bluuebunny/crossref_metadata_2025 huggingface dataset:
Formation processes at the Ohalo II submerged prehistoric campsite, Israel, inferred from soil micromorphology and magnetic susceptibility studies
Authors: Tsatskin Alexander , Nadel Dani
Published: March 2003

Soil‐geomorphic analysis coupled with micromorphology, SEM/EDS, magnetic susceptibility, and conventional sedimentological studies allowed us to reconstruct the site formation history and validate the archaeologically observed variability of human activities in the prehistoric camp of Ohalo II (19.5 ka B.P.), Sea of Galilee, Israel. The cultural layers rest upon the Late Pleistocene Lake Lisan deposits that accumulated under conditions of changing water supply and increasing rate of sedimentation from deep‐water varvelike deposits to basalt‐derived, near‐shore sandy lacustrine deposits. Intermittent occupation is recorded in some localities, indicating short‐term inundation episodes, which led to partial truncation and deformation of the sediments, primarily in the eastern lakeward part of the site. On the elevated, landward positions, incipient soils with strongly bioturbated profiles formed. Micromorphology demonstrates that intentional flooring was applied within the remains of brush huts, where millimeter‐sized, horizontally organized burnt and unheated vegetal tissues were likely to have been placed upon the compacted ground. In fireplaces, the cultural deposits in thin sections are composed of strongly mixed, abundant wood charcoal, ashes, and fishbone remains. Post‐depositional alterations were controlled by intermittent inundation of the site and salinization, which induced gypsum and pyrite deposition, primarily along decayed roots, and eventual pyrite oxidation. Accumulation of sodium and chlorine in the post‐occupation deposits is likely to have occurred because of discharge of saline groundwater. Although only suggestive at this stage of research, the conclusions drawn from magnetic susceptibility parameters of archaeologically related deposits at Ohalo II fit well with the micromorphological reconstructions and provide new information on the Late Pleistocene evolution of the Lake Lisan/Sea of Galilee fluctuating system. © 2003 Wiley Periodicals, Inc.
Stage specific inhibition of osteoblast lineage differentiation by FGF2 and noggin
Authors: Kalajzic I. , Kalajzic Z. , Hurley M.M. , Lichtler A.C. , Rowe David W.
Published: March 2003

Fibroblast growth factor 2 (FGF2) and noggin are two unrelated ligands of two distinctly different signaling pathways that have a similar inhibitory effect on osteoblast differentiation. Because of their differences, we postulated that they probably acted at a different stage within the osteoprogenitor differentiation pathway. This study was performed on primary murine bone cell cultures under conditions where alkaline phosphatase (AP) and type I collagen expression (Col1a1) were observed by day 7 (preosteoblast stage), followed by bone syaloprotein (BSP) at day 11 (early osteoblast) and osteocalcin (OC) by day 15–18 (mature osteoblast stage). FGF2 completely inhibited expression of AP and the mRNA transcript for Col1a1, while noggin showed only a partial inhibition of these markers of preosteoblast differentiation. However, the markers of differentiated osteoblasts (BSP and OC) were completely inhibited in both the FGF2 and noggin treated cultures, suggesting that noggin acts at later point in the osteoprogenitor differentiation pathway than FGF2. To further verify that the inhibition was occurring at a different stage of osteoblasts development, primary cultures derived from transgenic mice harboring segments of the collagen promoter driving green fluorescent protein (GFP) that activate at different levels of osteoblast differentiation were analyzed. Consistent with the endogenous markers, pOBCol3.6GFP and pOBCOL2.3GFP transgene activity was completely inhibited by continuous addition of FGF2, while noggin showed partial inhibition of pOBCol3.6GFP and complete inhibition of the pOBCol2.3GFP transgene. Upon removal of either agent, endogenous and GFP markers of osteoblast differentiation reappeared although at a different temporal pattern. This work demonstrates that FGF2 and noggin can reversibly modulate osteoblast lineage differentiation at different maturational stages. These agents may be useful to enrich for and maintain a population of osteoprogenitor cells at a defined stage of differentiation. J. Cell. Biochem. 88: 1168–1176, 2003. © 2003 Wiley‐Liss, Inc.
Capacitative calcium influx in human epithelial breast cancer and non‐tumorigenic cells occurs through Ca2+ entry pathways with different permeabilities to divalent cations
Authors: Baldi Carolina , Vazquez Guillermo , Boland Ricardo
Published: March 2003

