bluuebunny/crossref_metadata_2025 huggingface dataset:
The tmRNA System for Translational Surveillance and Ribosome Rescue
Authors: Moore Sean D. , Sauer Robert T.
Published: February 2007

The tmRNA system performs translational surveillance and ribosome rescue in all eubacteria and some eukaryotic organelles. This system intervenes when ribosomes read to the 3′ end of an mRNA or pause at internal codons with subsequent mRNA cleavage. A complex of alanyl-tmRNA (which functions as a tRNA and mRNA), SmpB protein, and EF-Tu•GTP binds stalled ribosomes, the nascent polypeptide is transferred to the alanine on tmRNA, and translation switches from the original message to a short tmRNA open reading frame (ORF) that encodes a degradation tag. Translation of the ORF and normal termination releases the tagged polypeptide for degradation and permits disassembly and recycling of ribosomal subunits for new rounds of protein synthesis. Structural and biochemical studies suggest mechanisms that keep tmRNA from interrupting normal translation and target ribosomes stalled with very short 3′ mRNA extensions. Additional biological roles of tmRNA include stress management and the regulation of transcriptional circuits.
Synapses: Sites of Cell Recognition, Adhesion, and Functional Specification
Authors: Yamada Soichiro , Nelson W. James
Published: February 2007

Synapses are specialized adhesive contacts characteristic of many types of cell-cell interactions involving neurons, immune cells, epithelial cells, and even pathogens and host cells. Cell-cell adhesion is mediated by structurally diverse classes of cell-surface glycoproteins, which form homophilic or heterophilic interactions across the intercellular space. Adhesion proteins bind to a cytoplasmic network of scaffolding proteins, regulators of the actin cytoskeleton, and signal transduction pathways that control the structural and functional organization of synapses. The themes of this review are to compare the organization of synapses in different cell types and to understand how different classes of cell adhesion proteins and cytoplasmic protein networks specify the assembly of functionally distinct synapses in different cell contexts.
The Eyes Absent Family of Phosphotyrosine Phosphatases: Properties and Roles in Developmental Regulation of Transcription
Authors: Jemc Jennifer , Rebay Ilaria
Published: February 2007

Integration of multiple signaling pathways at the level of their transcriptional effectors provides an important strategy for fine-tuning gene expression and ensuring a proper program of development. Posttranslational modifications, such as phosphorylation, play important roles in modulating transcription factor activity. The discovery that the transcription factor Eyes absent (Eya) possesses protein phosphatase activity provides an interesting new paradigm. Eya may regulate the phosphorylation state of either itself or its transcriptional cofactors, thereby directly affecting transcriptional output. The identification of a growing number of transcription factors with enzymic activity suggests that such dual-function proteins exert greater control of signaling events than previously imagined. Given the conservation of both its phosphatase and transcription factor activity across mammalian species, Eya provides an excellent model for studying how a single protein integrates these two functions under the influence of multiple signaling pathways to promote development.
The Biochemistry of Methane Oxidation
Authors: Hakemian Amanda S. , Rosenzweig Amy C.
Published: February 2007

Methanotrophic bacteria oxidize methane to methanol in the first step of their metabolic pathway. Two forms of methane monooxygenase (MMO) enzymes catalyze this reaction: soluble MMO (sMMO) and membrane-bound or particulate MMO (pMMO). pMMO is expressed when copper is available, and its active site is believed to contain copper. Whereas sMMO is well characterized, most aspects of pMMO biochemistry remain unknown and somewhat controversial. This review emphasizes advances in the past two to three years related to pMMO and to copper uptake and copper-dependent regulation in methanotrophs. The pMMO metal centers have been characterized spectroscopically, and the first pMMO crystal structure has been determined. Significant effort has been devoted to improving in vitro pMMO activity. Proteins involved in sMMO regulation and additional copper-regulated proteins have been identified, and the Methylococcus capsulatus (Bath) genome has been sequenced. Finally, methanobactin (mb), a small copper chelator proposed to facilitate copper uptake, has been characterized.
Chemical Evolution as a Tool for Molecular Discovery
Authors: Wrenn S. Jarrett , Harbury Pehr B.
Published: February 2007

In modern academic and industrial laboratories, evolutionary strategies are used routinely to identify biopolymers with novel activities. Large libraries of nucleic acids (∼1015) or peptides and proteins (∼1013) can be subjected to multiple rounds of selective pressure, amplification, and diversification, yielding individual sequences with desirable properties. Although the evolutionary approach is a powerful search tool, the chemical nature of biopolymers is not suited for all purposes. Application of evolutionary strategies to libraries of arbitrary chemical composition would overcome this problem, and radically change traditional small-molecule discovery. The chemical make-up of in vitro evolution libraries has necessarily been limited, because library synthesis relies on enzymes. A great deal of current research focuses on expanding the chemical repertoire of in vitro evolution by (a) broadening enzyme substrate specificities to include unnatural building blocks, or (b) developing methods to translate DNA sequences into multistep organic syntheses. We discuss the strengths and weaknesses of the approaches, review the successes, and consider the future of chemical evolution as a tool.
Thiol-oxidant monochloramine mobilizes intracellular Ca2+ in parietal cells of rabbit gastric glands
Authors: Walsh Breda M. , Naik Haley B. , Dubach J. Matthew , Beshire Melissa , Wieland Aaron M. , Soybel David I.
Published: February 2007

