bluuebunny/crossref_metadata_2025 huggingface dataset:
Local Property Taxation as a Strategic Planning Tool in UK: Can ‘Landvaluescape’ Play a Role at Local Levels?
Authors: Sayce S. , Vickers T. , Connellan O. , Morad Munir
Published: July 2008

In common with many countries of the world, there are concerns within planning and regeneration circles regarding the very slow progress towards sustainable development and a realization that for progress to be achieved there is a need for government to act. Consequently, the UK government is seeking, through a variety of instruments, including the land use planning system, to mitigate the environmental impact of development. Indeed the overarching aim of the extant land use legislation (in particular, the Planning and Compulsory Purchase Act 2004 and the Sustainable Communities Act 2007) is the promotion of sustainable communities, across the so-called ‘triple bottom line’ of economic well-being, social justice and environmental protection. This paper discusses geo-political developments in the approach to funding local and regional government and how the UK is affected by these. The paper considers research in Britain into the potential for using aggregated property valuations as a method of monitoring economic health at a national and local scale, by applying geo-spatial modelling and display techniques. Given advances in the application of modern information systems (including the capture, management and display of geo-spatial data), the authors assess the potential of such systems for the status of relevant datasets in the UK.
Short Article: Passive perceptual learning in relation to wine: Short-term recognition and verbal description
Authors: Hughson Angus L. , Boakes Robert A.
Published: July 2008

This experiment addressed the question of whether untutored experience of drinking wine improves human ability to discriminate between wines. Using a short-term recognition task a two-factor design compared more with less experienced wine drinkers (intermediates vs. novices) and a condition requiring description of the to-be-remembered wine samples with a control condition. Overall intermediates were more accurate than novices in selecting the target sample from a distractor set. The procedure was modelled on a previous study in which verbal descriptions reduced the performance of intermediates (verbal overshadowing), but here both novices and intermediates performed better in the description than in the control condition. The major result was to demonstrate that untutored experience can improve wine recognition (passive perceptual learning).
Short Article: Similarity and Binding in Memory: Bound to be Detrimental
Authors: Guérard Katherine , Tremblay Sébastien , Saint-Aubin Jean
Published: July 2008

The process of binding information from different modalities and sources into an object is ubiquitous in cognition and has been a problem for research and modelling efforts in psychology. This process has been considered by most researchers as necessarily always beneficial to memory. In the present study we provide evidence that binding can be detrimental through the propagation of vulnerabilities to interference. Phonologically similar and dissimilar letters were presented sequentially at different locations on a computer monitor. Participants had to recall either the letters in their order of presentation or the spatial locations at which the letters had appeared. Whether binding was encouraged or not—providing prior knowledge of which dimension to remember—phonological similarity had a detrimental effect on recall of locations. Such a finding poses a challenge to the view that binding is the panacea in enhancing memory capacity.
Nucleophosmin and its AML-associated mutant regulate c-Myc turnover through Fbw7γ
Authors: Bonetti Paola , Davoli Teresa , Sironi Cristina , Amati Bruno , Pelicci Pier Giuseppe , Colombo Emanuela
Published: July 2008

Mutations leading to aberrant cytoplasmic localization of nucleophosmin (NPM) are the most frequent genetic alteration in acute myelogenous leukemia (AML). NPM binds the Arf tumor suppressor and protects it from degradation. The AML-associated NPM mutant (NPMmut) also binds p19Arf but is unable to protect it from degradation, which suggests that inactivation of p19Arf contributes to leukemogenesis in AMLs. We report here that NPM regulates turnover of the c-Myc oncoprotein by acting on the F-box protein Fbw7γ, a component of the E3 ligase complex involved in the ubiquitination and proteasome degradation of c-Myc. NPM was required for nucleolar localization and stabilization of Fbw7γ. As a consequence, c-Myc was stabilized in cells lacking NPM. Expression of NPMmut also led to c-Myc stabilization because of its ability to interact with Fbw7γ and delocalize it to the cytoplasm, where it is degraded. Because Fbw7 induces degradation of other growth-promoting proteins, the NPM–Fbw7 interaction emerges as a central tumor suppressor mechanism in human cancer.
Mars promotes dTACC dephosphorylation on mitotic spindles to ensure spindle stability
Authors: Tan Shengjiang , Lyulcheva Ekaterina , Dean Jon , Bennett Daimark
Published: July 2008

Microtubule-associated proteins (MAPs) ensure the fidelity of chromosome segregation by controlling microtubule (MT) dynamics and mitotic spindle stability. However, many aspects of MAP function and regulation are poorly understood in a developmental context. We show that mars, which encodes a Drosophila melanogaster member of the hepatoma up-regulated protein family of MAPs, is essential for MT stabilization during early embryogenesis. As well as associating with spindle MTs in vivo, Mars binds directly to protein phosphatase 1 (PP1) and coimmunoprecipitates from embryo extracts with minispindles and Drosophila transforming acidic coiled-coil (dTACC), two MAPs that function as spindle assembly factors. Disruption of binding to PP1 or loss of mars function results in elevated levels of phosphorylated dTACC on spindles. A nonphosphorylatable form of dTACC is capable of rescuing the lethality of mars mutants. We propose that Mars mediates spatially controlled dephosphorylation of dTACC, which is critical for spindle stabilization.
Deadenylation is prerequisite for P-body formation and mRNA decay in mammalian cells
Authors: Zheng Dinghai , Ezzeddine Nader , Chen Chyi-Ying A. , Zhu Wenmiao , He Xiangwei , Shyu Ann-Bin
Published: July 2008

