bluuebunny/crossref_metadata_2025_split huggingface dataset:
DEADSouth protein localizes to germ plasm and is required for the development of primordial germ cells in Xenopus laevis
Authors: Yamaguchi Takeshi , Taguchi Ayaka , Watanabe Kenji , Orii Hidefumi 
Published: December 2012

Summary
DEADSouth mRNA is a component of germ plasm in Xenopus laevis and encodes a DDX25 DEAD-box RNA helicase. To determine the intracellular localization of DEADSouth protein, we injected mRNA encoding DEADSouth tagged with mCherry fluorescent protein into fertilized eggs from transgenic Xenopus expressing EGFP fused with a mitochondrial targeting signal. The DEADSouth-mCherry fusion protein was localized to the germ plasm, a mitochondria-rich region in primordial germ cells (PGCs). DEADSouth overexpression resulted in a reduction of PGC numbers after stage 20. Conversely, DEADSouth knockdown using an antisense locked nucleic acid gapmer inhibited movement of the germ plasm from the cortex to the perinuclear region, resulting in inhibition of PGC division at stage 12 and a decrease in PGC numbers at later stages. The knockdown phenotype was rescued by intact DEADSouth mRNA, but not mutant mRNA encoding inactive DEADSouth helicase. Surprisingly, it was also rescued by mouse vasa homolog and Xenopus vasa-like gene 1 mRNAs that encode DDX4 RNA helicases. The rescue was dependent on the 3′ untranslated region (3′UTR) of DEADSouth mRNA, which was used for PGC-specific expression. The 3′UTR contributed to localization of the injected mRNA to the germ plasm, resulting in effective localization of DEADSouth protein. These results demonstrate that localization of DEADSouth helicase to the germ plasm is required for proper PGC development in Xenopus laevis.
Ciliated sensory hair cell formation and function require the F-BAR protein syndapin I and the WH2 domain-based actin nucleator Cobl
Authors: Schüler Susann , Hauptmann Judith , Perner Birgit , Kessels Michael M. , Englert Christoph , Qualmann Britta 
Published: December 2012

Summary
During development, general body plan information must be translated into distinct morphologies of individual cells. Shaping cells is thought to involve cortical cytoskeletal components and Bin-Amphiphysin-Rvs167 (BAR) superfamily proteins. We therefore conducted comprehensive side-by-side loss-of-function studies of zebrafish orthologs of the F-BAR protein syndapin I and the actin nucleator Cobl. Zebrafish syndapin I associates with Cobl. The loss-of-function phenotypes of these proteins were remarkably similar and suggested a common function. Both cobl- and syndapin I-morphant fish showed severe swimming and balance-keeping defects, reflecting an impaired organization and function of the lateral line organ. Their lateral line organs lacked several neuromasts and showed an impaired functionality of the sensory hair cells within the neuromasts. Scanning electron microscopy revealed that sensory hair cells of both cobl- and syndapin I-morphant animals showed defects in the formation of both microtubule-dependent kinocilia and F-actin-rich stereocilia. Consistent with the kinocilia defects in sensory hair cells, body length was shortened and the development of body laterality, a process depending on motile cilia, was also impaired. Interestingly, Cobl and syndapin I both localized to the base of forming cilia. Rescue experiments demonstrated that proper formation of ciliated sensory hair cell rosettes relied on Cobl's syndapin I-binding Cobl homology domain, the actin-nucleating C-terminus of Cobl and the membrane curvature-inducing F-BAR domain of syndapin I. Our data thus suggest that the formation of distinct types of ciliary structures relies on membrane topology-modulating mechanisms that are based on F-BAR domain functions and on complex formation of syndapin I with the actin nucleator Cobl.
Get3 is a holdase chaperone and moves to deposition sites for aggregated proteins when membrane targeting is blocked
Authors: Powis Katie , Schrul Bianca , Tienson Heather , Gostimskaya Irina , Breker Michal , High Stephen , Schuldiner Maya , Jakob Ursula , Schwappach Blanche 
Published: December 2012

