bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA Expression Is Required for Pancreatic Islet Cell Genesis in the Mouse
Authors: Lynn Francis C. , Skewes-Cox Peter , Kosaka Yasuhiro , McManus Michael T. , Harfe Brian D. , German Michael S. 
Published: September 2007

OBJECTIVE—The generation of distinct cell types during the development of the pancreas depends on sequential changes in gene expression. We tested the hypothesis that microRNAs (miRNAs), which limit gene expression through posttranscriptional silencing, modulate the gene expression cascades involved in pancreas development.
RESEARCH DESIGN AND METHODS—miRNAs were cloned and sequenced from developing pancreata, and expression of a subset of these genes was tested using locked nucleic acid in situ analyses. To assess the overall contribution of miRNAs to pancreatic development, Dicer1, an enzyme required for miRNA processing, was conditionally deleted from the developing pancreas.
RESULTS—Sequencing of small RNAs identified over 125 miRNAs, including 18 novel sequences, with distinct expression domains within the developing pancreas. To test the developmental contribution of these miRNAs, we conditionally deleted the miRNA processing enzyme Dicer1 early in pancreas development. Dicer-null animals displayed gross defects in all pancreatic lineages, although the endocrine cells, and especially the insulin-producing β-cells, were most dramatically reduced. The endocrine defect was associated with an increase in the notch-signaling target Hes1 and a reduction in the formation of endocrine cell progenitors expressing the Hes1 target gene neurogenin3.
CONCLUSIONS—The expression of a unique profile of miRNAs is required during pancreas development and is necessary for β-cell formation.
l-Carnosine, a Substrate of Carnosinase-1, Influences Glucose Metabolism
Authors: Sauerhöfer Sibylle , Yuan Gang , Braun Gerald Stefan , Deinzer Martina , Neumaier Michael , Gretz Norbert , Floege Jürgen , Kriz Wilhelm , van der Woude Fokko , Moeller Marcus Johannes 
Published: September 2007

OBJECTIVE—Carnosinase 1 (CN1) is a secreted dipeptidase that hydrolyzes l-carnosine. Recently, we have identified an allelic variant of human CN1 (hCN1) that results in increased enzyme activity and is associated with susceptibility for diabetic nephropathy in human diabetic patients. We therefore hypothesized that l-carnosine in the serum represents a critical protective factor in diabetic patients.
RESEARCH DESIGN AND METHODS— l-carnosine serum levels were manipulated in db/db mice, a model of type 2 diabetes. In a transgenic approach, hCN1 cDNA was expressed under the control of a liver-specific promoter in db/db mice, mimicking the expression pattern of hCN1 in humans.
RESULTS—Fasting plasma glucose as well as A1C levels rose significantly earlier and remained higher in transgenic animals throughout life. Body weights were reduced as a result of significant glucosuria. In an opposite approach, nontransgenic db/db mice were supplemented with l-carnosine. In these latter mice, diabetes manifested significantly later and milder. In agreement with the above data, serum fasting insulin levels were low in the transgenic mice and elevated by l-carnosine feeding. Insulin resistance and insulin secretion were not significantly affected by l-carnosine serum levels. Instead, a significant correlation of l-carnosine levels with β-cell mass was observed.
CONCLUSIONS—hCN1-dependent susceptibility to diabetic nephropathy may at least in part be mediated by altered glucose metabolism in type 2 diabetic patients.
LPIN2 Is Associated With Type 2 Diabetes, Glucose Metabolism, and Body Composition
Authors: Aulchenko Yurii S. , Pullen Jan , Kloosterman Wigard P. , Yazdanpanah Mojgan , Hofman Albert , Vaessen Norbert , Snijders Pieter J.L.M. , Zubakov Dmitry , Mackay Ian , Olavesen Mark , Sidhu Balbinder , Smith Vicki E. , Carey Alisoun , Berezikov Eugene , Uitterlinden André G. , Plasterk Ronald H.A. , Oostra Ben A. , van Duijn Cornelia M. 
Published: September 2007

