bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards a metabolic engineering strain “commons”: An Escherichia coli platform strain for ethanol production
Authors: Woodruff Lauren B.A. , May Brian L. , Warner Joseph R. , Gill Ryan T. 
Published: January 2013

AbstractIn the genome‐engineering era, it is increasingly important that researchers have access to a common set of platform strains that can serve as debugged production chassis and the basis for applying new metabolic engineering strategies for modeling and characterizing flux, engineering complex traits, and optimizing overall performance. Here, we describe such a platform strain of E. coli engineered for ethanol production. Starting with a fully characterized host strain (BW25113), we site‐specifically integrated the genes required for homoethanol production under the control of a strong inducible promoter into the genome and deleted the genes encoding four enzymes from competing pathways. This strain is capable of producing >30 g/L of ethanol in minimal media with <2 g/L produced of any fermentative byproduct. Using this platform strain, we tested previously identified ethanol tolerance genes and found that while tolerance was improved under certain conditions, any effect on ethanol production or tolerance was lost when grown under production conditions. Thus, our findings reinforce the need for a metabolic engineering “commons” that could provide a set of platform strains for use in more sophisticated genome‐engineering strategies. Towards this end, we have made this production strain available to the scientific community. Biotechnol. Bioeng. 2013; 110: 1520–1526. © 2013 Wiley Periodicals, Inc.
An 'omics approach towards CHO cell engineering
Authors: Datta Payel , Linhardt Robert J. , Sharfstein Susan T. 
Published: January 2013

AbstractChinese hamster ovarian cells (CHO) cells have been extensively utilized for industrial production of biopharmaceutical products, such as monoclonal antibodies, human growth hormones, cytokines, and blood‐products. Recent advances in recombinant DNA technology have resulted in the bioengineering of CHO cells that have robust gene amplification systems and can also be adapted to grow in suspension cultures. In parallel, recent advances in techniques and tools for decoding the CHO cell genome, transcriptome, proteome, and glycome have led to new areas of study for better understanding the metabolic pathways in CHO cells with the long‐term goal of developing new biologics. This review paper discusses the recent advances in bioengineering strategies in CHO cell lines and the impact of the knowledge gained by CHO cell genomics, transcriptomics, and glycomics on the future of CHO‐cell engineering. Biotechnol. Bioeng. 2013; 110: 1255–1271. © 2013 Wiley Periodicals, Inc.
Clarification of recombinant proteins from high cell density mammalian cell culture systems using new improved depth filters
Authors: Singh Nripen , Pizzelli Kara , Romero Jonathan K. , Chrostowski James , Evangelist Greg , Hamzik James , Soice Neil , Cheng K.S. 
Published: January 2013

AbstractIncreasingly high cell density, high product titer cell cultures containing mammalian cells are being used for the production of recombinant proteins. These high productivity cultures are placing a larger burden on traditional downstream clarification and purification operations due to higher product and impurity levels. Controlled flocculation and precipitation of mammalian cell culture suspensions by acidification or using polymeric flocculants have been employed to enhance clarification throughput and downstream filtration operations. While flocculation is quite effective in agglomerating cell debris and process related impurities such as (host cell) proteins and DNA, the resulting suspension is generally not easily separable solely using conventional depth filtration techniques. As a result, centrifugation is often used for clarification of cells and cell debris before filtration, which can limit process configurations and flexibility due to the investment and fixed nature of a centrifuge. To address this challenge, novel depth filter designs were designed which results in improved primary and secondary direct depth filtration of flocculated high cell density mammalian cell cultures systems feeds, thereby providing single‐use clarification solution. A framework is presented here for optimizing the particle size distribution of the mammalian cell culture systems with the pore size distribution of the gradient depth filter using various pre‐treatment conditions resulting in increased depth filter media utilization and improved clarification capacity. Feed conditions were optimized either by acidification or by polymer flocculation which resulted in the increased average feed particle‐size and improvements in throughput with improved depth filters for several mammalian systems. Biotechnol. Bioeng. 2013; 110: 1964–1972. © 2013 Wiley Periodicals, Inc.
Heterocycles as Nonclassical Bioisosteres of α‐Amino Acids
Authors: Poulie Christian B. M. , Bunch Lennart 
Published: January 2013

