wide SNP Array analysis showed a de novo deletion in 22q11.21q11.22, the so‐called distal 22q11 microdeletion that involves the MAPK1 gene. A diagnosis of panic disorder was made and the patient was successfully treated with a daily dose of 20 mg citalopram. To our knowledge, this is the first adolescent patient with a long history of complaints about anxiety and a distal 22q11 microdeletion. We speculate that genes from the deleted region, especially MAPK1, increase the neurobiological susceptibility to anxiety disorders that may be a part of the psychopathological phenotype of the distal 22q11.2 microdeletion syndrome. © 2010 Wiley‐Liss, Inc.
The nosology of Richieri‐Costa/Guion‐Almeida syndrome(s)
Authors: Castori Marco , Cascone Piero , Brinelli Marco , Iannetti Giorgio , Grammatico Paola
Published: December 2010

Richieri‐Costa/Guion‐Almeida syndrome type 1 (RCGAS1) is a rare MR/MCA syndrome comprising developmental and growth delay, microcephaly, prominent supraorbital ridges, asymmetric ptosis and eyebrows, esotropia, nystagmus, eye colobomas, and cleft lip/palate. It was originally described in three brothers and an additional sporadic male. The same authors also described a further family with a partially overlapping condition in two sisters (Richieri‐Costa/Guion‐Almeida syndrome type 2, RCGAS2). We report on a sporadic, mentally retarded patient strongly resembling those of the original report of RCGAS1, but lacking some manifestations such as short stature and, possibly, some ocular changes. Results of 200 kb CGH‐array study were normal. By comparing the present and previously reported patients with RCGAS1 and 2, we tried to contribute to syndrome delineation and to separate them from conditions with similar facial anomalies. © 2010 Wiley‐Liss, Inc.
Richieri‐Costa–Pereira syndrome: A unique acrofacial dysostosis type. An overview of the Brazilian cases
Authors: Favaro Francine Pinheiro , Zechi‐Ceide Roseli Maria , Alvarez Camila Wenceslau , Maximino Luciana P. , Antunes Luis Fernando B. B. , Richieri‐Costa Antonio , Guion‐Almeida Maria Leine
Published: December 2010

We reported on 16 new Brazilian patients and review findings in 12 previously reported cases (25 apparently unrelated Brazilian families) from Hospital of Rehabilitation of Craniofacial Anomalies, presenting with Richieri‐Costa–Pereira syndrome. All patients display a unique pattern of anomalies consisting of microstomia, micrognathia, abnormal fusion of mandible, cleft palate/Robin sequence, absence of central lower incisors, minor ears anomalies, hypoplastic first ray, abnormal tibiae, hypoplastic halluces, and clubfeet. Learning disability was also a common finding. The sex‐ratio showed deviation toward to female (1.8F:1M). Recurrence in sibs was observed in nine instances and consanguinity in 11, supporting the hypothesis of autosomal recessive inheritance. Nineteen of the 25 families lived in São Paulo State, seven of them (10 affected individuals) from an isolated region named “Vale do Ribeira.” The geographic barrier of this region associated with the high incidence of the consanguineous matting suggested that this condition is caused by a rare mutation with a founder effect. With the exception of one patient in France, all known cases are of Brazilian origin. The causative gene of this rare syndrome remains unknown. © 2010 Wiley‐Liss, Inc.
Mitochondrial phylogeny of tamarins (Saguinus, Hoffmannsegg 1807) with taxonomic and biogeographic implications for theS. nigricollisspecies group
Authors: Matauschek Christian , Roos Christian , Heymann Eckhard W.
Published: December 2010

Tamarins of the genusSaguinus, subfamily Callitrichinae, represent one of the most diverse primate radiations. So far, about 35 taxa have been described, but detailed information about their taxonomy and phylogeny is still lacking. To further elucidate the phylogenetic relationships and the biogeographic history within the genus, and to contribute to a more reliable classification of its taxa, we sequenced the complete mitochondrial cytochromebgene and the hypervariable region I of the D‐loop. Therefore, we mainly used fecal samples from wild tamarins collected during two expeditions to the Peruvian Amazon, an area of high tamarin diversity. Our data suggest that the numerous taxa of theS. nigricollisspecies group are derived from a common ancestor that separated from the other representatives of the genus ∼10 mya. Most taxa of theS. nigricollisgroup form monophyletic clusters, which mainly originated in a single rapid radiation ∼2.9 mya.S. fuscicollisandS. nigricollisappear as polyphyletic taxa, but we could identify various clusters, which are mainly consistent with differences in coat coloration. We could confirm most of the existing taxa as distinct entities and suggest species status forfuscicollis, illigeri, lagonotus, leucogenys, nigricollis, nigrifrons,tripartitus, andweddelli. Our genetic data do not support a separate status formelanoleucusandgraellsi, but due to differences in fur coloration, we give them subspecies status. The species group most likely originated in western Amazonia and diversified during the decline of the Acre wetland and the formation of the Amazonian river system. Am J Phys Anthropol, 2011. © 2010 Wiley‐Liss, Inc.
Chemical Control of Stem Cell Fate and Developmental Potential
Authors: Lyssiotis Costas A. , Lairson Luke L. , Boitano Anthony E. , Wurdak Heiko , Zhu Shoutian , Schultz Peter G.
Published: December 2010

