bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution of Olfactory and Nonolfactory Surface Area in the Nasal Fossa of Microcebus murinus: Implications for Microcomputed Tomography and Airflow Studies
Authors: Smith Timothy D. , Eiting Thomas P. , Rossie James B. 
Published: May 2011

AbstractThe nasal fossa of most mammals exemplifies extreme skeletal complexity. Thin scrolls of bone (turbinals) that both elaborate surface area (SA) and subdivide nasal space are used as morphological proxies for olfactory and respiratory physiology. The present study offers additional details on the nasal fossa of the adult mouse lemur (Microcebus murinus), previously described by Smith and Rossie (Smith and Rossie [2008]; Anatomical Record 291:895–915). Additional, intervening histological sections of the specimen were used to map and quantify the distribution of olfactory and nonolfactory mucosa on the smaller turbinal of the frontal recess (FR; frontoturbinal) and those that occur between ethmoturbinals (ETs; interturbinals). A second adult Microcebus specimen, available as a dried skull, was scanned using microcomputed tomography (microCT) and reconstructed to infer the position of these turbinals within the nasal airway. Overall, turbinal bones comprise more than half of internal nasal SA. All ETs combined comprise about 30% of total nasal fossa SA, and contribute nearly half of all olfactory SA. Of these, the nasoturbinal (NT) is most completely covered with olfactory mucosa, whereas ET I is least covered with olfactory mucosa. The FR contributes significantly to total olfactory SA (ca. 20%). This recess and the single frontoturbinal within it lie in a more lateral pathway of airflow compared with interturbinals, which lie in more central zone just anterior to the olfactory recess of Microcebus. Variations in the turbinals and recesses that complicate central and paranasal in primates should be investigated further in light of zone‐specific distributions of olfactory receptors (ORs) that differ between these regions in rodents. Anat Rec, 2011 © 2011 Wiley‐Liss, Inc.
Masticatory HyperMuscularity is not Related to Reduced Cranial Volume in Myostatin‐Knockout Mice
Authors: Cray James , Kneib Jared , Vecchione Lisa , Byron Craig , Cooper Gregory M. , Losee Joseph E. , Siegel Michael I. , Hamrick Mark W. , Sciote James J. , Mooney Mark P. 
Published: May 2011

AbstractIt has been suggested recently that masticatory muscle size reduction in humans resulted in greater encephalization through decreased compressive forces on the cranial vault. Following this logic, if masticatory muscle size were increased, then a reduction in brain growth should also occur. This study was designed to test this hypothesis using a myostatin (GDF‐8) knockout mouse model. Myostatin is a negative regulator of skeletal muscle growth, and individuals lacking this gene show significant hypermuscularity. Sixty‐two [32 wild‐type (WT) and 30 GDF‐8 ‐/‐ knockout], 1, 28, 56, and 180‐day‐old CD‐1 mice were used. Body and masseter muscle weights were collected following dissection and standardized lateral and dorsoventral cephalographs were obtained. Cephalometric landmarks were identified on the radiographs and cranial volume was calculated. Mean differences were assessed using a two‐way ANOVA. KO mice had significantly greater body and masseter weights beginning at 28 days compared with WT controls. No significant differences in cranial volumes were noted between KO and WT. Muscle weight was not significantly correlated with cranial volume in 1, 28, or 180‐day‐old mice. Muscle weights exhibited a positive correlation with cranial volume at 56 days. Results demonstrate that masticatory hypermuscularity is not associated with reduced cranial volume. In contrast, there is abundant data demonstrating the opposite, brain growth determines cranial vault growth and masticatory apparatus only affects ectocranial morphology. The results presented here do not support the hypothesis that a reduction in masticatory musculature relaxed compressive forces on the cranial vault allowing for greater encephalization. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.
Multiprotein Deposits in Neurodegenerative Disorders: Our Experience in the Tissue Brain Bank of Navarra
Authors: Echávarri C. , Caballero M.C. , Aramendía A. , García‐Bragado F. , Tuñón T. 
Published: May 2011