Deadenylation is the major step triggering mammalian mRNA decay. One consequence of deadenylation is the formation of nontranslatable messenger RNA (mRNA) protein complexes (messenger ribonucleoproteins [mRNPs]). Nontranslatable mRNPs may accumulate in P-bodies, which contain factors involved in translation repression, decapping, and 5′-to-3′ degradation. We demonstrate that deadenylation is required for mammalian P-body formation and mRNA decay. We identify Pan2, Pan3, and Caf1 deadenylases as new P-body components and show that Pan3 helps recruit Pan2, Ccr4, and Caf1 to P-bodies. Pan3 knockdown causes a reduction of P-bodies and has differential effects on mRNA decay. Knocking down Caf1 or overexpressing a Caf1 catalytically inactive mutant impairs deadenylation and mRNA decay. P-bodies are not detected when deadenylation is blocked and are restored when the blockage is released. When deadenylation is impaired, P-body formation is not restorable, even when mRNAs exit the translating pool. These results support a dynamic interplay among deadenylation, mRNP remodeling, and P-body formation in selective decay of mammalian mRNA.
Structure of the actin-depolymerizing factor homology domain in complex with actin
Authors: Paavilainen Ville O. , Oksanen Esko , Goldman Adrian , Lappalainen Pekka
Published: July 2008

Actin dynamics provide the driving force for many cellular processes including motility and endocytosis. Among the central cytoskeletal regulators are actin-depolymerizing factor (ADF)/cofilin, which depolymerizes actin filaments, and twinfilin, which sequesters actin monomers and caps filament barbed ends. Both interact with actin through an ADF homology (ADF-H) domain, which is also found in several other actin-binding proteins. However, in the absence of an atomic structure for the ADF-H domain in complex with actin, the mechanism by which these proteins interact with actin has remained unknown. Here, we present the crystal structure of twinfilin's C-terminal ADF-H domain in complex with an actin monomer. This domain binds between actin subdomains 1 and 3 through an interface that is conserved among ADF-H domain proteins. Based on this structure, we suggest a mechanism by which ADF/cofilin and twinfilin inhibit nucleotide exchange of actin monomers and present a model for how ADF/cofilin induces filament depolymerization by weakening intrafilament interactions.
Primary microRNA transcript retention at sites of transcription leads to enhanced microRNA production
Authors: Pawlicki Jan M. , Steitz Joan A.
Published: July 2008

MicroRNAs (miRNAs) are noncoding RNAs with important roles in regulating gene expression. In studying the earliest nuclear steps of miRNA biogenesis, we observe that primary miRNA (pri-miRNA) transcripts retained at transcription sites due to the deletion of 3′-end processing signals are converted more efficiently into precursor miRNAs (pre-miRNAs) than pri-miRNAs that are cleaved, polyadenylated, and released. Flanking exons, which also increase retention at transcription sites, likewise contribute to increased levels of intronic pri-miRNAs. Consistently, efficiently processed endogenous pri-miRNAs are enriched in chromatin-associated nuclear fractions. In contrast, pri-miRNAs that accumulate to high nuclear levels after cleavage and polyadenylation because of the presence of a viral RNA element (the ENE of the Kaposi's sarcoma–associated herpes virus polyadenylated nuclear RNA) are not efficiently processed to precursor or mature miRNAs. Exogenous pri-miRNAs unexpectedly localize to nuclear foci containing splicing factor SC35; yet these foci are unlikely to represent sites of miRNA transcription or processing. Together, our results suggest that pri-miRNA processing is enhanced by coupling to transcription.
Cytopathicity of Chlamydia is largely reproduced by expression of a single chlamydial protease
Authors: Paschen Stefan A. , Christian Jan G. , Vier Juliane , Schmidt Franziska , Walch Axel , Ojcius David M. , Häcker Georg
Published: July 2008

Chlamydiae replicate in a vacuole within epithelial cells and commonly induce cell damage and a deleterious inflammatory response of unknown molecular pathogenesis. The chlamydial protease-like activity factor (CPAF) translocates from the vacuole to the cytosol, where it cleaves several cellular proteins. CPAF is synthesized as an inactive precursor that is processed and activated during infection. Here, we show that CPAF can be activated in uninfected cells by experimentally induced oligomerization, reminiscent of the activation mode of initiator caspases. CPAF activity induces proteolysis of cellular substrates including two novel targets, cyclin B1 and PARP, and indirectly results in the processing of pro-apoptotic BH3-only proteins. CPAF activation induces striking morphological changes in the cell and, later, cell death. Biochemical and ultrastructural analysis of the cell death pathway identify the mechanism of cell death as nonapoptotic. Active CPAF in uninfected human cells thus mimics many features of chlamydial infection, implicating CPAF as a major factor of chlamydial pathogenicity, Chlamydia-associated cell damage, and inflammation.
Complementation of a pathogenic IFNGR2 misfolding mutation with modifiers of N-glycosylation
Authors: Vogt Guillaume , Bustamante Jacinta , Chapgier Ariane , Feinberg Jacqueline , Boisson Dupuis Stephanie , Picard Capucine , Mahlaoui Nizar , Gineau Laure , Alcaïs Alexandre , Lamaze Christophe , Puck Jennifer M. , de Saint Basile Geneviève , Khayat Claudia Djambas , Mikhael Raymond , Casanova Jean-Laurent
Published: July 2008

