bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrophoretic deposition of chitosan–albumin and Alginate–albumin films
Authors: Ma R , Zhitomirsky I
Published: September 2009

Electrophoretic deposition methods have been developed for the fabrication of composite films containing biopolymers and bovine serum albumin (BSA). The mechanism of the deposition of chitosan–BSA films was based on electrophoresis of chitosan and BSA in acidic solutions, and co‐precipitation of insoluble chitosan and BSA in the high pH region at the cathode surface. The mechanism of the anodic deposition of alginic acid–BSA films was based on electrophoresis of alginate and BSA in basic solutions and precipitation of insoluble alginic acid and BSA in the low pH region at the anode surface. The deposition yield measurements and scanning electron microscopy investigations showed that the amount of the deposited material can be controlled by variation of the deposition time. Uniform films with thickness of 0–15 μm were obtained on conductive substrates. The films were studied by thermogravimetric analysis, differential thermal analysis and Fourier transform infrared spectroscopy.
The biomimetic deposition of carbonate apatite induced by titanium base calcium enriched silica films
Authors: Xiao X. F. , Liu R. F. , Gao Y. J.
Published: September 2009

In order to obtain a fast biomimetic coating on titanium substrates, calcium enriched silica films were prepared on pure titanium substrates by sol–gel method under the following conditions: pH = 3 and the molar ratio of tetraethyl orthosilicate (TEOS)/H2O/EtOH/Ca2+ = 1∶4∶11∶0·08. The titanium base calcium enriched silica film is soaked in a slightly supersaturated Ca/P solution, with the concentration of calcium ion and phosphate group being 1·5 times of that of simulated body fluid, for seven days, a uniform apatite layer is precipitated onto the surfaces of calcium enriched silica films, which is quite rapidly. The investigation adopted SEM, EDX, Fourier transform infrared spectroscope and XRD to indicate that the coating was carbonate hydroxyapatite. The results show that it is a feasible way to obtain carbonate hydroxyapatite through functionalising the pure titanium substrates by preparing calcium enriched silica films on it from a sol–gel method.
Flow behaviour and microstructural evolution of Ti-17 alloy with lamellar microstructure during hot deformation in α+β phase field
Authors: Wang K. X. , Zeng W. D. , Zhao Y. Q. , Lai Y. J. , Zhang X. M. , Zhou Y. G.
Published: September 2009

The effect of process variables on flow response and microstructure evolution during hot working of Ti-17 (Ti–5Al–2Sn–2Zr–4Mo–4Cr) alloy with lamellar microstructure was established using isothermal hot compression tests at strain rates of 0·001–10 s−1, test temperature between 780 and 860°C, and height reductions of 15–75. All of the flow curves exhibited a peak stress followed by noticeable flow softening, and tended to exhibit a noticeably lower rate of flow softening at the strain of the order of 0·7. The peak flow stress decreased with increasing temperature and decreasing strain rate. Flow softening of the Ti-17 alloy was caused by kinking, break-up and globularisation of lamellas during deformation and, to a small extent, by deformation heating. At high strain rate, adiabatic shear bands and flow localisation were observed to play a role in flow softening. In α+β phase region discontinuous yielding was discovered at higher temperature (⩾820°C) and 10 s−1. According to the deformation microstructure, lamellar α phase gradually kinked, broke up and globularised of lamellas resulting from the development of shear bands and the penetration of β phase during deformation in the α+β phase field. The degree of dynamic globularisation of α phase increased with increasing strains, temperature and decreasing strain rate.
Zigrasite, MgZr(PO4)2(H2O)4, a new phosphate mineral from the Dunton Quarry, Newry, Oxford County, Maine, USA
Authors: Hawthorne F. C. , Ball N. A. , Nizamoff J. W. , Simmons W. B.
Published: September 2009

Zigrasite, ideally MgZr(PO4)2(H2O)4, is a new secondary phosphate mineral from the giant 1972 gem tourmaline-bearing pocket at the Dunton Quarry, Newry, Oxford County, Maine, USA. It occurs as subhedral blocky grains sometimes exceeding 1 mm in maximum dimension and perched on tourmaline. These grains are complex aggregates ofthree distinct phases, zigrasite and two unnamed phases: the Ca analogue of zigrasite, CaZr(PO4)2(H2O)4, and Zr(PO3OH)2(H2O)4. Zigrasite is associated with tourmaline, microcline, quartz, albite, beryl, amblygonite-montebrasite, childreniteeosphorite and apatite, and crystallized as one of the latest minerals during pocket formation. It is offwhite to pale yellow or light tan, translucent with a white streak and a vitreous lustre, and shows light blue to pale yellow cathodoluminescence. Mohs hardness is 3 and the measured and calculated densities are 2.76(4) and 2.66 g/cm3. The mineral has imperfect cleavage in two directions, parallel to (010) and (001), shows no parting, is brittle and has a hackly fracture. In transmitted light, it is colourless and non-pleochroic, biaxial negative with α 1.597(1), β 1.622 (1), γ 1.635 (1), with 2V(meas) = 65.5(4)º and 2V(calc.) = 71º. Zigrasite is triclinic, P , a 5.3049(2) Å, b 9.3372(4) Å, c 9.6282(5) Å, α 97.348(1)º, β 91.534(1)º, γ 90.512(4)º, V 472.79(5) Å3, Z = 2. The seven strongest lines in the X-ray powder diffraction pattern are as follows: d (Ê), I, (hkl): 9.550, 100, (001); 4.108, 70, ; 4.008, 50, (111); 4.589, 40, (110); 3.177, 40, (112); 3.569, 30, (0 2), 2.660, 30, (200),(11),(130); 3.273, 20, (12). Chemical analysis by electron microprobe gave P2O5 37.59, ZrO2 32.27, HfO2 0.34, FeO 0.20, MgO 10.37, ZnO 0.17, F 0.13, LOI 18.60, less O:F 0.05 = total 99.62 wt.%. The resulting empirical formula is (–)Σ=0.99(Zr0.99Hf0.01)Σ=1.00 P2.00O8(H2O)4 on the basis of12 O atoms with H2O = 4 per formula unit from crystal-structure analysis, and the end-member formula is MgZr(PO4)2(H2O)4.
Fluoro-sodic-ferropedrizite, NaLi2(Fe22+Al2Li)Si8O22F2, a new mineral of the amphibole group from the Sutlug River, Tuva Republic, Russia: description and crystal structure
Authors: Oberti R. , Boiocchi M. , Ball N. A. , Hawthorne F. C.
Published: September 2009