The operation of capacitative Ca2+ entry (CCE) in human breast cancer (SKBR3) and non‐tumorigenic (HBL100) cell lines was investigated as an alternative Ca2+ entry route in these cells. Ca2+ readdition after thapsigargin‐induced store depletion showed activation of CCE in both cell lines. SKBR3 cells exhibited retarded store depletion and CCE decay kinetics compared to the non‐tumorigenic HBL100 cells, suggesting alterations in Ca2+ homeostasis. CCE was also highly permeable to Mn2+ and to a lesser extent to Sr2+, but not to Ba2+. In HBL100 cells, CCE is contributed (30%) by a Ca2+/Mn2+ permeable route insensitive to low (1 μM) Gd3+ and a Ca2+/Sr2+/Mn2+ permeable non‐selective pathway (70%) sensitive to 1 μM Gd3+. In SKBR3 cells, the relative contribution to CCE of both routes was opposite to that in non‐tumorigenic cells. J. Cell. Biochem. 88: 1265–1272, 2003. © 2003 Wiley‐Liss, Inc.
Inhibition of phosphatidylinositol 3‐kinase and p70S6 kinase blocks osteogenic protein‐1 induction of alkaline phosphatase activity in fetal rat calvaria cells
Authors: Shoba Lungile N.N. , Lee John C.
Published: March 2003

Published studies reveal that Osteogenic Protein‐1 (OP‐1) and insulin‐like growth factor‐I (IGF‐I) synergistically stimulate alkaline phosphatase (AP) activity and bone nodule formation in fetal rat calvaria (FRC) cells. In the present study, we examined whether there are interactions between the signal transduction pathways activated by these two growth factors. OP‐1 did not significantly affect the levels of IRS‐1, IRS‐2, the p85α subunit of phosphatidylinositol 3‐kinase (PI 3‐kinase) or the extracellular signal‐regulated kinase (ERK)‐2, but stimulated ERK‐1 protein by twofold. OP‐1 also induced phosphorylation of ERK‐1 and ‐2, but not of Akt/protein kinase B (PKB), a protein kinase that is downstream of PI 3‐kinase. By comparison, IGF‐I increased the levels of the phosphorylated forms of ERK‐1 and ‐2, and Akt/PKB. Inhibition of ERK activation by PD98059 did not significantly alter the stimulation of AP activity by OP‐1 or OP‐1 in combination with IGF‐I. In contrast, inhibition of PI 3‐kinase activity by LY294002 blocked the induction of AP activity by OP‐1 and OP‐1 plus IGF‐I. Treatment of cells with rapamycin, an inhibitor of the mammalian target of mTOR, resulted in a 47% and a 53% decrease in the AP activity induced by OP‐1 alone and by OP‐1 plus IGF‐I, respectively. These studies suggest that PI 3‐kinase and mTOR contribute to the induction of AP activity by OP‐1 and the synergistic effect of OP‐1 and IGF‐I on AP activity in FRC cells. J. Cell. Biochem. 88: 1247–1255, 2003. © 2003 Wiley‐Liss, Inc.
A synthetic peptide of link protein stimulates the biosynthesis of collagens II, IX and proteoglycan by cells of the intervertebral disc
Authors: Mwale Fackson , Demers Caroline N. , Petit Alain , Roughley Peter , Poole A. Robin , Steffen Thomas , Aebi Max , Antoniou John
Published: March 2003

To date, there have been no reports on the effect on disc cells of the intervertebral disc (IVD) of the amino terminal peptide of link protein (DHLSDNYTLDHDRAIH) (link N) which is generated by the cleavage of human link protein by stromelysins 1 and 2, gelatinase A and B, and collagenase between His16 and Ile17. However, link N has been shown to act as a growth factor and stimulate synthesis of proteoglycans and collagen by chondrocytes of human articular cartilage. There are also no studies on the effect of link N on type IX collagen in any tissue. In the studies reported here, a serum‐free pellet culture system has been used to examine whether link N can play a role in maintaining the integrity of disc matrix, specifically at the level of matrix assembly by cells of the IVD. Using this culture system, we determined the capacity of link N to stimulate accumulation of these matrix proteins in the annulus fibrosus (AF) and nucleus pulposus (NP). Gross inspection of separate AF and NP pellet cultures in the absence of link N revealed a progressive increase in size and a transition from “spherical” to “polygonal” pellets after centrifugation. Addition of 10 ng/ml link N resulted in increased pellet sizes for both AF and NP pellet cultures. Link N increased proteoglycan, type II and type IX collagen contents with an increase in DNA content over time. This study demonstrates that link N can act directly on disc cells to stimulate matrix production, which involves increased accumulation of proteoglycan, and types II and IX collagens. This study also identifies the value of pellet cultures for studies of the IVD cells in a serum‐free chemically defined medium, in which pellets can continue growing in size in response to growth factors with minimal cell loss. Link N may have value in stimulating the growth and regeneration of the damaged IVD. J. Cell. Biochem. 88: 1202–1213, 2003. © 2003 Wiley‐Liss, Inc.
In silico prediction of drug‐binding strengths to human serum albumin
Authors: Colmenarejo Gonzalo
Published: March 2003

