bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cadherin‐6 function in zebrafish retinal development
Authors: Liu Qin , Londraville Richard , Marrs James A. , Wilson Amy L. , Mbimba Thomas , Murakami Tohru , Kubota Fumitaka , Zheng Weiping , Fatkins David G. 
Published: May 2008

AbstractCadherin cell‐adhesion molecules play crucial roles in vertebrate development including the development of the visual system. Most studies have focused on examining functions of classical type I cadherins (e.g., cadherin‐2) in visual system development. There is little information on the function of classical type II cadherins (e.g., cadherin‐6) in the development of the vertebrate visual system. To gain insight into cadherin‐6 role in the formation of the retina, we analyzed differentiation of retinal ganglion cells (RGCs), amacrine cells, and photoreceptors in zebrafish embryos injected with cadherin‐6 specific antisense morpholino oligonucleotides. Differentiation of the retinal neurons in cadherin‐6 knockdown embryos (cdh6 morphants) was analyzed using multiple markers. We found that expression of transcription factors important for retinal development was greatly reduced, and expression of Notch‐Delta genes and proneural gene ath5 was altered in the cdh6 morphant retina. The retinal lamination was present in the morphants, although the morphant eyes were significantly smaller than control embryos due mainly to decreased cell proliferation. Differentiation of the RGCs, amacrine cells, and photoreceptors was severely disrupted in the cdh6 morphants due to a significant delay in neural differentiation. Our results suggest that cadherin‐6 plays an important role in the normal formation of the zebrafish retina. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008
Breaking the balance: Ocular BDNF‐injections induce visual asymmetry in pigeons
Authors: Manns Martina , Freund Nadja , Leske Oliver , Güntürkün Onur 
Published: May 2008

AbstractIn pigeons, asymmetric photic stimulation around hatch induces functional visual asymmetries that are accompanied by left–right differences in tectal cell sizes. Different aspects of light‐dependent neuronal differentiation are known to be mediated by the brain‐derived neurotrophic factor (BDNF). Therefore, we investigated by means of single or triple BDNF‐ or saline‐injections into the right eye of dark‐incubated pigeon hatchlings if ocular BDNF enrichment mimics the effects of biased visual input. As adults, the birds were tested in a grit–grain discrimination task to estimate the degree and direction of visual lateralization followed by a morphometric analysis of retinal and tectal cells. The grit–grain discrimination task demonstrated that triple BDNF‐injections enhanced visuoperceptual and visuomotor functioning of the left eye system. Morphometric analysis showed bilateral cell‐type dependent effects within the optic tectum. While single‐BDNF injections increased cell body sizes of calbindin‐positive efferent neurons, triple‐injections decreased cell sizes of parvalbumin‐positive cells. Moreover, single BDNF‐injections increased retinal cell sizes within the contralateral eye. Analysis of BDNF‐induced intracellular signaling demonstrated enhanced downstream Ras activation for at least 24 h within both tectal halves whereas activity changes within the contralateral retina could not be detected. This points to primarily tectal effects of ocular BDNF. In sum, exogenous BDNF modulates the differentiation of retinotectal circuitries and dose‐dependently shifts lateralized visuomotor processing towards the noninjected side. Since these effects are opposite to embryonic light stimulation, it is unlikely that the impact of light onto asymmetry formation is mediated by retinal BDNF. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008
Case Study on the Effects of Molecular Structure on the Mode of Polymorphic Transition Inducing Preferential Enrichment
Authors: Horiguchi Masahiro , Yabunaka Shinsuke , Iwama Sekai , Shimano Eiji , Lepp Zsolt , Takahashi Hiroki , Tsue Hirohito , Tamura Rui 
Published: May 2008