Potential applications of stem cells in medicine range from their inclusion in disease modeling and drug discovery to cell transplantation and regenerative therapies. However, before this promise can be realized several obstacles must be overcome, including the control of stem cell differentiation, allogeneic rejection and limited cell availability. This will require an improved understanding of the mechanisms that govern stem cell potential and the development of robust methods to efficiently control their fate. Recently, a number of small molecules have been identified that can be used both in vitro and in vivo as tools to expand stem cells, direct their differentiation, or reprogram somatic cells to a more naive state. These molecules have provided a wealth of insights into the signaling and epigenetic mechanisms that regulate stem cell biology, and are already beginning to contribute to the development of effective treatments for tissue repair and regeneration.
Preliminary study on the utilization of lignin as filler in ultra‐violet (UV) curable system
Authors: Rozman H. D. , Koay E. L. , Tay G. S.
Published: December 2010

In this study, Alcell lignin was used as filler in aliphatic urethane acrylate ultra violet (UV) curable resin system. The coating system was UV cured in the presence of free radical photoinitiator and cationic photoinitiator. The results showed that those with free radical photoinitiator produced coating film with higher degree of curing than those with cationic photoinitiator. The result of iodine number determination also showed that the unsaturated groups present in the UV curable system had reduced. This indicated that radical polymerization had taken place in the curing process of UV curable resin incorporated with lignin. In addition, the lignin content did not influence the curing process of the coating film. As for the coating film, it showed that the mechanical properties of the film were significantly influenced by the lignin content. This phenomenon was contributed by inherent stiffness of the lignin. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Effects of α‐amylase and glycerol levels on the composition optimization of poly(β‐hydroxybutyrate‐co‐valerate)/starch blended biodegradable resin analyzed with response surface methodology
Authors: Cheng Wen‐Yen , Peng Jinchyau , Lui Wai‐Bun
Published: December 2010

Response surface methodology was used to analyze the effects of the enzyme level (X2) and glycerol level (X1) on objective attributes [water solubility index (WSI), water absorption index (WAI), and maximum loading (Y3)] of a cornstarch/poly(β‐hydroxybutyrate‐co‐valerate) blended composite. A rotatable central composite design was used to develop models for the objective responses. The experiments were run at barrel temperatures of 160, 160, 165, and 165°C, with a screw speed of 40 rpm and complete feeding (filling ratio = 1). Responses were most affected by changes in X2 and to a lesser extent by X1. Individual contour plots of the different responses were overlaid, and regions meeting the optimal WSI of 8.73%, WAI of 3.94 g of gel/g of dry weight, and Y3 of 304.17 N were established at an X2 of 5.43 g and an X1 of 120.79 mL. These predicted values for the optimal process conditions were in good agreement with the experimental data. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Characterization of the fracture properties of aragonite‐ and calcite‐filled poly(ε‐caprolactone) by the essential work of fracture method
Authors: Tuba Ferenc , Oláh László , Nagy Péter
Published: December 2010

Biodegradable polymers, blends, and composites are often investigated during tissue engineering studies, but their fracture properties, which are important mechanical engineering characteristics, are often disregarded or wrongly treated. In this study, essential work of fracture tests were performed on calcium carbonate filled poly(ε‐caprolactone), a very ductile polymer, to determine the effects of different filler shapes (calcite spheres and aragonite whiskers), sizes, and contents on the fracture parameters. Increasing the filler content caused stability problems during crack propagation, and this influenced the self‐similarity of the load–displacement response and resulted in the yielding point being missed. Moreover, the yielding‐related essential work of fracture and the energy dissipating during yielding were found to be almost independent of the filler content and thus could be indicators of matrix–filler adhesion. A shape effect of aragonite whiskers appeared during stable crack propagation; the motion of the particles and the friction on their surface slightly increased the dissipated energy quantum and resulted in a more oriented molecular structure. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Fabrication of polymer‐gadolinium (III) complex nanomicelle from poly(ethylene glycol)‐polysuccinimide conjugate and diethylenetriaminetetraacetic acid‐gadolinium as magnetic resonance imaging contrast agents
Authors: Zhang Wei‐Lu , Yong Da‐Wei , Huang Jin , Yu Jia‐Hui , Liu Shi‐Yuan , Fan Ming‐Xia
Published: December 2010