Drug binding to Human Serum Albumin (HSA) is an area of intense research. The pharmacokinetics and pharmacodynamics of drugs are strongly affected by their binding to this protein. In this article, the field is reviewed, as well as our models to predict drug‐binding affinities to HSA from drug structure. The physiological role of HSA is described, as well as its influence in drug action. The crystal structures of this protein are discussed, emphasizing the two drug‐binding sites and the fatty acids binding sites observed therein. The advantages of using high‐performance affinity chromatography to rapidly screen drugs for HSA binding are explained. The different QSAR models for HSA binding of restricted families of drugs (both from other groups and our group) are enumerated. Finally, a detailed description of our general models to predict drug‐binding strengths to HSA from structure is given. It is expected for these models to be useful in drug design and pharmaceutical research. © 2003 Wiley Periodicals, Inc. Med Res Rev, 23, No. 3, 275‐301, 2003
Selection criteria for drug‐like compounds
Authors: Muegge Ingo
Published: March 2003

The fast identification of quality lead compounds in the pharmaceutical industry through a combination of high throughput synthesis and screening has become more challenging in recent years. Although the number of available compounds for high throughput screening (HTS) has dramatically increased, large‐scale random combinatorial libraries have contributed proportionally less to identify novel leads for drug discovery projects. Therefore, the concept of ‘drug‐likeness’ of compound selections has become a focus in recent years. In parallel, the low success rate of converting lead compounds into drugs often due to unfavorable pharmacokinetic parameters has sparked a renewed interest in understanding more clearly what makes a compound drug‐like. Various approaches have been devised to address the drug‐likeness of molecules employing retrospective analyses of known drug collections as well as attempting to capture ‘chemical wisdom’ in algorithms. For example, simple property counting schemes, machine learning methods, regression models, and clustering methods have been employed to distinguish between drugs and non‐drugs. Here we review computational techniques to address the drug‐likeness of compound selections and offer an outlook for the further development of the field. © 2003 Wiley Periodicals, Inc. Med Res Rev, 23, No. 3, 302‐321, 2003
What Determines the Costs of Repair and Rehabilitation of Flexor Tendon Injuries in Zone II? A Multiple Regression Analysis of Data from Southern Sweden
Authors: ROSBERG H. E. , CARLSSON K. S. , HÖJGÅRD S. , LINDGREN B. , LUNDBORG G. , DAHLIN L. B.
Published: March 2003

The epidemiology and costs of repair and rehabilitation of zone II flexor tendon injuries in 135 patients from the southern part of Sweden were analysed. The little finger was most frequently injured (43%), usually with a knife (46%), and 30% of the injuries were work related. Total median costs within the health-care sector for the injuries were SEK 48,500 (1 EURO=9.23 SEK, 4/1/2002). Costs in other sectors were SEK 93,000. Active mobilization or mobilization with rubber band traction increased costs within the health-care sector (SEK 7400 or SEK 6000, respectively) but improved range of movement (5–7%). Immobilization had a higher complication rate (rupture or need for secondary procedures), which in itself increased total costs by 57%. Nonlinear effects were found between age and costs within the health-care sector and the outcome.
Approaching Complex Cases With a Crisis Intervention Model and Teamwork
Authors: O'Daniel Julianne M. , Wells Deborah
Published: March 2003

Patients referred for genetic counseling may be in a state of crisis, feeling as though they are incapable of making decisions about the management of their pregnancy, genetic testing options and/or life planning issues. The role of the genetic counselor is to assist a patient through this crisis state by increasing the patient's understanding and by helping to facilitate decision making and adjustment to those decisions. In this paper we present a clinical genetic counseling case that was complicated by numerous medical and psychosocial issues. The wide scope of this case required the involvement of both a prenatal and a medical genetic counselor. Working as a team we utilized a crisis intervention model. Our counseling focused on identifying and isolating the issues, providing factual information, setting a time frame for decisions to be made, and encouraging social support and emotion‐focused coping strategies.
Antigen Delivery to Mucosa-Associated Lymphoid Tissues Using Liposomes as a Carrier
Authors: Zhou Fan , Neutra Marian R.
Published: March 2003

Oral vaccination requires an antigen delivery vehicle to protect the antigen and to enhance translocation of the antigen to the mucosa-associated lymphoid tissue. A variety of antigen delivery vehicles including liposomes have been studied for mucosal immunization. The advantages of liposome formulations are their particulate form and the ability to accommodate immunomodulators and targeting molecules in the same package. Many conventional liposomes are variably unstable in acids, pancreatic juice and bile. Nevertheless, carefully designed liposomes have demonstrated an impressive efficacy in inducing mucosal IgA responses, compared to free antigens and other delivery vehicles. However, liposomes as an oral vaccine vehicle are not yet optimized. To design liposomes that are stable in the harsh intestinal environment and are efficiently taken up by the M cells remains a challenge. This review summarizes recent research efforts using liposomes as an antigen carrier for oral vaccines with practical attention to liposome designs and interaction with the M cells.
A novel FUCA1 mutation causing fucosidosis in a Chinese boy
Authors: Ip P. , HGoh W. , Chan K. W. , Cheung P. T.
Published: March 2003