In Helicobacter pylori-induced gastritis, oxidants are generated through the interactions of bacteria in the lumen, activated granulocytes, and cells of the gastric mucosa. In this study we explored the ability of one such class of oxidants, represented by monochloramine (NH2Cl), to serve as agonists of Ca2+ accumulation within the parietal cell of the gastric gland. Individual gastric glands isolated from rabbit mucosa were loaded with fluorescent reporters for Ca2+ in the cytoplasm (fura-2 AM) or intracellular stores (mag-fura-2 AM). Conditions were adjusted to screen out contributions from metal cations such as Zn2+, for which these reporters have affinity. Exposure to NH2Cl (up to 200 μM) led to dose-dependent increases in intracellular Ca2+ concentration ([Ca2+]i), in the range of 200–400 nM above baseline levels. These alterations were prevented by pretreatment with the oxidant scavenger vitamin C or a thiol-reducing agent, dithiothreitol (DTT), which shields intracellular thiol groups from oxidation by chlorinated oxidants. Introduction of vitamin C during ongoing exposure to NH2Cl arrested but did not reverse accumulation of Ca2+ in the cytoplasm. In contrast, introduction of DTT or N-acetylcysteine permitted arrest and partial reversal of the effects of NH2Cl. Accumulation of Ca2+ in the cytoplasm induced by NH2Cl is due to release from intracellular stores, entry from the extracellular fluid, and impaired extrusion. Ca2+-handling proteins are susceptible to oxidation by chloramines, leading to sustained increases in [Ca2+]i. Under certain conditions, NH2Cl may act not as an irritant but as an agent that activates intracellular signaling pathways. Anti-NH2Cl strategies should take into account different effects of oxidant scavengers and thiol-reducing agents.
Phenylephrine hypertrophy, Ca2+-ATPase (SERCA2), and Ca2+ signaling in neonatal rat cardiac myocytes
Authors: Prasad A. M. , Ma H. , Sumbilla C. , Lee D. I. , Klein M. G. , Inesi G.
Published: February 2007

We endeavored to use a basic and well-controlled experimental system to characterize the extent and time sequence of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) involvement in the development of cardiac hypertrophy, including transcription, protein expression, Ca2+ transport, and cytoplasmic Ca2+ signaling. To this end, hypertrophy of neonatal rat cardiac myocytes in culture was obtained after adrenergic activation with phenylephrine (PE). Micrographic assessment of myocyte size, rise of [14C]phenylalanine incorporation and total protein expression, and increased transcription of atrial natriuretic factor demonstrated unambiguously the occurrence of hypertrophy. An early and prominent feature of hypertrophy was a reduction of the SERCA2 transcript, as determined by RT-PCR with reference to a stable marker such as glyceraldehyde-3-phosphate dehydrogenase. Reduction of Ca2+-ATPase protein levels and Ca2+ transport activity to ∼50% of control values followed with some delay, evidently as a consequence of a primary effect on transcription. Cytosolic Ca2+ signaling kinetics, measured with a Ca2+-sensitive dye after electrical stimuli, were significantly altered in hypertrophic myocytes. However, the effect of PE hypertrophy on cytosolic Ca2+ signaling kinetics was less prominent than observed in myocytes subjected to drastic SERCA2 downregulation with small interfering RNA or inhibition with thapsigargin (10 nM). We conclude that SERCA2 undergoes significant downregulation after hypertrophic stimuli, possibly due to lack of SERCA gene involvement by the hypertrophy transcriptional program. The consequence of SERCA2 downregulation on Ca2+ signaling is partially compensated by alternate Ca2+ transport mechanisms. These alterations may contribute to a gradual onset of functional failure in long-term hypertrophy.
Phenotypic characterization of taste cells of the mouse small intestine
Authors: Sutherland Kate , Young Richard L. , Cooper Nicole J. , Horowitz Michael , Blackshaw L. Ashley
Published: February 2007

Nutrient-evoked gastrointestinal reflexes are likely initiated by specialized epithelial cells located in the small intestine that detect luminal stimuli and release mediators that activate vagal endings. The G-protein α-gustducin, a key signal molecule in lingual taste detection, has been identified in mouse small intestine, where it may also subserve nutrient detection; however, the phenotype of α-gustducin cells is unknown. Immunohistochemistry was performed throughout the mouse small intestine for α-gustducin, enteroendocrine cell markers 5-HT and glucagon-like peptide-1 (GLP-1), and brush cell markers neuronal nitric oxide synthase and Ulex europaeus agglutinin-1 (UEA-1) lectin binding, singly, and in combination. α-Gustducin was expressed in solitary epithelial cells of the mid to upper villus, which were distributed in a regional manner with most occurring within the midjejunum. Here, 27% of α-gustducin cells colabeled for 5-HT and 15% for GLP-1; 57% of α-gustducin cells colabeled UEA-1, with no triple labeling. α-Gustducin cells that colabeled for 5-HT or GLP-1 were of distinct morphology and exhibited a different α-gustducin immunolabeling pattern to those colabeled with UEA-1. Neuronal nitric oxide synthase was absent from intestinal epithelium despite strong labeling in the myenteric plexus. We conclude that subsets of enteroendocrine cells in the midjejunum and brush cells (more generally distributed) are equipped to utilize α-gustducin signaling in mice. Intestinal taste modalities may be signaled by these enteroendocrine cells via the release of 5-HT, GLP-1, or coexpressed mediators or by brush cells via a nonnitrergic mediator in distinct regions of the intestine.
NHE8 mediates amiloride-sensitive Na+/H+exchange across mosquito Malpighian tubules and catalyzes Na+and K+transport in reconstituted proteoliposomes
Authors: Kang'ethe Wanyoike , Aimanova Karlygash G. , Pullikuth Ashok K. , Gill Sarjeet S.
Published: February 2007