Methoxy poly (ethylene glycol)‐graft‐α, β‐poly (aspartic acid) derivatives (mPEG‐g‐PAA‐N3) were synthesized by sequential ring‐opening reaction of polysuccinimide (PSI) with mPEG‐NH2 (MW: 2000 Da), and 1‐azido‐3‐aminopropane, respectively. Then N2‐(hex‐5‐yne)‐diethylenetriamine‐tetra‐t‐butylacetate (DTTA‐der) was conjugated to mPEG‐g‐PAA‐N3 by click cycloaddition. After deprotection of carboxylic groups, mPEG‐g‐PAA‐DTTA macromolecular ligands were obtained. MPEG‐g‐PAA‐(DTTA‐Gd) complex nanomicelles were fabricated from mPEG‐g‐PAA‐DTTA and Gadolinium chloride. The formation of nanomicelles was confirmed by fluorescence spectrophotoscopy and particle size measurements. It was found that all the nanomicelles showed spherical shapes with core‐shell structures and narrow size distributions. Their sizes ranged from 50 to 80 nm, suggesting their passive targeting potential to tumor tissue. With the increase of graft degree (GD) of mPEG, the sizes of mPEG‐g‐PAA‐(DTTA‐Gd) nanomicelles showed a tendency to decrease. Compared with gadopentetate dimeglumine (Gd‐DTPA), mPEG‐g‐PAA‐(DTTA‐Gd) nanomicelles showed essential decreased cytotoxicity to KB cell line and enhanced T1‐weighted signal intensity, especially at low concentration of gadolinium (III), suggesting their great potentials as magnetic resonance imaging contrast agents. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Novel dynamic vulcanization of polyethylene and ozonolysed natural rubber blends: Effect of curing system and blending ratio
Authors: Utara S. , Boochathum P.
Published: December 2010

Dynamic vulcanization was studied in terms of the change in α‐relaxation temperatures of the LDPE matrix, morphology, and mechanical properties of LDPE/ozonolysed NR blends which were vulcanized at various blend ratios and with different curing systems, i.e., peroxide and sulfur systems. The ozonolysed NR with Mw = 8.30 × 105 g mol−1 and Mn = 2.62 × 105 g mol−1, prepared by the in situ ozonolysis reaction of natural rubber latex, was used in this study. The significant change in the α‐relaxation temperature of LDPE in the LDPE/ozonolysed NR, dynamically vulcanized using the sulfur system, suggested that sulfur vulcanization of the blend gave a higher degree of crosslink density than using peroxide and corresponded with the improved damping property and homogenous phase morphology. However, the peroxide cured blends of LDPE/ozonolyzed NR gave more improvement of tensile strength and elongation at break than the sulfur cured system. Furthermore, the mechanical properties of tensile strength, elongation at break, and damping were improved by increasing the ozonolyzed natural rubber content in both DCP and sulfur cured blends. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Synthesis and characterization of grafted carboxymethyl guar gum
Authors: Adhikary P. , Krishnamoorthi S. , Singh R. P.
Published: December 2010

Graft copolymers of carboxymethyl guar gum (CMGG) and polyacrylamide (PAM) have been synthesized by grafting polyacrylamide chains onto carboxymethyl guar gum backbone using a ceric‐ion‐induced solution polymerization technique. By varying the amount of initiator, three different grades of graft copolymers are synthesized. The characterization of graft copolymer is carried out by FTIR, NMR, intrinsic viscosity measurement, SEM, SLS, DTG, and rheology. A comparison of flocculation efficiency of CMGG and its graft copolymer shows that the graft copolymer exhibits better flocculation performance. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Cure characteristics, swelling behaviors, and mechanical properties of carbon black filler reinforced EPDM/NBR blend system
Authors: Manoj K. C. , Kumari Prajitha , Unnikrishnan G.
Published: December 2010

The effect of carbon black fillers viz. semireinforcing furnace (SRF), high abrasion furnace (HAF) and intermediate super abrasion furnace (ISAF) carbon blacks on the cure, swelling and mechanical properties of 70/30 EPDM/NBR blend have been investigated. The maximum torque values have been found to be increased with increase in filler loading. Filledsystems have been found to exhibit a reduced solvent uptake tendency compared to the unfilled sample. Blends loaded with ISAF exhibited the lowest toluene uptake among the carbon black filled systems due to the better filler reinforcement. A more uniform morphology has been observed for ISAF‐filled samples compared to the other filler loaded systems. The improvement in the mechanical properties has been observed to be the highest for ISAF‐filled samples followed by HAF and SRF filled systems. This has been attributed to the smaller particle size of ISAF black. The experimental results of mechanical testing have been compared with various theoretical models. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Effect of molecular weight and testing rate on peel and shear strength of epoxidized natural rubber (ENR 50)‐based adhesives
Authors: Khan Imran , Poh B. T.
Published: December 2010