We report a 6‐year‐old boy with an intermediate form of fucosidosis.
Cationic Liposome-Mediated Gene Delivery In vivo
Authors: Smyth Templeton Nancy
Published: March 2003

Several improvements have been made in liposomal delivery, thus making this technology potentially useful for treatment of certain diseases in the clinic. Success in non-viral delivery is complicated and requires optimization of several components. These components include nucleic acid purification, plasmid design, formulation of the delivery vehicle, administration route and schedule, dosing, detection of gene expression, and others. With further improvements, broad use of non-viral delivery systems to treat human disorders should be possible.
Phenylketonuria in adulthood: A collaborative study
Authors: Koch R. , Burton B. , Hoganson G. , Peterson R. , Rhead W. , Rouse B. , Scott R. , Wolff J. , Stern A. M. , Guttler F. , Nelson M. , de la Cruz F. , Coldwell J. , Erbe R. , Geraghty M. T. , Shear C. , Thomas J. , Azen C.
Published: March 2003

During 1967–1983, the Maternal and Child Health Division of the Public Health Services funded a collaborative study of 211 newborn infants identified on newborn screening as having phenylketonuria (PKU). Subsequently, financial support was provided by the National Institute of Child Health and Human Development (NICHD). The infants were treated with a phenylalanine (Phe)‐restricted diet to age 6 years and then randomized either to continue the diet or to discontinue dietary treatment altogether. One hundred and twenty‐five of the 211 children were then followed until 10 years of age. In 1998, NICHD scheduled a Consensus Development Conference on Phenylketonuria and initiated a study to follow up the participants from the original Collaborative Study to evaluate their present medical, nutritional, psychological, and socioeconomic status.

Fourteen of the original clinics (1967–1983) participated in the Follow‐up Study effort. Each clinic director was provided with a list of PKU subjects who had completed the original study (1967–1983), and was asked to evaluate as many as possible using a uniform protocol and data collection forms. In a subset of cases, magnetic resonance imaging and spectroscopy (MRI/MRS) were performed to study brain Phe concentrations.

The medical evaluations revealed that the subjects who maintained a phenylalanine‐restricted diet reported fewer problems than the diet discontinuers, who had an increased rate of eczema, asthma, mental disorders, headache, hyperactivity and hypoactivity. Psychological data showed that lower intellectual and achievement test scores were associated with dietary discontinuation and with higher childhood and adult blood Phe concentrations. Abnormal MRI results were associated with higher brain Phe concentrations. Early dietary discontinuation for subjects with PKU is associated with poorer outcomes not only in intellectual ability, but also in achievement test scores and increased rates of medical and behavioural problems.
Gender differences in responses to traumatic events: A prospective study
Authors: Freedman Sara A. , Gluck Natali , Tuval‐Mashiach Rivka , Brandes Dalia , Peri Tuvia , Shalev Arieh Y.
Published: March 2003

Gender differences in psychological responses to motor vehicle accidents were examined as part of a large‐scale prospective study of PTSD. Participants were recruited from an emergency room (n = 275) and interviewed 1 week. 1 month, and 4 months later. No gender differences were seen in the prevalence or recovery from PTSD, or in symptom levels at 1‐ and 4 months. Women had a higher prevalence of lifetime‐ and postaccident generalized anxiety disorder. Gender differences were found regarding the type, but not the total number, of potentially traumatic events previously experienced. These results suggest that gender differences in responses to traumatic events are not explained by exposure as such, but rather may result from gender‐specific attrubutes of the event.
Bacteria-Host Cell Interaction Mediated by Cellular Cholesterol/Glycolipid-Enriched Microdomains
Authors: Shin Jeoung-Sook , Gao Zhimin , Abraham Soman N.
Published: March 2003