Summary
The endomembrane system of yeast contains different tail-anchored proteins that are post-translationally targeted to membranes via their C-terminal transmembrane domain. This hydrophobic segment could be hazardous in the cytosol if membrane insertion fails, resulting in the need for energy-dependent chaperoning and the degradation of aggregated tail-anchored proteins. A cascade of GET proteins cooperates in a conserved pathway to accept newly synthesized tail-anchored proteins from ribosomes and guide them to a receptor at the endoplasmic reticulum, where membrane integration takes place. It is, however, unclear how the GET system reacts to conditions of energy depletion that might prevent membrane insertion and hence lead to the accumulation of hydrophobic proteins in the cytosol. Here we show that the ATPase Get3, which accommodates the hydrophobic tail anchor of clients, has a dual function: promoting tail-anchored protein insertion when glucose is abundant and serving as an ATP-independent holdase chaperone during energy depletion. Like the generic chaperones Hsp42, Ssa2, Sis1 and Hsp104, we found that Get3 moves reversibly to deposition sites for protein aggregates, hence supporting the sequestration of tail-anchored proteins under conditions that prevent tail-anchored protein insertion. Our findings support a ubiquitous role for the cytosolic GET complex as a triaging platform involved in cellular proteostasis.
Actin-regulated feedback loop based on Phactr4, PP1 and cofilin maintains the actin monomer pool
Authors: Huet Guillaume , Rajakylä Eeva Kaisa , Viita Tiina , Skarp Kari-Pekka , Crivaro Marko , Dopie Joseph , Vartiainen Maria K. 
Published: December 2012

Summary
Phactr proteins bind actin and protein phosphatase 1 (PP1), and are involved in processes ranging from angiogenesis to cell cycle regulation. Phactrs share a highly conserved RPEL domain with the myocardin-related transcription factor (MRTF) family, where actin binding to this domain regulates both the nuclear localization and the activity of these transcription coactivators. We show here that in contrast to MRTF-A, the RPEL domain is dispensable for the subcellular localization of Phactr4. Instead, we find the domain facilitating competitive binding of monomeric actin and PP1 to Phactr4. Binding of actin to Phactr4 influences the activity of PP1 and the phosphorylation status of one of its downstream targets, cofilin. Consequently, at low actin monomer levels, Phactr4 guides PP1 to dephosphorylate cofilin. This active form of cofilin is then able to sever and depolymerize actin filaments and thus restore the actin monomer pool. Accordingly, our data discloses the central role of Phactr4 in a feedback loop, where actin monomers regulate their own number via the activation of a key regulator of actin dynamics. Depending on the protein context, the RPEL domain can thus elicit mechanistically different responses to maintain the cellular actin balance.
In tight junctions, claudins regulate the interactions between occludin, tricellulin and marvelD3, which, inversely, modulate claudin oligomerization
Authors: Cording Jimmi , Berg Johanna , Käding Nadja , Bellmann Christian , Tscheik Christian , Westphal Julie K. , Milatz Susanne , Günzel Dorothee , Wolburg Hartwig , Piontek Jörg , Huber Otmar , Blasig Ingolf Ernst 
Published: December 2012

Summary
Tight junctions seal the paracellular cleft of epithelia and endothelia, form vital barriers between tissue compartments and consist of tight-junction-associated marvel proteins (TAMPs) and claudins. The function of TAMPs and the interaction with claudins are not understood. We therefore investigated the binding between the TAMPs occludin, tricellulin, and marvelD3 and their interaction with claudins in living tight-junction-free human embryonic kidney-293 cells. In contrast to claudins and occludin, tricellulin and marvelD3 showed no enrichment at cell–cell contacts indicating lack of homophilic trans-interaction between two opposing cell membranes. However, occludin, marvelD3 and tricellulin exhibited homophilic cis-interactions, along one plasma membrane, as measured by fluorescence resonance energy transfer. MarvelD3 also cis-interacted with occludin and tricellulin heterophilically. Classic claudins, such as claudin-1 to -5 may show cis-oligomerization with TAMPs, whereas the non-classic claudin-11 did not. Claudin-1 and -5 improved enrichment of occludin and tricellulin at cell–cell contacts. The low mobile claudin-1 reduced the membrane mobility of the highly mobile occludin and tricellulin, as studied by fluorescence recovery after photobleaching. Co-transfection of claudin-1 with TAMPs led to changes of the tight junction strand network of this claudin to a more physiological morphology, depicted by freeze-fracture electron microscopy. The results demonstrate multilateral interactions between the tight junction proteins, in which claudins determine the function of TAMPs and vice versa, and provide deeper insights into the tight junction assembly.
Plexin B1 inhibits MET through direct association and regulates Shp2 expression in melanocytes
Authors: Soong Joanne , Scott Glynis 
Published: December 2012