AbstractBioisosterism of α‐amino acids is often accomplished by replacing the α‐carboxylate with one of the many known carboxylic acid bioisosteres. However, bioisosterism of the whole α‐amino acid moiety is accomplished with heterocyclic bioisosteres that often display an acidic function. In this Minireview, we summarized the reported heterocycles as nonclassical bioisosteres of α‐amino acids, which include quinoxaline‐2,4(1H)‐dione, quinoxaline‐2,3(1H)‐dione and quinolin‐2(1H)‐one, azagrevellin and azepine‐derived structures. The binding mode of the crystalized bioisosteres were compared with those of the crystalized α‐amino acids that bind in the same domain, and where no data on the crystal structure were available, the displacement studies of known orthosteric ligands were used. The reported bioisosteres share the following essential structural features for mimicking α‐amino acids: an aromatic ring system joined to a lactam ring system with an acidic feature next to the lactam carbonyl, where this acidic feature together with the lactam carbonyl can mimic the α‐carboxylate, and the lactam nitrogen together with the aromatic ring system can mimic the α‐ammonium. The majority of these heterocycles can be prepared from three common corresponding starting materials: the corresponding anilines, isatins or anthranilic esters. The data collected here show the potential of this class of bioisosteres in the design of glutamate receptor ligands and beyond.
Single‐Walled Carbon Nanotube/Polyaniline/n‐Silicon Solar Cells: Fabrication, Characterization, and Performance Measurements
Authors: Tune Daniel D. , Flavel Benjamin S. , Quinton Jamie S. , Ellis Amanda V. , Shapter Joseph G. 
Published: January 2013

AbstractCarbon nanotube–silicon solar cells are a recently investigated photovoltaic architecture with demonstrated high efficiencies. Silicon solar‐cell devices fabricated with a thin film of conductive polymer (polyaniline) have been reported, but these devices can suffer from poor performance due to the limited lateral current‐carrying capacity of thin polymer films. Herein, hybrid solar‐cell devices of a thin film of polyaniline deposited on silicon and covered by a single‐walled carbon nanotube film are fabricated and characterized. These hybrid devices combine the conformal coverage given by the polymer and the excellent electrical properties of single‐walled carbon nanotube films and significantly outperform either of their component counterparts. Treatment of the silicon base and carbon nanotubes with hydrofluoric acid and a strong oxidizer (thionyl chloride) leads to a significant improvement in performance.
Diabetes in pregnancy among indigenous women in Australia, Canada, New Zealand and the United States: a systematic review of the evidence for screening in early pregnancy
Authors: Chamberlain Catherine , McNamara Bridgette , Williams Emily D. , Yore Daniel , Oldenburg Brian , Oats Jeremy , Eades Sandra 
Published: January 2013

SummaryRecently proposed international guidelines for screening for gestational diabetes mellitus (GDM) recommend additional screening in early pregnancy for sub‐populations at a high risk of type 2 diabetes mellitus (T2DM), such as indigenous women. However, there are criteria that should be met to ensure the benefits outweigh the risks of population‐based screening. This review examines the published evidence for early screening for indigenous women as related to these criteria. Any publications were included that referred to diabetes in pregnancy among indigenous women in Australia, Canada, New Zealand and the United States (n = 145). The risk of bias was appraised. There is sufficient evidence describing the epidemiology of diabetes in pregnancy, demonstrating that it imposes a significant disease burden on indigenous women and their infants at birth and across the lifecourse (n = 120 studies). Women with pre‐existing T2DM have a higher risk than women who develop GDM during pregnancy. However, there was insufficient evidence to address the remaining five criteria, including the following: understanding current screening practice and rates (n = 7); acceptability of GDM screening (n = 0); efficacy and cost of screening for GDM (n = 3); availability of effective treatment after diagnosis (n = 6); and effective systems for follow‐up after pregnancy (n = 5). Given the impact of diabetes in pregnancy, particularly undiagnosed T2DM, GDM screening in early pregnancy offers potential benefits for indigenous women. However, researchers, policy makers and clinicians must work together with communities to develop effective strategies for implementation and minimizing the potential risks. Evidence of effective strategies for primary prevention, GDM treatment and follow‐up after pregnancy are urgently needed. Copyright © 2013 John Wiley & Sons, Ltd.
Dual effect of advanced glycation end products in pancreatic islet apoptosis
Authors: Costal Flavia , Oliveira Erika , Raposo Alexandre , Machado‐Lima Adriana , Peixoto Elisa , Roma Letícia , Santos Laila , Lopes Faria José B. , Carpinelli Angelo Rafael , Giannella‐Neto Daniel , Passarelli Marisa , Correa‐Giannella Maria Lucia 
Published: January 2013