Fluoro-sodic-ferropedrizite, ideally ANaBLi2C()TSi8O22WF2, is a new mineral of the amphibole group from the Sutlug River, Tuva Republic, Russia. It occurs at the endogenic contact of a Li-pegmatite with country rocks near to a diabase dyke and formed by reaction of the pegmatitic melt with the country rock. Fluoro-sodic-ferropedrizite occurs as prismatic to acicular crystals, ranging in length from 0.1–3 cm and widths of up to 50 μm. Crystals occur inparallel to sub-parallel aggregates up to 5 mm across ina matrix of calcite and plagioclase feldspar. Crystals are pale bluish-grey with a greyish-white streak.

Fluoro-sodic-ferropedrizite is brittle, has a Mohs hardness of ~6 and a splintery fracture; it is non-fluorescent with perfect {110} cleavage, no observable parting, and has a calculated density of 3.116 g cm–3. In plane-polarized light, it is pleochroic, X = pale purple-grey, Y = light grey, Z = colourless; X ^ a = 71.2º (in β acute), Y || b, Z ^ c = 83.4º (in β obtuse). Fluoro-sodic-ferropedrizite is biaxial positive, α = 1.642(1), β = 1.644(1), γ = 1.652(1); 2V(obs) = 68.0(3)º, 2V(calc) = 56.4º. Fluoro-sodic-ferropedrizite is monoclinic, space group C2/m, a = 9.3720(4) Å, b = 17.6312(8) Å, c = 5.2732(3) Å, β = 102.247(4)º, V = 851.5(2) Å3, Z = 2. The strongest ten X-ray diffraction lines in the powder patternare (d in Å ,(I),(hkl)): 8.146,(10),(110); 2.686,(9),(151); 3.008,(8),(310); 4.430,(7),(021); 2.485,(6),(02); 3.383,(4),(131); 2.876,(3),(51, 11); 2.199,(3),(12); 4.030,(2),(111) and 3.795,(2),(31). Analysis by a combination of electron microprobe and crystal-structure refinement gives SiO2 59.81, Al2O3 12.66, TiO2 0.09, FeO 10.32, MgO 5.56, MnO 0.73, ZnO 0.17, CaO 0.20, Na2O 2.81, Li2O 4.80, F 2.43, H2Ocalc 1.10, sum = 99.65 wt.%. The formula unit, calculated on the basis of 24(O,OH,F) is A(Na0.68)B(Li1.92Na0.05Ca0.03)C() T(Si7.98Al0.02)O22W(F1.03OH0.97). Crystal-structure refinement shows Li to be completely ordered at the M(3) and M(4) sites. Fluoro-sodic-ferropedrizite, ideally ANaBLi2C()TSi8O22WF2, is related to the theoretical end-member ‘sodic-pedrizite’, ANaBLi2C(Mg2Al2Li)TSi8O22W(OH)2, by the substitutions CFe2+ → CMg and WF → W(OH).
KSRP-PMR1-exosome association determines parathyroid hormone mRNA levels and stability in transfected cells
Authors: Nechama Morris , Peng Yong , Bell Osnat , Briata Paola , Gherzi Roberto , Schoenberg Daniel R , Naveh-Many Tally
Published: September 2009

Background

Parathyroid hormone (PTH) gene expression is regulated post-transcriptionally through the binding of the trans- acting proteins AU rich binding factor 1 (AUF1), Upstream of N-ras (Unr) and KH-type splicing regulatory protein (KSRP) to an AU rich element (ARE) in PTH mRNA 3'-UTR. AUF1 and Unr stabilize PTH mRNA while KSRP, recruiting the exoribonucleolytic complex exosome, promotes PTH mRNA decay.

Results

PTH mRNA is cleaved by the endoribonuclease polysomal ribonuclease 1 (PMR1) in an ARE-dependent manner. Moreover, PMR1 co-immunoprecipitates with PTH mRNA, the exosome and KSRP. Knock-down of either exosome components or KSRP by siRNAs prevents PMR1-mediated cleavage of PTH mRNA.

Conclusion

PTH mRNA is a target for the endonuclease PMR1. The PMR1 mediated decrease in PTH mRNA levels involves the PTH mRNA 3'-UTR ARE, KSRP and the exosome. This represents an unanticipated mechanism by which the decay of an ARE-containing mRNA is facilitated by KSRP and is dependent on both the exosome and an endoribonuclease.
Deep sequencing of Brachypodium small RNAs at the global genome level identifies microRNAs involved in cold stress response
Authors: Zhang Jingyu , Xu Yunyuan , Huan Qing , Chong Kang
Published: September 2009

Background

MicroRNAs (miRNAs) are endogenous small RNAs having large-scale regulatory effects on plant development and stress responses. Extensive studies of miRNAs have only been performed in a few model plants. Although miRNAs are proved to be involved in plant cold stress responses, little is known for winter-habit monocots. Brachypodium distachyon, with close evolutionary relationship to cool-season cereals, has recently emerged as a novel model plant. There are few reports of Brachypodium miRNAs.