AbstractA series of (±)‐N‐{2‐[4‐(2‐hydroxy‐3‐ethoxypropoxy)phenylcarbamoyl]ethyl}‐N‐methylpyrrolidinium p‐halobenzenesulfonates [(±)‐1a–c] were found to cause an unusual symmetry‐breaking enantiomeric resolution phenomenon called preferential enrichment, whereas the N‐methylpiperidinium analogues (±)‐N‐{2‐[4‐(2‐hydroxy‐3‐ethoxypropoxy)phenylcarbamoyl]ethyl}‐N‐methylpiperidinium p‐halobenzenesulfonates [(±)‐2a–c] failed to show this phenomenon. By X‐ray crystallographic and ATR‐FTIR spectroscopic studies, (±)‐1a–c were found to undergo the desired solvent‐assisted solid‐to‐solid polymorphic transition of the first‐formed and metastable γ‐form into the stable δ‐form, which could induce preferential enrichment. In contrast, (±)‐2a–c were subject to the undesired solvent‐mediated polymorphic transition of the γ‐form into the α2‐form, and similarly, (±)‐1d and (±)‐2d bearing a p‐toluenesulfonate ion also showed the undesired solvent‐mediated polymorphic transition of the γ‐form into the β‐form; in these cases, preferential enrichment was not observed. Accordingly, the structure of the cyclic ammonium group as well as the basicity of the p‐substituted benzenesulfonate ion largely affected the mode of the polymorphic transition. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Dynamic Kinetic Resolution of α‐Amino Acid Esters in the Presence of Aldehydes
Authors: Schichl Daniel A. , Enthaler Stephan , Holla Wolfgang , Riermeier Thomas , Kragl Udo , Beller Matthias 
Published: May 2008

AbstractA convenient procedure for the racemization of α‐amino acid esters in the presence of catalytic amounts of salicylaldehydes is described. The combination of this racemization protocol with lipase‐catalyzed ester hydrolysis allows successful dynamic kinetic resolution of various α‐amino acid esters. The corresponding α‐amino acids are obtained in high yield and optical purity.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Synthesis and Structural Characterization of Four Isomers of C70(n‐C3F7)8
Authors: Mutig Tatyana , Kemnitz Erhard , Troyanov Sergey I. 
Published: May 2008

AbstractThe first four isomers of C70(n‐C3F7)8 synthesized by the ampoule reaction of C70 with n‐C3F7I, isolated by HPLC, and characterized by X‐ray crystallography possess unprecedented addition patterns among C70X8 compounds. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Novel regions of acquired uniparental disomy discovered in acute myeloid leukemia
Authors: Gupta Manu , Raghavan Manoj , Gale Rosemary E. , Chelala Claude , Allen Christopher , Molloy Gael , Chaplin Tracy , Linch David C. , Cazier Jean‐Baptiste , Young Bryan D. 
Published: May 2008

AbstractThe acquisition of uniparental disomy (aUPD) in acute myeloid leukemia (AML) results in homozygosity for known gene mutations. Uncovering novel regions of aUPD has the potential to identify previously unknown mutational targets. We therefore aimed to develop a map of the regions of aUPD in AML. Here, we have analyzed a large set of diagnostic AML samples (n = 454) from young adults (age: 15–55 years) using genotype arrays. Acquired UPD was found in 17% of the samples with a nonrandom distribution particularly affecting chromosome arms 13q, 11p, and 11q. Novel recurrent regions of aUPD were uncovered at 2p, 17p, 2q, 17q, 1p, and Xq. Overall, aUPDs were observed across all cytogenetic risk groups, although samples with aUPD13q (5.4% of samples) belonged exclusively to the intermediate‐risk group as defined by cytogenetics. All cases with a high FLT3‐ITD level, measured previously, had aUPD13q covering the FLT3 gene. Significantly, none of the samples with FLT3‐ITD‐/FLT3‐TKD+ mutation exhibited aUPD13q. Of the 119 aUPDs observed, the majority (87%) were due to mitotic recombination while only 13% were due to nondisjunction. This study demonstrates aUPD is a frequent and significant finding in AML and pinpoints regions that may contain novel mutational targets. © 2008 Wiley‐Liss, Inc.
Inactivation of the cystatin E/M tumor suppressor gene in cervical cancer
Authors: Veena Mysore S. , Lee Grant , Keppler Daniel , Mendonca Marc S. , Redpath J. Leslie , Stanbridge Eric J. , Wilczynski Sharon P. , Srivatsan Eri S. 
Published: May 2008