AbstractBackgroundLoss of β‐cell function hastens deterioration of metabolic control in type 2 diabetes patients. Besides amyloid deposit and glucolipotoxicity, advanced glycation end products (AGEs) acting through their receptors (RAGE) seem to contribute to this process by promoting islet apoptosis. In order to investigate the role of AGEs in β‐cell deterioration, we evaluated the temporal and dose effects of AGE compounds on apoptosis rate, reactive oxygen species generation and expression of pro‐apoptotic and anti‐apoptotic genes in cultured islets.MethodsRat pancreatic islets were exposed or not for 24, 48, 72 and 96 h to albumin modified by glycoaldehyde. Apoptosis, reactive oxygen species and superoxide content and NADPH oxidase activity were evaluated as well as RNA expression of the genes Ager (codes for RAGE), Bax, Bcl2 and Nfkb1.ResultsIn 24 and 48 h, glycoaldehyde elicited a decrease in apoptosis rate in comparison with the control condition concomitantly with a reduction in Bax/Bcl2 RNA ratio and in Nfkb1 RNA expression. In contrast, after 72 and 96 h, glycoaldehyde promoted an increase in apoptosis rate concomitantly with an increase in Bax/Bcl2 RNA ratio and in Nfkb1 RNA expression. In 24 h, glycoaldehyde elicited a decrease in the islet content of reactive oxygen species, whereas after 48 and 72 h, it promoted an opposite effect, increasing superoxide generation. The NADPH oxidase inhibitor VAS2870 attenuated superoxide production, implicating NADPH oxidase as an important source of reactive oxygen species in islets exposed to AGEs.ConclusionsAlbumin modified by glycoaldehyde exerted a dual effect in cultured pancreatic islets, being protective against apoptosis after short exposure but pro‐apoptotic after prolonged exposure. Copyright © 2013 John Wiley & Sons, Ltd.
Conditional allelic replacement applied to genes encoding the histone variant H3.3 in the mouse
Authors: Tang Michelle C.W. , Jacobs Shelley A. , Wong Lee H. , Mann Jeffrey R. 
Published: January 2013

AbstractPost‐translational modifications to residues in core histones convey epigenetic information. Their function can be evaluated in amino acid substitution mutants, although to date this method has not been used in mice. To this end, we have evaluated gene targeting vectors designed for Cre recombinase‐mediated conditional allelic replacement at the two unlinked genes encoding the histone variant H3.3. The conditional alleles consist of an uninterrupted wild‐type H3.3 coding sequence upstream of a desired alternative or proxy coding sequence. The arrangement of two loxP sites allows Cre‐mediated replacement of the wild‐type coding sequence with the proxy. To demonstrate proof of principle, at each locus we replaced the wild‐type coding sequence with a fluorescent reporter. This produced null alleles that will be useful to analyse the effects of H3.3 deficiency in development. Each targeting vector can readily be retrofitted with a proxy coding sequence encoding a modified H3.3 protein. Such vectors will allow for the conditional substitution of specific residues in order to dissect the roles of H3.3 post‐translational modifications in development and disease. genesis, 51:142‒146, 2013. © 2013 Wiley Periodicals, Inc.
Synthesis and Structure of Seven‐Membered Metallacycloalkynes
Authors: Suzuki Noriyuki , Tsuchiya Takashi , Aihara Naoto , Iwasaki Masakazu , Saburi Masahiko , Chihara Teiji , Masuyama Yoshiro 
Published: January 2013