Results

High-throughput sequencing and whole-genome-wide data mining led to the identification of 27 conserved miRNAs, as well as 129 predicted miRNAs in Brachypodium. For multiple-member conserved miRNA families, their sizes in Brachypodium were much smaller than those in rice and Populus. The genome organization of miR395 family in Brachypodium was quite different from that in rice. The expression of 3 conserved miRNAs and 25 predicted miRNAs showed significant changes in response to cold stress. Among these miRNAs, some were cold-induced and some were cold-suppressed, but all the conserved miRNAs were up-regulated under cold stress condition.

Conclusion

Our results suggest that Brachypodium miRNAs are composed of a set of conserved miRNAs and a large proportion of non-conserved miRNAs with low expression levels. Both kinds of miRNAs were involved in cold stress response, but all the conserved miRNAs were up-regulated, implying an important role for cold-induced miRNAs. The different size and genome organization of miRNA families in Brachypodium and rice suggest that the frequency of duplication events or the selection pressure on duplicated miRNAs are different between these two closely related plant species.
The roles of tumor necrosis factor-alpha in colon tight junction protein expression and intestinal mucosa structure in a mouse model of acute liver failure
Authors: Song Hong-Li , Lv Sa , Liu Pei
Published: September 2009

Background

Spontaneous bacterial peritonitis (SBP) is a common clinical disease and one of the most severe complications of acute liver failure (ALF). Although the mechanism responsible for SBP is unclear, cytokines play an important role. The aim of this study was to investigate the effects of tumor necrosis factor-alpha (TNF-α) on the structure of the intestinal mucosa and the expression of tight junction (Zona Occludens 1; ZO-1) protein in a mouse model of ALF.

Methods

We induced ALF using D-galactosamine/lipopolysaccharide (GalN/LPS) or GalN/TNF-α and assessed the results using transmission electron microscopy, immunohistochemistry, Western blotting, ELISA and real-time quantitative PCR. The effects of administration of anti-TNF-α IgG antibody or anti-TNF-α R1 antibody before administration of GalN/LPS or GalN/TNF-α, respectively, on TNF-α were also assessed.

Results

Morphological abnormalities in the intestinal mucosa of ALF mice were positively correlated with serum TNF-α level. Electron microscopic analysis revealed tight junction (TJ) disruptions, epithelial cell swelling, and atrophy of intestinal villi. Gut bacteria invaded the body at sites where TJ disruptions occurred. Expression of ZO-1 mRNA was significantly decreased in both ALF models, as was the level of ZO-1 protein. Prophylactic treatment with either anti-TNF-α IgG antibody or anti-tumor necrosis factor-a receptor1 (anti-TNF-α R1) antibody prevented changes in intestinal tissue ultrastructure and ZO-1 expression.

Conclusion

TNF-α affects the structure of the intestinal mucosa, decreases expression of ZO-1, and affects the morphology of the colon in a mouse model of ALF. It also may participate in the pathophysiological mechanism of SBP complicated to ALF.
Integrating human stem cell expansion and neuronal differentiation in bioreactors
Authors: Serra Margarida , Brito Catarina , Costa Eunice M , Sousa Marcos FQ , Alves Paula M
Published: September 2009

Background

Human stem cells are cellular resources with outstanding potential for cell therapy. However, for the fulfillment of this application, major challenges remain to be met. Of paramount importance is the development of robust systems forin vitrostem cell expansion and differentiation. In this work, we successfully developed an efficient scalable bioprocess for the fast production of human neurons.

Results

The expansion of undifferentiated human embryonal carcinoma stem cells (NTera2/cl.D1 cell line) as 3D-aggregates was firstly optimized in spinner vessel. The media exchange operation mode with an inoculum concentration of 4 × 105cell/mL was the most efficient strategy tested, with a 4.6-fold increase in cell concentration achieved in 5 days. These results were validated in a bioreactor where similar profile and metabolic performance were obtained. Furthermore, characterization of the expanded population by immunofluorescence microscopy and flow cytometry showed that NT2 cells maintained their stem cell characteristics along the bioreactor culture time.

Finally, the neuronal differentiation step was integrated in the bioreactor process, by addition of retinoic acid when cells were in the middle of the exponential phase. Neurosphere composition was monitored and neuronal differentiation efficiency evaluated along the culture time. The results show that, for bioreactor cultures, we were able to increase significantly the neuronal differentiation efficiency by 10-fold while reducing drastically, by 30%, the time required for the differentiation process.

Conclusion

The culture systems developed herein are robust and represent one-step-forward towards the development of integrated bioprocesses, bridging stem cell expansion and differentiation in fully controlled bioreactors.
Saffron is a monomorphic species as revealed by RAPD, ISSR and microsatellite analyses
Authors: Rubio-Moraga Angela , Castillo-López Raquel , Gómez-Gómez Lourdes , Ahrazem Oussama
Published: September 2009

Background

Saffron (Crocus sativus) is considered the world's most expensive spice. Used mainly as a colorant for foodstuffs, it is highly appreciated for its aromatic and flavouring properties. Since no molecular markers for this species have been found in the literature, the objective of this study was to determine whether phenotypical differences found in C. sativus were supported by molecular analyses.