AbstractThe prevalence of neurodegenerative disorders increases dramatically with advancing age. Although in recent decades the study of many neurodegenerative disorders has evolved greatly, the concept of neurodegeneration still remains elusive. Although neurodegenerative disorders are classified according to the major components of protein deposits, coexpression of several abnormal proteins in the brain tissue is more common than that was previously thought. The aim of this report is to describe the type of protein deposits found in brains with neuropathological diagnosis of neurodegenerative disease. The report shows the experience obtained in the Brain Bank of Navarra (Spain). The target population for this retrospective descriptive study comprised 178 brains autopsied in the “Hospital of Navarra” in Pamplona between 1994 and 2004 and 201 brains donated to the Brain Bank of Pamplona between 2004 and 2009. The diagnosis of the 201 brains from the Brain Bank was 62 (30.8%) Alzheimer's disease (AD), 43 (21.3%) multiprotein deposit, 31 (15.4%) α‐synucleinopathies, 31 (15.4%) frontotemporal lobar degeneration (FTLD), 17 (8.4%) tauopathies, 9 (4.4%) prion disease, 6 (2.9%) vascular dementia (VD), and 2 (0.9%) Huntington's disease. Among the 43 cases with multiprotein deposits, we found 35 brains with deposits of 3 proteins (tau, β‐amyloid, and α‐synuclein). In these two series of brains, the high incidence of deposition of multiple proteins in neurodegenerative disorders is shown. Our results are in agreement with previous findings showing that tau, β‐amyloid, and α‐synuclein are the proteins most frequently deposited together. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.
Upregulation of LAPTM4B‐35 Promotes Malignant Transformation and Tumorigenesis in L02 Human Liver Cell Line
Authors: Li Li , Shan Yi , Yang Hua , Zhang Sha , Lin Ming , Zhu Ping , Chen Xin‐Yu , Yi Jing , Mcnutt Michael A. , Shao Gen‐Ze , Zhou Rou‐Li 
Published: May 2011

AbstractHepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms worldwide and is the second leading cause of cancer death in China. We have previously demonstrated that LAPTM4B‐35, encoded by lysosomal protein transmembrane 4 beta gene, is overexpressed in over 80% of HCCs and is a novel‐independent prognostic factor for metastasis, recurrence, and postoperative survival in HCC. In this study, we investigated the role of LAPTM4B‐35 in malignant transformation and tumorigenesis using L02 cells, a cell line originated from human normal liver cells. Our data show that replication‐deficient adenovirus vector‐mediated upregulation of LAPTM4B‐35 promotes anchorage‐independent proliferation and resistance to adriamycin‐induced apoptosis. Study of the underlying mechanisms demonstrated alterations of molecular events involved in these processes, which included the activation of phosphoinositide 3‐kinases (PI3K)/serine/threonine protein kinase B (PKB/AKT)/bcl‐xL/bcl‐2‐associated death promoter homolog (Bad) signaling pathway, inhibition of caspase‐3 activation, upregulation of Bcl‐2, and downregulation of Bax. In addition, upregulation of LAPTM4B‐35 in L02 cells resulted in tumorigenesis in 100% (6/6) of inoculated nude mice and accelerated the death of mice with xenografts in vivo. In conclusion, LAPTM4B‐35 promotes malignant transformation and tumorigenesis in human liver L02 cell line through promotion of deregulated proliferation and inhibition of apoptosis. These findings suggest that overexpression of LAPTM4B‐35 may play a critical role in hepatocarcinogenesis and therefore, may be a therapeutic target for HCC. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.
Increased sensitivity to apoptosis induced by methotrexate is mediated by JNK
Authors: Spurlock Charles F. , Aune Zachary T. , Tossberg John T. , Collins Patrick L. , Aune Jessica P. , Huston Joseph W. , Crooke Philip S. , Olsen Nancy J. , Aune Thomas M. 
Published: May 2011

AbstractObjectiveLow‐dose methotrexate (MTX) is an effective therapy for rheumatoid arthritis (RA), yet its mechanism of action is incompletely understood. The aim of this study was to explore the induction of apoptosis by MTX.MethodsFlow cytometry was performed to assess changes in the levels of intracellular proteins, reactive oxygen species (ROS), and apoptosis. Quantitative polymerase chain reaction was performed to assess changes in the transcript levels of select target genes in response to MTX.ResultsMTX did not directly induce apoptosis but rather “primed” cells for markedly increased sensitivity to apoptosis via either mitochondrial or death receptor pathways, by a JNK‐dependent mechanism. Increased sensitivity to apoptosis was mediated, at least in part, by MTX‐dependent production of ROS, JNK activation, and JNK‐dependent induction of genes whose protein products promote apoptosis. Supplementation with tetrahydrobiopterin blocked these MTX‐induced effects. Patients with RA who were receiving low‐dose MTX therapy expressed elevated levels of the JNK target gene, jun.ConclusionOur results support a model whereby MTX inhibits reduction of dihydrobiopterin to tetrahydrobiopterin, resulting in increased production of ROS, increased JNK activity, and increased sensitivity to apoptosis. The finding of increased jun levels in patients with RA receiving low‐dose MTX supports the notion that this pathway is activated by MTX in vivo and may contribute to the efficacy of MTX in inflammatory disease.
Outcomes from building system courseware for teaching and testing in a discipline‐based human structure curriculum
Authors: Reilly Frank D. 
Published: May 2011