OBJECTIVE—To identify the type 2 diabetes gene located at chromosome 18p11.
RESEARCH DESIGN AND METHODS—We investigated the region in a young genetically isolated population by genotyping 34 single nucleotide polymorphisms (SNPs) in 78 case subjects and 101 control subjects. Two SNPs were selected and followed up in two cohorts. The first cohort came from a general Dutch population. In this cohort, association with type 2 diabetes was investigated using 616 type 2 diabetic case subjects and 2,890 control subjects; association with oral glucose tolerance test data was performed in 361 normoglycemic people. Association with fat distribution was studied in the second replication cohort, consisting of 836 people from the genetically isolated population.
RESULTS—At the initial step, we found that the common C allele of SNP rs3745012 was associated with type 2 diabetes (odds ratio 2.01, P = 0.03). This SNP is located at the 3′ untranslated region of the LPIN2 gene, which is a plausible candidate for type 2 diabetes and obesity. In the cohort from the general Dutch population, we demonstrated that rs3745012 interacts with BMI in determination of type 2 diabetes: whereas in subjects with high BMI, the common C allele is associated with type 2 diabetes, the same allele exhibits a neutral or protective effect in lean subjects (P = 0.05 overall effect, P = 0.02 interaction). Most remarkably, rs3745012 strongly affected composite insulin sensitivity index (P = 0.006 for overall effect, P = 0.004 for interaction). In the second replication cohort, we found that the allele C of rs3745012 increases trunk-to-legs fat mass ratio (P = 0.001) and may affect other fat-related measurements.
CONCLUSIONS—rs3745012 SNP of the LPIN2 gene is associated with type 2 diabetes and fat distribution.
Phosphorylation Barriers to Skeletal and Cardiac Muscle Glucose Uptakes in High-Fat–Fed Mice
Authors: Fueger Patrick T. , Lee-Young Robert S. , Shearer Jane , Bracy Deanna P. , Heikkinen Sami , Laakso Markku , Rottman Jeffrey N. , Wasserman David H. 
Published: September 2007

OBJECTIVE—Muscle glucose uptake (MGU) is regulated by glucose delivery to, transport into, and phosphorylation within muscle. The aim of this study was to determine the role of limitations in glucose phosphorylation in the control of MGU during either physiological insulin stimulation (4 mU · kg−1· min−1) or exercise with chow or high-fat feeding.
RESEARCH DESIGN AND METHODS—C57BL/6J mice with (HK+/−) and without (WT) a 50% hexokinase (HK) II deletion were fed chow or high-fat diets and studied at 4 months of age during a 120-min insulin clamp or 30 min of treadmill exercise (n = 8–10 mice/group). 2-deoxy[3H]glucose was used to measure Rg, an index of MGU.
RESULTS—Body weight and fasting arterial glucose were increased by high-fat feeding and partial HK II knockout (HK+/−). Both high-fat feeding and partial HK II knockout independently created fasting hyperinsulinemia, a response that was increased synergistically with combined high-fat feeding and HK II knockout. Whole-body insulin action was suppressed by ∼25% with either high-fat feeding or partial HK II knockout alone but by &gt;50% when the two were combined. Insulin-stimulated Rg was modestly impaired by high-fat feeding and partial HK II knockout independently (∼15–20%) but markedly reduced by the two together (∼40–50%). Exercise-stimulated Rg was reduced by ∼50% with high-fat feeding and partial HK II knockout alone and was not attenuated further by combining the two.
CONCLUSIONS—In summary, impairments in whole-body metabolism and MGU due to high-fat feeding and partial HK II knockout combined during insulin stimulation are additive. In contrast, combining high-fat feeding and partial HK II knockout during exercise causes no greater impairment in MGU than the two manipulations independently. This suggests that MGU is impaired during exercise by high-fat feeding due to, in large part, a limitation in glucose phosphorylation. Together, these studies show that the high-fat–fed mouse is characterized by defects at multiple steps of the MGU system that are precipitated by different physiological conditions.
Common Variants of the Novel Type 2 Diabetes GenesCDKAL1andHHEX/IDEAre Associated With Decreased Pancreatic β-Cell Function
Authors: Pascoe Laura , Tura Andrea , Patel Sheila K. , Ibrahim Ibrahim M. , Ferrannini Ele , Zeggini Eleftheria , Weedon Michael N. , Mari Andrea , Hattersley Andrew T. , McCarthy Mark I. , Frayling Timothy M. , Walker Mark ,   for the RISC Consortium and the U.K. Type 2 Diabetes Genetics Consortium
Published: September 2007