Findings

Thirty primers from Operon Technologies were used in random amplified polymorphic DNA (RAPD) analysis, forty eight primers were screened using intersimple sequence repeats (ISSR) method and fifteen primers derived from a microsatellites library flanking sequences with repeat motifs were assayed in forty three isolates of C. sativus from eleven different countries and a C. kotschyanus isolate was used as outgroup. No polymorphic bands were detected in any of the accessions combining the different approaches used in this study.

Conclusion

According to our findings, all accessions appear identical clones, not only because morphological characters but also at a molecular level. These data strongly suggested that C. sativus is a monomorphic species. Thus, genome sequencing is needed to find molecular markers for saffron.
Nonclassic Lipoid Congenital Adrenal Hyperplasia Masquerading as Familial Glucocorticoid Deficiency
Authors: Metherell Louise A. , Naville Danielle , Halaby George , Begeot Martine , Huebner Angela , Nürnberg Gudrun , Nürnberg Peter , Green Jane , Tomlinson Jeremy W. , Krone Nils P. , Lin Lin , Racine Michael , Berney Dan M. , Achermann John C. , Arlt Wiebke , Clark Adrian J. L.
Published: September 2009

Context: Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex. Affected individuals are deficient in cortisol and, if untreated, are likely to succumb to hypoglycemia and/or overwhelming infection. Mutations of the ACTH receptor (MC2R) and the melanocortin 2 receptor accessory protein (MRAP), FGD types 1 and 2 respectively, account for approximately 45% of cases.

Objective: A locus on chromosome 8 has previously been linked to the disease in three families, but no underlying gene defect has to date been identified.

Design: The study design comprised single-nucleotide polymorphism genotyping and mutation detection.

Setting: The study was conducted at secondary and tertiary referral centers.

Patients: Eighty probands from families referred for investigation of the genetic cause of FGD participated in the study.

Interventions: There were no interventions.

Results: Analysis by single-nucleotide polymorphism array of the genotype of one individual with FGD previously linked to chromosome 8 revealed a large region of homozygosity encompassing the steroidogenic acute regulatory protein gene, STAR. We identified homozygous STAR mutations in this patient and his affected siblings. Screening of our total FGD patient cohort revealed homozygous STAR mutations in a further nine individuals from four other families.

Conclusions: Mutations in STAR usually cause lipoid congenital adrenal hyperplasia, a disorder characterized by both gonadal and adrenal steroid deficiency. Our results demonstrate that certain mutations in STAR (R192C and the previously reported R188C) can present with a phenotype indistinguishable from that seen in FGD.

Partial loss-of-function mutations in StAR can present with glucocorticoid deficiency alone; genetic diagnosis in familial glucocorticoid deficiency is therefore important for correct replacement therapy and genetic counseling.
8-Cl-Adenosine Inhibits Proliferation and Causes Apoptosis in B-Lymphocytes via Protein Kinase A-Dependent and Independent Effects: Implications for Treatment of Carney Complex-Associated Tumors
Authors: Robinson-White Audrey J. , Bossis Ioannis , Hsiao Hui-Pin , Nesterova Maria , Leitner Wolfgang W. , Stratakis Constantine A.
Published: September 2009

Context: Carney complex, a multiple neoplasia syndrome, characterized primarily by spotty skin pigmentation and a variety of endocrine and other tumors, is caused by mutations in PRKAR1A, the gene that codes for the RIα subunit of protein kinase A (PKA). PKA controls cell proliferation in many cell types. The cAMP analogue 8-Cl-adenosine (8-Cl-ADO) is thought to inhibit cancer cell proliferation.

Objective: The objective of the study was to study the antiproliferative effects of 8-Cl-ADO on growth and proliferation in B-lymphocytes of Carney complex patients that have PKA defects and to determine whether 8-CL-ADO could be used as a therapeutic agent in the treatment of Carney complex-associated tumors.

Design: We used a multiparametric approach (i.e. growth and proliferation assays, PKA, and PKA subunit assays, cAMP and 3H-cAMP binding assays, and apoptosis assays) to understand the growth and proliferative effects of 8-Cl-ADO on human B-lymphocytes.

Results: 8-Cl-ADO inhibited proliferation, mainly through its intracellular transport and metabolism, which induced apoptosis. PKA activity, cAMP levels, and 3H-cAMP binding were increased or decreased, respectively, by 8-Cl-ADO, whereas PKA subunit levels were differentially affected. 8-Cl-ADO also inhibited proliferation induced by G protein-coupled receptors for isoproterenol and adenosine, as well as proliferation induced by tyrosine kinase receptors.

Conclusions: 8-Cl-ADO in addition to unambiguously inhibiting proliferation and inducing apoptosis in a PKA-independent manner also has PKA-dependent effects that are unmasked by a mutant PRKAR1A. Thus, 8-Cl-ADO could serve as a therapeutic agent in patients with Carney complex-related tumors.