AbstractWe have previously localized a cervical cancer tumor suppressor gene to a 300 kb interval of 11q13. Analysis of candidate genes revealed loss of expression of cystatin E/M, a lysosomal cysteine protease inhibitor, in 6 cervical cancer cell lines and 9 of 11 primary cervical tumors. Examination of the three exons in four cervical cancer cell lines, 19 primary tumors, and 21 normal controls revealed homozygous deletion of exon 1 sequences in one tumor. Point mutations were observed in six other tumors. Two tumors contained mutations at the consensus binding sites for cathepsin L, a lysosomal protease overexpressed in cervical cancer. Introduction of these two point mutations using site directed mutagenesis resulted in reduced binding of mutated cystatin E/M to cathepsin L. Although mutations were not observed in any cell lines, four cell lines and 12 of 18 tumors contained promoter hypermethylation. Reexpression of cystatin E/M was observed after 5′aza 2‐deoxycytidiene and/or Trichostatin A treatment of cervical cancer cell lines, HeLa and SiHa, confirming promoter hypermethylation. Ectopic expression of cystatin E/M in these two cell lines resulted in growth suppression. There was also suppression of soft agar colony formation by HeLa cells expressing the cystatin E/M gene. Reexpression of cystatin E/M resulted in decreased intracellular and extracellular expression of cathepsin L. Overexpression of cathepsin L resulted in increased cell growth which was inhibited by the reintroduction of cystatin E/M. We conclude, therefore, that cystatin E/M is a cervical cancer suppressor gene and that the gene is inactivated by somatic mutations and promoter hypermethylation. © 2008 Wiley‐Liss, Inc.
Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: Potential role in progression
Authors: Scotto Luigi , Narayan Gopeshwar , Nandula Subhadra V. , Arias‐Pulido Hugo , Subramaniyam Shivakumar , Schneider Achim , Kaufmann Andreas M. , Wright Jason D. , Pothuri Bhavana , Mansukhani Mahesh , Murty Vundavalli V. 
Published: May 2008

AbstractRecurrent karyotypic abnormalities are a characteristic feature of cervical cancer (CC) cells, which may result in deregulated expression of important genes that contribute to tumor initiation and progression. To examine the role of gain of the long arm of chromosome 20 (20q), one of the common chromosomal gains in CC, we evaluated CC at various stages of progression using single nucleotide polymorphism (SNP) array, gene expression profiling, and fluorescence in situ hybridization (FISH) analyses. This analysis revealed copy number increase (CNI) of 20q in >50% of invasive CC and identified two focal amplicons at 20q11.2 and 20q13.13 in a subset of tumors. We further demonstrate that the acquisition of 20q gain occurs at an early stage in CC development and the high‐grade squamous intraepithelial lesions (HSIL) that exhibit 20q CNI are associated (P = 0.05) with persistence or progression to invasive cancer. We identified a total of 26 overexpressed genes as consequence of 20q gain (N = 14), as targets of amplicon 1 (N = 9; two genes also commonly expressed with 20q gain) and amplicon 2 (N = 6; one gene also commonly expressed with 20q gain). These include a number of functionally important genes in cell cycle regulation (E2F1, TPX2, KIF3B, PIGT, and B4GALT5), nuclear function (CSEL1), viral replication (PSMA7 and LAMA5), methylation and chromatin remodeling (ASXL1, AHCY, and C20orf20), and transcription regulation (TCEA2). Our findings implicate a role for these genes in CC tumorigenesis, represent an important step toward the development of clinically significant biomarkers, and form a framework for testing as molecular therapeutic targets. © 2008 Wiley‐Liss, Inc.
Duplex architecture and late‐orogenic backthrusting in Foredeep Units of the Northern Apennines (Italy)
Authors: Feroni Andrea Cerrina , Levi Nicola , Ottria Giuseppe 
Published: May 2008

AbstractThe Northern Apennines of Italy is a fold and thrust belt that resulted from the NE‐ward progressive overthrusting of a Mesoalpine stacking (the ocean‐derived Ligurian Units) onto the detached sedimentary cover of the Adria plate continental margin (Foredeep Units). The Futa Pass area represents a key sector for the reconstruction of the deformation history of two Foredeep Units (Acquerino and Carigiola Units). The tectonic evolution of this sector is characterized by the superposition of three main deformation stages, with a constant NNE–SSW compression direction. The oldest structure is represented by the NNE‐verging Acquerino Unit duplex structure, the roof thrust of which is represented by the Ligurian stacking basal thrust. The interpretation of this structure as a large‐scale duplex is supported by the presence in the outer sectors of the Northern Apennines belt of Ligurian Units directly overthrust on younger Foredeep Units. In the second deformation stage the NNE‐verging Tavaiano Thrust developed. This regionally significant tectonic surface juxtaposes the Acquerino Unit (already developed as a duplex) and the overlying Ligurian Units, onto the Carigiola Unit. During this stage the fault pattern of the Carigiola Unit was also developed, characterized by two conjugate fault systems, coherent with a NNE–SSW maximum compression direction. During the last deformation stage, a backthrusting with a top‐to‐the SSW sense of movement (the Marcoiano Backthrust) brings the Carigiola Unit and its tectonic cover over the Acquerino and Ligurian Units, with the development of a large footwall syncline. The deformation history presented here differs from previous studies, and so provides a contribution to the debate on Northern Apennines tectonic evolution. Copyright © 2008 John Wiley & Sons, Ltd.
Inflammatory stress exacerbates lipid accumulation in hepatic cells and fatty livers of apolipoprotein E knockout mice
Authors: Ma Kun L. , Ruan Xiong Z. , Powis Stephen H. , Chen Yaxi , Moorhead John F. , Varghese Zac 
Published: May 2008

