bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of leptin and leptin‐receptor gene polymorphisms on serum lipids in Japanese obese children
Authors: Okada T , Ohzeki T , Nakagawa Y , Sugihara S , Arisaka O ,   The Study Group of Pediatric Obesity and Its related Metabolism
Published: February 2010

AbstractAim:  Leptin is one of the factors affecting serum lipid profile. We investigated the association between serum lipids and leptin/leptin receptor (LEPR) gene polymorphisms in obese Japanese children.Methods:  One hundred and thirty‐six obese children (99 males and 37 females, relative weight over than 20%) from 5 to 17 years of age were recruited from 10 institutes. Four known polymorphisms in leptin gene [(+19)A G, (−2548)G A, (−188)C A, (−633)C T] and four known polymorphisms in LEPR gene [Lys109Arg, Gln223Arg, Pro(G)1019Pro(A), Ser(T)343Ser(C)] were determined using polymerase chain reaction‐restriction fragment length polymorphism‐based analyses.Results:  No associations were found between leptin gene polymorphisms and serum lipid profile. On the other hand, Lys109Arg and Ser343Ser polymorphism in LEPR gene, but not Gln223Arg or Pro1019Pro, had significant relationships with serum lipid profile; lower total and low‐density lipoprotein cholesterol levels in Arg109Arg homozygotes, and lower TG levels in Ser343Ser(C/C) homozygotes. In addition, LEPR gene also associated with relative weight; Arg109Arg homozygotes had higher relative weight and Ser343Ser(C/C) homozygotes had lower one.Conclusion:  These results suggest that LEPR gene polymorphisms may partly contribute to serum lipid profile in obese children.
The Weitzenböck machine
Authors: Semmelmann Uwe , Weingart Gregor 
Published: February 2010

AbstractWeitzenböck formulas are an important tool in relating local differential geometry to global topological properties by means of the so-called Bochner method. In this article we give a unified treatment of the construction of all possible Weitzenböck formulas for all irreducible, non-symmetric holonomy groups. We explicitly construct a basis of the space of Weitzenböck formulas. This classification allows us to find customized Weitzenböck formulas for applications such as eigenvalue estimates or Betti number estimates.
Peptide Fragments of a β-Defensin Derivative with Potent Bactericidal Activity
Authors: Reynolds Natalie L. , De Cecco Martin , Taylor Karen , Stanton Chloe , Kilanowski Fiona , Kalapothakis Jason , Seo Emily , Uhrin Dusan , Campopiano Dominic , Govan John , Macmillan Derek , Barran Perdita , Dorin Julia R. 
Published: February 2010

ABSTRACT

β-Defensins are known to be both antimicrobial and able to chemoattract various immune cells. Although the sequences of paralogous genes are not highly conserved, the core defensin structure is retained. Defb14-1C
V
has bactericidal activity similar to that of its parent peptide (murine β-defensin Defb14) despite all but one of the canonical six cysteines being replaced with alanines. The 23-amino-acid N-terminal half of Defb14-1C
V
is a potent antimicrobial while the C-terminal half is not. Here, we use a library of peptide derivatives to demonstrate that the antimicrobial activity can be localized to a particular region. Overlapping fragments of the N-terminal region were tested for their ability to kill Gram-positive and Gram-negative bacteria. We demonstrate that the most N-terminal fragments (amino acids 1 to 10 and 6 to 17) are potent antimicrobials against Gram-negative bacteria whereas fragments based on sequence more C terminal than amino acid 13 have very poor activity against both Gram-positive and -negative types. We further test a series of N-terminal deletion peptides in both their monomeric and dimeric forms. We find that bactericidal activity is lost against both Gram types as the deletion region increases, with the point at which this occurs varying between bacterial strains. The dimeric form of the peptides is more resistant to the peptide deletions, but this is not due just to increased charge. Our results indicate that the primary sequence, together with structure, is essential in the bactericidal action of this β-defensin derivative peptide and importantly identifies a short fragment from the peptide that is a potent bactericide.
Pyrazole compound BPR1P0034 with potent and selective anti-influenza virus activity
Authors: Shih Shin-Ru , Chu Tzu-Yun , Reddy Gadarla Randheer , Tseng Sung-Nain , Chen Hsiun-Ling , Tang Wen-Fang , Wu Ming-sian , Yeh Jiann-Yih , Chao Yu-Sheng , Hsu John TA , Hsieh Hsing-Pang , Horng Jim-Tong 
Published: February 2010