OBJECTIVE— Type 2 diabetes is characterized by impaired pancreatic β-cell function and decreased insulin sensitivity. Genome-wide association studies have identified common, novel type 2 diabetes susceptibility loci within the FTO, CDKAL1, CDKN2A/CDKN2B, IGF2BP2, HHEX/IDE, and SLC30A8 gene regions. Our objective was to explore the relationships between the diabetes-associated alleles and measures of β-cell function and whole-body insulin sensitivity.RESEARCH DESIGN AND METHODS— A total of 1,276 healthy subjects of European ancestry were studied at 19 centers. Indexes of β-cell function (including 30-min insulin response and glucose sensitivity) were derived from a 75-g oral glucose tolerance test, and whole-body insulin sensitivity (M/I) was assessed by hyperinsulinemic-euglycemic clamp. Genotype/phenotype relationships were studied by linear trend analysis correcting for age, sex, and recruitment center.RESULTS— CDKAL1 and HHEX/IDE diabetes-associated alleles were both associated with decreased 30-min insulin response (both P = 0.0002) and decreased pancreatic β-cell glucose sensitivity (P = 9.86 × 10−5 and 0.009, respectively), and these relationships remained after correction for M/I. The FTO susceptibility allele showed a weak but consistent association with increased adiposity, which in turn was linked to a decrease in M/I. However, none of the other novel diabetes susceptibility alleles were associated with insulin sensitivity.CONCLUSIONS— CDKAL1 and HHEX/IDE diabetes-associated alleles are associated with decreased pancreatic β-cell function, including decreased β-cell glucose sensitivity that relates insulin secretion to plasma glucose concentration. We confirmed the association between the FTO allele and increased adiposity, but none of the other novel susceptibility alleles were associated with whole-body insulin sensitivity.
Attenuation of Amydgala and Frontal Cortical Responses to Low Blood Glucose Concentration in Asymptomatic Hypoglycemia in Type 1 Diabetes
Authors: Dunn Joel T. , Cranston Iain , Marsden Paul K. , Amiel Stephanie A. , Reed Laurence J. 
Published: September 2007

OBJECTIVE—Loss of ability to recognize hypoglycemia (hypoglycemia unawareness) increases risk of severe hypoglycemia threefold in insulin-treated diabetes. We set out to investigate the cerebral correlates of unawareness in type 1 patients.
RESEARCH DESIGN AND METHODS—Regional changes in brain glucose kinetics were measured using [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET), in 13 men with type 1 diabetes—6 with hypoglycemia awareness and 7 with hypoglycemia unawareness—at euglycemia (5 mmol/l) and hypoglycemia (2.6 mmol/l), in random order.
RESULTS—Epinephrine responses to hypoglycemia were reduced in hypoglycemia unawareness (P &lt; 0.0003), as were symptoms. Statistical parametric mapping (SPM) of FDG uptake using SPM2 at a statistical threshold of P &lt; 0.005 showed increased FDG uptake in left amygdala in hypoglycemia awareness, but not in hypoglycemia unawareness (region of interest analysis −0.40 ± 1.03 vs. 3.66 ± 0.42, respectively; P = 0.007), and robust increase in bilateral ventral striatum during hypoglycemia (region of interest analysis hypoglycemia unawareness 3.52 ± 1.02 vs. awareness 6.1 ± 0.53; P = 0.054). Further analysis at the statistical threshold of P &lt; 0.01 showed bilateral attenuated activation of brain stem regions and less deactivation in lateral orbitofrontal cortex in hypoglycemia unawareness.
CONCLUSIONS—Ventral striatal, amygdala, brain stem, and orbitofrontal responses to hypoglycemia indicate engagement of appetitive motivational networks, associated with integrated behavioral responses to hypoglycemia. Reduced responses in these networks in hypoglycemia unawareness, particularly failure of amygdala and orbifrontal cortex responses, suggest habituation of higher behavioral responses to hypoglycemia as a basis for unawareness. New approaches may be needed to restore awareness effectively in practice.
Selected Italian Projects
Authors: Peckham Andrew , Tozzi Lucia 
Published: September 2007

AbstractRationalism remains at the sidelines of contemporary architecture in Italy – a latent current rather than a leading force. Andrew Peckham and Lucia Tozzi reveal how this stubborn but rich seam is manifesting itself: in Cino Zucchi's substantial housing scheme on the outskirts of Milan; Werner Tscholl's insertion into Schloss Sigmundskron/Castel Firmiano; Beniamino Servino's continued work on the Nursery School in Formicola, Caserta; and C+S Associati's Nursery School at Covolo di Pederobba in Treviso. Copyright © 2007 John Wiley & Sons, Ltd.
An Interview with Giorgio Grassi
Authors: Tozzi Lucia 
Published: September 2007

AbstractIn January 2007, Lucia Tozzi visited Giorgio Grassi's office in Milan. Their conversation touched on Grassi's recent work on Leon Battista Alberti, which is examined here in the context of Grassi's obliquely expressed views on contemporary architecture and the cult of personality. As perhaps the most intellectually rigorous and formally consistent Rationalist architect of his generation, Grassi's work and thinking retain a hermetic aspect, but one notable for its philosophical self‐questioning and underlying political commitment. Copyright © 2007 John Wiley & Sons, Ltd.
Concrete Constructs: The Limits of Rationalism in Swiss Architecture
Authors: Moravánszky Ákos 
Published: September 2007