The dependence of peel strength and shear strength of epoxidized natural rubber (ENR‐50)‐based pressure sensitive adhesive on molecular weight and rate of testing was investigated using coumarone‐indene as the tackifying resin. Toluene and polyethylene terephthalate were used as the solvent and substrate respectively, throughout the study. A SHEEN hand coater was used to coat the adhesive on the substrate at a coating thickness of 120 μm. All the adhesion properties were determined by a Llyod Adhesion Tester operating at different rates of testing. Result shows that peel strength and shear strength increases up to an optimum molecular weight of 4.2 × 104 of ENR 50. For peel strength, the observation is attributed to the combined effects of wettability and mechanical strength of rubber at the optimum molecular weight, whereas for the shear strength, it is ascribed to the optimum cohesive and adhesive strength which enhances the shear resistance of the adhesive. Peel strength and shear strength also increases with increase in rate of testing, an observation which is associated to the viscoeslastic response of the adhesive. DSC and FTIR study confirms the miscibility of tackifier and the ENR 50. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Locations of the Motor Endplate Band and Motoneurons Innervating the Sternomastoid Muscle in the Rat
Authors: Zhang Xiaolin , Mu Liancai , Su Hungxi , Sobotka Stanislaw
Published: December 2010

Sternocleidomastoid (SCM) is a long muscle with two bellies, sternomastoid (SM) and cleidomastoid (CM) in the lateral side of the neck. It has been widely used as muscle and myocutaneous flap for reconstruction of oral cavity and facial defects and as a candidate for reinnervation studies. Therefore, exact neuroanatomy of the SCM is critical for guiding reinnervation procedures. In this study, SM in rats were investigated to document banding pattern of motor endplates (MEPs) using whole‐mount acetylcholinesterase (AChE) staining and to determine locations of the motoneurons innervating the muscle using retrograde horseradish peroxidase (HRP) tracing technique. The results showed that the MEPs in the SM and CM were organized into a single band which was located in the middle portion of the muscle. After HRP injections into the MEP band of the SM, ipsilaterally labeled motoneurons were identified in the caudal medulla oblongata (MO), C1, and C2. The SM motoneurons were found to form a single column in lower MO and dorsomedial (DM) nucleus in C1. In contrast, the labeled SM motoneurons in C2 formed either one (DM nucleus), two [DM and ventrolateral (VL) nuclei], or three [DM, VL, and ventromedial (VM)] columns. These findings are important not only for understanding the neural control of the muscle but also for evaluating the success rate of a given reinnervation procedure when the SM is chosen as a target muscle. Anat Rec, 2011. © 2010 Wiley‐Liss, Inc.
Allometric and Metameric Shape Variation in Pan Mandibular Molars: A Digital Morphometric Analysis
Authors: Singleton Michelle , Rosenberger Alfred L. , Robinson Chris , O'neill Rob
Published: December 2010

The predominance of molar teeth in fossil hominin assemblages makes the patterning of molar shape variation a topic of bioanthropological interest. Extant models are the principal basis for understanding dental variation in the fossil record. As the sister taxon to the hominin clade, Pan is one such model and the only widely accepted extant hominid model for both interspecific and intraspecific variation. To explore the contributions of allometric scaling and meristic variation to molar variation in Pan, we applied geometric shape analysis to 3D landmarks collected from virtual replicas of chimpanzee and bonobo mandibular molars. Multivariate statistical analysis and 3D visualization of metameric and allometric shape vectors were used to characterize shape differences and test the hypothesis that species of Pan share patterns of metameric variation and molar shape allometry. Procrustes‐based shape variables were found to effectively characterize crown shape, sorting molars into species and tooth‐row positions with ≥95% accuracy. Chimpanzees and bonobos share a common pattern of M1–M2 metameric variation, which is defined by differences in the relative position of the metaconid, size of the hypoconulid, curvature of the buccal wall, and proportions of the basins and foveae. Allometric scaling of molar shape is homogeneous for M1 and M2 within species, but bonobo and chimpanzee allometric vectors are significantly different. Nevertheless, the common allometric shape trend explains most molar‐shape differences between P. paniscus and P. troglodytes. When allometric effects are factored out, chimpanzee and bonobo molars are not morphometrically distinguishable. Implications for hominid taxonomy and dietary reconstruction are discussed. Anat Rec, 2011. © 2010 Wiley‐Liss, Inc.
The Atrioventricular Region of the Teleost Heart. A Distinct Heart Segment
Authors: Icardo José M. , Colvee Elvira
Published: December 2010

