bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical regulation of the Cyr61/CCN1 and CTGF/CCN2 proteins
Authors: Chaqour Brahim , Goppelt‐Struebe Margarete
Published: July 2006

Cells in various anatomical locations are constantly exposed to mechanical forces from shear, tensile and compressional forces. These forces are significantly exaggerated in a number of pathological conditions arising from various etiologies e.g., hypertension, obstruction and hemodynamic overload. Increasingly persuasive evidence suggests that altered mechanical signals induce local production of soluble factors that interfere with the physiologic properties of tissues and compromise normal functioning of organ systems. Two immediate early gene‐encoded members of the family of the Cyr61/CTGF/Nov proteins referred to as cysteine‐rich protein 61 (Cyr61/CCN1) and connective tissue growth factor (CTGF/CCN2), are highly expressed in several mechanical stress‐related pathologies, which result from either increased externally applied or internally generated forces by the actin cytoskeleton. Both Cyr61 and CTGF are structurally related but functionally distinct multimodular proteins that are expressed in many organs and tissues only during specific developmental or pathological events. In vitro assessment of their biological activities revealed that Cyr61 expression induces a genetic reprogramming of angiogenic, adhesive and structural proteins while CTGF promotes distinctively extracellular matrix accumulation (i.e., type I collagen) which is the principal hallmark of fibrotic diseases. At the molecular level, expression of the Cyr61 and CTGF genes is regulated by alteration of cytoskeletal actin dynamics orchestrated by various components of the signaling machinery, i.e., small Rho GTPases, mitogen‐activated protein kinases, and actin binding proteins. This review discusses the mechanical regulation of the Cyr61 and CTGF in various tissues and cell culture models with a special attention to the cytoskeletally based mechanisms involved in such regulation.
Unveiling a Ghost of Amazonian Rain Forests: Camponotus mirabilis, Engineer of Guadua Bamboo1
Authors: Davidson D. W. , Castro‐Delgado S. R. , Arias J. A. , Mann J.
Published: July 2006

Camponotus mirabilis (Hymenoptera: Formicidae) is a highly specialized resident of live Guadua bamboo in western Amazonia. Workers in established colonies open and invade young, unlignified culms, and mature polydomous colonies occupy several‐to‐many adjacent stems. Multistoried carton shelves support brood inside culms, and larvae are nourished by honeydew of coccids (Cryptostigma guadua). Constructing a system of stem holes and wicks, C. mirabilis modifies occupied stems in ways that produce passive water evacuation. Nocturnally foraging workers gather both prey and wood fiber, a component of wicks. Diurnally, they boil aggressively from agitated stems, and are attacked by parasitic phorid flies (Diptera: Phoridae). Culms housing C. mirabilis are stouter and more erect than are unoccupied stems but are opened regularly by capuchin monkeys (Cebus apella) searching for brood and perhaps reproductive castes. Damaged by monkeys, weak‐walled Guadua stems frequently collapse and are abandoned by ants. Breakdown of brood shelves leaves nutrient‐rich carton suspended in water within basal internodes, but isotopic analyses fail to show that occupied culms utilize either nitrogen from carton or carbon respired by ants or decomposing debris. Lower foliar nitrogen concentration in occupied than in control stems suggests that coccids and ants parasitize host resources. A prior experimental survey of bamboo ants may have missed C. mirabilis because females found new colonies in culms occupied by another bamboo specialist, and established colonies invade only young bamboo growth.
Behavioural and endocrinological parameters of female African and Asian elephants Loxodonta africana and Elephas maximus in the peripartal period
Authors: SZDZUY K. , DEHNHARD M. , STRAUSS G. , EULENBERGER K. , HOFER H.
Published: July 2006

Reproduction of African elephants Loxodonta africana and Asian elephants Elephas maximus has in the past been poor in European zoos and juvenile survival has been low. A range of potential complications, such as stillbirths or maternal aggression towards the calf, makes it imperative that the date of parturition is predicted as accurately as possible. Behavioural, endocrinological and physiological data were collected from three pregnant elephants for up to 3 months prior to parturition in order to assess their value for predicting the date of birth. Behavioural observations indicated that activity, particularly the frequency of stereotypic behaviour, increased prior to parturition. Pregnant cows grew restless and exhibited frequent excretion, tail beating against the vulva and excessive throwing of hay or sand against the belly. Our results suggest that observations of prepartal behavioural changes are a useful indicator for predicting parturition, particularly for veterinarians and keepers who are familiar with the usual behaviour patterns of the animals in their care. Measurement of luteal activity indicated that luteo‐lysis occurred 2‐3 days prior to parturition in both elephant species. Thus, endocrinological analysis provides an excellent and accurate prediction of the timing of parturition.
A review of injuries caused by elephants in captivity: an examination of predominant factors
Authors: GORE M. , HUTCHINS M. , RAY J.
Published: July 2006

Injuries to people caused by elephants in zoos can be lethal. Data on incidents of injury to keepers and visitors were collated from newspaper articles, personal communications with zoo directors and keepers, and published information from the European Elephant Group. Although the data were not of consistent quality and detail across the three sources, the causes and frequency of incidents were analysed to see whether analogies could be drawn about how and why accidents occur. The greater our understanding of these factors, the more likely it is that the number of elephant‐related injuries and deaths that happen in zoos can be reduced. Data are presented on a number of factors that relate to elephants, keeping staff, management practices and the circumstances surrounding known injuries and deaths.
An overview of the conservation status of and threats to rhinoceros species in the wild
Authors: AMIN R. , THOMAS K. , EMSLIE R. H. , FOOSE T. J. , STRIEN N. VAN
Published: July 2006