AbstractÁkos Moravánszky explains why for him ‘the traces of Mediterranean Rationalism in the new Swiss‐German architecture are like the imitation stitching on the moulded plastic dashboard of a new car’. It is an influence which, despite the undeniable impact of Aldo Rossi and the Ticino School at ETH Zurich in the 1970s, remains skin‐deep, sharing little with the present in terms of ideology or the interpretation of the historic past. Copyright © 2007 John Wiley & Sons, Ltd.
Selected Swiss Projects
Authors: Schmiedeknecht Torsten 
Published: September 2007

AbstractTorsten Schmiedeknecht describes four Swiss buildings that adopt a formal language of Rationalist rigour to dramatic effect. Despite all being institutional buildings, they vary widely in their treatments interpreting a Rationalist vocabulary in very different ways, from the unstinting austerity of GWJ Architekten's UVEK Administration Centre to Andrea Bassi's intentionally playful La Maladière Primary School in Neuchâtel. Copyright © 2007 John Wiley & Sons, Ltd.
Schinkel's Order: Rationalist Tendencies in German Architecture
Authors: Durth Werner , May Roland 
Published: September 2007

AbstractGermany can be viewed as the natural home of the Rationalist impulse. Two of Germany's most influential architects, Karl Friedrich Schinkel and Mies van der Rohe, have been admired the world over for their sense of tectonic order and purist form. Werner Durth and Roland May trace a modern history of the tendency, which began with the early 20th‐century rediscovery of Schinkel and has been continued to the present in the work of OM Ungers. Copyright © 2007 John Wiley & Sons, Ltd.
Selected German Projects
Authors: Durth Werner , May Roland 
Published: September 2007

AbstractIn the last two decades, Rationalism has been revisited in Germany. As Werner Durth and Roland May demonstrate in these four projects it can provide very different strategies for dealing with often complex urban contexts, whether it provides: ‘order for disparate surroundings’ as in the Ohel Jakob Synagogue in Munich; a consistent vocabulary for the regeneration of a Modernist GDR housing scheme as at Thuringia; a representative elegance and inbuilt flexibility as at Frankfurt Airport's Terminal 3; or a means of reasserting the orientation and materiality of earlier buildings on an existing site as in Hans Kollhoff's Het Palais Condominium in Breda in the Netherlands. Copyright © 2007 John Wiley & Sons, Ltd.
Dialogues with OMU
Authors: Peckham Andrew , Schmiedeknecht Torsten 
Published: September 2007

AbstractIn January 2007, guest‐editors Andrew Peckham and Torsten Schmiedeknecht met with OM Ungers in the library of his Belvederestrasse house in Cologne Müngersdorf.1 A ‘round table’ discussion followed, with the architect, his wife, daughter and archivist, prompting a series of dialogues with Ungers centred on his built works, projects, thinking and teaching. The authors gained a unique insight into Ungers' varied and often influential career, and took the opportunity to re‐examine the preconceptions surrounding it. Copyright © 2007 John Wiley & Sons, Ltd.
French Rationalism: A Broken Tradition
Authors: Abram Joseph 
Published: September 2007

AbstractFrom the golden era of 1960s Rationalism to the present Inquietude Lucide, Joseph Abram describes the Rationalist tendencies in French architecture. Once dominated by the spectres of Le Corbusier and Auguste Perret, the rational was deeply embedded in French tectonic culture. Despite the current reassertion of the rational, the future, as Abram explains, appears less certain. Copyright © 2007 John Wiley & Sons, Ltd.
An Open and Flexible Tradition
Authors: Montaner Josep Maria 
Published: September 2007

AbstractThere is a rich tradition of Rationalist architecture in Spain, dating back to the years immediately after the Spanish Civil War and then the period of postwar recovery in the 1950s. Josep Maria Montaner explains how this has developed across time into a contemporary interpretation of Rationalism that is versatile and inclusive, often combining Functionalist ideas with a stripped‐back repertoire of materials and elements. Copyright © 2007 John Wiley & Sons, Ltd.
Selected Spanish Projects
Authors: Montaner Josep Maria 
Published: September 2007

AbstractJosep Maria Montaner describes four buildings that epitomise the flexibility of the Rationalist tendency in Spain. These span the Mies‐inspired minimalism of Javier Garcia Solera; housing schemes that are designed around the present needs of their occupants for adaptable and well‐ventilated spaces, despite being influenced by earlier Rationalist vocabularies; and Carlos Ferrater's JC Decaux Headquarters in Madrid that uses ‘the order and tradition’ of Modernist architecture to create continuity with existing buildings on its site. Copyright © 2007 John Wiley & Sons, Ltd.
Gert Wingårdh
Authors: Hebb Timothy Tore 
Published: September 2007