Following a blood meal, the mosquito Aedes aegypti will have acquired an enormous sodium load that must be rapidly excreted to restore ion homeostasis. It is a process that demands robust sodium and fluid transport capabilities. Even though the identities of the components involved in this ion transport across the mosquito Malpighian tubule epithelia have not been completely determined, electrophysiological studies suggest the contribution of a Na+/H+exchanger extruding cations into the lumen driven secondarily by the proton gradient created by the V-type H+-ATPase in the tubules' apical membrane. We have identified the putative exchanger and designated it AeNHE8. Immunolocalization studies demonstrated that AeNHE8 is expressed in the apical membranes of Malpighian tubules, gastric caecae, and rectum. When heterologously expressed in salt-sensitive yeast cells lacking Na+extrusion and Na+/H+exchange proteins, AeNHE8 rescues the salt-sensitive phenotype and restores the cells' ability to grow in high NaCl media. Furthermore, heterologous expression of AeNHE8 in NHE-deficient fibroblast cells results in an amiloride-sensitive22Na+uptake. To determine the exchanger's kinetic properties, we reconstituted membranes from yeast cells expressing the protein into lipid proteoliposomes and assayed for cation-dependent H+exchange by fluorimetric methods. Our results indicate that AeNHE8 mediates saturable exchange of Na+and K+for H+. We propose that AeNHE8 may be coupled to the inward H+gradient across the Malpighian tubules and plays a role in the extrusion of excess sodium and potassium while maintaining steady intracellular pH in the principal cells.
Gene Expression Signatures for Tumor Progression, Tumor Subtype, and Tumor Thickness in Laser-Microdissected Melanoma Tissues
Authors: Jaeger Jochen , Koczan Dirk , Thiesen Hans-Juergen , Ibrahim Saleh M. , Gross Gerd , Spang Rainer , Kunz Manfred
Published: February 2007

Purpose: To better understand the molecular mechanisms of malignant melanoma progression and metastasis, gene expression profiling was done of primary melanomas and melanoma metastases.

Experimental Design: Tumor cell–specific gene expression in 19 primary melanomas and 22 melanoma metastases was analyzed using oligonucleotide microarrays after laser-capture microdissection of melanoma cells. Statistical analysis was done by random permutation analysis and support vector machines. Microarray data were further validated by immunohistochemistry and immunoblotting.

Results: Overall, 308 genes were identified that showed significant differential expression between primary melanomas and melanoma metastases (false discovery rate ≤ 0.05). Significantly overrepresented gene ontology categories in the list of 308 genes were cell cycle regulation, mitosis, cell communication, and cell adhesion. Overall, 47 genes showed up-regulation in metastases. These included Cdc6, Cdk1, septin 6, mitosin, kinesin family member 2C, osteopontin, and fibronectin. Down-regulated genes included E-cadherin, fibroblast growth factor binding protein, and desmocollin 1 and desmocollin 3, stratifin/14-3-3σ, and the chemokine CCL27. Using support vector machine analysis of gene expression data, a performance of >85% correct classifications for primary melanomas and metastases was reached. Further analysis showed that subtypes of primary melanomas displayed characteristic gene expression patterns, as do thin tumors (≤1.0 mm Breslow thickness) compared with intermediate and thick tumors (>2.0 mm Breslow thickness).

Conclusions: Taken together, this large-scale gene expression study of malignant melanoma identified molecular signatures related to metastasis, melanoma subtypes, and tumor thickness. These findings not only provide deeper insights into the pathogenesis of melanoma progression but may also guide future research on innovative treatments.
Expression of Voltage-Gated Potassium Channels in Human and Mouse Colonic Carcinoma
Authors: Ousingsawat Jiraporn , Spitzner Melanie , Puntheeranurak Supaporn , Terracciano Luigi , Tornillo Luigi , Bubendorf Lukas , Kunzelmann Karl , Schreiber Rainer
Published: February 2007

Purpose: Voltage-gated Kv potassium channels, like ether a go-go (EAG) channels, have been recognized for their oncogenic potential in breast cancer and other malignant tumors.

Experimental Design: We examined the molecular and functional expression of Kv channels in human colonic cancers and colon of mice treated with the chemical carcinogens dimethylhydrazine and N-methyl-N-nitrosourea. The data were compared with results from control mice and animals with chemically induced DSS colitis.

Results: Electrogenic salt transport by amiloride-sensitive Na+ channels and cyclic AMP–activated cystic fibrosis transmembrane conductance regulator Cl− channels were attenuated during tumor development and colitis, whereas Ca2+-dependent transport remained unchanged. Kv channels, in particular Eag-1, were enhanced during carcinogenesis. Multiplex reverse transcription-PCR showed increased mRNA expression for Kv1.3, Kv1.5, Kv3.1, and members of the Eag channel family, after dimethylhydrazine and N-methyl-N-nitrosourea treatment. Eag-1 protein was detected in the malignant mouse colon and human colonic cancers. Genomic amplification of Eag-1 was found in 3.4% of all human colorectal adenocarcinoma and was an independent marker of adverse prognosis.