Summary
Plexin B1, the receptor for Semaphorin 4D (Sema4D), is expressed by melanocytes in the skin. We recently showed that Sema4D suppresses activation of the hepatocyte growth factor receptor, MET, in melanocytes, and that knockdown of Plexin B1 results in activation of MET. MET signaling mediates proliferation, survival and migration in melanocytes, and its activation is associated with transformation of melanocytes to melanoma. In this report we investigated the mechanism by which Plexin B1 inhibits MET activation. Our results show that Plexin B1 and MET exist as an oligomeric receptor-receptor complex in melanocytes, and that receptor association is increased by Sema4D. MET and Plexin B1 receptor complexes were identified along the cell body of melanocytes, and Sema4D increased receptor association on dendrites, suggesting that Sema4D regulates MET-dependent processes at precise locations on the melanocyte. Despite activation of MET, Plexin B1 knockdowns proliferated slowly and showed increased apoptosis compared with controls. Shp2, a non-receptor protein tyrosine phosphatase, translates growth and survival signals from MET and other receptor tyrosine kinases. Plexin B1 knockdowns had markedly lower levels of Shp2 compared with controls, and Sema4D upregulated Shp2 expression at the protein and message level in normal melanocytes. Functional studies showed that blockade of Shp2 activity abrogated MET-dependent activation of Erk1/Erk2 and Akt in melanocytes. These results suggest a complex role for Sema4D and Plexin B1 in orchestrating signaling from the MET receptor in melanocytes. Because Shp2 is a downstream adaptor protein for multiple receptors, Sema4D may control the effects of several growth factors on melanocytes through regulation of Shp2.
Role of Ser129 phosphorylation of α-synuclein in melanoma cells
Authors: Lee Byung Rho , Matsuo Yasuhiro , Cashikar Anil G. , Kamitani Tetsu 
Published: December 2012

Summaryα-Synuclein, a protein central to Parkinson's disease, is frequently expressed in melanoma tissues, but not in non-melanocytic cutaneous carcinoma and normal skin. Thus, α-synuclein is not only related to Parkinson's disease, but also to melanoma. Recently, epidemiologists reported co-occurrence of melanoma and Parkinson's disease in patients, suggesting that these diseases could share common pathogenetic components and that α-synuclein might be one of these. In Parkinson's disease, phosphorylation of α-synuclein at Ser129 plays an important role in the pathobiology. However, its role in melanoma is not known. Here, we show the biological relevance of Ser129 phosphorylation in human melanoma cells. First, we have identified an antibody that reacts with Ser129-unphosphorylated α-synuclein but not with Ser129-phosphorylated α-synuclein. Using this and other antibodies to α-synuclein, we investigated the role of Ser129 phosphorylation in human melanoma SK-MEL28 and SK-MEL5 cells. Our immunofluorescence microscopy showed that the Ser129-phosphorylated form, but not the Ser129-unphosphorylated form, of α-synuclein localizes to dot-like structures at the cell surface and the extracellular space. Furthermore, immuno-electron microscopy showed that the melanoma cells release microvesicles in which Ser129-phosphorylated α-synuclein localizes to the vesicular membrane. Taken together, our studies suggest that the phosphorylation of Ser129 leads to the cell surface translocation of α-synuclein along the microtubule network and its subsequent vesicular release in melanoma cells.
Novel Strategies to Test Biological Hypotheses in Early Drug Development for Advanced Prostate Cancer
Authors: Ferraldeschi Roberta , Attard Gerhardt , de Bono Johann S 
Published: December 2012

BACKGROUND
Major advances in our understanding of the underlying biology of prostate cancer have helped to herald a new era in the treatment of castration-resistant prostate cancer (CRPC), with 5 new agents having shown a survival advantage in the last 3 years and an impressive number of promising novel agents now entering the clinic.

CONTENT
We discuss the challenges facing drug development for CRPC and strategies to meet these challenges, with a focus not only on the development of predictive and intermediate endpoint biomarkers, but also on novel hypothesis-testing, biomarker-driven clinical trial designs.