This article reports the morphological characteristics of the atrioventricular (AV) region of the teleost heart. A total of 29 teleost species belonging to 19 families and 10 orders were analyzed. The study includes hearts with entirely trabeculated ventricles and hearts possessing a ventricular compacta. In all cases, the AV region is formed by a ring of compact myocardium surrounded by a connective tissue ring. The myocardium contains vessels in most species having entirely trabeculated ventricles, and in all species possessing a compacta. The ring of connective tissue is rich in collagen and elastin, partially isolating the AV muscle from the surrounding musculature. Continuity between the AV muscle and the atrial and ventricular musculature is always observed. The AV muscle supports the AV valves, which are formed by two leaflets, lack papillary muscles, show a collagenous fibrosa on the atrial side, and present a variable number of cells and a variable amount of extracellular material. Ventricular trabeculae attach to the AV muscle. These trabeculae may help to bear the stress generated by ventricular contraction and may constitute a preferential pathway for the conduction of electrical impulses. In all teleosts studied, the AV region can be recognized as a distinct morphological segment interposed between the atrium and the ventricle. The morphological characteristics of the AV segment appear to be species specific. Anat Rec, 2011. © 2010 Wiley‐Liss, Inc.
Differential Expression of Metallothionein in Gastrointestinal Stromal Tumors and Gastric Carcinomas
Authors: Soo Eliza Ting‐Li , NG Cheng‐Teng , Yip George Wai‐Cheong , Koo Chuay Yeng , Nga Min‐En , Tan Puay‐Hoon , Bay Boon‐Huat
Published: December 2010

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that account for about 2% of gastric tumors. Metallothioneins (MTs) are multifunctional proteins associated with carcinogenesis and known to be coded by 10 functional MT genes. This study evaluated MT mRNA and protein expression in GISTs and compared the expression levels with gastric carcinomas. An immunohistochemical study of MT protein expression was performed in 15 GISTs (specifically located in the stomach) and 38 early stage gastric carcinomas. The percentage of cells stained and intensity of staining were determined. MT‐2A mRNA expression was investigated in 6 GISTs and 6 early stage gastric carcinoma patients. All GISTs displayed positive nuclear immunostaining, with most GISTs having predominantly mildly stained nuclei (93.3%). On the other hand, 37 out of 38 gastric carcinoma cases were positively stained for nuclear MT with 24 cases (63.2%) exhibiting predominantly mild nuclear staining, 7 cases (18.4%) moderate nuclear staining, and 6 cases (15.8%) strong nuclear staining. Nuclear MT expression was found to be significantly lower in GIST samples when compared with gastric carcinoma tissues based on the percentage stained and immunoreactive score. We then established that the MT‐2A gene transcript was the most abundant MT isoform in MKN28 gastric cancer cells and analyzed its expression in GIST and gastric carcinoma tissues. We found that GISTs had significantly lower MT‐2A mRNA levels than gastric carcinoma tissues. Lower MT‐2A gene expression and nuclear MT protein expression in GISTs when compared with gastric carcinomas may reflect their different underlying biology and divergent histogenesis. Anat Rec, 2011. © 2010 Wiley‐Liss, Inc.
“Anatomical” View of the Protein Composition and Protein Characteristics for Gloydius shedaoensis Snake Venom via Proteomics Approach
Authors: Liu Shuqing , Yang Fan , Zhang Qiaoqiao , Sun Ming‐Zhong , Gao Ying , Shao Shujuan
Published: December 2010

The bioactive protein components from snake venom complexes have been utilized for studies of enzymology, structural biology, and pharmacology. The Gloydius shedaoensis snake (GSS) is the only snake species found exclusively at the Chinese Shedao (snake) Island in Dalian. To investigate the protein components of Chinese GSS venom (GSSV), we initialized a proteomic assay for GSSV by the combination of sodium dodecyl sulfate‐polyacrylamide gel electrophoresis with high‐performance liquid chromatography (HPLC)‐nanoelectrospray ionization tandem mass spectrometry (nESI‐MS/MS). Thirty gel bands visualized by Coomassie blue staining were excised and digested by trypsin. The tryptic‐digested peptides were separated by HPLC and subsequently sequenced by nESI‐MS/MS. Twenty‐four types of proteins were identified by searching the mass spectrometry data against NCBInr database through TurboSequest Bioworks. The most abundant proteins are phospholipase A2, metalloproteinase, L‐amino acid oxidase (LAAO), serine protease/thrombin‐like enzyme. Except for 20 types of known snake venom proteins, the homolog peptides of hypothetical protein PFLC2230, LOC495267 protein, DEAD/DEAH box helicase‐like, and pancreatic trypsin 1 from other organisms are matched for GSSV protein components. Mass spectrometric data also indicated that (i) dimerization happens to PLA2s as monomer and dimer of PLA2s coexist in GSSV and (ii) truncation or hydrolysis might happen to LAAOs as three molecular‐weight‐ranged LAAO species are present in GSSV. The results provide an “anatomical” view of the protein composition and important information for protein characteristics of GSSV. Anat Rec, 2011. © 2010 Wiley‐Liss, Inc.
Pharmacokinetics of a combination of Δ9‐Tetrahydro‐cannabinol and celecoxib in a porcine model of hemorrhagic shock
Authors: Vaddady Pavan K. , Mehrotra Nitin , Zhang Xiaofeng , Yates Charles R. , Moore Bob M. , Meibohm Bernd
Published: December 2010