Gram negative bacterial infection is a leading cause of fatality and is attributed, at least in part, to the bacteria's capacity to persist in the host in spite of appropriate antibiotic therapy. It has been suggested that bacteria evade antibiotics by hiding within host cells. We sought to investigate this important aspect of infections in mast cells, which are inflammatory cells found in close proximity to the host-environment interface and which have recently been reported to play a crucial role in the early innate immune response to bacteria. We examined mast cell interactions with FimH-expressing E. coli, one of the major opportunistic pathogens of humans. We determined that in serum free conditions, these bacteria were able to trigger mast cell uptake without loss of bacterial viability. CD48, a mannose containing GPI (glycosylphosphatidylinositol)-linked molecule was found to be the receptor of FimH-expressing E. coli in mouse mast cells. We found that the internalization via CD48 was blocked by filipin, a cholesterol binding drug known to disrupt cholesterol/glycolipid-enriched microdomains and the bacteria-encasing vacuoles were rich in cholesterol inside cells. Interestingly, we found that mast cells subsequently expelled majority of the intracellular bacteria in 24 hours. This expulsion process was blocked by lovastatin/cyclodextrin treatment, which is known to inhibit cellular trafficking of cholesterol/glycolipid-enriched microdomains. Thus, the bacterial entry into and expulsion from mast cells were critically dependent on cholesterol/glycolipid-enriched microdomains, which represents a novel mode of tussle between the pathogen and the mast cell occurring in opsonin deficient sites in the body or even at other sites in naive or immunocompromised hosts which have low systemic levels of E. coli specific antibody.
Lysosomal α-D-mannosidase
Authors: Beccari Tommaso , Stinchi Sofia , Orlacchio Aldo
Published: March 2003

α-mannosidosis in the human is an autosomal recessive lysosomal storage disease caused by a deficiency of lysosomal α-D-mannosidasea actvity. Lysosomal α-D-mannosidase is involved in the catabolism of N-linked glycoproteins through the sequential degradation of high-mannose, hybrid and complex oligosaccharides. This review is focused on human, mouse, bovine and feline genes coding for lysosomal α-D-mannosidase. In particular the exon-intron structure of the genes, their promoters, and the identification of mutations causing the disease have been examined. The construction, by homologous recombination, of a mouse model of α-mannosidosis is reported.
Mannosylphosphodolichol Synthase Activity is Associated with a 32 kDa Phosphoprotein
Authors: Banerjee Dipak K. , Dasilva Jaime J. , Bigio Betzaida
Published: March 2003

Failure of actinomycin D to block the activation of Dol-P-Man synthase in isoproterenol-treated capillary endothelial cells, supported that isoproterenol effect was not mediated by active transcription of the Dol-P-Man synthase gene during a short-term β-adrenoreceptor stimulation. Instead, it was a net effect of protein phosphorylation by cAMP-dependent protein kinase. Using antibody as a probe we have now demonstrated that Dol-P-Man synthase activity is associated with a 32 kDa ER phosphoprotein.
Effect of Ethanol on Enzymatic Activity of Fungal Laccases
Authors: Rodakiewicz-Nowak J. , Haber J. , Pozdnyakova N. , Leontievsky A. , Golovleva L. A.
Published: March 2003

Blue laccase from Coriolus versicolor and blue and yellow laccases from Panus tigrinus were isolated, purified and studied in acetate buffer solutions, with and without addition of various amounts of ethanol, using syringaldazine and 2,6-dimethoxyphenol as substrates. Effect of ethanol on blue laccases could be successfully described using the mixed inhibition model, over the range of 0–2.5 M ethanol concentrations. Yellow laccase from P. tigrinus behaves differently, which may be explained by the presence of some extra molecules in its structure, which possibly stabilize the enzyme and might be exchanged in ethanol solutions.
Glossopharyngeal neuralgia with cardiac syncope treated by glossopharyngeal rhizotomy and microvascular decompression
Authors: Ozenci M. , Karaoguz R. , Conkbayir C. , Altin T. , Kanpolat Y.
Published: March 2003

A glossopharyngeal neuralgia case with cardiac asystole is presented. The sinus mode dysfunction and subsequent syncope with pain appears to be the most important life-threatening symptom in the late period of the disease. Because of cardiac symptoms induced by intense vagal stimulation, this case was considered to be vagoglossopharyngeal neuralgia. Several medical and surgical alternatives have been proposed for its treatment. In the presented case the cause of disease was compression of lower cranial nerves in the right cerebello-pontine angle (CPA) by the vertebro-basilar arterial system. Carbamazepine and pacing were determined ineffective, so the patient was treated surgically by cutting the glossopharyngeal nerve and by decompression of the vagal nerve at the CPA. The sinus arrest and paroxysmal pain attacks disappeared and the patient's life returned to normal.
Perceived importance as a mediator of the relationship between training assignment and training motivation
Authors: Tsai Wei‐Chi , Tai Wei‐Tao
Published: March 2003

In this study, we examined whether employees’ perceived importance of the training program would be one variable that mediates the relationship between training assignment and training motivation. Data were collected from 184 employees belonging to 18 banks who attended government‐sponsored training programs in Northern Taiwan. Participants were asked to complete two questionnaires: one at the beginning of the training program and the other at the middle. Results supported our hypothesis and showed that, compared to those who were volunteers, the employees who attended the training on a mandatory basis had a higher motivation for training. Moreover, organizations that force their employees to attend a given training program send out a clear message to employees that such training is important. As employees perceive the training to be central to the achievement of organizational objectives, their training motivation increases.
Human Serum Paraoxonase 1 Decreases Macrophage Cholesterol Biosynthesis
Authors: Rozenberg Orit , Shih Diana M. , Aviram Michael
Published: March 2003

Objective—

Human serum paraoxonase 1 (PON1) activity is inversely related to the risk of developing an atherosclerotic lesion, which contains cholesterol-loaded macrophage foam cells. To assess a possible mechanism for this relationship, we analyzed the effect of PON1 on cellular cholesterol biosynthesis.