Germline mutations may cause human disease by various mechanisms. Missense and other in-frame mutations may be deleterious because the mutant proteins are not correctly targeted, do not function correctly, or both. We studied a child with mycobacterial disease caused by homozygosity for a novel in-frame microinsertion in IFNGR2. In cells transfected with the mutant allele, most of the interferon γ receptor 2 (IFN-γR2) protein was retained within the cell, and that expressed on the cell surface had an abnormally high molecular weight (MW). The misfolding mutation was not gain-of-glycosylation, as it created no new N-glycosylation site. The mutant IFNGR2 allele was null, as the patient's cells did not respond to IFN-γ. Based on the well-established relationship between protein N-glycosylation and protein quality control processes, we tested 29 compounds affecting maturation by N-glycosylation in the secretory pathway. Remarkably, up to 13 of these compounds reduced the MW of surface-expressed mutant IFN-γR2 molecules and restored cellular responsiveness to IFN-γ. Modifiers of N-glycosylation may therefore complement human cells carrying in-frame and misfolding, but not necessarily gain-of-glycosylation, mutations in genes encoding proteins subject to trafficking via the secretory pathway. Some of these compounds are available for clinical use, paving the way for clinical trials of chemical complementation for various human genetic traits.
Transvection mediated by the translocated cyclin D1 locus in mantle cell lymphoma
Authors: Liu Hui , Huang Jing , Wang Jin , Jiang Shuguang , Bailey Alexis S. , Goldman Devorah C. , Welcker Markus , Bedell Victoria , Slovak Marilyn L. , Clurman Bruce , Thayer Mathew , Fleming William H. , Epner Elliot
Published: July 2008

In mantle cell lymphoma (MCL) and some cases of multiple myeloma (MM), cyclin D1 expression is deregulated by chromosome translocations involving the immunoglobulin heavy chain (IgH) locus. To evaluate the mechanisms responsible, gene targeting was used to study long-distance gene regulation. Remarkably, these targeted cell lines lost the translocated chromosome (t(11;14)). In these MCL and MM cells, the nonrearranged cyclin D1 (CCND1) locus reverts from CpG hypomethylated to hypermethylated. Reintroduction of the translocated chromosome induced a loss of methylation at the unrearranged CCND1 locus, providing evidence of a transallelic regulatory effect. In these cell lines and primary MCL patient samples, the CCND1 loci are packaged in chromatin-containing CCCTC binding factor (CTCF) and nucleophosmin (NPM) at the nucleolus. We show that CTCF and NPM are bound at the IgH 3′ regulatory elements only in the t(11;14) MCL cell lines. Furthermore, NPM short hairpin RNA produces a specific growth arrest in these cells. Our data demonstrate transvection in human cancer and suggest a functional role for CTCF and NPM.
Discriminating gene expression profiles of memory B cell subpopulations
Authors: Ehrhardt Götz R.A. , Hijikata Atsushi , Kitamura Hiroshi , Ohara Osamu , Wang Ji-Yang , Cooper Max D.
Published: July 2008

Morphologically and functionally distinct subpopulations of human memory B (BMem) cells are identifiable by either their expression of CD27 or Fc receptor–like 4 (FCRL4), an immunoglobulin domain containing a receptor with strong inhibitory potential. We have conducted comparative transcriptome and proteome analyses of FCRL4+ and FCRL4− BMem cells and found that these two subsets have very distinctive expression profiles for genes encoding transcription factors, cell-surface proteins, intracellular signaling molecules, and modifiers of the cell-cycle status. Among the differentially expressed transcription factors, runt-related transcription factor 1 (RUNX1) transcript levels were up-regulated in FCRL4− cells, whereas RUNX2 transcripts were preferentially detected in FCRL4+ cells. In vitro evidence for FCRL4 promoter responsiveness and in vivo promoter occupancy suggested that RUNX transcription factors are involved in the generation of these BMem cell subpopulations. A distinctive signature profile was defined for the FCRL4+ BMem cells by their expression of CD11c, receptor activator for nuclear factor κB ligand, and FAS cell-surface proteins, in combination with increased levels of SOX5, RUNX2, DLL1, and AICDA expression. We conclude that this recently identified subpopulation of BMem cells, which normally resides in epithelial tissue-based niches, may serve a unique role in mucosal defense and, conversely, as a target for neoplastic transformation events.
Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals
Authors: Moir Susan , Ho Jason , Malaspina Angela , Wang Wei , DiPoto Angela C. , O'Shea Marie A. , Roby Gregg , Kottilil Shyam , Arthos James , Proschan Michael A. , Chun Tae-Wook , Fauci Anthony S.
Published: July 2008

Human immunodeficiency virus (HIV) disease leads to impaired B cell and antibody responses through mechanisms that remain poorly defined. A unique memory B cell subpopulation (CD20hi/CD27lo/CD21lo) in human tonsillar tissues was recently defined by the expression of the inhibitory receptor Fc-receptor-like-4 (FCRL4). In this study, we describe a similar B cell subpopulation in the blood of HIV-viremic individuals. FCRL4 expression was increased on B cells of HIV-viremic compared with HIV-aviremic and HIV-negative individuals. It was enriched on B cells with a tissuelike memory phenotype (CD20hi/CD27−/CD21lo) when compared with B cells with a classical memory (CD27+) or naive (CD27−/CD21hi) B cell phenotype. Tissuelike memory B cells expressed patterns of homing and inhibitory receptors similar to those described for antigen-specific T cell exhaustion. The tissuelike memory B cells proliferated poorly in response to B cell stimuli, which is consistent with high-level expression of multiple inhibitory receptors. Immunoglobulin diversities and replication histories were lower in tissuelike, compared with classical, memory B cells, which is consistent with premature exhaustion. Strikingly, HIV-specific responses were enriched in these exhausted tissuelike memory B cells, whereas total immunoglobulin and influenza-specific responses were enriched in classical memory B cells. These data suggest that HIV-associated premature exhaustion of B cells may contribute to poor antibody responses against HIV in infected individuals.
A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease
Authors: Björkqvist Maria , Wild Edward J. , Thiele Jenny , Silvestroni Aurelio , Andre Ralph , Lahiri Nayana , Raibon Elsa , Lee Richard V. , Benn Caroline L. , Soulet Denis , Magnusson Anna , Woodman Ben , Landles Christian , Pouladi Mahmoud A. , Hayden Michael R. , Khalili-Shirazi Azadeh , Lowdell Mark W. , Brundin Patrik , Bates Gillian P. , Leavitt Blair R. , Möller Thomas , Tabrizi Sarah J.
Published: July 2008

Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities. We examined the peripheral immune system and found widespread evidence of innate immune activation detectable in plasma throughout the course of HD. Interleukin 6 levels were increased in HD gene carriers with a mean of 16 years before the predicted onset of clinical symptoms. To our knowledge, this is the earliest plasma abnormality identified in HD. Monocytes from HD subjects expressed mutant huntingtin and were pathologically hyperactive in response to stimulation, suggesting that the mutant protein triggers a cell-autonomous immune activation. A similar pattern was seen in macrophages and microglia from HD mouse models, and the cerebrospinal fluid and striatum of HD patients exhibited abnormal immune activation, suggesting that immune dysfunction plays a role in brain pathology. Collectively, our data suggest parallel central nervous system and peripheral pathogenic pathways of immune activation in HD.
Semantic reclassification of the UMLS concepts
Authors: Fan Jung-Wei , Friedman Carol
Published: July 2008

Summary: Accurate semantic classification is valuable for text mining and knowledge-based tasks that perform inference based on semantic classes. To benefit applications using the semantic classification of the Unified Medical Language System (UMLS) concepts, we automatically reclassified the concepts based on their lexical and contextual features. The new classification is useful for auditing the original UMLS semantic classification and for building biomedical text mining applications.

Availability:  http://www.dbmi.columbia.edu/~juf7002/reclassify_production

Contact:  fan@dbmi.columbia.edu

Supplementary information: Supplementary data is available at http://www.dbmi.columbia.edu/~juf7002/reclassify_production.
Metagenomics reveals our incomplete knowledge of global diversity
Authors: Pignatelli Miguel , Aparicio Gabriel , Blanquer Ignacio , Hernández Vicente , Moya Andrés , Tamames Javier
Published: July 2008

Contact:  Javier.tamames@uv.es
Variations in Amino Acid and Protein Contents of Wheat During Milling and Northern‐Style Steamed Breadmaking
Authors: Jiang Xiaoling , Hao Zhi , Tian Jichun
Published: July 2008

To determine the variations of amino acid and protein during milling and steamed breadmaking, two types of wheat cultivars belonging to soft and hard wheat types were used. The results showed that losses occurred in 17 amino acids during milling. The mean loss of threonine (18.0%) was the highest, which was followed by proline (15.5%), methionine (15.1%), and histidine (15.1%). The losses of tyrosine and lysine were the lowest (8.1 and 9.7%, respectively). Losses were also found for 17 amino acids during steamed breadmaking. The highest loss was observed in alanine (17.1%), with tyrosine (12.5%) close behind, and leucine (4.3%) exhibiting the lowest loss. The mean protein contents for whole‐wheat meal, flour, and steamed bread prepared from the test materials were 15.25, 14.27, and 14.33%, respectively. This meant that protein content decreased during milling; however, a slight increase was observed during steamed breadmaking. Amino acid scores of lysine in whole‐wheat meal, flour, and steamed bread prepared from the test materials were 45.4, 41.0, and 38.2, respectively. The general trend in the variations of protein and amino acids was similar in the two wheat cultivars tested.
Effect of Isomaltooligosaccharide Syrup on Quality Characteristics of Sponge Cake
Authors: Lee Ching‐Ching , Wang Hsueh‐Fang , Lin Sheng‐Dun
Published: July 2008

Sponge cakes were formulated using isomaltooligosaccharide (IMO) syrup as a sweetener to replace 0, 25, 50, 75, and 100% sucrose. The qualities of cakes were evaluated by physicochemical, microbiological, and sensory evaluation analyses. The viscosity in cake batter, cake volume, crumb Hunter a value, and IMO contents of baked cakes increased with increasing IMO syrup level, whereas the specific gravity in cake batter, crust L a b, and crumb L and b values, and hardness of baked cakes showed a reverse trend. The crust and crumb of cakes became darker and less yellow and had a better tender and less sweet texture as IMO syrup level increased and sucrose decreased. The degree of overall liking of cakes increased with increasing IMO syrup level. Total plate counts exceeded 105 CFU/g for cakes stored at 25°C for three days and <103 CFU/g for the samples stored at 5°C for seven days. The changes in the moisture content, water activity, L a b values, and IMO contents of samples did not differ during storage. Overall, sucrose in the formulation of sponge cakes could be partially or fully replaced with IMO syrup.
Production of Oat Cakes from Extruded Pellets
Authors: Han L. , Huff H. E. , Hsieh F.
Published: July 2008

Puffed oat cakes were prepared by puffing the extruded oat pellets with a rice cake machine using independent variables of extrudate moisture contents (30 and 34%, wb), tempering moisture content (10, 12, and 14%, wb), heating temperature (238, 243, 249, and 254°C), and heating times (4, 6, and 8 sec). All four processing variables had significant effects on oat cake physical properties (specific volume, color, hardness, and integrity). Heating time had the most significant effect. Increasing heating time resulted in oat cakes with increased specific volume, integrity, and redness but lower lightness and yellowness. An acceptable product could be made using oat pellets extruded at either 30 or 34% moisture, dried to 9%, and then tempered to 12–14% moisture, and heated to 243–254°C for 8 sec. High correlations were observed between instrumental and sensory descriptive analysis.
Physicochemical Properties of Wheat Fractionated by Wheat Kernel Thickness and Separated by Kernel Specific Density
Authors: Yinian Li , Jun Wang , Weizhong Xie , Daxin Lu , Weimin Ding
Published: July 2008