This paper summarizes the recent status of rhinoceros species, as provided by IUCN Species Survival Commission's Rhinoceros Specialist Groups, and describes some of the current conservation measures. At the time of writing there arec.14 950 rhinoceros remaining in Africa andc.2850 in Asia. During the last decade conservation initiatives have achieved notable successes; however, numbers of some species and subspecies have declined over this period and three subspecies are close to extinction. The illegal demand for rhinoceros horn and the subsequent poaching this generates continue to pose a serious threat to rhinoceros populations worldwide. However, experience indicates that where anti‐poaching efforts are concentrated above minimum threshold levels population losses as a result of poaching can be reduced to a low and sustainable level. However, not all populations receive sufficient protection and declining budgets of range‐state governments for field conservation are a major cause for concern. The role of donor support is, therefore, becoming increasingly important. For some subspecies lack of adequate habitat protection rather than lack of suitable habitat is a major constraint for population expansion and growth. Many rhinoceros populations in Africa are managed as part of bigger meta‐populations. However, sub‐optimal biological management is also reducing population growth rates in a number of populations.
Population management of rhinoceros in captivity
Authors: FOOSE T. J. , WIESE R. J.
Published: July 2006

Captive‐breeding programmes are important components of conservation strategies for rhinoceros. Rhinoceros in zoos can serve as (1) genetic and demographic reservoirs to reinforce wild populations as the need and opportunity occur, and (2) ambassadors to increase public awareness and support, especially financial, for conservation of wild populations. However, for these functions, rhinoceros in captivity must be managed scientifically and co‐operatively to produce viable populations. Population‐management programmes for Black rhinocerosDiceros bicornis, White rhinocerosCeratotherium simumand Indian rhinocerosRhinoceros unicornisare operating in various regions of the zoo world, especially North America [Species Survival Plans (SSP)] and Europe [European Endangered Species Programmes (EEP)]. Analyses indicate that rhinoceros populations in captivity are achieving variable levels of viability. In SSP and EEP populations Black rhinoceros and White rhinoceros are genetically but not demographically satisfactory, while Indian rhinoceros is healthy demographically but limited genetically. Improvement is needed and could be achieved through better management.
Aquarium design for the Portuguese man‐of‐war Physalia phy salis
Authors: PIERCE J.
Published: July 2006

Maintaining the Portuguese man‐of‐war Physalia physalis in captivity, either for display or study, has not been successful to date. A new aquarium was designed and constructed in an attempt to simulate natural conditions so more could be learned about the husbandry requirements of this species. The prototype aquarium increased longevity, up to four to seven times that of previous attempts, and promoted natural behaviours. Inside the aquarium six acrylic containment cylinders, each containing one Portuguese man‐of‐war, held the animals away from the sides and the force of water being drawn down through the cylinders retained the centred position of the specimens. Detailed information is given on the design of the aquarium in relation to the natural behaviour of the Portuguese man‐of‐war.
Hypotonic stress activates BK channels in clonal kidney cells via purinergic receptors, presumably of the P2Y1subtype
Authors: Hafting T. , Haug T. M. , Ellefsen S. , Sand O.
Published: July 2006

Aim: Membrane stretch due to cell swelling may cause a minute leakage of adenosine triphosphate (ATP) that stimulates endogenous purinergic receptors. The following elevation of the cytosolic‐free Ca2+concentration ([Ca2+]i) may then participate in cell volume regulation. The aim of the present study was to test if purinergic receptors and large conductance Ca2+activated K+(BK) channels are activated in response to hypotonic stress in clonal kidney cells (Vero cells).

Methods: The methods used are fura‐2 microfluorometry, cell‐attached patch clamp and reverse‐transcriptase polymerase chain reaction (RT‐PCR).

Results: Subjecting cells to hypotonic stress for 10 s by exposure to a solution with 45% reduced osmolality induced a transient rise in [Ca2+]i. This response persisted in virtually Ca2+‐free extracellular solution, demonstrating that Ca2+was mainly released from intracellular stores. The hypotonically induced elevation of [Ca2+]iwas completely inhibited by the P2 receptor antagonists suramine (100 μm) and pyridoxalphosphate‐6‐azophenyl‐2′4′‐disulphonate (PPADS; 20 μm), indicating that extracellular ATP is crucial for the [Ca2+]iincrease. RT‐PCR revealed the expression of mRNA for P2Y1receptors in Vero cells. The putatively selective P2Y1antagonist PPADS did completely block Ca2+responses to both ATP and hypotonic stress, suggesting that P2Y1receptors are mediating the response. Furthermore, patch clamp recordings in cell‐attached configuration revealed that BK channels are activated in response to hypotonic stress.

Conclusion: Vero cells express functional purinergic receptors, presumably of the P2Y1subtype. These receptors are responsible for the elevation of [Ca2+]ievoked by hypotonic stress. The concurrent activation of BK channels permits K+efflux that may contribute to regulatory volume decrease.
The 3-Deaza and 7-Deaza Derivatives of 5'-Amino-5'-deoxy-5'-noraristeromycin
Authors: Yang Minmin , Serbessa Tesfaye , Schneller Stewart W.
Published: July 2006

The 3-deaza and 7-deaza derivatives of 5'-amino-5'-deoxy-5'-noraristeromycin (6 and 7, respectively) have been prepared from the common starting material (+)-(1R,4S)-4-hydroxycyclopent-2-en-1-yl acetate (8). Two Pd(0)-catalyzed allylic substitution reactions afforded the desired azide intermediates, 12 and 16, which were transformed to target compounds by standard procedures. These compounds were evaluated against a large number of viruses and found to be inactive except for weak effect against hepatitis B virus: 6, EC50 4.7 μM (3TC EC50 0.056 μM); 7, EC50 4.8 μM (3TC EC50 0.063 μM).
Specific incremental field test for aerobic fitness in tennis
Authors: Girard O , Chevalier R , Leveque F , Micallef J P , Millet G P
Published: July 2006

Objectives:To compare metabolic and cardiorespiratory responses between subjects undergoing incremental treadmill (non-specific) and tennis field based (sport specific) tests.