AbstractThis study investigated the educational benefits of system‐based lecture notes and interactive learning objects in a peripheral nervous system component of a traditional first‐year medical school human anatomy course. The impetus for the investigation was anecdotal evidence suggesting enhanced learner satisfaction with the learning resources. Retrospective review of existing data from 2006 to 2009 was undertaken to quantify (1) the effects of Web‐based system courseware on examination item performance, and (2) differences among learner opinions regarding the benefit level of the five different types of interactive learning objects as evaluated by instructional design questionnaires. Interactive patient‐based case studies (IPCS) and review games (Games), simulated interactive patients (SIP), flashcards, and unit quizzes (Quizzes) developed in‐house have been peer‐reviewed and published in MedEdPORTAL. Statistics included one‐way analysis of variance, Tukey's post hoc test, and power meta‐analysis (d). Examination item analysis scores remained significantly higher (P ≤ 0.05; d = 0.3938) for learners receiving the instructional treatment incorporating system‐based lecture notes and interactive learning objects than for those not receiving this treatment. Using questionnaires with a five‐point Likert scale, students reported favorably on the benefit level of all learning objects. They rated the SIP and IPCS significantly higher (P ≤0.05) and games significantly lower (P ≤ 0.05) than in previous years, indicating a change in learner preferences. This study reaffirms that online system‐based instructional techniques improve student examination performance and overall student satisfaction. Learners indicated stronger preferences for SIP and IPCS over exercises encouraging passive memorization of anatomical content. Anat Sci Educ. © 2011 American Association of Anatomists.
Do repeated arrays of regulatory small‐RNA genes elicit genomic imprinting?
Authors: Labialle Stéphane , Cavaillé Jérôme 
Published: May 2011

AbstractThe basic premise of the host‐defense theory is that genomic imprinting, the parent‐of‐origin expression of a subset of mammalian genes, derives from mechanisms originally dedicated to silencing repeated and retroviral‐like sequences that deeply colonized mammalian genomes. We propose that large clusters of tandemly‐repeated C/D‐box small nucleolar RNAs (snoRNAs) or microRNAs represent a novel category of sequences recognized as “genomic parasites”, contributing to the emergence of genomic imprinting in a subset of chromosomal regions that contain them. Such a view is supported by evidence derived from studies of the imprinted snoRNA‐ and/or miRNA‐encoding Dlk1‐Dio3, Snurf‐Snrpn, Sfbmt2, and C19MC domains. While adding a new piece to the challenging puzzle of mammalian genome history, this hypothesis also reinforces the notion that dissecting the features and molecular mechanisms that discriminate between “foreign” and “endogenous” sequences is of crucial importance in the field of mammalian epigenetics.
Ammonia‐oxidizing bacteria dominates over ammonia‐oxidizing archaea in a saline nitrification reactor under low DO and high nitrogen loading
Authors: Ye Lin , Zhang Tong 
Published: May 2011

AbstractA continuous nitrification reactor treating saline wastewater was operated for almost 1 year under low dissolved oxygen (DO) levels (0.15–0.5 mg/L) and high nitrogen loadings (0.26–0.52 kg‐N/(m3 day)) in four phases. The diversity and abundance of ammonia‐oxidizing archaea (AOA) and ammonia‐oxidizing bacteria (AOB) were analyzed by cloning, terminal restriction fragment length polymorphism (T‐RFLP) and quantitative polymerase chain reaction (qPCR). The results showed that there were only one dominant AOA species and one dominant AOB species in the reactor in all of the four experimental phases. The amoA gene of the dominant AOA only had a similarity of 89.3% with the cultured AOA species Nitrosopumilus maritimus SCM1. All of the AOB species detected in the reactor belong to Nitrosomonas genus and it was found that the AOB populations changed with the ammonium loadings and DO levels. The abundance of AOB in the reactor was ∼40 times larger than that of AOA, and the ratio of AOB to AOA increased significantly up to ∼2,000 to ∼4,000 with the increase of ammonium loading, indicating that AOB are much more competitive than AOA in high ammonium environments and probably AOA play a less important role than AOB in the nitrification reactors. Biotechnol. Bioeng. 2011;108: 2544–2552. © 2011 Wiley Periodicals, Inc.
Comparative metabolic capabilities for Micrococcus luteus NCTC 2665, the “Fleming” strain, and actinobacteria
Authors: Rokem J. Stefan , Vongsangnak Wanwipa , Nielsen Jens 
Published: May 2011