Methods and Results—

Mouse peritoneal macrophages (MPMs) were harvested from PON1-deficient mice (PON1° and PON1°/E° mice on the genetic background of C57BL/6J and E° mice, respectively). PON1°/E° mice exhibited a significantly 51% increased atherosclerotic lesion area and 35% increased macrophage cholesterol content compared with control E° mice. In parallel, macrophage cholesterol biosynthesis rates were increased in PON1-deficient mice MPMs by 50% compared with their controls. Incubation of macrophages with human PON1 revealed a dose-dependent inhibitory effect (up to 84%) on macrophage cholesterol biosynthesis. We demonstrated a PON1 phospholipase-A
2
–like activity on MPMs, evidenced by release of polyunsaturated fatty acids and formation of lysophosphatidylcholine. On incubation of macrophages with lysophosphatidylcholine, a dose-dependent inhibition (up to 40%) of cellular cholesterol biosynthesis was noted. The inhibitory effect of PON1 on macrophage cholesterol biosynthesis was shown to be downstream to mevalonate, probably at the lanosterol metabolic point.

Conclusions—

PON1 inhibits macrophage cholesterol biosynthesis and atherogenesis probably through its phospholipase-A
2
–like activity.
Dexamethasone Induces Rapid Serine-Phosphorylation and Membrane Translocation of Annexin 1 in a Human Folliculostellate Cell Line via a Novel Nongenomic Mechanism Involving the Glucocorticoid Receptor, Protein Kinase C, Phosphatidylinositol 3-Kinase, and Mitogen-Activated Protein Kinase
Authors: Solito Egle , Mulla Abeda , Morris John F. , Christian Helen C. , Flower Roderick J. , Buckingham Julia C.
Published: March 2003

Our recent studies on rat pituitary tissue suggest that the annexin 1 (ANXA1)-dependent inhibitory actions of glucocorticoids on ACTH secretion are effected via a paracrine mechanism that involves protein kinase C (PKC)-dependent translocation of a serine-phosphorylated species of ANXA1 (Ser-P-ANXA1) to the plasma membrane of the nonsecretory folliculostellate cells. In the present study, we have used a human folliculostellate cell line (PDFS) to explore the signaling mechanisms that cause the translocation of Ser-P-ANXA1 to the membrane together with Western blot analysis and flow cytometry to detect the phosphorylated protein. Exposure of PDFS cells to dexamethasone caused time-dependent increases in the expression of ANXA1 mRNA and protein, which were first detected within 2 h of steroid contact. This genomic response was preceded by the appearance within 30 min of substantially increased amounts of Ser-P-ANXA1 and by translocation of the phosphorylated protein to the cell surface. The prompt membrane translocation of Ser-P-ANXA1 provoked by dexamethasone was inhibited by the glucocorticoid receptor, antagonist, mifepristone, but not by actinomycin D or cycloheximide, which effectively inhibit mRNA and protein synthesis respectively in our preparation. It was also inhibited by a nonselective PKC inhibitor (PKC9–31), by a selective inhibitor of Ca2+-dependent PKCs (Go 6976) and by annexin 5 (which sequesters PKC in other systems). In addition, blockade of phosphatidylinositiol 3-kinase (wortmannin) or MAPK pathways with PD 98059 or UO 126 (selective for MAPK kinse 1 and 2) prevented the steroid-induced translocation of Ser-P-ANXA1 to the cell surface. These results suggest that glucocorticoids induce rapid serine phosphorylation and membrane translocation of ANXA1 via a novel nongenomic, glucocorticoid receptor-dependent mechanism that requires MAPK, phosphatidylinositiol 3-kinase, and Ca2+-dependent PKC pathways.
Ghrelin-Induced Food Intake Is Mediated via the Orexin Pathway
Authors: Toshinai Koji , Date Yukari , Murakami Noboru , Shimada Mitsushi , Mondal Muhtashan S. , Shimbara Takuya , Guan Jian-Lian , Wang Qing-Ping , Funahashi Hisayuki , Sakurai Takeshi , Shioda Seiji , Matsukura Shigeru , Kangawa Kenji , Nakazato Masamitsu
Published: March 2003