AbstractBackgroundInfluenza viruses are a major cause of morbidity and mortality around the world. More recently, a swine-origin influenza A (H1N1) virus that is spreading via human-to-human transmission has become a serious public concern. Although vaccination is the primary strategy for preventing infections, influenza antiviral drugs play an important role in a comprehensive approach to controlling illness and transmission. In addition, a search for influenza-inhibiting drugs is particularly important in the face of high rate of emergence of influenza strains resistant to several existing influenza antivirals.MethodsWe searched for novel anti-influenza inhibitors using a cell-based neutralization (inhibition of virus-induced cytopathic effect) assay. After screening 20,800 randomly selected compounds from a library from ChemDiv, Inc., we found that BPR1P0034 has sub-micromolar antiviral activity. The compound was resynthesized in five steps by conventional chemical techniques. Lead optimization and a structure-activity analysis were used to improve potency. Time-of-addition assay was performed to target an event in the virus life cycle.ResultsThe 50% effective inhibitory concentration (IC50) of BPR1P0034 was 0.42 ± 0.11 μM, when measured with a plaque reduction assay. Viral protein and RNA synthesis of A/WSN/33 (H1N1) was inhibited by BPR1P0034 and the virus-induced cytopathic effects were thus significantly reduced. BPR1P0034 exhibited broad inhibition spectrum for influenza viruses but showed no antiviral effect for enteroviruses and echovirus 9. In a time-of-addition assay, in which the compound was added at different stages along the viral replication cycle (such as at adsorption or after adsorption), its antiviral activity was more efficient in cells treated with the test compound between 0 and 2 h, right after viral infection, implying that an early step of viral replication might be the target of the compound. These results suggest that BPR1P0034 targets the virus during viral uncoating or viral RNA importation into the nucleus.ConclusionsTo the best of our knowledge, BPR1P0034 is the first pyrazole-based anti-influenza compound ever identified and characterized from high throughput screening to show potent (sub-μM) antiviral activity. We conclude that BPR1P0034 has potential antiviral activity, which offers an opportunity for the development of a new anti-influenza virus agent.
Antineoplastic effects of an Aurora B kinase inhibitor in breast cancer
Authors: Gully Christopher P , Zhang Fanmao , Chen Jian , Yeung James A , Velazquez-Torres Guermarie , Wang Edward , Yeung Sai-Ching Jim , Lee Mong-Hong 
Published: February 2010

Abstract

Background
Aurora B kinase is an important mitotic kinase involved in chromosome segregation and cytokinesis. It is overexpressed in many cancers and thus may be an important molecular target for chemotherapy. AZD1152 is the prodrug for AZD1152-HQPA, which is a selective inhibitor of Aurora B kinase activity. Preclinical antineoplastic activity of AZD1152 against acute myelogenous leukemia, multiple myeloma and colorectal cancer has been reported. However, this compound has not been evaluated in breast cancer, the second leading cause of cancer deaths among women.

Results
The antineoplastic activity of AZD1152-HQPA in six human breast cancer cell lines, three of which overexpress HER2, is demonstrated. AZD1152-HQPA specifically inhibited Aurora B kinase activity in breast cancer cells, thereby causing mitotic catastrophe, polyploidy and apoptosis, which in turn led to apoptotic death. AZD1152 administration efficiently suppressed the tumor growth in a breast cancer cell xenograft model. In addition, AZD1152 also inhibited pulmonary metastatic nodule formation in a metastatic breast cancer model. Notably, it was also found that the protein level of Aurora B kinase declined after inhibition of Aurora B kinase activity by AZD1152-HQPA in a time- and dose-dependent manner. Investigation of the underlying mechanism suggested that AZD1152-HQPA accelerated protein turnover of Aurora B via enhancing its ubiquitination.