AbstractInvited for this month's cover is the group of Noriyuki Suzuki at Sophia University. The image shows how [3]comulene couples with an alkyne on the zirconium atoms.
Preparation of Polyethylenimine‐Functionalized Graphene Oxide Composite and Its Application in Electrochemical Ammonia Sensors
Authors: Song Min , Xu Juan 
Published: January 2013

AbstractIn this study, branched polyethyleneimine (PEI) was covalently linked to carboxylic acid functionalized graphene (GO‐COOH) to form GO‐COOH/PEI composites. Transmission electron microscopy, Fourier transform infrared spectroscopy, Raman spectra and thermogravimetric analysis were used to characterize the obtained composites. Electrochemical measurements indicated that the modification of the composites on the electrode could efficiently enhance the voltammetric response, suggesting the potential application for making electrochemical sensors. Moreover, our results also indicated that the electrocatalytic oxidation of ammonia could be observed on the GO‐COOH/PEI composites modified glassy carbon electrode. Consequently, our observations demonstrated that GO‐COOH/PEI composites were excellent materials for electrochemical sensing.
Prolymphocytic leukemia: Histologic findings in atypical cases
Authors: Owens Michael R. , Strauchen James A. , Rowe Jacob M. , Bennett John M. 
Published: January 2013

AbstractSignificant enlargement of peripheral lymph nodes is not characteristic of prolymphocytic leukemia. The absence of this physical feature of the disease has been so consistent in previous reports that it has come to have considerable importance in the differential diagnosis of prolymphocytic leukemia. We describe two cases of prolymphocytic leukemia, in which, in sharp contrast to other published cases, striking lymphadenopathy was present throughout the clinical course. In one case, the disease responded dramatically, but briefly, to l‐asparaginase. The immunologic characteristics of cells from lymph nodes suggested that in both cases, the leukemic process was B‐cell type. The features of the prolymphocytic proliferation in lymph nodes and the utility of Wright‐Giemsa stained touch preparations have been emphasized.
Clinical and prognostic relevance of the Kiel classification of non‐Hodgkin lymphomas results of a prospective multicenter study by the Kiel Lymphoma Study Group
Authors: Brittinger G. , Bartels H. , Common H. , Dühmke E. , Fülle H. H. , Gunzer U. , Gyenes T. , Heinz R. , König E. , Meusers P. , Paukstat M. , Pralle H. , Theml H. , Köpcke W. , Thieme C. , Zwingers T. , Musshoff K. , Stacher A. , Brücher H. , Herrmann F. , Ludwig W. D. , Pribilla W. , Burger‐Schüler A. , Löhr G. W. , Gremmel H. , Oertel J. , Gerhartz H. , Koeppen K.‐M. , Boll I. , Huhn D. , Binder T. , Schoengen A. , Nowicki L. , Pees H. W. , Scheurlen P. G. , Leopold H. , Wannenmacher M. , Schmidt M. , Löffler H. , Michlmayr G. , Thiel E. , Zettel R. , Rühl U. , Wilke H. J. , Schwarze E.‐W. , Stein H. , Feller A. C. , Lennert K. ,   KIEL LYMPHOMA STUDY GROUP
Published: January 2013