The hypothalamus regulates energy intake by integrating the degree of starvation or satiation with the status of the environment through a variety of neuronal and blood-derived signals. Ghrelin, a peptide produced in the stomach and hypothalamus, stimulates feeding and GH secretion. Centrally administered ghrelin exerts an orexigenic activity through the neuropeptide Y (NPY) and agouti-related protein systems. The interaction between ghrelin and other hypothalamic orexigenic peptides, however, has not been clarified. Here, we investigated the anatomical interactions and functional relationship between ghrelin and two orexigenic peptides, orexin and melanin-concentrating hormone (MCH), present in the lateral hypothalamus. Ghrelin-immunoreactive axonal terminals made direct synaptic contacts with orexin-producing neurons. Intracerebroventricular administration of ghrelin induced Fos expression, a marker of neuronal activation, in orexin-producing neurons but not in MCH-producing neurons. Ghrelin remained competent to induce Fos expression in orexin-producing neurons following pretreatment with anti-NPY IgG. Pretreatment with anti-orexin-A IgG and anti-orexin-B IgG, but not anti-MCH IgG, attenuated ghrelin-induced feeding. Administration of NPY receptor antagonist further attenuated ghrelin-induced feeding in rats treated with anti-orexin-IgGs. Ghrelin-induced feeding was also suppressed in orexin knockout mice. This study identifies a novel hypothalamic pathway that links ghrelin and orexin in the regulation of feeding behavior and energy homeostasis.
Comprehension of arithmetic word problems by fifth‐grade pupils: Representations and selection of information
Authors: Moreau Stéphanie , Coquin‐Viennot Danièle
Published: March 2003

Background: Understanding word problems leads to the construction of different levels of representation. Some levels specify the elements which are indispensable for solving the problem (problem model, PM) and others specify the agents, actions and events in everyday concepts (situation model, SM).

Aims: By studying how the information is selected, we try to specify the nature of the representations constructed during the reading of a word problem: understanding a problem leads to the construction of two complementary levels of representation (PM and SM) or to the construction of only one representation (PM)?

Sample: Ninety‐one fifth‐grade pupils (mean age 10 years 9 months) took part in this study and were divided into two groups according to their mathematical ability.

Method: As well as the information considered as indispensable for solving the problems (solving information), different types of information (situational information) were introduced into standard word problems. In a first task, participants were asked to select the information in order to ‘make the word problem as short as possible’ (locate the elements used for developing PM). In a second task, they were asked to select the information in order to ‘make the word problem easier to understand’ (determine whether the participants developed a SM).

Results: The participants successfully differentiated between the solving information and the situational information. An interaction was also observed between the type of information and the task. The mathematical ability of the participants was seen to have an influence on the selection of situational information.

Conclusion: Understanding leads to the construction of two complementary representation levels: the problem model and the situation model.
Entropy and Eschatology: A Comment on Kutrovátz's Paper "Heat Death in Ancient and Modern Thermodynamics"
Authors: Ćirković Milan M.
Published: March 2003

Recent intriguing discussion of heat death by Kutrovátz is critically examined. It is shown that there exists another way of answering the heat death puzzle, already present in the ancient philosophical tradition. This alternative route relies not only on the final duration of time (which has been re-discovered in modern times), but also on the notion of observational self-selection, which has received wide publicity in the last several decades under the title of the anthropic principle(s). We comment here on some further deficiencies of the account of Kutrovátz. Although the questions Kutrovátz raises are important and welcome, there are several errors in his treatment of cosmology which mar his account of the entire topic. In addition, the nascent discipline of physical eschatology holds promise of answering the basic explanatory task concerning the future evolution of the universe without appealing to metaphysics. This is a completely novel feature in the history of science, in contradistinction to the historical examples discussed by Kutrovátz.
Blue Light Inhibits Mitosis in Tissue Culture Cells
Authors: Gorgidze L. A. , Oshemkova S. A. , Vorobjev I. A.
Published: March 2003

Irradiation of the mitotic (prophase and prometaphase) tissue culture PK (pig kidney embryo) cells using mercury arc lamp and band-pass filters postponed or inhibited anaphase onset. The biological responses observed after irradiation were: (i) normal cell division, (ii) delay in metaphase and then normal anaphase and incomplete cytokinesis, (iii) exit into interphase without separation of chromosomes, (iv) complete mitotic blockage. Cell sensitivity to the light at wavelengths from 423 and 488 nm was nearly the same; to the near UV light (wavelength 360 nm) it was 5–10 times more; to the green light (wavelength >500 nm) it was at least 10 times less. To elucidate the possible mechanism of the action of blue light we measured cell adsorption and examined cell autofluorescence. Autofluorescence of cytoplasmic granules was exited at wavelengths of 450–490 nm, but not at >500 nm. In mitotic cells fluorescent granules accumulated around the spindle. We suppose blue light irradiation induces formation of the free radicals and/or peroxide, and thus perturb the checkpoint system responsible for anaphase onset.
A Novel Phosphorylated Lipid Counteracts Activation of the Renal Plasma Membrane (Ca2+ + Mg2+)ATPase by Endogenous Phosphatidylinositol-4-Phosphate
Authors: Guilherme Adilson , Reis-Silva Cledson , Moraes-Albuquerque Jorge H. , Oliveira Mecia M. , Vieyra Adalberto
Published: March 2003