Methods:Nine junior competitive tennis players randomly performed two incremental protocols to exhaustion: a treadmill test (TT) and a tennis specific fitness test (FT). The FT consisted of repeated displacements replicating the game of tennis at increasing speed on a court. In both tests, ventilatory variables and heart rate (HR) were determined at the ventilatory threshold (VT), respiratory compensation point (RCP), and maximal loads (max). Blood lactate concentration was determined at the point of volitional fatigue.

Results:Percentage (mean (SD)) maximal HR (83.6 (5.1)v83.0 (2.8) and 92.1 (2.1)v92.3 (2.1)%, respectively) and percentage maximal oxygen uptake (VO2max) (69.4 (8.1)v73.5 (6.1) and 84.4 (6.5)v85.5 (8.7)%, respectively) at the VT and RCP were not different between the FT and TT subjects, whereas VO2maxwas higher in the FT than in the TT (63.8 (3.0)v58.9 (5.3) ml/min/kg; p<0.05). Blood lactate concentration (10.7 (3.0)v10.6 (4.3) mmol/l) did not differ between the TT and FT.

Conclusions:Although cardiorespiratory variables were not different at submaximal intensities between the two tests, VO2maxvalues derived from laboratory measurements were underestimated. Using field testing in addition to treadmill testing provides a better measurement of a player’s individual fitness level and may be routinely used to accurately prescribe appropriate aerobic exercise training.
TWO PARALLEL 1-D FFT ALGORITHMS WITHOUT ALL-TO-ALL COMMUNICATION
Authors: AL NA'MNEH RAMI , PAN W. DAVID , YOO SEONG-MOO
Published: July 2006

Computing the 1-D Fast Fourier Transform (FFT) using the conventional six-step FFT algorithm on parallel computers requires intensive all-to-all communication due to the necessity of matrix transpose in three steps. This all-to-all communication is a limiting factor in improving the performance of FFT in its parallel implementations. In this paper, we present two parallel algorithms for implementing the 1-D FFT without all-to-all communication between processors, at the expense of increased inner-processor computation as compared to the conventional six-step FFT algorithm. Our analysis reveals the advantage of these two algorithms over the six-step FFT algorithm in parallel systems where the cost of inter-processor communication outweighs the cost of inner-processor computation. As a case study, we choose a 32-node Beowulf cluster with fast processors (running at 2 GHz) but relatively slow inter-processor communication (over a 100 Mbit/s switch). Simulation results on this cluster demonstrate that the proposed no-communication FFT algorithms can achieve a speedup ranging from 1.1 to 1.5 over the six-step FFT algorithm.
CacheFlow: Cache Optimizations for Data Driven Multithreading
Authors: Kyriacou Costas , Evripidou Paraskevas , Trancoso Pedro
Published: July 2006

Data-Driven Multithreading is a non-blocking multithreading model of execution that provides effective latency tolerance by allowing the computation processor do useful work, while a long latency event is in progress. With the Data-Driven Multithreading model, a thread is scheduled for execution only if all of its inputs have been produced and placed in the processor's local memory. Data-driven sequencing leads to irregular memory access patterns that could affect negatively cache performance. Nevertheless, it enables the implementation of short-term optimal cache management policies. This paper presents the implementation of CacheFlow, an optimized cache management policy which eliminates the side effects due to the loss of locality caused by the data-driven sequencing, and reduces further cache misses. CacheFlow employs thread-based prefetching to preload data blocks of threads deemed executable. Simulation results, for nine scientific applications, on a 32-node Data-Driven Multithreaded machine show an average speedup improvement from 19.8 to 22.6. Two techniques to further improve the performance of CacheFlow, conflict avoidance and thread reordering, are proposed and tested. Simulation experiments have shown a speedup improvement of 24% and 32%, respectively. The average speedup for all applications on a 32-node machine with both optimizations is 26.1.
Ultrastructural remodeling of fast skeletal muscle fibers induced by invalidation of creatine kinase
Authors: Novotová Marta , Pavlovičová Michaela , Veksler Vladimir I. , Ventura-Clapier Renée , Zahradník Ivan
Published: July 2006

Understanding muscle adaptation to various stimuli is difficult because of the complex nature of stimuli and responses. In particular, responses to perturbations in energy metabolism require careful examination, because they may involve both structural and functional elements. To estimate the structural component of the myocyte adaptation to energetic deficiency, we used transgenic mice with blocked expression of mitochondrial and cytosolic creatine kinases (CK). The ultrastructure was analyzed using the stereological method of vertical sections applied to electron microscopic images of ultrathin longitudinal sections of fast muscle fibers of gastrocnemius, known to adapt to CK deficiency by increasing oxidative metabolism. The lack of CK induced a profound structural adaptation response that included changes in the volume and surface densities of major organelles. In addition, using a new stereological parameter, the environment of an organelle, substantial changes in the mitochondrial neighborhood were identified pointing to their relocation closer to the major sites of energy consumption, supposedly to compensate for invalidated energy transfer. Using quantitative arguments, we have shown for the first time that spatial relations among organelles of muscle cells undergo adaptation in response to nonstructural stimuli like metabolic deficiency.
AKT phosphorylation is essential for insulin-induced relaxation of rat vascular smooth muscle cells
Authors: Lee Jin Hee , Ragolia Louis
Published: July 2006