SUMMARY
With several promising agents now entering the clinic, there is increasing pressure to rethink drug development for CRPC to ensure that novel agents are appropriately evaluated and that patients and resources are appropriately allocated. We envision that biomarker-driven, reiterative clinical trials will have a major impact on CRPC treatment through the testing of robust scientific hypotheses with rationally designed drugs and drug combinations administered to selected patients.
Long-term clinical data and molecular defects in the STAR gene in five Greek patients
Authors: Sertedaki Amalia , Dracopoulou Maria , Voutetakis Antonis , Stefanaki Kalliopi , Rontogianni Dimitra , Magiakou Alexandra-Maria , Kanaka-Gantenbein Christina , Chrousos George , Dacou-Voutetakis Catherine 
Published: December 2012

ContextSteroidogenic acute regulatory (STAR) gene mutations lead to adrenal and gonadal failure. Interesting, though as yet unexplained, features are the formation of ovarian cysts and the potential presence of CNS findings.ObjectiveTo report biochemical, genetic, and long-term clinical data in five Greek patients from four different families withSTARgene defects (three 46,XX and two 46,XY).Methods and resultsAll patients presented in early infancy with adrenal insufficiency. TheSTARgene mutation c.834del11bp, detected in three of our patients, completely alters the carboxyl end of the STAR protein and has not thus far been described in other population groups. These three patients belong to three separate families, possibly genetically related, as they live in different villages located in a small region of a Greek island. However, their interrelationship has not been proven. A second mutation, p.W250X, detected in our fourth family, was previously described only in two Serbian patients. Ovarian cysts were detected ultrasonographically in our 46,XX patients and seemed to respond to a low dose of a contraceptive. The histology of an excised ovarian cyst was diagnosed as a corpus luteum (CL) cyst. In two out of the four patients who had undergone brain magnetic resonance imaging, asymptomatic Chiari-1 malformation was observed.ConclusionsThe occurrence ofSTARgene mutation c.834del11bp in three families living in a restricted geographic region could indicate either a founder effect or simply reflect a spread of this defect in a highly related population. The ovarian histological findings suggest that ovarian cysts detected ultrasonographically in 46,XX individuals withSTARgene defects may be CL cysts. The Chiari-1 malformation in two of our patients may be part of theSTARgene mutation phenotype. Nevertheless, more data are needed to confirm or disprove the existence of specific CNS pathology in patients withSTARgene mutations.
Structure characterization of organic-inorganic nanocomposites formed by the sol-gel polycondensation
Authors: Matìjka Libor 
Published: December 2012

AbstractThe organic-inorganic (O-I) hybrid networks were prepared from well-defined O-I precursors (a) alkoxysilane-endcapped oligomers (ASO) and (b) epoxy-functional silsesquioxane (SSQO) clusters (EC). ASO precursors were crosslinked by sol-gel polycondensation and EC by the reaction of the epoxy groups with oligomeric diamine Jeffamine D2000. Formation, structure and mechanical properties of the networks were followed by SEC, NMR, SAXS and DMA. The O-I block copolymer network is composed of SSQO domains forming network junctions linked by an oligomer chain. Structure of the SSQO crosslink “points” ranges from compact polyhedral cages to large loose SSQO clusters in dependence on the precursor type and catalysis of the sol-gel process. Interphase interaction and mechanical properties of the O-I networks are discussed.
Soluble, High Molecular Weight Polysilsesquioxanes with Carboxylate Functionalities
Authors: Rahimian Kamyar , Loy Douglas A. , Wheeler David R. 
Published: December 2012

AbstractHigh molecular weight polysilsesquioxanes with carboxylate functionalities were prepared by sol-gel polymerization of organotrialkoxysilanes bearing tert-butyl ester groups. Trialkoxysilyl-containing monomers of the type (RO)3Si(CH2)3C(O)OtBu (R = Me, Et) were prepared by hydrosilation of the corresponding vinylic tert-butyl esters CH3CHCH2C(O)OtBu. Acid- or base-catalyzed polymerization of the monomers leads to very high molecular weight polymers with relatively narrow polydispersities. The polymerization results in complete condensation of the alkoxy groups while the tert-butyl ester functionality remains fully intact. Partial or full deprotection of the tert-butyl group can easily be achieved to yield the corresponding carboxylic acid polymers. The ester and carboxylic acid functionalities of these new materials allow for their potential use in a variety of applications such as scavenging of heavy metals.
Novel Materials Based on Organic-Tungsten Oxide Hybrid Systems
Authors: Ingham Bridget , Chong Shen V. , Tallon Jeff L. 
Published: December 2012