AbstractClinical and prognostic relevance of the Kiel classification of non‐Hodgkin lymphomas (NHL) was investigated in 1127 patients entering a prospective multicenter observation study. Survival of the 782 (69–4 per cent) patients with low‐grade malignant NHL (lymphocytic lymphomas, predominantly B‐CLL, LP immunocytoma, centrocytic lymphoma, centroblastic‐centrocytic lymphoma) exceeded that of the 341 patients (30–2 per cent) with high‐grade malignant NHL (centroblastic, immunoblastic, lymphoblastic lymphomas). Prognosis was best in centroblastic‐centrocytic lymphoma and in B‐CLL and least favorable in immunoblastic and lymphoblastic lymphomas. Survival of LP immunocytoma and centrocytic lymphoma patients was intermediate after 2 to 2·5 years of follow‐up. Corresponding to histopathology, pattern of survival curves of low‐grade malignant NHL (slow decline, no plateauing) differed from that of high‐grade malignant NHL (rapid decline, subsequent plateauing). Prognosis of B‐CLL was superior to that of LP immunocytoma. Stages I and II were more frequent in centroblastic‐centrocytic lymphoma (21 per cent) than in LP immunocytoma (2·5 per cent) and centrocytic lymphoma (11 per cent). Ability of radiotherapy to induce stable complete remissions in stage III of centroblastic‐centrocytic lymphoma indicates prolonged restriction of lymphoma to the lymphatic system. In immunoblastic and centroblastic lymphomas, stages I and II were diagnosed in 34 and 38 per cent of cases, respectively, but only in stage I/IE of centroblastic lymphoma prolonged remissions were achieved by radiotherapy. In advanced high‐grade malignant NHL marked improvement of prognosis was solely possible by induction of complete remissions whereas in corresponding low‐grade malignant lymphomas also partial remissions were prognostically relevant.
Serum beta 2‐microglobulin in lymphoproliferative and myeloproliferative diseases
Authors: Child J. Anthony , Kushwaha Muk Ram Singh 
Published: January 2013

AbstractThe serum levels of beta 2‐microglobulin (β2m), which is the light chain moiety of the HLA (‐A, ‐B, ‐C) antigens, are increased in many of the haematological malignancies. In the lymphoproliferative disorders there is generally an association between serum β2m and estimates of tumour load. This relationship is especially close in myelomatosis, where serum β2m is a powerful prognostic indicator and can be used in stratification and monitoring. Increases in serum β2m are also frequent in the myeloproliferative disorders, notably in myelofibrosis, and in the myelodysplastic syndromes; particularly high levels are seen in chronic myelomonocytic leukaemia. In addition to suggested cellular sources of the β2m in these diseases—malignant lymphoid cells and cells of the monocyte‐macrophage series—the possibility that T lymphocyte sub‐sets could be important contributors to the increased β2m production is discussed.
Interactions and connectivity between runoff generation processes of different spatial scales
Authors: Bachmair Sophie , Weiler Markus 
Published: January 2013

AbstractMonitoring runoff generation processes in the field is a prerequisite for developing conceptual hydrological models and theories. At the same time, our perception of hydrological processes strongly depends on the spatial and temporal scale of observation. Therefore, the aim of this study is to investigate interactions between runoff generation processes of different spatial scales (plot scale, hillslope scale, and headwater scale). Different runoff generation processes of three hillslopes with similar topography, geology and soil properties, but differences in vegetation cover (grassland, coniferous forest, and mixed forest) within a small v‐shaped headwater were measured: water table dynamics in wells with high spatial and temporal resolution, subsurface flow (SSF) of three 10 m wide trenches at the bottom of the hillslopes subdivided into two trench sections each, overland flow at the plot scale, and catchment runoff. Bachmair et al. () found a high spatial variability of water table dynamics at the plot scale. In this study, we investigate the representativity of SSF observations at the plot scale versus the hillslope scale and vice versa, and the linkage between hillslope dynamics (SSF and overland flow) and streamflow. Distinct differences in total SSF within each 10 m wide trench confirm the high spatial variability of the water table dynamics. The representativity of plot scale observations for hillslope scale SSF strongly depends on whether or not wells capture spatially variable flowpaths. At the grassland hillslope, subsurface flowpaths are not captured by our relatively densely spaced wells (3 m), despite a similar trench flow response to the coniferous forest hillslope. Regarding the linkage between hillslope dynamics and catchment runoff, we found an intermediate to high correlation between streamflow and hillslope hydrological dynamics (trench flow and overland flow), which highlights the importance of hillslope processes in this small watershed. Although the total contribution of SSF to total event catchment runoff is rather small, the contribution during peak flow is moderate to substantial. Additionally, there is process synchronicity between spatially discontiguous measurement points across scales, potentially indicating subsurface flowpath connectivity. Our findings stress the need for (i) a combination of observations at different spatial scales, and (ii) a consideration of the high spatial variability of SSF at the plot and hillslope scale when designing monitoring networks and assessing hydrological connectivity. Copyright © 2013 John Wiley & Sons, Ltd.