Conclusions: The study predicts an oncogenic role of Kv and Eag channels for the development of colonic cancer. These channels may represent an important target for a novel pharmacotherapy of colonic cancer.
WWOX Expression in Different Histologic Types and Subtypes of Non–Small Cell Lung Cancer
Authors: Donati Valentina , Fontanini Gabriella , Dell'Omodarme Matteo , Prati Maria Cristina , Nuti Simona , Lucchi Marco , Mussi Alfredo , Fabbri Muller , Basolo Fulvio , Croce Carlo Maria , Aqeilan Rami Ishaq
Published: February 2007

Purpose: Non–small cell lung cancer (NSCLC) has heterogeneous histopathologic classification and clinical behavior and very low survival rate. WWOX (WW domain-containing oxidoreductase) is a tumor suppressor gene, and its expression is altered in several cancers. The purpose of this study is to better define the role of WWOX in NSCLC tumorigenesis and progression by determining its pathogenetic and prognostic significance.

Experimental Design: WWOX protein expression was evaluated by immunohistochemistry in 170 patients with NSCLC (101 squamous cell carcinomas, 66 adenocarcinomas, 3 large cell carcinomas) and was correlated with histopathologic (histotype, subtype, grade, tumor-node-metastasis, stage, index of cell proliferation Ki67/MIB1) and clinical (age, gender, local recurrences, distant metastases, overall survival, and disease-free survival) characteristics.

Results: WWOX expression was absent/reduced in 84.9% of NSCLCs, whereas it was normal in 80.5% of adjacent normal lung tissues. WWOX expression was strongly associated with tumor histology (P = 1.1 × 10−5) and histologic grade (P = 0.0081): the percentage of cases with absent/strongly reduced WWOX expression was higher in squamous cell carcinomas and in poorly differentiated tumors. Regarding adenocarcinoma, bronchioloalveolar pattern showed normal WWOX expression in 62.5% of the cases, whereas in solid and acinar patterns, a prevalence of cases with absent/very low WWOX expression was observed (79.2% and 50%, respectively). Finally, weak WWOX staining intensity was related to the high index of cell proliferation (P = 0.0012).

Conclusions: Our results suggest that the loss of WWOX expression plays different roles in tumorigenesis of distinct histotypes and subtypes of NSCLC and is related to high aggressiveness (G3; high proliferating activity) of tumors.
Tropical Atmospheric Variability Forced by Oceanic Internal Variability
Authors: Jochum Markus , Deser Clara , Phillips Adam
Published: February 2007

Atmospheric general circulation model experiments are conducted to quantify the contribution of internal oceanic variability in the form of tropical instability waves (TIWs) to interannual wind and rainfall variability in the tropical Pacific. It is found that in the tropical Pacific, along the equator, and near 25°N and 25°S, TIWs force a significant increase in wind and rainfall variability from interseasonal to interannual time scales. Because of the stochastic nature of TIWs, this means that climate models that do not take them into account will underestimate the strength and number of extreme events and may overestimate forecast capability.
On the Tribological Properties of PTFE Filled with Alumina Nanoparticles and Graphite
Authors: Xiang Dinghan , Li Ke , Shu Weicai , Xu Zhong
Published: February 2007

Methods used to reinforce self-lubricating polymers generally also cause a significant increase in coefficient of friction, so that a trade-off must be made between coefficient of friction and wear resistance. Polytetrafluoroethylene (PTFE) composites filled with alumina nanoparticles and graphite were prepared by compression molding. Friction and wear experiments were carried out in a reciprocating sliding tribotester at a reciprocating frequency of 1.0 Hz, contact pressure of 5.0 MPa and relative humidity of (75 3)%. The nanocomposites slid against a 45 carbon steel track. Results showed that PTFE + 15 wt% alumina + 5 wt% graphite composite (D) exhibited a coefficient of steady-state friction lower than PTFE + 15 wt% alumina composite (B), while wear resistance of composite D is higher than composite B, and by about 200 times higher than unfilled PTFE. This behavior originates from the effective lubrication of graphite that possesses an extremely low coefficient of friction under the high humidity condition.
No detectable effect of RNA-binding protein Hfq absence in Staphylococcus aureus
Authors: Bohn Chantal , Rigoulay Candice , Bouloc Philippe
Published: February 2007

Background

The RNA-binding protein Hfq is involved in stress and virulence of several pathogens, probably due to its role as mediator in small RNA (sRNA)-mRNA interactions. In this study, we investigate the function of Hfq in the Gram-positive pathogen Staphylococcus aureus, by constructing hfq null mutant derivatives.

Results

We report that unexpectedly, in S. aureus, Hfq does not seem to play a crucial role in stress response, RNAIII or spa mRNA quantity and exoprotein expression, as tested in three virulent genetic backgrounds. Moreover, a global analysis of the RN6390 hfq mutant, which tests ~ 2000 phenotypes, supports our results concerning the non-implication of Hfq in stress response, and shows that Hfq is also not involved in resistance to several chemical agents and antibiotics and does not seem to be implicated in metabolic pathways.

Conclusion

Our data suggest that although sRNA-mRNA interactions in S. aureus are decisive for gene expression regulation, they do not require the RNA-chaperone protein Hfq. These interactions possibly require an RNA-chaperone protein other than Hfq, which remains to be found.
Continued spread of HIV among injecting drug users in southern Sichuan Province, China
Authors: Yin Lu , Qin Guangming , Qian Han-Zhu , Zhu Yu , Hu Wei , Zhang Li , Chen Kanglin , Wang Yunxia , Liu Shizhu , Zhou Feng , Xing Hui , Ruan Yuhua , Wang Ning , Shao Yiming
Published: February 2007

Objective

To estimate HIV prevalence among injecting drug users (IDUs) in a drug trafficking city in southwest Sichuan Province, China.