Conclusions
It was shown that AZD1152 is an effective antineoplastic agent for breast cancer, and our results define a novel mechanism for posttranscriptional regulation of Aurora B after AZD1152 treatment and provide insight into dosing regimen design for this kinase inhibitor in metastatic breast cancer treatment.
Alterations in the complement cascade in post-traumatic stress disorder
Authors: Hovhannisyan Lilit P , Mkrtchyan Gohar M , Sukiasian Samvel H , Boyajyan Anna S 
Published: February 2010

AbstractBackgroundIn the present study we assessed the functional state of the major mediator of the immune response, the complement system, in post-traumatic stress disorder (PTSD).MethodsThirty one PTSD patients within 13 years from traumatic event and the same number of sex- and age-matched healthy volunteers were involved in this study. In the blood serum of the study subjects hemolytic activities of the classical and alternative complement pathways, as well as the activities of the individual complement components have been measured. Correlation analysis between all measured parameters was also performed.ResultsAccording to the results obtained PTSD is characterized by hyperactivation of the complement classical pathway, hypoactivation of the complement alternative pathway and overactivation of the terminal pathway.ConclusionsThe results obtained provide further evidence on the involvement of the inflammatory component in pathogenesis of PTSD.
Konsensusprotokoll zur Standardisierung von Entnahme und Biobanking des Liquor cerebrospinalis1 / A consensus protocol for the standardisation of cerebrospinal fluid collection and biobanking
Authors: Teunissen Charlotte E. , Petzold Axel , Bennett Jeffrey L. , Berven Frode S. , Brundin Lou , Comabella Manuel , Franciotta Diego , Federiksen Jette L. , Fleming John O. , Furlan Roberto , Hintzen Rogier Q. , Hughes Steve G. , Johnson Michael H. , Krasulova Eva , Kuhle Jens , Magnone Maria-Chiara , Rajda Cecilia , Rejdak Konrad , Schmidt Holly K. , Pesch Vincent van , Waubant Emmanuelle , Wolf Christian , Giovannoni Gavin , Deisenhammer Florian , Hegen Harald , Hemmer Bernhard , Tumani Hayrettin T. 
Published: February 2010

Zusammenfassung
Die Erforschung von Biomarkern in Körperflüssigkeiten bei neurodegenerativen und neuroinflammatorischen Erkrankungen blickt auf eine langjährige Geschichte zurück. Dennoch werden nur wenige Liquor cerebrospinalis (Liquor)-Biomarker in der klinischen Praxis verwendet. Einer der problematischen Faktoren in der Liquorbiomarker-Forschung ist die eingeschränkte Aussagekraft von Studien aufgrund einer nicht ausreichend großer Anzahl von Proben, die in Studien von einzelnen Zentren akquiriert werden können. Deshalb ist die Kooperation zwischen mehreren Zentren erforderlich, um große Biobanken von definierten Proben zu etablieren. Standardisierte Protokolle für Biobanking sind unumgänglich, um die durch die größere Anzahl von Liquorproben gewonnene statistische Aussagekraft sicherzustellen und nicht durch mangelhafte Präanalytik einzuschränken. Hier wird ein Konsensusbericht über Leitlinien zu Liquorentnahme und Biobanking durch das BioMS-eu Netzwerk für Liquorbiomarker-Forschung in Multipler Sklerose präsentiert. Schwerpunkte des Berichts sind Liquorentnahme, präanalytische Faktoren und klinische sowie sonstige Informationen. Biobanking-Protokolle sind für Liquor-Biobanken im Rahmen der Erforschung jeder neurologischen Krankheit anwendbar.
Ungebundenes (freies) Bilirubin: eine bessere Grundlage für die Bewertung des Icterus neonatorum1 / Unbound (free) bilirubin: improving the paradigm for evaluating neonatal jaundice
Authors: Ahlfors Charles E. , Wennberg Richard P. , Ostrow J. Donald , Tiribelli Claudio 
Published: February 2010