Two wheat cultivars, soft white winter wheat Yang‐mai 11 and hard white winter wheat Zheng‐mai 9023, were fractionated by kernel thickness into five sections; the fractionated wheat grains in the 2.7–3.0 mm section were separated sequentially into three fractions according to kernel specific density. Physical properties of unfractionated, fractionated, and separated wheat grains and the physicochemical properties of processed wheat flour were determined. Test weight, relative density, and whiteness of flour in the middle kernel thicknesses were maximal and those properties decreased with increasing or decreasing kernel thickness; they also decreased with decreasing kernel specific density. Extensigraph properties showed the same results. Water absorption of flour and kernel hardness increased with increasing kernel thickness and decreasing kernel specific density. The farinograph properties also were related to kernel thickness and specific density. Pasting viscosity increased with increasing kernel thickness for sections from <2.5 mm to 3.0–3.2 mm, except that the >3.2 mm section was lowest; the kernels with the lightest specific density also were lowest. Thus, the quality of wheat grains with the greatest kernel thickness was not the best, and in fact may be the worst. The quality of wheat grains with small kernel thickness and light kernel specific density generally were worst. Most physicochemical properties of unfractionated and unseparated wheat grains were accurately predicted by the weighted‐average of the different kernel thickness sections and different kernel specific density fractions, except relative density, falling number, dough development time, and pasting temperature.
Phenolic Content and Antioxidant Properties of Bran in 51 Wheat Cultivars
Authors: Verma Brij , Hucl Pierre. , Chibbar Ravindra N.
Published: July 2008

Whole‐grain‐based diets have been suggested to reduce the incidence of cardiovascular disease and colon cancer. Phenolic compounds, most of which are present in the wheat bran, may be one of the factors contributing to whole‐grain health benefits. We measured the free, bound, and total phenolic content and antioxidant activity in the bran of 51 wheat cultivars belonging to eight Western Canadian spring wheat market classes grown in a replicated trial at Saskatoon, Saskatchewan, Canada. The free phenolic (extracted with 80% v/v aqueous ethanol) content ranged from 854.1 ± 265.1 to 1,754.9 ± 240.3 μg/g of bran gallic acid equivalent (GAE). Saponification followed by a liquid‐liquid solvent extraction released bound phenols ranging from 2,304.9 ± 483.0 to 5,386.1 ± 927.5 μg/g of bran GAE, contributing 66–82% of the total wheat bran phenolic content. Total phenolic content ranged from 3,406.4 ± 32.3 to 6,702.7 ± 19.6 μg/g of bran GAE, with the average being 5,197.2 ± 804.9 μg/g of bran GAE. Antioxidant activity ranged from 11.86 ± 2.59 to 20.12 ± 0.51%, while the overall average was 15.6 ± 2.2%. Based on varietal means, antioxidant activity correlated with free, bound, and total phenolic content (r = 0.8, P < 0.05).
Pasting Characteristics of Maize Starch Heat‐Treated with Different Water‐Ethanol Mixtures
Authors: Kurakake Masahiro , Noguchi Masahiro , Fujioka Kiyofumi , Komaki Toshiaki
Published: July 2008

Pasting characteristics of maize starch heat‐treated with six different water‐to‐ethanol ratios (%wt base 0:100, 10:90, 20:80, 30:70, 40:60, 50:50) were investigated; treated starches were called EW 0, 10, 20, 30, 40, and 50, respectively. Endotherms in DSC analysis shifted to a higher temperature as the water content in water‐ethanol mixture increased. The removed amount of fatty acids was much higher in treatments for EW 10, 20, and 30. The RVA peak viscosity of EW 10 and 20 were highest among the treated starches and setbacks were more than twice that of untreated starch. The characteristic change in the RVA viscogram corresponded to the amount of leached amylose from the granule. EW 30 displays similar properties as conventional heat‐moisture‐treated starch, but maintained a higher viscosity of ≈300 RVU throughout the heating process. In treatment with water‐ethanol mixtures, heat‐moisture treatment and defatting effects generated new types of modified starches. EW 40 and 50 had no clear pasting peak on RVA, and showed a viscosity at low temperature similar to granular cold water gelling.
Bulk Carbohydrate Grain Filling of Barley β‐Glucan Mutants Studied by 1H HR MAS NMR
Authors: Seefeldt Helene Fast , Larsen Flemming Hofmann , Viereck Nanna , Wollenweber Bernd , Engelsen S⊘ren Balling
Published: July 2008