Hemorrhagic shock involves loss of a substantial portion of circulating blood volume leading to diminished cardiac output and oxygen delivery to peripheral tissues. In situations where an immediate resuscitation cannot be provided, pharmacotherapy with a novel combination of Δ9‐tetrahydro‐cannabinol (THC) and celecoxib (CEL) is currently investigated as an alternative strategy to prevent organ damage. In the present study, 28 Yorkshire × Landrace pigs were used to study the pharmacokinetics of THC and CEL in an established porcine model of hemorrhagic shock. Pigs in hemorrhagic shock received 0.5, 1 or 4 mg/kg THC and 2 mg/kg CEL, while normotensive pigs received 1 mg/kg THC and 2 mg/kg CEL by intravenous injection. THC and CEL plasma concentrations were simultaneously determined by LC‐MS/MS. Pharmacokinetic parameters and their between animal variability were obtained using standard non‐compartmental analysis as well as a compartmental analysis using nonlinear mixed effects modeling. The concentration–time profiles of THC and CEL followed a multi‐exponential decline and their pharmacokinetics were similar in hemorrhagic shock and normotensive conditions, despite the substantial change in hemodynamics in the animals with shock. This interesting finding might be due to the pharmacologic effect of the THC/CEL combination, which is intended to maintain adequate perfusion of vital organs in shock. Overall, this study established THC and CEL pharmacokinetics in a porcine shock model and provides the basis for dose selection in further studies of THC and CEL in this indication. Copyright © 2010 John Wiley & Sons, Ltd.
Exposure assessment in front of a multi‐band base station antenna
Authors: Kos Bor , Valič Blaž , Kotnik Tadej , Gajšek Peter
Published: December 2010

This study investigates occupational exposure to electromagnetic fields in front of a multi‐band base station antenna for mobile communications at 900, 1800, and 2100 MHz. Finite‐difference time‐domain method was used to first validate the antenna model against measurement results published in the literature and then investigate the specific absorption rate (SAR) in two heterogeneous, anatomically correct human models (Virtual Family male and female) at distances from 10 to 1000 mm. Special attention was given to simultaneous exposure to fields of three different frequencies, their interaction and the additivity of SAR resulting from each frequency. The results show that the highest frequency—2100 MHz—results in the highest spatial‐peak SAR averaged over 10 g of tissue, while the whole‐body SAR is similar at all three frequencies. At distances >200 mm from the antenna, the whole‐body SAR is a more limiting factor for compliance to exposure guidelines, while at shorter distances the spatial‐peak SAR may be more limiting. For the evaluation of combined exposure, a simple summation of spatial‐peak SAR maxima at each frequency gives a good estimation for combined exposure, which was also found to depend on the distribution of transmitting power between the different frequency bands. Bioelectromagnetics 32:234–242, 2011. © 2010 Wiley‐Liss, Inc.
Integrating DNA barcode data and taxonomic practice: Determination, discovery, and description
Authors: Goldstein Paul Z. , DeSalle Rob
Published: December 2010

DNA barcodes, like traditional sources of taxonomic information, are potentially powerful heuristics in the identification of described species but require mindful analytical interpretation. The role of DNA barcoding in generating hypotheses of new taxa in need of formal taxonomic treatment is discussed, and it is emphasized that the recursive process of character evaluation is both necessary and best served by understanding the empirical mechanics of the discovery process. These undertakings carry enormous ramifications not only for the translation of DNA sequence data into taxonomic information but also for our comprehension of the magnitude of species diversity and its disappearance. This paper examines the potential strengths and pitfalls of integrating DNA sequence data, specifically in the form of DNA barcodes as they are currently generated and analyzed, with taxonomic practice.
Heterologous production of polyunsaturated fatty acids in Saccharomyces cerevisiae causes a global transcriptional response resulting in reduced proteasomal activity and increased oxidative stress
Authors: Ruenwai Rawisara , Neiss Andrea , Laoteng Kobkul , Vongsangnak Wanwipa , Dalfard Arastoo Badoei , Cheevadhanarak Supapon , Petranovic Dina , Nielsen Jens
Published: December 2010

Due to their health benefits there is much interest in developing microbial processes for efficient production of polyunsaturated fatty acids (PUFAs). In this study we co‐expressed Mucor rouxii Δ12‐ and Δ6‐desaturase genes in Saccharomyces cerevisiae, which resulted in a yeast strain that accumulated linoleic acid and γ‐linolenic acid in the different lipid species. Additionally, the strain contained higher levels of phospholipids and lower levels of ergosterol than the reference strain. Integrated analysis of the transcriptome revealed decreased expression of genes involved in ergosterol biosynthesis, but more unexpectedly it also pointed towards attenuated activity of the ubiquitin‐proteasome system and a reduced oxidative stress response. In vitro and in vivo measurements showed reduced levels of all three proteasomal activities and also increased levels of reactive oxidative species in the PUFA‐producing strain. Overall our results clearly show that PUFAs in yeast can be detrimental for several key cellular pathways, such as the oxidative stress response and proteasomal activity, suggesting that the membrane composition is of vital importance for these processes.
β‐peptoid “Foldamers”—Why the additional methylene unit?
Authors: Olsen Christian A.
Published: December 2010