AbstractPutative gene predictions of the Gram positive actinobacteria Micrococcus luteus (NCTC 2665, “Fleming strain”) was used to construct a genome scale reconstruction of the metabolic network for this organism. The metabolic network comprises 586 reactions and 551 metabolites, and accounts for 21% of the genes in the genome. The reconstruction was based on the annotated genome and available biochemical information. M. luteus has one of the smallest genomes of actinobacteria with a circular chromosome of 2,501,097 base pairs and a GC content of 73%. The metabolic pathways required for biomass production in silico were determined based on earlier models of actinobacteria. The in silico network is used for metabolic comparison of M. luteus with other actinomycetes, and hence provides useful information for possible future biotechnological exploitation of this organism, e.g., for production of biofuels. Biotechnol. Bioeng. 2011;108: 2770–2775. © 2011 Wiley Periodicals, Inc.
Evaluation of protein engineering and process optimization approaches to enhance antibody drug manufacturability
Authors: Conley Greg P. , Viswanathan Malini , Hou Ying , Rank Doug L. , Lindberg Allison P. , Cramer Steve M. , Ladner Robert C. , Nixon Andrew E. , Chen Jie 
Published: May 2011

AbstractA potent single digit picomolar fully human monoclonal antibody (hMAb) inhibitor with a high degree of specificity to the antigen of interest was identified from a phage display library. The hMAb, however, exhibited a high degree of hydrophobicity and easily formed insoluble aggregates when purified using a Protein A based generic process. Strategies were designed using both protein engineering and process development approaches to optimize the molecule's amino acid sequence and its behavior in process conditions. The insoluble aggregation issue was brought under control by one single amino acid mutation in CDR region or by switching to non‐ProA based purification process. Our study therefore presents the rational manufacturability design for future monoclonal antibody product and its purification process under the quality by design concept by either engineering the drug molecule to adapt existing platform process or optimizing the process to fit the specific properties of the drug product. Biotechnol. Bioeng. 2011;108: 2634–2644. © 2011 Wiley Periodicals, Inc.
The role of polymer nanolayer architecture on the separation performance of anion‐exchange membrane adsorbers: I. Protein separations
Authors: Bhut Bharat V. , Weaver Justin , Carter Andrew R. , Wickramasinghe S. Ranil , Husson Scott M. 
Published: May 2011

AbstractThis contribution describes the preparation of strong anion‐exchange membranes with higher protein binding capacities than the best commercial resins. Quaternary amine (Q‐type) anion‐exchange membranes were prepared by grafting polyelectrolyte nanolayers from the surfaces of macroporous membrane supports. A focus of this study was to better understand the role of polymer nanolayer architecture on protein binding. Membranes were prepared with different polymer chain graft densities using a newly developed surface‐initiated polymerization protocol designed to provide uniform and variable chain spacing. Bovine serum albumin and immunoglobulin G were used to measure binding capacities of proteins with different size. Dynamic binding capacities of IgG were measured to evaluate the impact of polymer chain density on the accessibility of large size protein to binding sites within the polyelectrolyte nanolayer under flow conditions. The dynamic binding capacity of IgG increased nearly linearly with increasing polymer chain density, which suggests that the spacing between polymer chains is sufficient for IgG to access binding sites all along the grafted polymer chains. Furthermore, the high dynamic binding capacity of IgG (>130 mg/mL) was independent of linear flow velocity, which suggests that the mass transfer of IgG molecules to the binding sites occurs primarily via convection. Overall, this research provides clear evidence that the dynamic binding capacities of large biologics can be higher for well‐designed macroporous membrane adsorbers than commercial membrane or resin ion‐exchange products. Specifically, using controlled polymerization leads to anion‐exchange membrane adsorbers with high binding capacities that are independent of flow rate, enabling high throughput. Results of this work should help to accelerate the broader implementation of membrane adsorbers in bioprocess purification steps. Biotechnol. Bioeng. © 2011 Wiley Periodicals, Inc.
Protein switches identified from diverse insertion libraries created using S1 nuclease digestion of supercoiled‐form plasmid DNA
Authors: Tullman Jennifer , Guntas Gurkan , Dumont Matthew , Ostermeier Marc 
Published: May 2011