8-Cl-adenosine inhibits cancer cell proliferation, and induces apoptosis in B lymphocytes of Carney complex patients by PKA-independent and dependent effects that are unmasked by a mutant PRKAR1A.
Dual modes of rabies P-protein association with microtubules: a novel strategy to suppress the antiviral response
Authors: Moseley Gregory W. , Lahaye Xavier , Roth Daniela M. , Oksayan Sibil , Filmer Richard P. , Rowe Caitlin L. , Blondel Danielle , Jans David A.
Published: September 2009

Conventional nuclear import is independent of the cytoskeleton, but recent data have shown that the import of specific proteins can be either facilitated or inhibited by microtubules (MTs). Nuclear import of the P-protein from rabies virus involves a MT-facilitated mechanism, but here, we show that P-protein is unique in that it also undergoes MT-inhibited import, with the mode of MT-interaction being regulated by the oligomeric state of the P-protein. This is the first demonstration that a protein can utilise both MT-inhibited and MT-facilitated import mechanisms, and can switch between these different modes of MT interaction to regulate its nuclear trafficking. Importantly, we show that the P-protein exploits MT-dependent mechanisms to manipulate host cell processes by switching the import of the interferon-activated transcription factor STAT1 from a conventional to a MT-inhibited mechanism. This prevents STAT1 nuclear import and signalling in response to interferon, which is vital to the host innate antiviral response. This is the first report of MT involvement in the viral subversion of interferon signalling that is central to virus pathogenicity, and identifies novel targets for the development of antiviral drugs or attenuated viruses for vaccine applications.
Nuclear signaling by the APP intracellular domain occurs predominantly through the amyloidogenic processing pathway
Authors: Goodger Zoë V. , Rajendran Lawrence , Trutzel Annette , Kohli Bernhard M. , Nitsch Roger M. , Konietzko Uwe
Published: September 2009

Proteolytic processing of the amyloid precursor protein (APP) occurs via two alternative pathways, localized to different subcellular compartments, which result in functionally distinct outcomes. Cleavage by a β-γ sequence generates the Aβ peptide that plays a central role in Alzheimer's disease. In the case of α-γ cleavage, a secreted neurotrophic molecule is generated and the Aβ peptide cleaved and destroyed. In both cases, a cytosolic APP intracellular domain (AICD) is generated. We have previously shown that coexpression of APP with the APP-binding protein Fe65 and the histone acetyltransferase Tip60 results in the formation of nuclear complexes (termed AFT complexes), which localize to transcription sites. We now show that blocking endocytosis or the pharmacological or genetic inhibition of the endosomal β-cleavage pathway reduces translocation of AICD to these nuclear AFT complexes. AICD signaling further depends on active transport along microtubules and can be modulated by interference with both anterograde and retrograde transport systems. Nuclear signaling by endogenous AICD in primary neurons could similarly be blocked by inhibiting β-cleavage but not by α-cleavage inhibition. This suggests that amyloidogenic cleavage, despite representing the minor cleavage pathway of APP, is predominantly responsible for AICD-mediated nuclear signaling.
The nuclear periphery of embryonic stem cells is a transcriptionally permissive and repressive compartment
Authors: Luo Li , Gassman Katherine L. , Petell Lydia M. , Wilson Christian L. , Bewersdorf Joerg , Shopland Lindsay S.
Published: September 2009

Chromatin adapts a distinct structure and epigenetic state in embryonic stem cells (ESCs), but how chromatin is three-dimensionally organized within the ESC nucleus is poorly understood. Because nuclear location can influence gene expression, we examined the nuclear distributions of chromatin with key epigenetic marks in ESC nuclei. We focused on chromatin at the nuclear periphery, a compartment that represses some but not all associated genes and accumulates facultative heterochromatin in differentiated cells. Using a quantitative, cytological approach, we measured the nuclear distributions of genes in undifferentiated mouse ESCs according to epigenetic state and transcriptional activity. We found that trimethyl histone H3 lysine 27 (H3K27-Me3), which marks repressed gene promoters, is enriched at the ESC nuclear periphery. In addition, this compartment contains 10-15% of chromatin with active epigenetic marks and hundreds of transcription sites. Surprisingly, comparisons with differentiated cell types revealed similar nuclear distributions of active chromatin. By contrast, H3K27-Me3 was less concentrated at the nuclear peripheries of differentiated cells. These findings demonstrate that the nuclear periphery is an epigenetically dynamic compartment that might be distinctly marked in pluripotent ESCs. In addition, our data indicate that the nuclear peripheries of multiple cell types can contain a significant fraction of both active and repressed genes.
Tunnel Vision: Local Behavioral Influences on Consumer Decisions in Product Search
Authors: Häubl Gerald , Dellaert Benedict G. C. , Donkers Bas
Published: September 2009

We introduce and test a behavioral model of consumer product search that extends a baseline normative model of sequential search by incorporating nonnormative influences that are local in the sense that they reflect consumers' undue sensitivity to recently encountered alternatives. We propose two types of such local behavioral influences that, at each stage of a search process, can manifest themselves both in which of the products inspected up to that point is deemed to be the most preferred one (the product comparison decision) and whether to terminate the search at that stage (the stopping decision). The first of these influences is that consumers respond excessively to the attractiveness of the currently inspected product, at the expense of all others (“focalism”). The second proposed behavioral influence is that consumers overreact to the difference in attractiveness between the current product and the one encountered just prior to it (“local contrast”). Converging evidence from two experiments, which combine to guarantee both high internal and high external validity, provides support for the proposed behavioral influences. Our findings demonstrate that consumers' product comparison and stopping decisions in sequential product search are jointly governed by normative principles and by the proposed local behavioral influences.
Psychosocial safety climate as a precursor to conducive work environments, psychological health problems, and employee engagement
Authors: Dollard Maureen F. , Bakker Arnold B.
Published: September 2009