The field of peptoid (i.e., N‐alkylglycine) research has been thriving since the first publications on this molecular design appeared in 1992. A highly efficient and modular synthetic platform, which is compatible with automation and ready generation of combinatorial libraries, was published the same year. This has enabled the investigation of numerous compounds with this architecture, and ligands with a wide variety of interesting biological targets have thus been discovered. Furthermore, detailed biophysical and structural studies focusing on the investigation of the conformational space adopted and three‐dimensional folding of these peptidemimics have been undertaken. The same is true for β‐peptides (i.e., oligomers composed of β‐amino acids). Since the first publication describing peptide mimics combining these two structural modifications [the N‐alkyl‐β‐alanines (β‐peptoids)] in 1998, on the other hand, the application of this backbone construct has appeared much more sparsely in the literature. The present perspective article will provide an overview of the data obtained for β‐peptoid‐containing peptide mimics as well as a discussion of the future challenges associated with this type of backbone modification. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 561–566, 2011.
Nonadditivity in the alpha‐helix to coil transition
Authors: Wood Gregory G. , Clinkenbeard Drew A. , Jacobs Donald J.
Published: December 2010

The Lifson‐Roig Model (LRM) and all its variants describe the α‐helix to coil transition in terms of additive component‐free energies within a free energy decomposition scheme, and these contributions are interpreted through sequence‐context dependent nucleation and propagation parameters. Although this phenomenological approach is able to adequately fit experimental data on helix content and heat capacity, the number of required parameters increases dramatically with additional sequence variation. Moreover, due to nonadditive competing microscopic effects that are difficult to disentangle within a LRM, large uncertainties within the parameters emerge. We offer an alternative view that removes the need for sequence‐context parameterization by focusing on individual microsopic interactions within a free energy decomposition and explicitly account for nonadditivity in conformational entropy through network rigidity using a Distance Constraint Model (DCM). We apply a LRM and a DCM to previously published experimental heat capacity and helix content data for a series of heterogeneous polypeptides. Both models describe the experimental data well, and the parameters from both models are consistent with prior work. However, the number of DCM parameters is independent of sequence‐variability, the parameter values exhibit better transferability, and the helix nucleation is predicted by the DCM explicitly through the nonadditive nature of conformational entropy. The importance of these results is that the DCM offers a system‐independent approach for modeling stability within polypeptides and proteins, where the demonstrated accuracy for the α‐helix to coil transition over a series of heterogeneous polypeptides described here is one case in point. © 2010 Wiley Periodicals, Inc. Biopolymers 95: 240–253, 2011.
Peptoid origins
Authors: Zuckermann Ronald N.
Published: December 2010

Peptoid oligomers were initially developed as part of a larger basic research effort to accelerate the drug‐discovery process in the biotech/biopharma industry. Their ease of synthesis, stability, and structural similarity to polypeptides made them ideal candidates for the combinatorial discovery of novel peptidomimetic drug candidates. Diverse libraries of short peptoid oligomers provided one of the first demonstrations in the mid‐1990s that high‐affinity ligands to pharmaceutically relevant receptors could be discovered from combinatorial libraries of synthetic compounds. The solid‐phase submonomer method of peptoid synthesis was so efficient and general that it soon became possible to explore the properties of longer polypeptoid chains in a variety of areas beyond drug discovery (e.g., diagnostics, drug delivery, and materials science). Exploration into protein‐mimetic materials soon followed, with the fundamental goal of folding a non‐natural sequence‐specific heteropolymer into defined secondary or tertiary structures. This effort first yielded the peptoid helix and much later the peptoid sheet, both of which are secondary‐structure mimetics that are close relatives to their natural counterparts. These crucial discoveries have brought us closer to building proteinlike structure and function from a non‐natural polymer and have provided great insight into the rules governing polymer and protein folding. The accessibility of peptoid synthesis to chemists and nonchemists alike, along with a lack of information‐rich non‐natural polymers available to study, has led to a rapid growth in the field of peptoid science by many new investigators. This work provides an overview of the initial discovery and early developments in the peptoid field. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 545–555, 2011.
Peptoid conformational free energy landscapes from implicit‐solvent molecular simulations in AMBER
Authors: Voelz Vincent A. , Dill Ken A. , Chorny Ilya
Published: December 2010