AbstractThe physical and electronic properties of tungsten oxide and some related hybrid materials have been examined via various spectroscopic techniques and the results complemented by ab initio computation. Hybrid materials based on intercalated straight-chain σ,ω-diaminoalkanes in between sheets of corner-shared tungsten-oxide octahedra exhibit from XRD a linear expansion in the interlayer spacing with increasing number of carbon atoms in the amines. UV-visible diffuse reflectance spectra of several hybrid powders indicate a dominant absorption edge centred at 4.0 eV, with no apparent trend among the different samples as the alkyl chain length changes. This is higher than that of tungsten trioxide powder, which has an absorption edge centred at 2.8 eV. Ab initio calculations show that these experimental values may relate to the indirect band-gap energies of the respective compounds rather than the optical band gap. This was confirmed from the absorption coefficient results of WO3 thin films which yield a strong edge at 4.0 eV. Similar measurements of hybrid films with 1,12-diaminododecane as the organic spacer showed absorption throughout the visible range, with weak features at 4.2 and 4.9 eV.
Methane/water Adsorption Properties of Synthetic Imogolite Nanotubes
Authors: Ohashi Fumihiko , Tomura Shinji , Wada Shin-Ichiro 
Published: December 2012

AbstractAluminosilicate nanotubes (imogolite) have been synthesized from highly concentrated inorganic solutions by hydrothermal treatment. These can be converted to microporous nanofibers with a pore radius in the range of 0.3-0.6 nm referring to the results from the nitrogen adsorption isotherm. The water vapor adsorption isotherms indicated that the natural imogolite plotted a proportional isothermal curve where the amount of adsorbed water increased in proportion to P/P0: the maximum amount of adsorbed water was ca. 60 wt%. The synthetic imogolite showed a rapid increase at 0.9-0.95 range of P/P0 and achieved a maximum of ca. 80 wt%, with a better methane storage property than that of the usual compressed natural gas storage. In order to obtain a high ratio of water adsorption and a large methane storage capacity, it is necessary to control the micro/meso porous structure and the hydrophilic/hydrophobic surface affinity. It is expected that the synthetic imogolite might become a multipurpose adsorbent.
Reverse Micelle Synthesis of Zirconia Powders: The Use of Hydrogen Peroxide as Washing Solvent
Authors: Singh Harpreet , Graeve Olivia A. 
Published: December 2012

AbstractYttria-stabilized zirconia nanopowders were synthesized using AOT/isooctane reverse micelles. XRD results showed that the powders were tetragonal with crystallite sizes ranging between approximately 1-50 nm depending on the thermal treatment given to the powders. BET surface area analysis of the powders gave a specific surface area of 230 m2/g for the assynthesized powders and 19.3 m2/g for the powders treated at 1000°C. This results in equivalent powder particle diameters of 4 nm and 52 nm, respectively. Washing of the powders is a very significant step for successful post-processing of powders obtained by AOT/isooctane reverse micelles. The use of ethanol and dry ether did not remove AOT, as determined from EDS measurements. Subsequent experiments showed that a novel solvent (hydrogen peroxide) was effective in removing AOT from the powders. The reason for the effectiveness of the new solvent is its capacity to decompose the AOT into weak acids, which are easily washed away with deionized water.
Enfants en souffrance, enseignants en difficulté
Authors: Raguideau Maryse 
Published: December 2012

Résumé La scolarisation des enfants avec troubles du comportement relève parfois du parcours du combattant, et la déstabilisation généralisée participe à cette difficulté. Qui sont ces élèves en souffrance qui mettent nos classes à mal ? Il y a des propositions à retenir pour les accompagner, et si elles ne sont pas des solutions en soi, elles n’en sont pas moins incontournables. L’observation fine et dynamique, le travail en équipe et l’alliance éducative avec les parents en font partie.