AbstractWe demonstrate that S1 nuclease converts supercoiled plasmid DNA to unit‐length, linear dsDNA through the creation of a single, double‐stranded break in a plasmid molecule. These double‐stranded breaks occur not only in the origin of replication near inverted repeats but also at a wide variety of locations throughout the plasmid. S1 nuclease exhibits this activity under conditions typically employed for the nuclease's single‐stranded nuclease activity. Thus, S1 nuclease digestion of plasmid DNA, unlike analogous digestion with DNaseI, effectively halts after the first double‐stranded break. This property makes easier the construction of large domain insertion libraries in which the goal is to insert linear DNA at a variety of locations throughout a plasmid. We used this property to create a library in which a circularly permuted TEM1 β‐lactamase gene was inserted throughout a plasmid containing the gene encoding Escherichia coli ribose binding protein. Gene fusions that encode allosteric switch proteins in which ribose modulates β‐lactamase catalytic activity were isolated from this library using a combination of a genetic selection and a screen. Biotechnol. Bioeng. 2011;108: 2535–2543. © 2011 Wiley Periodicals, Inc.
Trends and outcomes after surgical lower limb revascularization in England
Authors: Moxey P W , Hofman D , Hinchliffe R J , Jones K , Thompson M M , Holt P J E 
Published: May 2011

Abstract

Background
The aim was to analyse contemporary data on the number of surgical revascularization procedures performed each year in England, and their outcome.

Methods
Hospital Episode Statistics and Office for National Statistics data were used to quantify numbers and identify factors associated with outcome after all femoropopliteal and femorodistal bypass procedures performed between 2002 and 2006. Outcome measures were repeat bypass, major amputation, death and a composite measure. Single-level multivariable logistic regression modelling was used to quantify the effect of these variables on outcome.

Results
A total of 21 675 femoropopliteal and 3458 femorodistal bypass procedures were performed. Mean in-hospital mortality rates were 6·7 and 8·0 per cent respectively. One-year survival rates were 82·8 and 79·1 per cent; both increased over the study interval. The mean 1-year major amputation rate after femoropopliteal bypass was 10·4 per cent, which decreased significantly over the 5 years (P &lt; 0·001); after distal bypass the rate of 20·8 per cent remained unchanged (P = 0·456). Diabetes mellitus and chronic kidney disease were significant predictors of adverse outcome for both procedures: odds ratio (OR) at 1 year 1·56 (95 per cent confidence interval 1·46 to 1·67; P &lt; 0·001) and 2·15 (1·88 to 2·45; P &lt; 0·001) respectively for femoropopliteal bypass. Previous femoral angioplasty was associated with an increased rate of major amputation 1 year after proximal bypass (OR 1·18, 1·05 to 1·33; P = 0·004).

Conclusion
Although all mortality rates are improving, the major amputation rate remains high after femorodistal bypass. Adverse events occurred after 37·6 per cent of femoropopliteal and 49·7 per cent of femorodistal bypasses; diabetes and chronic renal failure were the main predictors of poor outcome.
Roimatacene: An Antibiotic against Gram‐Negative Bacteria Isolated from Cystobacter ferrugineus Cb G35 (Myxobacteria)
Authors: Zander Wiebke , Gerth Klaus , Mohr Kathrin I. , Kessler Wolfgang , Jansen Rolf , Müller Rolf 
Published: May 2011

AbstractRoimatacene (1) was isolated from the myxobacterium Cystobacter ferrugineus strain Cb G35 in a bioactivity‐guided process, by following the antimicrobial activity against Escherichia coli. Since 1 was extremely sensitive to oxygen, a protective isolation and handling protocol was developed, by utilizing the free radical scavenger 4‐ethoxyphenol. The structure of 1 was determined by HRMS, 1D and 2D NMR spectroscopy and chemical derivatization to acetonides and Mosher esters to finally establish the absolute configuration. Methionine and acetate were identified as building blocks in the biosynthesis of 1 by feeding experiments with differently 13C‐labeled precursors. The antimicrobial activity of 1 was determined in a broad screening revealing 1 to inhibit several Gram‐negative bacteria.