Insulin resistance, a major factor in the development of type 2 diabetes, is known to be associated with defects in blood vessel relaxation. The role of Akt on insulin-induced relaxation of vascular smooth muscle cell (VSMC) was investigated using siRNA targeting Akt (siAKTc) and adenovirus constructing myristilated Akt to either suppress endogenous Akt or overexpress constitutively active Akt, respectively. siAKTc decreased both basal and insulin-induced phosphorylations of Akt and glycogen synthase kinase 3β, abolishing insulin-induced nitric oxide synthase (iNOS) expression. cGMP-dependent kinase 1α (cGK1α) and myosin-bound phosphatase (MBP) activities, both downstream of iNOS, were also decreased. siAKTc treatment resulted in increased insulin and ANG II-stimulated phosphorylation of contractile apparatus, such as MBP substrate (MYPT1) and myosin light chain (MLC20), accompanied by increased Rho-associated kinase α (ROKα) activity, demonstrating the requirement of Akt for insulin-induced vasorelaxation. Corroborating these results, constitutively active Akt upregulated the signaling molecules involved in insulin-induced relaxation such as iNOS, cGK1α, and MBP activity, even in the absence of insulin stimulation. On the contrary, the contractile response involving the phosphorylation of MYPT1 and MLC20, and increased ROKα activity stimulated by ANG II were all abolished by overexpressing active Akt. In conclusion, we demonstrated here that insulin-induced VSMC relaxation is dependent on Akt activation via iNOS, cGK1α, and MBP activation, as well as the decreased phosphorylations of MYPT1 and MLC20 and decreased ROKα activity.
Mapping of the Functional Interconnections Between Thalamic Reticular Neurons Using Photostimulation
Authors: Lam Ying-Wan , Nelson Christopher S. , Sherman S. Murray
Published: July 2006

The thalamic reticular nucleus is strategically located in the axonal pathways between thalamus and cortex, and reticular cells exert strong, topographic inhibition on thalamic relay cells. Although evidence exists that reticular neurons are interconnected through conventional and electrical synapses, the spatial extent and relative strength of these synapses are unclear. To address these issues, we used uncaging of glutamate by laser-scanning photostimulation to provide precisely localized and consistent activation of reticular cell bodies and dendrites in an in vitro slice preparation from the rat as a means to study reticulo-reticular connections. Among the 47 recorded reticular neurons, 29 (62%) received GABAergic axodendritic input from an area immediately surrounding each of the recorded cell bodies, and 8 (17%) responded with depolarizing spikelets, suggesting inputs through electrical synapses. We also found that TTX completely blocked all evoked IPSCs, implying that any dendrodendritic synapses between reticular cells either are relatively weak, have no nearby glutamatergic receptors, or are dependent on back-propagation of action potentials. Finally, we showed that the GABAergic connections between reticular cells are weaker than those from reticular cells to relay cells. Our results suggest that the GABAergic axodendritic synapse is the dominant form of reticulo-reticular connectivity, and because they are much weaker than the reticulo-relay cell synapses, their functional purpose may be to regulate the spatial extent of the reticular inhibition on relay cells.
Circulating Tumor Cells at Each Follow-up Time Point during Therapy of Metastatic Breast Cancer Patients Predict Progression-Free and Overall Survival
Authors: Hayes Daniel F. , Cristofanilli Massimo , Budd G. Thomas , Ellis Matthew J. , Stopeck Alison , Miller M. Craig , Matera Jeri , Allard W. Jeffrey , Doyle Gerald V. , Terstappen Leon W.W.M.
Published: July 2006

Purpose: We reported previously that ≥5 circulating tumor cells (CTC) in 7.5 mL blood at baseline and at first follow-up in 177 patients with metastatic breast cancer (MBC) were associated with poor clinical outcome. In this study, additional follow-up data and CTC levels at subsequent follow-up visits were evaluated.

Experimental Design: CTCs were enumerated in 177 MBC patients before the initiation of a new course of therapy (baseline) and 3 to 5, 6 to 8, 9 to 14, and 15 to 20 weeks after the initiation of therapy. Progression-free survival (PFS) and overall survival (OS) times were calculated from the dates of each follow-up blood draw. Kaplan-Meier plots and survival analyses were done using a threshold of ≥5 CTCs/7.5 mL at each blood draw.

Results: Median PFS times for patients with <5 CTC from each of the five blood draw time points were 7.0, 6.1, 5.6, 7.0, and 6.0 months, respectively. For patients with ≥5 CTC, median PFS from these same time points was significantly shorter: 2.7, 1.3, 1.4, 3.0, and 3.6 months, respectively. Median OS for patients with <5 CTC from the five blood draw time points was all >18.5 months. For patients with ≥5 CTC, median OS from these same time points was significantly shorter: 10.9, 6.3, 6.3, 6.6, and 6.7 months, respectively. Median PFS and OS times at baseline and up to 9 to 14 weeks after the initiation of therapy were statistically significantly different.