Zusammenfassung

Hintergrund: Die Konzentration des Gesamtbilirubins (BT) in Serum oder Plasma war lange Zeit die klinische Standard-Laboratoriumsuntersuchung für die Bewertung eines Neugeborenenikterus, obwohl Studien zeigten, dass keine enge Korrelation zwischen BT und dem Auftreten einer akuten Bilirubin-Enzephalopathie (ABE) oder ihrer Folgezustände [Tod, klassischer Kernikterus oder Bilirubin-induzierte neurologische Dysfunktion (BIND)] besteht. Die schlechte Korrelation zwischen BT und ABE wird üblicherweise auf Störeinflüsse durch Komorbidität (z.B. Hämolysezustände, Frühgeburtlichkeit, Asphyxie oder Infektion) zurückgeführt. Es mehren sich jedoch die Hinweise darauf, dass BT per se kein guter Indikator ist, weil die Bilirubinkonzentration im Zentralnervensystem – und somit das Auftreten der ABE und ihrer Folgezustände – weniger von der Gesamtbilirubinkonzentration in Serum oder Plasma als von der Konzentration des ungebundenen oder freien (d.h. im Plasma nicht an Proteine gebundenen) Bilirubins (Bf) abhängt.

Inhalt: In dieser Übersichtsarbeit werden (a) die komplexen Beziehungen zwischen den in Serum oder Plasma bestimmten Bilirubinkonzentrationen und der ABE, (b) die geschichtlichen Grundlagen der limitierten Verwendung von Bf in der Klinik, (c) die Peroxidase-Methode zur Bestimmung von Bf sowie technische und andere Aspekte, die für die Anpassung der Methode an die klinische Routine erforderlich sind, (d) die klinischen Erfahrungen mit der Anwendung von Bf beim Management des Icterus neonatorum und (e) die Bedeutung der Bf-Bestimmung für wissenschaftliche Fragestellungen zur Pathobiochemie des Bilirubins dargestellt.

Zusammenfassung: Immer mehr Daten aus klinischen Studien, klinischer Erfahrung und Grundlagenforschung zur Neurotoxizität von Bilirubin sprechen dafür, dass der Parameter Bf zügig in die Routinediagnostik bei ikterischen Neugeborenen aufgenommen werden sollte.
Fission Yeast Hsk1 (Cdc7) Kinase Is Required After Replication Initiation for Induced Mutagenesis and Proper Response to DNA Alkylation Damage
Authors: Dolan William P , Le Anh-Huy , Schmidt Henning , Yuan Ji-Ping , Green Marc , Forsburg Susan L 
Published: February 2010

Abstract
Genome stability in fission yeast requires the conserved S-phase kinase Hsk1 (Cdc7) and its partner Dfp1 (Dbf4). In addition to their established function in the initiation of DNA replication, we show that these proteins are important in maintaining genome integrity later in S phase and G2. hsk1 cells suffer increased rates of mitotic recombination and require recombination proteins for survival. Both hsk1 and dfp1 mutants are acutely sensitive to alkylation damage yet defective in induced mutagenesis. Hsk1 and Dfp1 are associated with the chromatin even after S phase, and normal response to MMS damage correlates with the maintenance of intact Dfp1 on chromatin. A screen for MMS-sensitive mutants identified a novel truncation allele, rad35 (dfp1-(1–519)), as well as alleles of other damage-associated genes. Although Hsk1–Dfp1 functions with the Swi1–Swi3 fork protection complex, it also acts independently of the FPC to promote DNA repair. We conclude that Hsk1–Dfp1 kinase functions post-initiation to maintain replication fork stability, an activity potentially mediated by the C terminus of Dfp1.
Serotype 19A Is the Most Common Serotype Causing Invasive Pneumococcal Infections in Children
Authors: Kaplan Sheldon L. , Barson William J. , Lin Philana L. , Stovall Stephanie H. , Bradley John S. , Tan Tina Q. , Hoffman Jill A. , Givner Laurence B. , Mason Edward O. 
Published: February 2010

OBJECTIVE:
The purpose of this study was to monitor the clinical and microbiologic features of invasive infections caused by Streptococcus pneumoniae among children before and after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7).