Temporal and genotypic differences in bulk carbohydrate accumulation in three barley genotypes differing in the content of mixed linkage β‐(1→3),(1→4)‐D‐glucan (β‐glucan) and starch were investigated using proton high‐resolution, magic angle spinning, nuclear magnetic resonance (1H HR MAS NMR) during grain filling. For the first time, 1H HR MAS NMR spectra of flour from immature barley seeds are analyzed. Spectral assignments are made using two‐dimensional (2D) NMR methods. Both α‐ and β‐glucan biosynthesis were characterized by inspection of the spectra as well as by calibration to the reference methods for starch and β‐glucan content. Starch was quantified with very good calibrations to the α‐(1→4) peak (5.29–5.40 ppm) and the region 3.67–3.83 ppm covering starch glycopyranosidic protons from H5 and H6. In contrast, the spectral inspection of the β‐anomeric region 4.45–4.85 ppm showed unexpected lack of intensity in the high β‐glucan mutant lys5f at seed maturity, resulting in poor calibration to reference β‐glucan content. We hypothesize that the lack of β‐glucan signal in lys5f indicates partial immobilization of the β‐glucan that appears to be either genotypic dependent or water/β‐glucan ratio dependent.
NELF-mediated stalling of Pol II can enhance gene expression by blocking promoter-proximal nucleosome assembly
Authors: Gilchrist Daniel A. , Nechaev Sergei , Lee Chanhyo , Ghosh Saikat Kumar B. , Collins Jennifer B. , Li Leping , Gilmour David S. , Adelman Karen
Published: July 2008

The Negative Elongation Factor (NELF) is a transcription regulatory complex that induces stalling of RNA polymerase II (Pol II) during early transcription elongation and represses expression of several genes studied to date, including Drosophila Hsp70, mammalian proto-oncogene junB, and HIV RNA. To determine the full spectrum of NELF target genes in Drosophila, we performed a microarray analysis of S2 cells depleted of NELF and discovered that NELF RNAi affects many rapidly inducible genes involved in cellular responses to stimuli. Surprisingly, only one-third of NELF target genes were, like Hsp70, up-regulated by NELF-depletion, whereas the majority of target genes showed decreased expression levels upon NELF RNAi. Our data reveal that the presence of stalled Pol II at this latter group of genes enhances gene expression by maintaining a permissive chromatin architecture around the promoter-proximal region, and that loss of Pol II stalling at these promoters is accompanied by a significant increase in nucleosome occupancy and a decrease in histone H3 Lys 4 trimethylation. These findings identify a novel, positive role for stalled Pol II in regulating gene expression and suggest that there is a dynamic interplay between stalled Pol II and chromatin structure.
Rad53 regulates replication fork restart after DNA damage in Saccharomyces cerevisiae
Authors: Szyjka Shawn J. , Aparicio Jennifer G. , Viggiani Christopher J. , Knott Simon , Xu Weihong , Tavaré Simon , Aparicio Oscar M.
Published: July 2008

Replication fork stalling at a DNA lesion generates a damage signal that activates the Rad53 kinase, which plays a vital role in survival by stabilizing stalled replication forks. However, evidence that Rad53 directly modulates the activity of replication forks has been lacking, and the nature of fork stabilization has remained unclear. Recently, cells lacking the Psy2–Pph3 phosphatase were shown to be defective in dephosphorylation of Rad53 as well as replication fork restart after DNA damage, suggesting a mechanistic link between Rad53 deactivation and fork restart. To test this possibility we examined the progression of replication forks in methyl-methanesulfonate (MMS)-damaged cells, under different conditions of Rad53 activity. Hyperactivity of Rad53 in pph3Δ cells slows fork progression in MMS, whereas deactivation of Rad53, through expression of dominant-negative Rad53-KD, is sufficient to allow fork restart during recovery. Furthermore, combined deletion of PPH3 and PTC2, a second, unrelated Rad53 phosphatase, results in complete replication fork arrest and lethality in MMS, demonstrating that Rad53 deactivation is a key mechanism controlling fork restart. We propose a model for regulation of replication fork progression through damaged DNA involving a cycle of Rad53 activation and deactivation that coordinates replication restart with DNA repair.
Transcriptional coactivators PGC-1α and PGC-lβ control overlapping programs required for perinatal maturation of the heart
Authors: Lai Ling , Leone Teresa C. , Zechner Christoph , Schaeffer Paul J. , Kelly Sean M. , Flanagan Daniel P. , Medeiros Denis M. , Kovacs Attila , Kelly Daniel P.
Published: July 2008

Oxidative tissues such as heart undergo a dramatic perinatal mitochondrial biogenesis to meet the high-energy demands after birth. PPARγ coactivator-1 (PGC-1) α and β have been implicated in the transcriptional control of cellular energy metabolism. Mice with combined deficiency of PGC-1α and PGC-1β (PGC-1αβ−/− mice) were generated to investigate the convergence of their functions in vivo. The phenotype of PGC-1β−/− mice was minimal under nonstressed conditions, including normal heart function, similar to that of PGC-1α−/− mice generated previously. In striking contrast to the singly deficient PGC-1 lines, PGC-1αβ−/− mice died shortly after birth with small hearts, bradycardia, intermittent heart block, and a markedly reduced cardiac output. Cardiac-specific ablation of the PGC-1β gene on a PGC-1α-deficient background phenocopied the generalized PGC-1αβ−/− mice. The hearts of the PGC-1αβ−/− mice exhibited signatures of a maturational defect including reduced growth, a late fetal arrest in mitochondrial biogenesis, and persistence of a fetal pattern of gene expression. Brown adipose tissue (BAT) of PGC-1αβ−/− mice also exhibited a severe abnormality in function and mitochondrial density. We conclude that PGC-1α and PGC-1β share roles that collectively are necessary for the postnatal metabolic and functional maturation of heart and BAT.
A nucleostemin family GTPase, NS3, acts in serotonergic neurons to regulate insulin signaling and control body size
Authors: Kaplan Daniel D. , Zimmermann Gregor , Suyama Kaye , Meyer Tobias , Scott Matthew P.
Published: July 2008