Conclusions: Detection of elevated CTCs at any time during therapy is an accurate indication of subsequent rapid disease progression and mortality for MBC patients.
Mouse Models of Lung Cancer
Authors: Dutt Amit , Wong Kwok-Kin
Published: July 2006

Human lung cancer is responsible for ∼30% of all cancer deaths worldwide with >160,000 deaths in the United States alone annually. Recent advances in the identification of novel mutations relevant to lung cancer from a myriad of genomic studies might translate into meaningful diagnostic and therapeutic progress. Towards this end, a genetic model animal system that can validate the oncogenic roles of these mutations in vivo would facilitate the understanding of the pathogenesis of lung cancer as well as provide ideal preclinical models for targeted therapy testing. The mouse is a promising model system, as complex human genetic traits causal to lung cancer, from inherited polymorphisms to somatic mutations, can be recapitulated in its genome via genetic manipulation. We present here a brief overview of the existing mouse models of lung cancers and the challenges and opportunities for building the next generation of lung cancer mouse models.
Novel Combinations Based on Epidermal Growth Factor Receptor Inhibition
Authors: Adjei Alex A.
Published: July 2006

In spite of recent advances in molecular biology leading to the introduction of clinically active novel agents, such as imatinib, erlotinib, and bevacizumab, therapy of the most common epithelial tumors, such as lung cancer, remains unsuccessful. The diversity of molecular abnormalities in these tumors is felt to partly contribute to their resistance to therapy. It is, therefore, widely accepted that one approach to improving the efficacy of cancer therapy is the development of rational, hypothesis-based combinations of anticancer agents that may exhibit synergistic cytotoxic interactions. A number of empirical combination studies with the epidermal growth factor receptor and classic cytotoxic agents were undertaken in clinical trials, with disappointing results. It is, therefore, felt that preclinical combinations of epidermal growth factor receptor inhibitors and other novel agents, based on sound knowledge of complementary signaling pathways whose concerted inhibition would be hypothesized to inhibit growth, is the reasonable approach in the future. A brief overview of some of these pathways (mammalian target of rapamycin, vascular endothelial growth factor receptor, and ras/mitogen-activated protein kinase signaling) is provided in this review.
Manuscripts as Sources for Linguistic Research
Authors: Grund Peter
Published: July 2006

This article explores the problematic issue of using editions as sources for studies of English historical morpho-syntax. It presents a methodological case study of the variation between he and it in reference to inanimate objects (such as mercury) in Mirror of Lights, an alchemical text that survives in multiple copies from the fifteenth and sixteenth centuries. The study reveals that the manuscript versions differ greatly in how they employ he and it, underscoring that linguistic studies based on one version would provide very different results from those using another version as the source. The article argues that it is crucial that such manuscript variation is taken into consideration in morpho-syntactic studies. It suggests that an electronic edition that incorporates all copies of the text would make the full variation available to linguists, while a traditional critical edition would highlight the pattern of one version but obscure or ignore the patterns of other manuscripts. The article also discusses the more general problem of including a multiversion text such as the Mirror of Lights into a corpus and suggests some possible solutions.
A combined approach to data mining of textual and structured data to identify cancer-related targets
Authors: Pospisil Pavel , Iyer Lakshmanan K , Adelstein S James , Kassis Amin I
Published: July 2006

Background

We present an effective, rapid, systematic data mining approach for identifying genes or proteins related to a particular interest. A selected combination of programs exploring PubMed abstracts, universal gene/protein databases (UniProt, InterPro, NCBI Entrez), and state-of-the-art pathway knowledge bases (LSGraph and Ingenuity Pathway Analysis) was assembled to distinguish enzymes with hydrolytic activities that are expressed in the extracellular space of cancer cells. Proteins were identified with respect to six types of cancer occurring in the prostate, breast, lung, colon, ovary, and pancreas.

Results

The data mining method identified previously undetected targets. Our combined strategy applied to each cancer type identified a minimum of 375 proteins expressed within the extracellular space and/or attached to the plasma membrane. The method led to the recognition of human cancer-related hydrolases (on average, ~35 per cancer type), among which were prostatic acid phosphatase, prostate-specific antigen, and sulfatase 1.

Conclusion

The combined data mining of several databases overcame many of the limitations of querying a single database and enabled the facile identification of gene products. In the case of cancer-related targets, it produced a list of putative extracellular, hydrolytic enzymes that merit additional study as candidates for cancer radioimaging and radiotherapy. The proposed data mining strategy is of a general nature and can be applied to other biological databases for understanding biological functions and diseases.
Expression of mammalian GPCRs in C. elegansgenerates novel behavioural responses to human ligands
Authors: Teng Michelle S , Dekkers Martijn PJ , Ng Bee Ling , Rademakers Suzanne , Jansen Gert , Fraser Andrew G , McCafferty John
Published: July 2006

Background

G-protein-coupled receptors (GPCRs) play a crucial role in many biological processes and represent a major class of drug targets. However, purification of GPCRs for biochemical study is difficult and current methods of studying receptor-ligand interactions involvein vitrosystems.Caenorhabditis elegansis a soil-dwelling, bacteria-feeding nematode that uses GPCRs expressed in chemosensory neurons to detect bacteria and environmental compounds, making this an ideal system for studyingin vivoGPCR-ligand interactions. We sought to test this by functionally expressing two medically important mammalian GPCRs, somatostatin receptor 2 (Sstr2) and chemokine receptor 5 (CCR5) in the gustatory neurons ofC. elegans.

Results

Expression of Sstr2 and CCR5 in gustatory neurons allowC. elegansto specifically detect and respond to somatostatin and MIP-1α respectively in a robust avoidance assay. We demonstrate that mammalian heterologous GPCRs can signal via different endogenous Gαsubunits inC. elegans, depending on which cells it is expressed in. Furthermore, pre-exposure of GPCR transgenic animals to its ligand leads to receptor desensitisation and behavioural adaptation to subsequent ligand exposure, providing further evidence of integration of the mammalian GPCRs into theC. eleganssensory signalling machinery. In structure-function studies using a panel of somatostatin-14 analogues, we identified key residues involved in the interaction of somatostatin-14 with Sstr2.