DESIGN:
We conducted a 15-year prospective surveillance study of all invasive pneumococcal infections in children. The sample included infants and children at 8 children's hospitals in the United States with culture-proven invasive S pneumoniae infections.

RESULTS:
Since the implementation of routine PCV7 immunization in 2000, invasive infections have decreased yearly from 2001 through 2004, to a nadir of 151 infections; the rate then increased from 2005 through 2008. Compared with the pre-PCV7 era, a greater proportion of children with invasive pneumococcal infection had an underlying condition in the post-PCV7 period. Compared with the total number of annual admissions, the number of 19A isolates increased significantly from 2001 to 2008 (P &lt; .00001). In 2007 and 2008, only 16 isolates (4%) were vaccine serotypes; 19A accounted for 46% (168 of 369) of the non-PCV7 serotypes. Thirty percent of the 19A isolates were multidrug resistant. Serotypes 1, 3, and 7F accounted for 22% of the non-PCV7 serotypes. Among children with invasive pneumococcal infections, the likelihood of a 19A serotype increased with the number of preceding PCV7 doses.

CONCLUSIONS:
Since 2005, the number of invasive pneumococcal infections in children has increased at 8 children's hospitals, primarily as a result of serotype 19A isolates, one third of which were resistant to multiple antibiotics in 2007 and 2008. Continued surveillance is necessary to detect emerging serotypes after the planned introduction of 13-valent or other pneumococcal vaccines.
Reporting of corticosteroid use in systemic disease trials: Evidence from a systematic review of the potential impact on treatment effect
Authors: Pagnoux Christian , Dechartres Agnès , Giraudeau Bruno , Seror Raphaèle , Guillevin Loïc , Ravaud Philippe 
Published: February 2010

AbstractObjectiveTo study how corticosteroid therapy is planned and described in reports of systemic disease trials and estimate the impact of the between‐arm difference in corticosteroid dose on treatment effect.MethodsWe performed a systematic review of PubMed and Cochrane databases on all reports of randomized systemic disease trials with corticosteroids as a cointervention. Data were extracted on the trial characteristics and results, planning of corticosteroid use, and dose. Success rates were adjusted for corticosteroid use for studies with available data and a binary outcome. Because the exact impact of between‐arm differences in corticosteroid dose on success rates is unknown, we tested different values for the impact of a difference of 1 unit (1 mg for daily dosage or 250 mg for cumulative dose at the end of the trial).ResultsA total of 139 trials were identified, including 79 investigating lupus and 30 investigating vasculitis. Planned management of corticosteroid use was specified in 101 reports (72.7%), with a fully described tapering scheme in 33 (23.7%). Corticosteroid consumption for each arm was given in 60 reports (43.2%), with a comparison of daily or cumulative dosage at the end of the trial in 32 (23.0%). An attempt to adjust for corticosteroid use was described in 2 (1.5%). With a value of 2.5% for the impact of a 1‐unit difference in corticosteroid dose, adjustment yielded changes in success rate differences exceeding 10% in 11 (46%) of the 24 reports analyzed.ConclusionFor systemic disease trials, use of corticosteroids as a cointervention is often inadequately planned and reported and could affect treatment effect.
Nogo‐A antibodies and training reduce muscle spasms in spinal cord‐injured rats
Authors: Gonzenbach Roman R. , Gasser Pascal , Zörner Björn , Hochreutener Eva , Dietz Volker , Schwab Martin E. 
Published: February 2010