Growth and body size are regulated by the CNS, integrating the genetic developmental program with assessments of an animal’s current energy state and environmental conditions. CNS decisions are transmitted to all cells of the animal by insulin/insulin-like signals. The molecular biology of the CNS growth control system has remained, for the most part, elusive. Here we identify NS3, a Drosophila nucleostemin family GTPase, as a powerful regulator of body size. ns3 mutants reach <60% of normal size and have fewer and smaller cells, but exhibit normal body proportions. NS3 does not act cell-autonomously, but instead acts at a distance to control growth. Rescue experiments were performed by expressing wild-type ns3 in many different cells of ns3 mutants. Restoring NS3 to only 106 serotonergic neurons rescued global growth defects. These neurons are closely apposed with those of insulin-producing neurons, suggesting possible communication between the two neuronal systems. In the brains of ns3 mutants, excess serotonin and insulin accumulate, while peripheral insulin pathway activation is low. Peripheral insulin pathway activation rescues the growth defects of ns3 mutants. The findings suggest that NS3 acts in serotonergic neurons to regulate insulin signaling and thus exert global growth control.
Control of differentiation in a self-renewing mammalian tissue by the histone demethylase JMJD3
Authors: Sen George L. , Webster Daniel E. , Barragan Deborah I. , Chang Howard Y. , Khavari Paul A.
Published: July 2008

The recent discovery of H3K27me3 demethylases suggests that H3K27me3 may dynamically regulate gene expression, but this potential role in mammalian tissue homeostasis remains uncharacterized. In the epidermis, a tissue that balances stem cell self-renewal with differentiation, H3K27me3, occupies the promoters of many differentiation genes. During calcium-induced differentiation, H3K27me3 was erased at these promoters in concert with loss of PcG protein occupancy and increased binding by the H3K27me3 demethylase, JMJD3. Within epidermal tissue, JMJD3 depletion blocked differentiation, while active JMJD3 dominantly induced it. These results indicate that epigenetic derepression by JMJD3 controls mammalian epidermal differentiation.
Cdc7–Drf1 kinase links chromosome cohesion to the initiation of DNA replication in Xenopus egg extracts
Authors: Takahashi Tatsuro S. , Basu Abhijit , Bermudez Vladimir , Hurwitz Jerard , Walter Johannes C.
Published: July 2008

To establish functional cohesion between replicated sister chromatids, cohesin is recruited to chromatin before S phase. Cohesin is loaded onto chromosomes in the G1 phase by the Scc2–Scc4 complex, but little is known about how Scc2–Scc4 itself is recruited to chromatin. Using Xenopus egg extracts as a vertebrate model system, we showed previously that the chromatin association of Scc2 and cohesin is dependent on the prior establishment of prereplication complexes (pre-RCs) at origins of replication. Here, we report that Scc2–Scc4 exists in a stable complex with the Cdc7–Drf1 protein kinase (DDK), which is known to bind pre-RCs and activate them for DNA replication. Immunodepletion of DDK from Xenopus egg extracts impairs chromatin association of Scc2–Scc4, a defect that is reversed by wild-type, but not catalytically inactive DDK. A complex of Scc4 and the N terminus of Scc2 is sufficient for chromatin loading of Scc2–Scc4, but not for cohesin recruitment. These results show that DDK is required to tether Scc2–Scc4 to pre-RCs, and they underscore the intimate link between early steps in DNA replication and cohesion.
Serotonin and insulin signaling team up to control growth in Drosophila: Figure 1.
Authors: Ruaud Anne-Françoise , Thummel Carl S.
Published: July 2008

Neuroendocrine signaling pathways play a central role in modulating animal body size in response to environmental signals. Little is known, however, regarding how these neuroendocrine circuits are controlled. An important advance in this area is reported in this issue of Genes & Development by Kaplan and colleagues (pp. 1877–1893), who show that serotonergic neurons regulate the growth of peripheral tissues in Drosophila through the insulin/IGF pathway.
Liver receptor homolog 1 is essential for ovulation
Authors: Duggavathi Rajesha , Volle David H. , Mataki Chikage , Antal Maria C. , Messaddeq Nadia , Auwerx Johan , Murphy Bruce D. , Schoonjans Kristina
Published: July 2008

Female fertility requires normal ovarian follicular growth and ovulation. The nuclear receptor liver receptor homolog 1 has been implicated in processes as diverse as bile acid metabolism, steroidogenesis, and cell proliferation. In the ovary, Lrh1 is expressed exclusively in granulosa and luteal cells. Using somatic targeted mutagenesis, we show that mice lacking Lrh1 in granulosa cells are sterile, due to anovulation. The preovulatory stimulus fails to elicit cumulus expansion, luteinization, and follicular rupture in these mice. Multiple defects, including severely reduced transactivation of the Lrh1 target gene, nitric oxide synthase 3, leads to increased intrafollicular estradiol levels in the absence of Lrh1. This further causes dysfunction of prostaglandin and hyaluronic acid cascades and interrupts cumulus expansion. Lack of Lrh1 also interferes with progesterone synthesis because of failure of normal expression of the Lrh1 targets, steroidogenic acute regulatory protein and cytochrome P450 side-chain cleavage. In addition, expression of extracellular matrix proteases essential for ovulation is compromised. These results demonstrate that Lrh1 is a regulator of multiple mechanisms essential for maturation of ovarian follicles and for ovulation. Lrh1 is therefore a key modulator of female fertility and a potential target for contraception.
Early vertebrate whole genome duplications were predated by a period of intense genome rearrangement
Authors: Hufton Andrew L. , Groth Detlef , Vingron Martin , Lehrach Hans , Poustka Albert J. , Panopoulou Georgia
Published: July 2008