AbstractFrom his main office in Gothenburg, Sweden's second city, Gert Wingårdh has spawned a practice that has brought him national success. He has completed two embassy buildings for the Swedish foreign office in Washington DC and Berlin and two major museums. Timothy Tore Hebb describes the work of an architect whose designs are able to be both responsive to the natural environment and ingenious in their juxtapositions and contrasts. Copyright © 2007 John Wiley & Sons, Ltd.
Home Body
Authors: van Schaik Leon 
Published: September 2007

AbstractLeon van Schaik reviews Households, a compelling photographic documentary project by artist and architect Mark Robbins, which portrays actual people in their own homes. Eschewing the ‘somnolent’ mode of styled interior photography, which is more about what people wish for rather than where they actually live, Robbins captures the intimacy of everyday domestic settings and relationships and in so doing engages ‘architecture with the full panoply of human emotions’. Copyright © 2007 John Wiley & Sons, Ltd.
Structural Changes in the BODIPY Dye PM567 Enhancing the Laser Action in Liquid and Solid Media
Authors: García‐Moreno I. , Amat‐Guerri F. , Liras M. , Costela A. , Infantes L. , Sastre R. , López Arbeloa F. , Bañuelos Prieto J. , López Arbeloa Í. 
Published: September 2007

AbstractIn the search for more efficient and photostable solid‐state dye lasers, newly synthesized analogs of the borondipyrromethene (BODIPY) dye PM567, bearing the polymerizable methacryloyloxypropyl group at position 2 (PMoMA) or at positions 2 and 6 (PDiMA), have been studied in the form of solid copolymers with methyl methacrylate (MMA). The parent dye PM567, as well as the model analogs bearing the acetoxypropyl group in the same positions, PMoAc and PDiAc, respectively, have been also studied both in liquid solvents and in solid poly(MMA) (PMMA) solution. Although in liquid solution PMoAc and PDiAc have the same photophysical properties as PM567, PDiAc exhibited a photostability up to 10 times higher than that of PM567 in ethanol under 310 nm‐irradiation. The possible stabilization factors of PDiAc have been analyzed and discussed on the basis of the redox potentials, the ability for singlet molecular oxygen [O2(1Δg)] generation, the reactivity with O2(1Δg), and quantum mechanical calculations. Both PMoAc and PDiAc, pumped transversally at 532 nm, lased in liquid solution with a high (up to 58 %), near solvent‐independent efficiency. This enhanced photostabilization has been also observed in solid polymeric and copolymeric media. While the solid solution of the model dye PDiAc in PMMA showed a lasing efficiency of 33 %, with a decrease in the laser output of ca. 50 % after 60 000 pump pulses (10 Hz repetition rate) in the same position of the sample, the solid copolymer with the double bonded chromophore, COP(PDiMA‐MMA), showed lasing efficiencies of up to 37 %, and no sign of degradation in the laser output after 100 000 similar pump pulses. Even under the more demanding repetition rate of 30 Hz, the laser emission from this material remained at 67 % of its initial laser output after 400 000 pump pulses, which is the highest laser photostability achieved to date for solid‐state lasers based on organic polymeric materials doped with laser dyes. This result indicates that the double covalent linkage of the BODIPY chromophore to a PMMA polymeric matrix is even more efficient than the simple linkage, for its photostabilization under laser operation.
Correlations between Percolation Threshold, Dispersion State, and Aspect Ratio of Carbon Nanotubes
Authors: Li J. , Ma P. C. , Chow W. S. , To C. K. , Tang B. Z. , Kim J.‐K. 
Published: September 2007

AbstractCritical factors that determine the percolation threshold of carbon nanotube (CNT)‐reinforced polymer nanocomposites are studied. An improved analytical model is developed based on an interparticle distance concept. Two dispersion parameters are introduced in the model to correctly reflect the different dispersion states of CNTs in the matrix—entangled bundles and well‐dispersed individual CNTs. CNT–epoxy nanocomposites with different dispersion states are fabricated from the same constituent materials by employing different processing conditions. The corresponding percolation thresholds of the nanocomposites vary over a wide range, from 0.1 to greater than 1.0 wt %, and these variations are explained in terms of dispersion parameters and aspect ratios of CNTs. Important factors that control the percolation threshold of nanocomposites are identified based on the comparison between modeling data and experimental results.