Methods

A total of 314 IDUs was invited to participate in the cross-sectional survey in 2004 through community outreach recruitment and peer referrals. Blood sample was taken for HIV antibody testing and a structured questionnaire was administered to collect information on socio-demographics, drug using and sexual behaviors.

Results

HIV prevalence among IDUs was 17.8% (56/314), about one half higher than that in previous survey in 2002 (11.3%, 43/379). Yi and other minority ethnicity (Odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7–5.8; P < 0.001), and total times of sharing injecting equipments 1–9 times versus none, OR, 2.7; 95% CI 1.2–6.2; P = 0.02; and ≥10 times versus none, OR, 7.5; 95% CI, 3.2–17.7; P < 0.001) were independent risk factors for HIV infection.

Conclusion

IDUs with high prevalence rates of HIV and equipment sharing behavior in the drug trafficking city may serve a source for further spread of HIV to other areas in China. The increasing trend of HIV epidemic among IDUs underscores the urgency of scaling up interventions.
Complementary and Alternative Medicine Among Advanced Cancer Patients Enrolled on Phase I Trials: A Study of Prognosis, Quality of Life, and Preferences for Decision Making
Authors: Hlubocky Fay J. , Ratain Mark J. , Wen Ming , Daugherty Christopher K.
Published: February 2007

Purpose

We sought to describe complementary and alternative medicine (CAM) usage among phase I trial participants and to describe these patients' treatment decision-making preferences, awareness of prognosis, survival, and quality of life.

Patients and Methods

Advanced cancer patients enrolling onto phase I trials were surveyed regarding biologically based CAM use. Decision-making preferences and awareness of prognosis were assessed using validated and/or standardized instruments. The Functional Assessment of Cancer Therapy–General instrument was used to assess quality of life. Univariate and multivariate analyses were performed to detect differences between CAM users and nonusers.

Results

Of 212 interviewed patients, 34% (n = 72) described taking biologically based CAM. Median age of those taking biologically based CAM was 55 years, compared with 62 years for nonusers (P < .005). There were no statistically significant differences found between CAM usage and preferences for degree of patient involvement in medical decision making. Those patients who acknowledged that their deaths were likely to occur within 1 year were more likely to admit to prior CAM use (70% v 34%; P = .02). CAM users had poorer overall quality of life compared with nonusers (87.0 ± 12.4 v 91.2 ± 14.7; P = .007). No differences in survival were identified.

Conclusion

Prior CAM use among phase I cancer trial patients studied was common and associated with age, stated acknowledgment of prognosis, and quality of life. Patients enrolling onto early-phase trials should be questioned about CAM use. Additional study is needed to determine the frequency of use of those biologically based CAM agents that threaten the accuracy of early-phase cancer trial data.
Ghrelin Interacts with Human Plasma Lipoproteins
Authors: De Vriese Carine , Hacquebard Mirjam , Gregoire Françoise , Carpentier Yvon , Delporte Christine
Published: February 2007

Ghrelin, a peptide hormone produced predominantly by the stomach, stimulates food intake and GH secretion. The Ser3 residue of ghrelin is mainly modified by a n-octanoic acid. In the human bloodstream, ghrelin circulates in two forms: octanoylated and desacylated. We previously demonstrated that ghrelin is desoctanoylated in human serum by butyrylcholinesterase (EC 3.1.1.8) and other esterase(s), whereas in rat serum, only carboxylesterase (EC 3.1.1.1) is involved. The aims of this study were to determine the role of lipoprotein-associated enzymes in ghrelin desoctanoylation and the role of lipoproteins in the transport of circulating ghrelin. Our results show that ghrelin desoctanoylation mostly occurred in contact with low-density lipoproteins (LDLs) and lipoprotein-poor plasma subfractions. Butyrylcholinesterase and platelet-activating factor acetylhydrolase (EC 3.1.1.47) were responsible for the ghrelin hydrolytic activity of the lipoprotein-poor plasma and LDL subfractions, respectively. Moreover, we observed that ghrelin is associated with triglyceride-rich lipoproteins (TRLs), high-density lipoproteins (HDLs), very high-density lipoproteins (VHDLs), and to some extent LDLs. In conclusion, we report that the presence of the acyl group is necessary for ghrelin interaction with TRLs and LDLs but not HDLs and VHDLs. Ghrelin interacts via its N- and C-terminal parts with HDLs and VHDLs. This suggests that, whereas TRLs mostly transport acylated ghrelin, HDLs and VHDLs transport both ghrelin and des-acyl ghrelin.
Acto-myosin reorganization and PAR polarity inC. elegans
Authors: Cowan Carrie R. , Hyman Anthony A.
Published: February 2007

The symmetry-breaking event during polarization of C. elegansembryos is an asymmetric rearrangement of the acto-myosin network, which dictates cell polarity through the differential recruitment of PAR proteins. The sperm-supplied centrosomes are required to initiate this cortical reorganization. Several questions about this event remain unanswered: how is the acto-myosin network regulated during polarization and how does acto-myosin reorganization lead to asymmetric PAR protein distribution? As we discuss,recent studies show that C. elegans embryos use two GTPases, RHO-1 and CDC-42, to regulate these two steps in polarity establishment. Although RHO-1 and CDC-42 control distinct aspects of polarization, they function interdependently to regulate polarity establishment in C. elegansembryos.
Amotl2 is essential for cell movements in zebrafish embryo and regulates c-Src translocation
Authors: Huang Huizhe , Lu Fu-I , Jia Shunji , Meng Shu , Cao Ying , Wang Yeqi , Ma Weiping , Yin Kun , Wen Zilong , Peng Jingrong , Thisse Christine , Thisse Bernard , Meng Anming
Published: February 2007