AbstractObjectiveSpinal cord injury (SCI) leads to permanent motor and sensory deficits due to the damage of ascending and descending fiber tracts. In addition, malfunctions such as neuropathic pain or muscle spasms develop in many patients, possibly caused by injury‐induced plastic changes of neuronal circuits above and below the lesion. New treatment strategies for spinal cord injury aim at enhancing plasticity and neurite growth, for example, by blocking the key neurite growth inhibitor Nogo‐A or its downstream effectors. It is therefore crucial to investigate potential effects of such treatments on malfunctions such as muscle spasms. In addition, locomotor training, now a standard therapeutic tool to improve walking ability in incomplete SCI subjects, can be expected to influence the rearrangement of spinal cord circuits and the development of muscle spasms and other malfunctions.Methods and ResultsHere we present and validate a new rat model for muscle spasms after incomplete SCI and show that both intrathecal anti–Nogo‐A antibody treatment and locomotor training, started early after injury, permanently reduce the development of muscle spasms.InterpretationThe results show that an antibody‐mediated suppression of the growth inhibitory protein Nogo‐A leads to functional recovery and a lower level of malfunctions, suggesting the formation of functionally meaningful connections in the damaged spinal cord. Treadmill training early after SCI also has a beneficial effect. ANN NEUROL 2010;68:48–57
Protective effect of PEGylation against poly(amidoamine) dendrimer‐induced hemolysis of human red blood cells
Authors: Wang Wei , Xiong Wei , Zhu Yanhong , Xu Huibi , Yang Xiangliang 
Published: February 2010

AbstractPoly(amidoamine) (PAMAM) dendrimers are widely used in medical applications. However, dendrimers bearing positively charged surface groups are prone to destabilize cell membrane and cause cell lysis. The lytic effect of dendrimers on red blood cells (RBCs) namely hemolysis is extremely dangerous when administered in vivo. To diminish the hematologic toxicity, we modified PAMAM dendrimers with poly(ethylene glycol) (PEG) of three molecular weights (2k, 5k, and 20k). The protective effect of PEGylation against PAMAM dendrimer‐induced hemolysis was studied. RBCs morphology and surface structure were analyzed by optical microscopy (OM) and atomic force microscopy (AFM). The results indicated that PAMAM and PEG‐2k modified dendrimers induced hemolysis at 0.1 and 0.5 mg/mL respectively, whereas PEG‐5k and PEG‐20k modified dendrimers showed no significant difference in hemolysis compared with control even at 5 mg/mL. OM and AFM investigation indicated PAMAM and PEG‐2k modified dendrimers caused RBCs aggregation and lysis. However, no changes were observed in the overall shape of RBCs treated with PEG‐5k and PEG‐20k modified dendrimers. The surface roughness of RBCs treated with PEGylated dendrimers were far lower than that of RBCs treated with PAMAM dendrimers. This study demonstrated that hemocompatibility of PAMAM dendrimers could be greatly enhanced by PEGylation. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010
Effect of Crosslinker Length and Composition on the Hydrophobicity and Thermomechanical Response of Acrylate‐Based Shape‐Memory Polymers
Authors: Warren P. Daniel , McGrath Dominic V. , Vande Geest Jonathan P. 
Published: February 2010

AbstractChemical and mechanical experiments are reported to elucidate the macroscopic effects of crosslinker length and composition on the thermomechanical response of acrylate‐based SMPs. To this end, EGA‐based formulations underwent a battery of basic tests which revealed that by increasing crosslinker chain length, polymer Tg can be decreased but there will be increases in compliance, step recoverability, and damping in a glassy state. Addition of methacrylate groups can cause increases in swelling, Tg, storage modulus in shorter chains, and greater damping at a rubbery state. All tested polymers exhibited mild hydrophilicity. PEGDA formulations exhibited good recoverability and could be an option for vascular applications.magnified image