Conclusion

Our results illustrate a remarkable evolutionary plasticity in interactions between mammalian GPCRs andC. eleganssignalling machinery, spanning 800 million years of evolution. Thisin vivosystem, which imparts novel avoidance behaviour onC. elegans, thus provides a simple means of studying and screening interaction of GPCRs with extracellular agonists, antagonists and intracellular binding partners.
Wnt2b/β-catenin-mediated canonical Wnt signaling determines the peripheral fates of the chick eye
Authors: Cho Seo-Hee , Cepko Constance L.
Published: July 2006

Wnt signaling orchestrates multiple aspects of central nervous system development, including cell proliferation and cell fate choices. In this study, we used gene transfer to activate or inhibit canonical Wnt signaling in vivo in the developing eye. We found that the expression of Wnt2b or constitutively active (CA) β-catenin inhibited retinal progenitor gene(RPG) expression and the differentiation of retinal neurons. In addition, Wnt signal activation in the central retina was sufficient to induce the expression of markers of the ciliary body and iris, two tissues derived from the peripheral optic cup (OC). The expression of a dominant-negative (DN)allele of Lef1, or of a Lef1-engrailed fusion protein, led to the inhibition of expression of peripheral genes and iris hypoplasia, suggesting that canonical Wnt signaling is required for peripheral eye development. We propose that canonical Wnt signaling in the developing optic vesicle (OV) and OC plays a crucial role in determining the identity of the ciliary body and iris. Because wingless (wg) plays a similar role in the induction of peripheral eye tissues of Drosophila, these findings indicate a possible conservation of the process that patterns the photoreceptive and support structures of the eye.
Arabidopsis SPA proteins regulate photoperiodic flowering and interact with the floral inducer CONSTANS to regulate its stability
Authors: Laubinger Sascha , Marchal Virginie , Gentilhomme José , Wenkel Stephan , Adrian Jessika , Jang Seonghoe , Kulajta Carmen , Braun Helen , Coupland George , Hoecker Ute
Published: July 2006

The four-member SPA protein family of Arabidopsis acts in concert with the E3 ubiquitin ligase COP1 to suppress photomorphogenesis in dark-grown seedlings. Here, we demonstrate that SPA proteins are, moreover, essential for photoperiodic flowering. Mutations in SPA1 cause phyA-independent early flowering under short day (SD) but not long day (LD) conditions, and this phenotype is enhanced by additional loss of SPA3 and SPA4 function. These spa1 spa3 spa4 triple mutants flower at the same time in LD and SD, indicating that the SPA gene family is essential for the inhibition of flowering under non-inductive SD. Among the four SPA genes, SPA1 is necessary and sufficient for normal photoperiodic flowering. Early flowering of SD-grown spa mutant correlates with strongly increased FT transcript levels, whereas COtranscript levels are not altered. Epistasis analysis demonstrates that both early flowering and FT induction in spa1 mutants is fully dependent on CO. Consistent with this finding, SPA proteins interact physically with CO in vitro and in vivo, suggesting that SPA proteins regulate CO protein function. Domain mapping shows that the SPA1-CO interaction requires the CCT-domain of CO, but is independent of the B-box type Zn fingers of CO. We further show that spa1 spa3 spa4 mutants exhibit strongly increased CO protein levels, which are not caused by a change in COgene expression. Taken together, our results suggest, that SPA proteins regulate photoperiodic flowering by controlling the stability of the floral inducer CO.
Short-term energy regulation of whitebellied sunbirds (Nectarinia talatala): effects of food concentration on feeding frequency and duration
Authors: Köhler A. , Verburgt L. , Nicolson S. W.
Published: July 2006

Avian nectarivores show compensatory feeding by adjusting their volumetric intake in response to variation in nectar concentration. This study used an infrared photo-detection system to investigate the short-term feeding patterns of whitebellied sunbirds (Nectarinia talatala) consuming three different sucrose concentrations (10, 20 and 30% w/w). Sunbirds increased their feeding frequency on the most dilute diet, but there was no change in feeding duration. Thus, the increase in total time spent feeding on the dilute diet was due to the increased feeding frequency. No difference in short-term feeding patterns was found between the 20% and 30% diets. Total time spent feeding was extremely short on all diets (96-144 s in every hour). Birds maintained the same steady increase in body mass over the course of the day on all three diets. Daily rhythms in feeding patterns were evident, with longer feeding duration and lower feeding frequency in the early morning and evening than during the rest of the day. Because ingestion rates on a particular diet may vary through the day, caution must be exercised in using feeding duration as a surrogate for meal size. Individual birds varied greatly in their feeding patterns irrespective of diet concentration.
The Heats of Dilution in Atactic Polymethyl Methacrylate Solutions
Authors: Kagemoto Akihiro , Murakami Sachio , Fujishiro Ryoichi
Published: July 2006