Angiomotin (Amot), the founding member of the Motin family, is involved in angiogenesis by regulating endothelial cell motility, and is required for visceral endoderm movement in mice. However, little is known about biological functions of the other two members of the Motin family, Angiomotin-like1(Amotl1) and Angiomotin-like2 (Amotl2). Here, we have identified zebrafish amotl2 as an Fgf-responsive gene. Zebrafish amotl2 is expressed maternally and in restricted cell types zygotically. Knockdown of amotl2 expression delays epiboly and impairs convergence and extension movement, and amotl2-deficient cells in mosaic embryos fail to migrate properly. This coincides with loss of membrane protrusions and disorder of F-actin. Amotl2 partially co-localizes with RhoB-or EEA1-positive endosomes and the non-receptor tyrosine kinase c-Src. We further demonstrate that Amotl2 interacts preferentially with and facilitates outward translocation of the phosphorylated c-Src, which may in turn regulate the membrane architecture. These data provide the first evidence that amotl2 is essential for cell movements in vertebrate embryos.
Polycomb group genes are required for neural stem cell survival in postembryonic neurogenesis ofDrosophila
Authors: Bello Bruno , Holbro Niklaus , Reichert Heinrich
Published: February 2007

Genes of the Polycomb group (PcG) are part of a cellular memory system that maintains appropriate inactive states of Hox gene expression in Drosophila. Here, we investigate the role of PcG genes in postembryonic development of the Drosophila CNS. We use mosaic-based MARCM techniques to analyze the role of these genes in the persistent larval neuroblasts and progeny of the central brain and thoracic ganglia. We find that proliferation in postembryonic neuroblast clones is dramatically reduced in the absence of Polycomb, Sex combs extra, Sex combs on midleg, Enhancer of zeste or Suppressor of zeste 12. The proliferation defects in these PcG mutants are due to the loss of neuroblasts by apoptosis in the mutant clones. Mutation of PcG genes in postembryonic lineages results in the ectopic expression of posterior Hox genes, and experimentally induced misexpression of posterior Hox genes, which in the wild type causes neuroblast death, mimics the PcG loss-of-function phenotype. Significantly, full restoration of wild-type-like properties in the PcG mutant lineages is achieved by blocking apoptosis in the neuroblast clones. These findings indicate that loss of PcG genes leads to aberrant derepression of posterior Hox gene expression in postembryonic neuroblasts, which causes neuroblast death and termination of proliferation in the mutant clones. Our findings demonstrate that PcG genes are essential for normal neuroblast survival in the postembryonic CNS of Drosophila. Moreover, together with data on mammalian PcG genes, they imply that repression of aberrant reactivation of Hox genes may be a general and evolutionarily conserved role for PcG genes in CNS development.
Miami Heat: Patent Law, Informed Consent and Benefit-Sharing
Authors: Rimmer Matthew
Published: February 2007

This article considers whether the granting of patents in respect of biomedical genetic research should be conditional upon the informed consent of research participants. It focuses upon several case studies.
Developing Biotechnology Legal Systems in Developing Countries: The Case for Malaysia (Part II)
Authors: Jusoh Sufian
Published: February 2007

Among the rights are to exploit the patented invention; to assign or transmit the patent; and, to conclude licence contracts without the consent of the patent owner. Exploitation includes, in relation to a products, to make, import, offer for sale sell or use such products; stocking such product for the purpose of offering for sale, selling or using it; and in respect of a process, exploitation means using the process and doing any acts referred to above in respect of a product obtained directly as a result of the process.
Legal Limitations on Genetic Research and the Commercialisation of its Results in the Republic of Croatia
Authors: Mutabzija Jasmina , Kunda Ivana
Published: February 2007

Freedom of research is the underlining principle of any scientific activity. It has been restated in many international and national legal instruments. Thus, Article 15 of the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine of 1997 (hereinafter: the Convention on Human Rights and Biomedicine), lays down the general rule:
Reduced X-Linked Diversity in Derived Populations of House Mice
Authors: Baines John F , Harr Bettina
Published: February 2007

Contrasting patterns of X-linked vs. autosomal diversity may be indicative of the mode of selection operating in natural populations. A number of observations have shown reduced X-linked (or Z-linked) diversity relative to autosomal diversity in various organisms, suggesting a large impact of genetic hitchhiking. However, the relative contribution of other forces such as population bottlenecks, variation in reproductive success of the two sexes, and differential introgression remains unclear. Here, we survey 13 loci, 6 X-linked and 7 autosomal, in natural populations of the house mouse (Mus musculus) subspecies complex. We studied seven populations of three different subspecies, the eastern house mouse M. musculus castaneus, the central house mouse M. m. musculus, and the western house mouse M. m. domesticus, including putatively ancestral and derived populations for each. All populations display lower diversity on the X chromosomes relative to autosomes, and this effect is most pronounced in derived populations. To assess the role of demography, we fit the demographic parameters that gave the highest likelihood of the data using coalescent simulations. We find that the reduction in X-linked diversity is too large to be explained by a simple demographic model in at least two of four derived populations. These observations are also not likely to be explained by differences in reproductive success between males and females. They are consistent with a greater impact of positive selection on the X chromosome, and this is supported by the observation of an elevated KA and elevated KA/KS ratios on the rodent X chromosome. A second contribution may be that the X chromosome less readily introgresses across subspecies boundaries.
Adult Mouse Myometrial Label-Retaining Cells Divide in Response to Gonadotropin Stimulation
Authors: Szotek Paul P. , Chang Henry L. , Zhang LiHua , Preffer Frederic , Dombkowski David , Donahoe Patricia K. , Teixeira Jose
Published: February 2007