Abstract

The prevailing theory in non-alcoholic fatty liver disease (NAFLD) is the “two-hit” hypothesis. The first hit mainly consists of lipid accumulation, and the second is subsequent systemic inflammation. The current study was undertaken to investigate whether inflammatory stress exacerbates lipid accumulation in liver and its underlying mechanisms. We used interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) stimulation in human hepatoblastoma cell line (HepG2) cells and primary hepatocytes

in vitro,

and casein injection in apolipoprotein E knockout mice

in vivo

to induce inflammatory stress. The effects of inflammatory stress on cholesterol accumulation were examined by histochemical staining and a quantitative intracellular cholesterol assay. The gene and protein expressions of molecules involved in cholesterol trafficking were examined by real-time polymerase chain reaction (PCR) and western blot. Cytokine production in the plasma of apolipoprotein E knockout mice was measured by enzyme-linked immunosorbent assay. Our results showed that inflammatory stress increased cholesterol accumulation in hepatic cells and in the livers of apolipoprotein E knockout mice. Further analysis showed that inflammatory stress increased the expression of low-density lipoprotein (LDL) receptor (LDLr), sterol regulatory element–binding protein (SREBP) cleavage activating protein (SCAP), and SREBP-2. Confocal microscopy showed that IL-1β increased the translocation of SCAP/SREBP-2 complex from endoplasmic reticulum (ER) to Golgi in HepG2 cells, thereby activating LDLr gene transcription. IL-1β, TNF-α, and systemic inflammation induced by casein injection also inhibited expression of adenosine triphosphate–binding cassette transporter A1 (ABCA1), peroxisome proliferator-activated receptor-α (PPAR-α), and liver X receptor-α (LXRα). This inhibitory effect may cause cholesterol efflux reduction.

Conclusion

: Inflammatory stress up-regulates LDLr-mediated cholesterol influx and down-regulates ABCA1-mediated cholesterol efflux

in vivo and in vitro

. This may exacerbate the progression of NAFLD by disrupting cholesterol trafficking control, especially during the second hit phase of liver damage. (Hepatology 2008.)
“Toxic memory” via chaperone modification is a potential mechanism for rapid mallory-denk body reinduction
Authors: Strnad Pavel , Tao Guo-Zhong , So Phillip , Lau Kenneth , Schilling Jim , Wei Yuquan , Liao Jian , Omary Bishr M. 
Published: May 2008

Abstract

The cytoplasmic hepatocyte inclusions, Mallory-Denk bodies (MDBs), are characteristic of several liver disorders, including alcoholic and nonalcoholic steatohepatitis. In mice, MDBs can be induced by long-term feeding with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 3 to 4 months or rapidly reformed in DDC-induced then recovered mice by DDC refeeding or exposure to a wide range of toxins for only 5 to 7 days. The molecular basis for such a rapid reinduction of MDBs is unknown. We hypothesized that protein changes retained after DDC priming contribute to the rapid MDB reappearance and associate with MDB formation in general terms. Two-dimensional differential-in-gel-electrophoresis coupled with mass spectrometry were used to characterize protein changes in livers from the various treatment groups. The alterations were assessed by real-time reverse-transcription polymerase chain reaction and confirmed by immunoblotting. DDC treatment led to pronounced charged isoform changes in several chaperone families, including Hsp25, 60, 70, GRP58, GRP75, and GRP78, which lasted at least for 1 month after discontinuation of DDC feeding, whereas changes in other proteins normalized during recovery. DDC feeding also resulted in altered expression of Hsp72, GRP75, and Hsp25 and in functional impairment of Hsp60 and Hsp70 as determined using a protein complex formation and release assay. The priming toward rapid MDB reinduction lasts for at least 3 months after DDC discontinuation, but becomes weaker after prolonged recovery. MDB reinduction parallels the rapid increase in p62 and Hsp25 levels as well as keratin 8 cross-linking that is normally associated with MDB formation.