In order to ascertain the dependence of the interaction parameter, χH, between the polymer and the solvent molecules on the polymer concentration, the heats of dilution in an atactic polymethyl methacrylate solution have been measured for the polymers with the degrees of polymerization of 3000 and 7800. It was found that the values of χH obtained are dependent on the concentration in all the solvents used, as in the solutions of polystyrene and polybutadiene reported as in previous papers. χH depends also on the molecular weight, this is in agreement with the suggestion by Huggins (J. Am. Chem. Soc., 86, 3535 (1964)).
A Spectrophotometric Study on the Thorium Complex of o-Carboxyphenyl-azo-chromotropic Acid
Authors: Tôei Kyoji , Miyata Haruo , Harada Takuji
Published: July 2006

o-Carboxyphenyl-azo-chromotropic acid was synthesized as a colorimetric reagent for thorium. The acid dissociation constants of the reagent have been determined spectrophotometrically at 25°C and μ=0.1 (NaClO4). The pK1 (for the dissociation of the carboxyl group) and the pK2 (for the dissociation of the naphtholic hydroxyl groups) were 3.20 and 10.17 respectively. The reagent forms a violet 1 : 1 complex with thorium, showing an absorption maximum at 565 mμ in an acidic solution. The apparent stability constant of the thorium complex was measured spectrophotometrically.
The Syntheses of Benzofuran-carboxylic Acids and the Acetylation of Their Esters
Authors: Kawase Yoshiyuki , Takashima Matsuko
Published: July 2006

Acetyl derivatives of 2, 3-dimethylbenzofuran and their methyl homologs were derived into the corresponding carboxylic acids by the haloform reaction, and the acetylation of thier esters by the Friedel-Crafts reaction was studied. The keto-esters obtained were hydrolyzed to give keto-acids, which were then further oxidized into dicarboxylic acids by the haloform reaction and decarboxylated to acetylbenzofurans. On the other hand, the dicarboxylic acids were also obtained by the oxidation of diacetylbenzofurans. By the haloform reaction of hindered acetyl compounds, we obtained only halogenated ketones, which it was difficult to hydrolyze to give carboxylic acids. After the structures of these products had been determined and compared, it became clear that the acetylation of 5-alkoxycarbonyl-2, 3-dimethylbenzofurans furnished the 6-acetylated compounds, while that of 6-alkoxycarbonyl compounds and their methyl homologs furnished the 4-acetylated compounds.
Studies of the ζ-Potential of Natural and Synthetic Fibers in Dye Solutions. XVII. ζ-Potential and Surface Dyeability of Drawn Nylon 6 Fiber in an Acid Dye Solution
Authors: Suzawa Toshiro , Saito Tomoyuki , Shinohara Hideki
Published: July 2006

In order to ascertain the relation between the change in the fine structure and the dyeability of the nylon 6 fiber with its drawing, the ζ-potential, the surface dye adsorption, and the total dye adsorption of the drawn nylon 6 fiber in an acidic solution (pH 3.0) of acid dye—Orange II and Orange I were determined. The crystallinity and the birefringence of the fiber increase as the draw ratio increases. The isoelectric points of the fibers with the draw ratios of 1 (undrawn), 3, and 4 are pH 5.2, pH 5.4, and pH 5.4 respectively. The increase in the dye concentration changed the sign of the ζ-potential of these fibers in a dye solution from positive to negative and increased the absolute values of the ζ-potential. Moreover, it was suggested that these fibers combine with dye by electrostatic bonds. The surface dye adsorption as calculated from the difference between the surface charge density, Δσ, of the system with dye and that without dye increased in any case as the dye concentration increased. These values became smaller in the order of draw ratios: 1 (undrawn), 3, and 4. The total dye adsorption as well as the surface dye adsorption increased with the increase in the dye concentration and decreased with the drawing. Moreover, the surface areas covered by adsorbed dye molecules, which were calculated from the slope of the graph between the surface dye adsorption and the total dye adsorption, were 4.4, 2.9, and 1.8×106cm2/g fiber in the order of draw ratios: 1 (undrawn), 3, and 4. Also, the effect of the molecular structure of the dye on the ζ-potential, the surface dye adsorption, and the total dye adsorption was discussed.
Polarographic Behavior of Diethylenetriaminepentaacetic Acid at the Dropping Mercury Electrode
Authors: Kodama Mutsuo , Kimura Akiko
Published: July 2006

Anodic waves of DTPA at DME in the presence and in the absence of calcium(II) and magnesium(II) ions were studied systematically, and the stability constants of mercury(II)-DTPA chelates were determined. The electrode reaction for the anodic waves of DTPA proceeds reversibly in a polarographic sense. In the presence of magnesium(II) ions, however, DTPA gives an irreversible wave. This may be ascribed to the slow reaction of the magnesium(II)-DTPA chelate. The use of DTPA as a titrant in the amperometric titration of metal ions which do not yield a polarographic wave under the usual polarographic conditions was also discussed briefly.
The Cyclization of Ethyl Cyanoacetate and Ketones by Ammonium Acetate
Authors: Sakurai Akio , Midorikawa Hiroshi
Published: July 2006

It was found that a cyclized product containing one nitrogen atom could be obtained by the reaction of ethyl cyanoacetate with various ketones in the presence of excessive ammonium acetate. On the basis of this experiment, pyridone derivatives such as 3-cyano-5,6-dihydro-4,6-dialkyl-6-methyl-2-pyridones (I), pyridine derivatives such as 3-cyano-4,6-dialkyl-2-hydroxypyridines (IV), quinoline derivatives such as 4-alkyl-3-cyano-2-hydroxy-5,6,7,8-tetrahydroquinolines (VII), and related heterocyclic compounds were prepared.
Heat Capacities and Thermodynamic Properties of Ammonium Nitrate Crystal: Phase Transitions between Stable and Metastable Phases
Authors: Nagatani Masanori , Seiyama Tetsuro , Sakiyama Minoru , Suga Hiroshi , Seki Syûzô
Published: July 2006