Conditional deletion of β-catenin in the Müllerian duct mesenchyme results in a degenerative uterus characterized by replacement of the myometrial smooth muscle with adipose tissue. We hypothesized that the mouse myometrium houses somatic smooth muscle progenitor cells that are hormonally responsive and necessary for remodeling and regeneration during estrous cycling and pregnancy. We surmise that the phenotype observed in β-catenin conditionally deleted mice is the result of dysregulation of these progenitor cells. The objective of this study was to identify the mouse myometrial smooth muscle progenitor cell and its niche, define the surface marker phenotype, and show a functional response of these cells to normal myometrial cycling. Uteri were labeled with 5-bromo-2′-deoxyuridine (BrdU) and chased for up to 14 weeks. Myometrial label-retaining cells (LRCs) were observed in the myometrium and stroma throughout the chase period. After 12 weeks, phenotypic analysis of the LRCs by immunofluorescence demonstrated that the majority of LRCs colocalized with α-smooth muscle actin, estrogen receptor-α, and β-catenin. Flow cytometry of myometrial cells identified a myometrial Hoechst 33342 effluxing “side population” that expresses MISRII-Cre-driven YFP. Functional response of LRCs was investigated by human chorionic gonadotropin stimulation of week 12 chase mice and demonstrated sequential proliferation of LRCs in the endometrial stroma, followed by the myometrium. These results suggest that conventional myometrial regeneration and repair is executed by hormonally responsive stem or progenitor cells derived from the Müllerian duct mesenchyme.

Disclosure of potential conflicts of interest is found at the end of this article.
Thoreau on Poverty and Magnanimity
Authors: Woodson Thomas
Published: February 2007

In Walden and his other mature writings Thoreau often approaches the social problem of poverty not through the directly assertive rhetoric of the Transcendentalist reformers, but by associating certain poor men with the Aristotelian quality of “greatness of soul”. This American, democratic, magnanimous hero lives quietly close to nature, but he is “a prince in disguise”, reincarnating “the worthies of antiquity”, the gods and heroes of classical mythology and history. Walden contains both a sharp awareness of how the Protestant ethic leads to economic hypocrisy in the New Englander's attitude toward the poor and a highly imaginative art of characterization, through which Thoreau transforms the innocent poor into heroes like those of contemporary American romances. But his political essays of the 1850's, particularly those on slavery and the heroic revolutionary activities of John Brown, reveal the limitations of Thoreau's art. His mythopoeic characterization of Brown comes too easily, emerging from a simplistic, abstract, merely polemical response to evil. “Magnanimity” becomes sheer brute force. Thoreau's characters thus lack the dimension of tragic magnanimity; his account of Brown has none of the mysterious innocence of Melville's Billy Budd, whose life and death present striking parallels to Brown's.
The Structure of Platero y Yo
Authors: Predmore Michael P.
Published: February 2007

Studying the structure of Platero y Yo makes explicit the organization and arrangement of expressive material as a unified whole. Why does Platero begin the way it does and why does it end the way it does? What are the inner principle or principles that tie together the various lyric chapters into a poetic unity? Several key patterns of imagery and events provide clues to the structure and meaning of Platero: the butterfly imagery which presides over the beginning and the ending of the work, occurrences of gratuitous bloodletting in the season of spring, the almost imperceptible disappearance of conditioned violence in the season of winter, the death of Platero in the month of February, the juxtaposition of life and death, violence and harmony throughout the entire work. All of these patterns and events are endowed with full symbolic significance by the seasonal cycle and by the theme of death and rebirth as a process of metamorphosis.
Matthew Arnold's Tragic Vision
Authors: Farrell John P.
Published: February 2007

In spite of his commitment to the classical tradition, Matthew Arnold saw tragedy not as man's violation of a supernal order, but as his victimization by a historical order. Arnold's essay on Lord “Falkland”, rather than the 1853 Preface, provides us with our most useful guide to his understanding of the tragic experience. In “Falkland” Arnold explicitly indicates that history becomes a tragic action in epochs of revolution when civilized life breaks down into a clash between a superannuated orthodoxy and a banal radicalism. In such periods, gifted individuals are left to wander, hopelessly, between two worlds. Four important works are informed by this vision. Empedocles on Etna shows that the protagonist's crisis is precipitated by the isolation Empedocles suffers in a world dominated by superstition on the one hand and sophistry on the other. “Lucretius” was to have used a similar background, the revolutionary clash between the conservative “Milonians” and the democratic “Clodians”. In Balder Dead Arnold turned to the myth of the Twilight of the Gods in order to dramatize the theme of “Falkland”. Finally, the heroine in Merope is forced to choose between the barbarism of the old order and the nullity of the new one.
Research on The Teaching of English Under Project English
Authors: Steinberg Erwin R.
Published: February 2007