Conclusion:

Persistent posttranslational modifications in chaperone proteins, coupled with protein cross-linking and altered chaperone expression and function likely contribute to the “toxic memory” of DDC-primed mice. We hypothesize that similar changes are important contributors to inclusion body formation in several diseases. (Hepatology 2008.)
The membrane protein ATPase class I type 8B member 1 signals through protein kinase C zeta to activate the farnesoid X receptor
Authors: Frankenberg Tamara , Miloh Tamir , Chen Frank Y. , Ananthanarayanan Meena , Sun An-Qiang , Balasubramaniyan Natarajan , Arias Irwin , Setchell Kenneth D. R. , Suchy Frederick J. , Shneider Benjamin L. 
Published: May 2008

Abstract

Prior loss-of-function analyses revealed that

ATPase class I type 8B member 1

[familial intrahepatic cholestasis 1 (FIC1)] posttranslationally activated the farnesoid X receptor (FXR). Mechanisms underlying this regulation were examined by gain-of-function studies in UPS cells, which lack endogenous FIC1 expression. FXR function was assayed in response to wild-type and mutated FIC1 expression constructs with a human bile salt export pump (BSEP) promoter and a variety of cellular localization techniques. FIC1 overexpression led to enhanced phosphorylation and nuclear localization of FXR that was associated with FXR-dependent activation of the BSEP promoter. The FIC1 effect was lost after mutation of the FXR response element in the BSEP promoter. Despite similar levels of FIC1 protein expression, Byler disease FIC1 mutants did not activate BSEP, whereas benign recurrent intrahepatic cholestasis mutants partially activated BSEP. The FIC1 effect was dependent on the presence of the FXR ligand, chenodeoxycholic acid. The effect of FIC1 on FXR phosphorylation and nuclear localization and its effects on BSEP promoter activity could be blocked with protein kinase C zeta (PKC ζ) inhibitors (pseudosubstrate or small interfering RNA silencing). Recombinant PKC ζ directly phosphorylated immunoprecipitated FXR. The mutation of threonine 442 of FXR to alanine yielded a dominant negative protein, whereas the phosphomimetic conversion to glutamate resulted in FXR with enhanced activity and nuclear localization. Inhibition of PKC ζ in Caco-2 cells resulted in activation of the human apical sodium-dependent bile acid transporter promoter.

Conclusion:

These results demonstrate that FIC1 signals to FXR via PKC ζ. FIC1-related liver disease is likely related to downstream effects of FXR on bile acid homeostasis. Benign recurrent intrahepatic cholestasis emanates from a partially functional FIC1 protein. Phosphorylation of FXR is an important mechanism for regulating its activity. (Hepatology 2008;48:1896-1905.)
Influence of evaporation from the forest floor on evapotranspiration from the dry canopy
Authors: Daikoku Kenichi , Hattori Shigeaki , Deguchi Aiko , Aoki Yu , Miyashita Mari , Matsumoto Kazuho , Akiyama Junichi , Iida Shinichi , Toba Tae , Fujita Yuji , Ohta Takeshi 
Published: May 2008

AbstractEvaporation from the forest floor (Ef) of a secondary broad‐leaved forest was monitored for 1 year at 30 min intervals using a closed chamber system. The diurnal and seasonal variation of Ef and forest structure were analysed for days undisturbed by rainfall. The diurnal change in Ef reached a maximum at about 14:00 and gradually decreased towards midnight along with the vapour pressure deficit (D). Although Ef comprised about 20% of evapotranspiration from the dry canopy (Et), it had only a small influence on diurnal evaporation efficiency (β) characteristics above the canopy because its diurnal range was much smaller than that of Et. Although leaf emergence and leaf fall clearly affected available energy (Ae) beneath the canopy, the influence was not clear with Ef. In contrast, seasonal variation in Ef was strongly correlated with D and Ae above the canopy, and the determination coefficient (R2) changed with the Bowen ratio (B). At night, Et was almost equal to Ef when the friction velocity (u*) ranged between 0·2 and 0·4 m s−1. The ratio of Ef to Et was exponentially correlated with leaf area index (LAI) when the soil was not dry. The ratio of Ef to Et was mainly influenced by LAI and soil moisture, but the existence of understory vegetation did not have a strong influence. Copyright © 2008 John Wiley & Sons, Ltd.