The heat capacities of ammonium nitrate were measured between 15 and 410°K for the stable and metastable phases by use of adiabatic- and conduction-type calorimeters. The phase transformations between stable phases; i.e., V–IV, IV–III, III–II and II–I, and the metastable one between IV and II, were all found to be of first-order type. The direct transition between V and II, which is only realized for the sample treated with a minute amount of surface active agent, was ascertained to be typical higher-order type. Heat and entropy of transition of five kinds of transitions were determined. These results conclude that the heat capacity data by Stephenson et  al. at low temperature region are much more reliable than the recent values by Eichenauer et  al. The possibility of the existence of the seventh phase below 156°K has been proposed.
Studies of the Alkaline Earth Complexes in Various Solutions. III. Calcium(II) and Strontium(II) Complexes with Sulfate and Oxalate Ions in 1m Perchlorate Media
Authors: Hasegawa Yuko , Maki Kiyohiko , Sekine Tatsuya
Published: July 2006

The complex formation of calcium and strontium with sulfate and oxalate ions has been studied in 1 m perchlorate media at 25 °C by a liquid-liquid distribution method. The radioisotopes, calcium-45 and strontium-85 at tracer concentrations were used in conjunction with, thenoyltrifluoroacetone in methylisobutylketone or in carbon tetrachloride containing tributyl-phosphate. The complex formation was determined by a graphical method from the decrease in the extraction of the metal ions with the increases in the concentration of sulfate or oxalate ions in the aqueous phase. The results were explained by the formation of the first and the second complexes, and the stability constants, βn=[MLn2−2n]⁄[M2+][L2−]n, were determined as follows; Sulfate systems, Ca(II): logβ1=1.10, logβ2=1.36, Sr(II): log⁄β1=0.72, logβ2=1.29. Oxalate systems, Ca(II): logβ1=1.66, logβ2=2.69, Sr(II): logβ1=1.25, logβ2=1.90.
Kinetic Study of the Reaction between Uranium Monocarbide and Water Vapor
Authors: Hori Yoshio , Mukaibo Takashi
Published: July 2006

The rate of the reaction between uranium monocarbide and water vapor was investigated in a flow system under the conditions of 53–90°C and 20–120 mmHg. The rate of evolution and the composition of gases were measured by means of a gas chromatograph. The reaction versus time curve was sigmoid-shaped and found to be divided into three parts. Avrami’s equation for nucleation and growth fit the first part. The second part was expressed by a quasi first order reaction. Rate constants for the first and the second parts were found to depend on the water vapor pressure, obeying Langmuir’s adsorption isotherm. The activation energy for reaction and the heat of adsorption for the first part were determined to be 13.0 and 3.9 kcal/mol respectively.
Studies of Organic Peroxides. X. The Reaction of Benzoyl Peroxide with Secondary Amines
Authors: Kashino Setsuo , Mugino Yutaka , Hasegawa Shigeo
Published: July 2006

The reaction of benzoyl peroxide with secondary amines, namely diphenylamine, diethylamine, piperidine and pyrrolidine was studied in benzene. The rates of reactions were followed by the thermal analysis and the titration method. The rates of reactions of these amines increase in the order diethylamine<diphenylamine<piperidine<pyrrolidine. The effect of the p, p′-substituents of benzoyl peroxide on the reaction rate was examined. The Hammett relationship with respect to p, p′-substituents held for all amines with positive ρ values. It was concluded that the reactions involve nucleophilic attack by the amines on the peroxide. Stoichiometry of the reaction was also examined by the method of thermal analysis. Diethylamine reacts with the peroxide in the 2 : 1 amine-peroxide ratio, while piperidine about 1.3 : 1 and diphenylamine 0.6 : 1, respectively. ESR spectra showed that diphenylamine and diethylamine produce fairly stable free radicals in low yields, while piperidine and pyrrolidine do not yield, detectable free radicals.
The Synthesis of Cyclic α-Amino Acids. I
Authors: Umezawa Sumio , Kinoshita Mitsuhiro , Yanagisawa Hiroaki
Published: July 2006

The reactions of α, β-unsaturated α-nitroesters with dienes produced cyclic α-nitroesters. In all cases, a mixture of diastereoisomers was obtained. Catalytic hydrogenation, followed by hydrolysis, gave a number of cyclic α-amino acids which are closely related to natural terpenes. The NMR spectra of some of these compounds were useful in making structural assignments.
Copolymerization of Cyclic Olefins, Trimethylethylene and Tetramethylethylene with Acrylonitrile
Authors: Yasufuku Katsutoshi , Nozakura Shun’ichi , Murahashi Shunsuke
Published: July 2006

The radical copolymerizations of cyclopentene, cyclohexene, cycloheptene, cyclooctene, trimethyl-, and tetramethyl-ethylene with acrylonitrile (AN, M1) were carried out, and the reactivities of these monomers toward the AN radical (1/r1) were found to be as follows: cyclopentene, 0.21; cyclohexene, 0.13; cycloheptene, 0.15; cyclooctene, 0.35; trimethylethylene, 0.37, and tetramethylethylene, 0.25. The reactivity of these internal olefins in radical polymerization was discussed.
Studies on Geometric Isomerism by Nuclear Magnetic Resonance. IV. Structure of α-Cyano-β-amino-β-alkylacrylic Esters
Authors: Hayashi Toshio , Hori Isaburo , Baba Hideo , Midorikawa Hiroshi
Published: July 2006

The NMR spectra of α-cyano-β-amino-β-alkylacrylic esters prepared from α-cyano-β-methoxy-β-alkylacrylic esters and simple amines have been studied. It has been found that these aminoesters, in a variety of solvents, are all present in an intramolecular hydrogen-bonded enamine form with a chelate ring.