Researchers, supported by data from polyploid plants, have suggested that whole genome duplication (WGD) may induce genomic instability and rearrangement, an idea which could have important implications for vertebrate evolution. Benefiting from the newly released amphioxus genome sequence (Branchiostoma floridae), an invertebrate that researchers have hoped is representative of the ancestral chordate genome, we have used gene proximity conservation to estimate rates of genome rearrangement throughout vertebrates and some of their invertebrate ancestors. We find that, while amphioxus remains the best single source of invertebrate information about the early chordate genome, its genome structure is not particularly well conserved and it cannot be considered a fossilization of the vertebrate preduplication genome. In agreement with previous reports, we identify two WGD events in early vertebrates and another in teleost fish. However, we find that the early vertebrate WGD events were not followed by increased rates of genome rearrangement. Indeed, we measure massive genome rearrangement prior to these WGD events. We propose that the vertebrate WGD events may have been symptoms of a preexisting predisposition toward genomic structural change.
Medial auditory thalamus inactivation prevents acquisition and retention of eyeblink conditioning
Authors: Halverson Hunter E. , Poremba Amy , Freeman John H.
Published: July 2008

The auditory conditioned stimulus (CS) pathway that is necessary for delay eyeblink conditioning was investigated using reversible inactivation of the medial auditory thalamic nuclei (MATN) consisting of the medial division of the medial geniculate (MGm), suprageniculate (SG), and posterior intralaminar nucleus (PIN). Rats were given saline or muscimol infusions into the MATN contralateral to the trained eye before each of four conditioning sessions with an auditory CS. Rats were then given four additional sessions without infusions to assess savings from the initial training. All rats were then given a retention test with a muscimol infusion followed by a recovery session. Muscimol infusions through cannula placements within 0.5 mm of the MGm prevented acquisition of eyeblink conditioned responses (CRs) and also blocked CR retention. Cannula placements more than 0.5 mm from the MATN did not completely block CR acquisition and had a partial effect on CR retention. The primary and secondary effects of MATN inactivation were examined with 2-deoxy-glucose (2-DG) autoradiography. Differences in 2-DG uptake in the auditory thalamus were consistent with the cannula placements and behavioral results. Differences in 2-DG uptake were found between groups in the ipsilateral auditory cortex, basilar pontine nuclei, and inferior colliculus. Results from this experiment indicate that the MATN contralateral to the trained eye and its projection to the pontine nuclei are necessary for acquisition and retention of eyeblink CRs to an auditory CS.
c-Rel, an NF-κB family transcription factor, is required for hippocampal long-term synaptic plasticity and memory formation
Authors: Ahn Hyung Jin , Hernandez Caterina M. , Levenson Jonathan M. , Lubin Farah D. , Liou Hsiou-Chi , Sweatt J. David
Published: July 2008

Transcription is a critical component for consolidation of long-term memory. However, relatively few transcriptional mechanisms have been identified for the regulation of gene expression in memory formation. In the current study, we investigated the activity of one specific member of the NF-κB transcription factor family, c-Rel, during memory consolidation. We found that contextual fear conditioning elicited a time-dependent increase in nuclear c-Rel levels in area CA1 and DG of hippocampus. These results suggest that c-rel is active in regulating transcription during memory consolidation. To identify the functional role of c-Rel in memory formation, we characterized c-rel−/−mice in several behavioral tasks. c-rel−/−mice displayed significant deficits in freezing behavior 24 h after training for contextual fear conditioning but showed normal freezing behavior in cued fear conditioning and in short-term contextual fear conditioning. In a novel object recognition test, wild-type littermate mice exhibited a significant preference for a novel object, but c-rel−/−mice did not. These results indicate that c-rel−/−mice have impaired hippocampus-dependent memory formation. To investigate the role of c-Rel in long-term synaptic plasticity, baseline synaptic transmission and long-term potentiation (LTP) at Schaffer collateral synapses in c-rel−/−mice was assessed. c-rel−/−slices had normal baseline synaptic transmission but exhibited significantly less LTP than did wild-type littermate slices. Together, our results demonstrate that c-Rel is necessary for long-term synaptic potentiation in vitro and hippocampus-dependent memory formation in vivo.
Shifting from implicit to explicit knowledge: Different roles of early- and late-night sleep
Authors: Yordanova Juliana , Kolev Vasil , Verleger, Rolf , Bataghva Zhamak , Born Jan , Wagner Ullrich
Published: July 2008

Sleep has been shown to promote the generation of explicit knowledge as indicated by the gain of insight into previously unrecognized task regularities. Here, we explored whether this generation of explicit knowledge depends on pre-sleep implicit knowledge, and specified the differential roles of slow-wave sleep (SWS) vs. rapid eye movement (REM) sleep in this process. Implicit and explicit knowledge (insight) related to a hidden regularity were assessed in an associative motor-learning task (number reduction task, NRT), which was performed in two sessions (initial practice and retest) separated by 3 h of either early-night sleep, rich in SWS, or of late-night sleep, rich in REM sleep. About half of the participants developed signs of implicit rule knowledge (i.e., speeded reaction times for responses determined by the hidden regularity) at initial practice preceding early or late sleep. Of these, half developed explicit knowledge across early-night sleep, significantly more than across late-night sleep. In contrast, late-night subjects preferentially remained on the level of implicit rule knowledge after sleep. Participants who did not develop implicit knowledge before sleep had comparable rates of transition to implicit or explicit knowledge across early and late sleep. If subjects gained explicit knowledge across sleep, this was associated with lower amounts of REM sleep, specifically in the late-night group. SWS predominant during the early night may restructure implicit memory representations in a way that allows creating an explicit representation afterward, whereas REM sleep in the late night appears to stabilize them in their implicit form.