We constructed a model of workplace psychosocial safety climate (PSC) to explain the origins of job demands and resources, worker psychological health, and employee engagement. PSC refers to policies, practices, and procedures for the protection of worker psychological health and safety. Using the job demands–resources framework, we hypothesized that PSC as an upstream organizational resource influenced largely by senior management, would precede the work context (i.e., job demands and resources) and would in turn predict psychological health and work engagement via mediation and moderation pathways. We operationalized PSC at the school level and tested meso‐mediational models using two‐level (longitudinal) hierarchical linear modelling in a sample of Australian education workers (N = 209–288). Data were repeated measures separated by 12 months, nested within 18 schools. PSC predicted change in individual psychological health problems (psychological distress, emotional exhaustion) through its relationship with individual job demands (work pressure and emotional demands). PSC moderated the relationship between emotional demands and emotional exhaustion. PSC predicted change in employee engagement, through its relationship with skill discretion. The results show that the PSC construct is a key upstream component of work stress theory and a logical intervention site for work stress intervention.
The impact of reemployment on access to the latent and manifest benefits of employment and mental health
Authors: Hoare P. Nancey , Machin M. Anthony
Published: September 2009

This study focused on the impact of reemployment on access to both the latent and manifest benefits of employment, and mental health. Existing theories predicted that reemployment would positively affect these variables. One hundred and fifteen unemployed participants in South East Queensland, Australia, completed two paper‐and‐pencil surveys administered 6 months apart that included measures of financial hardship, financial strain, access to the latent benefits (collective purpose, social contact, status, activity, and time structure), and mental health (as measured by the 12‐item General Health Questionnaire). Participants who gained employment (N = 58) were better off financially, reported greater access to social contact and time structure and had significant improvements in their mental health at Time 2. Participants who remained unemployed showed no change over time. Whilst these results highlight that there is a strong positive impact of reemployment, it is acknowledged that the picture is much more complex than what we have reported here. We recommend that structured programmes be available before unemployment is experienced, particularly those that have a beneficial preventive effect on mental health among those participants most at risk of psychological disorders.
Genome-wide expression analyses establish dendritic cells as a new osteoclast precursor able to generate bone-resorbing cells more efficiently than monocytes
Authors: Gallois A , Lachuer J , Yvert G , Wierinckx A , Brunet F , Rabourdin-Combe C , Delprat C , Jurdic P , Mazzorana M
Published: September 2009

Dendritic cells (DCs), mononuclear cells that initiate immune responses, and osteoclasts (OCs), multinucleated bone-resorbing cells, are hematopoietic cells derived from monocytic precursor cells. Using in vitro generated dendritic cells, we previously showed that human and murine DCs could transdifferentiate into resorbing osteoclasts in the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). In this study we globally compared by transcriptomic profiling this new osteoclast differentiation pathway from DCs with the canonical differentiation pathway from monocytes. DNA chip data revealed that starting from two very distinct cell types, treatment with M-CSF and RANKL generated two highly similar types of osteoclast. In particular, DC-derived osteoclasts expressed all the characteristic marker genes of monocyte-derived osteoclasts. Two major molecular events could be observed during osteoclastogenesis: downregulation of a large set of monocyte or DC specific markers, together with upregulation of characteristic osteoclast marker genes. Most interestingly, our transcriptomic data showed a closer molecular profile between DCs and OCs than between monocytes and OCs. Our data establish DCs as a new osteoclast precursor able to generate OCs more efficiently than monocytes. © 2010 American Society for Bone and Mineral Research.
Graphic designers' activities during the conceptual design phase of client-initiated projects
Authors: Tan Stella , Melles Gavin , Lee Nicolette
Published: September 2009

This paper outlines a study investigating the strategies and activities undertaken by mid-weight graphic designers during the conceptual design phase of client-initiated projects. Descriptions of design activities in the literature are most often derived from disciplines such as architecture,
and product engineering. More abstract approaches, which describe graphic design as undefinable or a linear step process do not address professional design as a situated practice. While these studies are informative, they are also limited, as they are not based on the specific nature of practice
in graphic design. The aim of the study presented in this paper was to understand graphic design practice through the investigation of the activities and strategies undertaken by working mid-weight graphic designers. Specifically, it considers the tool-mediated activities of designers as a
situated practice during the conceptual stage of designing for client-initiated projects. Employing ethnographic methods, three cases were investigated, in order to generate a thick description of these design processes.
Does the Middle Temporal Area Carry Vestibular Signals Related to Self-Motion?
Authors: Chowdhury Syed A. , Takahashi Katsumasa , DeAngelis Gregory C. , Angelaki Dora E.
Published: September 2009

Recent studies have described vestibular responses in the dorsal medial superior temporal area (MSTd), a region of extrastriate visual cortex thought to be involved in self-motion perception. The pathways by which vestibular signals are conveyed to area MSTd are currently unclear, and one possibility is that vestibular signals are already present in areas that are known to provide visual inputs to MSTd. Thus, we examined whether selective vestibular responses are exhibited by single neurons in the middle temporal area (MT), a visual motion-sensitive region that projects heavily to area MSTd. We compared responses in MT and MSTd to three-dimensional rotational and translational stimuli that were either presented using a motion platform (vestibular condition) or simulated using optic flow (visual condition). When monkeys fixated a visual target generated by a projector, half of MT cells (and most MSTd neurons) showed significant tuning during the vestibular rotation condition. However, when the fixation target was generated by a laser in a dark room, most MT neurons lost their vestibular tuning whereas most MSTd neurons retained their selectivity. Similar results were obtained for free viewing in darkness. Our findings indicate that MT neurons do not show genuine vestibular responses to self-motion; rather, their tuning in the vestibular rotation condition can be explained by retinal slip due to a residual vestibulo-ocular reflex. Thus, the robust vestibular signals observed in area MSTd do not arise through inputs from area MT.
The Neural Network for Chemotaxis to Tastants in Caenorhabditis elegans Is Specialized for Temporal Differentiation
Authors: Thiele Tod R. , Faumont Serge , Lockery Shawn R.
Published: September 2009