To test the accuracy of existing AMBER force field models in predicting peptoid conformation and dynamics, we simulated a set of model peptoid molecules recently examined by Butterfoss et al. (JACS 2009, 131, 16798–16807) using QM methods as well as three peptoid sequences with experimentally determined structures. We found that AMBER force fields, when used with a Generalized Born/Surface Area (GBSA) implicit solvation model, could accurately reproduce the peptoid torsional landscape as well as the major conformers of known peptoid structures. Enhanced sampling by replica exchange molecular dynamics (REMD) using temperatures from 300 to 800 K was used to sample over cis–trans isomerization barriers. Compared to (Nrch)5 and cyclo‐octasarcosyl, the free energy of N‐(2‐nitro‐3‐hydroxyl phenyl)glycine–N‐(phenyl)glycine has the most “foldable” free energy landscape, due to deep trans‐amide minima dictated by N‐aryl sidechains. For peptoids with (S)‐N(1‐phenylethyl) (Nspe) side chains, we observe a discrepancy in backbone dihedral propensities between molecular simulations and QM calculations, which may be due to force field effects or the inability to capture n → π* interactions. For these residues, an empirical φ‐angle biasing potential can “rescue” the backbone propensities seen in QM. This approach can serve as a general strategy for addressing force fields without resorting to a complete reparameterization. Overall, this study demonstrates the utility of implicit–solvent REMD simulations for efficient sampling to predict peptoid conformational landscapes, providing a potential tool for first‐principles design of sequences with specific folding properties. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 639–650, 2011.
Temperature‐dependent higher order structures of the (Pro‐Pro‐Gly)10‐modified dendrimer
Authors: Suehiro Tomoyuki , Tada Tomoko , Waku Tomonori , Tanaka Naoki , Hongo Chizuru , Yamamoto Shinya , Nakahira Atsushi , Kojima Chie
Published: December 2010

Collagen is the most abundant protein in mammals and is widely used as a biomaterial for tissue engineering and drug delivery. We previously reported that dendrimers and linear polymers, modified with collagen model peptides (Pro‐Pro‐Gly)5, form a collagen‐like triple‐helical structure; however, its triple helicity needs improvement. In this study, a collagen‐mimic dendrimer modified with the longer collagen model peptides, (Pro‐Pro‐Gly)10, was synthesized and named PPG10‐den. Circular dichroism analysis shows that the efficiency of the triple helix formation in PPG10‐den was much improved over the original. The X‐ray diffraction analysis suggests that the higher order structure was similar to the collagen triple helix. The thermal stability of the triple helix in PPG10‐den was higher than in the PPG10 peptide itself and our previous collagen‐mimic polymers using (Pro‐Pro‐Gly)5. Interestingly, PPG10‐den also assembled at low temperatures. Self‐assembled structures with spherical and rod‐like shapes were observed by transmission electron microscopy. Furthermore, a hydrogel of PPG10‐den was successfully prepared which exhibited the sol‐gel transition around 45°C. Therefore, the collagen‐mimic dendrimer is a potential temperature‐dependent biomaterial. © 2010 Wiley Periodicals, Inc. Biopolymers 95: 270–277, 2011.
Pretreatment of rat bone marrow mesenchymal stem cells with a combination of hypergravity and 5‐azacytidine enhances therapeutic efficacy for myocardial infarction
Authors: Ling Shu‐Kuan , Wang Rui , Dai Zhong‐Quan , Nie Jie‐Lin , Wang Hong‐Hui , Tan Ying‐Jun , Cao Hong‐Qing , Huang Zeng‐Ming , Wan Yu‐Min , Li Ying‐Hui
Published: December 2010

Background and Purpose: The in vivo cardiac differentiation and functional effects of unmodified adult bone marrow mesenchymal stem cells (BMSCs) after myocardial infarction (MI) is controversial. Our previous results suggested that hypergravity promoted the cardiomyogenic differentiation of BMSCs, and thus we postulated that ex vivo pretreatment of BMSCs using hypergravity and 5‐azacytidine (5‐Aza) would lead to cardiomyogenic differentiation and result in superior biological and functional effects on cardiac regeneration of infarcted myocardium. Methods: We used a rat MI model generated by ligation of the coronary artery. Homogeneous rat BMSCs were isolated, culture expanded, and differentiated into a cardiac lineage by adding hypergravity (2G) for 3 days and 5‐Aza (50 lmol/L, 24 h). Rats underwent BMSCs (labeled with DAPI) injection after the infarction and were randomized into five groups. Group A rats received the control medium, Group B rats received unmodified BMSCs, Group C rats received BMSCs treated with hypergravity, Group D rats received BMSCs treated with 5‐Aza, and Group E rats received BMSCs treated with 5‐Aza and hypergravity (n = 6). Results: After hypergravity and 5‐Aza treatment, BMSCs showed positive for the early muscle and cardiac markers GATA‐4, MEF‐2, and Nkx2‐5 with RT‐PCR. We also found that hypergravity could enhance the activities of MEF‐2 via promoting the nuclear export of HDAC5. The frozen section showed that the implanted BMSCs labeled with DAPI survived and angiogenesis was identified at the implantation site. In Groups B, C, D, and E rats, pre‐treated BMSCs colocalized with α‐actinin, and Group E rats showed a significantly larger increase in left ventricular function. Conclusions: The biological ex vivo cardiomyogenic differentiation of adult BMSCs with hypergravity and 5‐Aza prior to their transplantation is feasible and appears to improve their in vivo cardiac differentiation as well as the functional recovery in a rat model of the infarcted myocardium. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011