Last September, PMLA carried a report by J. N. Hook, the first Coordinator of Project English, on “Project English: The First Year.”1 It is now time for a report from the second Coordinator, even as the third, John C. Gerber, assumes responsibility for the still evolving program. The Original Program Project English is a little more than two and a half years old. It is considerably different now, however, from what it was when we first heard of it in the late fall of 1961. Then, for example, we were warned that one should stress reading and writing when presenting a proposal. Literature, somehow, was suspect.
Languages in Hawaii
Authors: Aspinwall Dorothy Brown
Published: February 2007

In Hawaii six languages are spoken by sizable groups of people in addition to the official language, English, and the lingua franca, Pidgin. They are: Japanese, Hawaiian, Cantonese, Korean, Portuguese, and Ilocano. No exact figures exist for the numbers of speakers in each group. Some indication, however, can be gained by consulting the 1950 census distribution by “race” of the Islands' population: Japanese 39%, Caucasian 23%, Hawaiian 17%, Filipino 12%, Chinese 6.4%, Korean 1.4%, other 1.2%. Allowance must also be made for the facts that some Hawaiians cannot speak Hawaiian, that some of our Chinese speak Mandarin, and that about ten percent of the local Filipinos speak Visayan or Tagalog rather than Ilocano. Obviously, in a government report, the Portuguese are included as Caucasians; locally they are considered a group apart.
Applied Linguistics in the Classroom
Authors: Moulton William G.
Published: February 2007

When our Secretary, George Winchester Stone, asked me last July to address this meeting on the general topic of language teaching and linguistics, it was only with considerable hesitation that I finally agreed to accept. There has been far too much loose talk recently about the application of linguistics to language teaching, and I did not wish to add to it. In some circles linguistics has turned into a sort of fad. There are those who talk of the “linguistic method” of language teaching, as if to oppose it to some hypothetical “non-linguistic method” used in the benighted past. And at meetings of language teachers, bright young things walk up to me and ask, apparently in all seriousness: “Excuse me, professor, but would you please tell me how linguistics handles the subjunctive?” Needless to say, I have no answers to such questions; they merely embarrass me. Linguistics is not a teaching method, but a growing body of knowledge and theory; and though it may offer helpful answers to some of the problems of language teaching, it surely does not know all the answers.
XII. —A Discrepancy in Two of Schiller's Letters
Authors: Jonas J. B. E.
Published: February 2007

On pages 94 and 116, respectively, of Vol. I of Jonas's edition of Schiller's Letters, we find the following two communications: 52. An Reinwald. Bauerbach d. 29. Jenn. Zwischen 11 und 12 Uhr des Nachts [Mittwoch 1783]. Hier, mein lieber Freund, haben Sie das versprochene Gedicht, das, wenn ich es noch einmal überlese keinen Werth hat, als den guten Willen seines Verfaszers. Meine L. Millerin geht mir im Kopf herum. Sie glauben nicht, wie es mich Zwang kostet, mich in eine andre Dichtart hineinzuarbeiten.
I.—Notes on the Influence of E. T. A. Hoffmann Upon Edgar Allan Poe
Authors: Gruener Gustav
Published: February 2007

In his Preface to The Tales of the Grotesque and Arabesque Poe, while discussing the character and style of these tales, says: “I am led to think it is this prevalence of the ‘Arabesque’ in my serious tales, which has induced one or two critics to tax me, in all friendliness, with what they have been pleased to term ‘Germanism’ and gloom. The charge is in bad taste, and the grounds of accusation have not been sufficiently considered. Let us admit for a moment that the ‘phantasy-pieces’ now given are ‘Germanic’ or what not…. But the truth is that, with a single exception, there is no one of these stories in which the scholar should recognize the distinctive features of that species of pseudo-horror which we are taught to call Germanic, for no better reason than that some of the secondary names of German literature have become identified with its folly. If in many of my productions terror has been the thesis, I maintain that terror is not of Germany, but of the soul.” In this passage, though himself possessed with almost a monomania for discovering ‘plagiarism’ in other writers, (nowadays we should rather speak of 'influences'), Poe practically denies similar charges brought against him. And, in this denial, he takes occasion to lunge a side thrust at Hoffmann in his reference to 'phantasypieces' and ‘some secondary names of German literature‘—as will be seen later.
VI.—The Author of the Pearl, Considered in the Light of his Theological Opinions
Authors: Brown Carleton F.
Published: February 2007

Among the English poets of the fourteenth century the one who deserves the seat next to Chaucer is the anonymous author of the four poems: Sir Gawayne and the Green Knight, The Pearl, Cleanness, and Patience. The singular beauty of these poems has long stimulated scholars to the most diligent efforts to discover their author.

The first attempt to identify the unknown poet was made in 1838 by Dr. Edwin Guest, who confidently assigned these poems to Huchown, the mysterious Scotch poet mentioned by the chronicler Wyntoun. At one time or another, almost every piece of fourteenth century verse which shows a northerly dialect has been ascribed to Huchown; this identification of our author was therefore natural, if not inevitable. In the following year Sir Frederic Madden, in his edition of Sir Gawayne, accepted Dr. Guest's opinion that Huchown was its author. At the same time he recognized the fact that the poem in its present form is not in the Scotch dialect, and suggested as an explanation that it had been rewritten “by a scribe of the Midland counties.” With this recognition that Sir Gawayne as we have it is in the Midland rather than the Scottish dialect, there was manifestly slender reason for continuing to suppose that Huchown was the author.