Chemotaxis inCaenorhabditis elegansdepends critically on the rate of change of attractant concentration computed as the worm moves through its environment. This computation depends, in turn, on the neuron class ASE, a left–right pair of pair of chemosensory neurons that is functionally asymmetric such that the left neuron is an on-cell, whereas the right neuron is an off-cell. To determine whether this coding strategy is a general feature of chemosensation inC. elegans, we imaged calcium responses in all chemosensory neurons known or in a position to contribute to chemotaxis to tastants in this organism. This survey revealed one new class of on-cells (ADF) and one new class of off-cells (ASH). Thus, the ASE class is unique in having both an on-cell and an off-cell. We also found that the newly characterized on-cells and off-cells promote runs and turns, respectively, mirroring the pattern reported previously for ASEL and ASER. Our results suggest that theC. eleganschemotaxis network is specialized for the temporal differentiation of chemosensory inputs, as required for chemotaxis.
Laminin Alters Fyn Regulatory Mechanisms and Promotes Oligodendrocyte Development
Authors: Relucio Jenne , Tzvetanova Iva D. , Ao Wei , Lindquist Sabine , Colognato Holly
Published: September 2009

Mutations inLAMA2, the gene for the extracellular matrix protein laminin-α2, cause a severe muscular dystrophy termed congenital muscular dystrophy type-1A (MDC1A). MDC1A patients have accompanying CNS neural dysplasias and white matter abnormalities for which the underlying mechanisms remain unknown. Here, we report that in laminin-deficient mice, oligodendrocyte development was delayed such that oligodendrocyte progenitors accumulated inappropriately in adult brains. Conversely, laminin substrates were found to promote the transition of oligodendrocyte progenitors to newly formed oligodendrocytes. Laminin-enhanced differentiation was Src family kinase-dependent and resulted in the activation of the Src family kinase Fyn. In laminin-deficient brains, however, increased Fyn repression was accompanied by elevated levels of the Src family kinase negative regulatory proteins, Csk (C-terminal Src kinase), and its transmembrane adaptor, Cbp (Csk-binding protein). These findings indicate that laminin deficiencies delay oligodendrocyte maturation by causing dysregulation of signaling pathways critical for oligodendrocyte development, and suggest that a normal role for CNS laminin is to promote the development of oligodendrocyte progenitors into myelin-forming oligodendrocytes via modulation of Fyn regulatory molecules.
Discharge Profiles of Identified GABAergic in Comparison to Cholinergic and Putative Glutamatergic Basal Forebrain Neurons across the Sleep–Wake Cycle
Authors: Hassani Oum Kaltoum , Lee Maan Gee , Henny Pablo , Jones Barbara E.
Published: September 2009

Whereas basal forebrain (BF) cholinergic neurons are known to participate in processes of cortical activation during wake (W) and paradoxical sleep (PS or P, also called REM sleep), codistributed GABAergic neurons have been thought to participate in processes of cortical deactivation and slow-wave sleep (SWS or S). To learn the roles the GABAergic neurons might play, in relation to cholinergic and glutamatergic neurons, we juxtacellularly recorded and labeled neurons during natural sleep–wake states in head-fixed rats. Neurobiotin (Nb)-labeled cells were identified immunohistochemically as choline acetyltransferase (ChAT)+, glutamic acid decarboxylase (GAD)+, or ChAT−/GAD−. Of the latter, some were identified as glutamatergic by immunostaining of their terminals with the vesicular glutamate transporter (VGluT2). In contrast to ChAT+ neurons, which all discharged maximally during W and PS, GAD+ neurons comprised multiple sleep–wake subgroups. Some GABAergic neurons discharged maximally during W and PS, as WP-max active cells (36%), and in positive correlation with gamma electroencephalographic (EEG) activity. Some discharged maximally during SWS, as S-max active cells (28%), and in positive correlation with delta EEG activity. Others increased their discharge progressively during sleep to discharge maximally during PS, as P-max active cells (36%), and in negative association with electromyographic (EMG) activity. ChAT−/GAD− cells comprised WP-max (46%), S-max (17%), P-max (17%), and W-max active cells (14%), whose discharge was positively correlated with EMG activity. GABAergic neurons would thus play similar or reciprocal roles to other cholinergic and glutamatergic BF neurons in regulating cortical activity and muscle tone along with behavior across sleep–wake states.
Transformation of Polarized Light Information in the Central Complex of the Locust
Authors: Heinze Stanley , Gotthardt Sascha , Homberg Uwe
Published: September 2009

Many insects perceive theE-vector orientation of polarized skylight and use it for compass navigation. In locusts, polarized light is detected by photoreceptors of the dorsal rim area of the eye. Polarized light signals from both eyes are integrated in the central complex (CC), a group of neuropils in the center of the brain. Thirteen types of CC neuron are sensitive to dorsally presented, polarized light (POL-neurons). These neurons interconnect the subdivisions of the CC, particularly the protocerebral bridge (PB), the upper and lower divisions of the central body (CBU, CBL), and the adjacent lateral accessory lobes (LALs). All POL-neurons show polarization-opponency, i.e., receive excitatory and inhibitory input at orthogonalE-vector orientations. To provide physiological evidence for the direction of information flow through the polarization vision network in the CC, we analyzed the functional properties of the different cell types through intracellular recordings. Tangential neurons of the CBL showed highest signal-to-noise ratio, received either ipsilateral polarized-light input only or, together with CL1 columnar neurons, had eccentric receptive fields. Bilateral polarized-light inputs with zenith-centered receptive fields were found in tangential neurons of the PB and in columnar neurons projecting to the LALs. Together with other physiological parameters, these data suggest a flow of information from the CBL (input) to the PB and from here to the LALs (output). This scheme is supported by anatomical data and suggests transformation of purely sensoryE-vector coding at the CC input stage to position-invariant coding of 360°-compass directions at the output stage.
NMDA Receptor Phosphorylation at a Site Affected in Schizophrenia Controls Synaptic and Behavioral Plasticity
Authors: Li Bo , Devidze Nino , Barengolts Denis , Prostak Naseem , Sphicas Eleana , Apicella Alfonso J. , Malinow Roberto , Emamian Effat S.
Published: September 2009

Phosphorylation of the NR1 subunit of NMDA receptors (NMDARs) at serine (S) 897 is markedly reduced in schizophrenia patients. However, the role of NR1 S897 phosphorylation in normal synaptic function and adaptive behaviors are unknown. To address these questions, we generated mice in which the NR1 S897 is replaced with alanine (A). This knock-in mutation causes severe impairment in NMDAR synaptic incorporation and NMDAR-mediated synaptic transmission. Furthermore, the phosphomutant animals have reduced AMPA receptor (AMPAR)-mediated synaptic transmission, decreased AMPAR GluR1 subunit in the synapse, and impaired long-term potentiation. Finally, the mutant mice exhibit behavioral deficits in social interaction and sensorimotor gating. Our results suggest that an impairment in NR1 phosphorylation leads to glutamatergic hypofunction that can contribute to behavioral deficits associated with psychiatric disorders.
A Novel Postsynaptic Group II Metabotropic Glutamate Receptor Role in Modulating Baroreceptor Signal Transmission
Authors: Sekizawa Shin-ichi , Bechtold Andrea G. , Tham Rick C. , Bonham Ann C.
Published: September 2009

The nucleus tractus solitarius (NTS) is essential for orchestrating baroreflex control of blood pressure. When a change in blood pressure occurs, the information is transmitted by baroreceptor afferent fibers to the central network by glutamate binding to ionotropic glutamate receptors on second-order baroreceptor neurons. Glutamate also activates presynaptic group II and III metabotropic glutamate receptors (mGluRs), depressing both glutamate and GABA release to modulate baroreceptor signal transmission. Here we present a novel role for postsynaptic group II mGluRs to further fine-tune baroreceptor signal transmission at the first central synapses. In a brainstem slice with ionotropic glutamate and GABA receptors blocked, whole-cell patch-clamp recordings of second-order baroreceptor neurons revealed that two group II mGluR agonists evoked concentration-dependent membrane hyperpolarizations. The hyperpolarization remained when a presynaptic contribution was prevented with Cd2+, was blocked by a postsynaptic intervention of intracellular dialysis of the G-protein signaling inhibitor, was mimicked by endogenous release of glutamate by tractus solitarius stimulation, and was prevented by a group II mGluR antagonist. Postsynaptic localization of group II mGluRs was confirmed by fluorescent confocal immunohistochemistry and light microscopy. Group II mGluR induced-currents consisted of voltage-dependent outward and inward components, prevented by tetraethylammonium chloride and tetrodotoxin, respectively. In contrast to group II mGluR-induced hyperpolarization, there was no effect on intrinsic excitability as determined by action potential shape or firing in response to depolarizing current injections. The data suggest a novel mechanism for postsynaptic group II mGluRs to fine-tune baroreceptor signal transmission in the NTS.
Parallel Preoptic Pathways for Thermoregulation
Authors: Yoshida Kyoko , Li Xiaodong , Cano Georgina , Lazarus Michael , Saper Clifford B.
Published: September 2009

Sympathetic premotor neurons in the rostral medullary raphe (RMR) regulate heat conservation by tail artery vasoconstriction and brown adipose tissue thermogenesis. These neurons are a critical relay in the pathway that increases body temperature. However, the origins of the inputs that activate the RMR during cold exposure have not been definitively identified. We investigated the afferents to the RMR that were activated during cold by examining Fos expression in retrogradely labeled neurons after injection of cholera toxin B subunit (CTb) in the RMR. These experiments identified a cluster of Fos-positive neurons in the dorsomedial hypothalamic nucleus and dorsal hypothalamic area (DMH/DHA) with projections to the RMR that may mediate cold-induced elevation of body temperature. Also, neurons in the median preoptic nucleus (MnPO) and dorsolateral preoptic area (DLPO) and in the A7 noradrenergic cell group were retrogradely labeled but lacked Fos expression, suggesting that they may inhibit the RMR. To investigate whether individual or common preoptic neurons project to the RMR and DMH/DHA, we injected CTb into the RMR and Fluorogold into the DMH/DHA. We found that projections from the DLPO and MnPO to the RMR and DMH/DHA emerge from largely separate neuronal populations, indicating they may be differentially regulated. Combined cell-specific lesions of MnPO and DLPO, but not lesions of either one alone, caused baseline hyperthermia. Our data suggest that the MnPO and DLPO provide parallel inhibitory pathways that tonically inhibit the DMH/DHA and the RMR at baseline, and that hyperthermia requires the release of this inhibition from both nuclei.