The plasma membrane (Ca2+ + Mg2+)ATPase is activated by acidic phospholipids in reconstituted systems. In this report it is shown that reversible phosphorylation of endogenous phosphatidylinositol regulates the renal plasma membrane (Ca2+ + Mg2+)ATPase, and that a novel phosphorylated lipid that can be isolated from the same membrane strongly counteracts the stimulatory effect of phosphatidylinositol-4-phosphate.
Extracellular Reduction of Cat1 Free Radical by Transformed Human Hepatocytes
Authors: Bernas Tytus , Dobrucki Jurek
Published: March 2003

Redox activities associated with plasma membranes of nonphagocytic animal and plant cells have been reported by several authors. However, the natural substrates, structure and biological role of these putative enzyme systems are not known. Data indicating extracellular reduction of a nitroxide free radical Cat1 (1-oxy-4-trimethylamine-2,2,6,6,tetramethyl-piperidine) by hepatocytes were thought to be artefactual. We report evidence in support of a notion that Cat1 as well as a tetrazolium salt, CTC (5-cyano-2,3-ditolyl tetrazolium chloride), are reduced extracellularly, probably at the cell surface, by human HepG2 hepatoma cells. These data provide evidence confirming the existence of a yet unidentified reducing activity associated with outer surface of plasma membranes of transformed human hepatocytes.
The Terminal Enzymes of Sialic Acid Metabolism: Acylneuraminate Pyruvate-Lyases
Authors: Schauer Roland , Sommer Ulf , Krüger Dorothea , van Unen Henrieke , Traving Christina
Published: March 2003

The acylneuraminate pyruvate-lyase gene from Clostridium perfringens was sequenced and found to be most similar to the lyase gene from Haemophilus influenzae. Both the recombinant clostridial enzyme and the native enzyme from pig kidney were purified in larger amounts and characterized. The properties of the porcine lyase are similar to the microbial ones. However, the much higher degree of similarity in comparison to the microbial enzymes that was found between porcine lyase peptides and two putative mammalian lyase sequences show that the latter form an own group apart from the microbial lyases. Actual models of the acylneuraminate pyruvate-lyase reaction are discussed.
Reporting Results of Large-Scale Assessment in Psychologically and Educationally Meaningful Terms
Authors: Watermann Rainer , Klieme Eckhard
Published: March 2003

Summary In their function as a specific form of evaluation in the educational system, large-scale assessments are used to describe overall structures, salient features, and outcomes of educational processes. Whether this kind of evaluation is meaningful on the system level, and whether its results are likely to be of use for classroom practice, teacher training, and curriculum design is wholly dependent on the validity of the test instruments. The crucial issues here are the validity of instruments with regard to the curricula of different countries, the underlying proficiency dimensions, and the appropriate behavior-oriented criteria for the interpretation of test scores. Using the TIMS upper secondary school study as an illustrative example, we discuss methods for the validation of large-scale assessments and present results from the field of mathematics. Analyses of the cognitive demands of test items based on psychological conceptualizations of mathematical problem solving are combined with a behavior-oriented interpretation of different levels of a latent proficiency scale (proficiency scaling). Findings from the TIMSS advanced mathematics test show that proficiency scaling is a useful heuristic tool that can be used to integrate test theory, cognitive psychology, and didactics, and thus presents a meaningful way of interpreting the results of comparative studies - not only in terms of “ranking,” but also in terms of process components and cognitive demands.
Theoretical Levels in the Evaluation of Motivational Trainings
Authors: Schober Barbara , Ziegler Albert
Published: March 2003

Summary Ascertaining the effectiveness of a motivational training is considered one of the most difficult functions of evaluation research since one must account for numerous biases that can distort the results. When conducting an evaluation of a complex training - not just a single measurement - one is confronted with the problem that the evaluation is executing a simultaneous test of an entire family of theories. These embrace (1) the motivational theory that underlies the conception of the motivational training, (2) the promotional goals that are derived from these theories, and (3) the practical implementation of a training that aims to attain these promotional goals. A further problem is the asymmetry inherent in the findings of evaluations that can either attest to or cast doubt over the success of a training. In the first case, one runs the risk of overgeneralizing positive results; in the second, one is faced with the difficulty of determining the precise source of these negative results, which can be anchored on one of three different levels. This article offers, from a metatheoretical perspective, a few preliminary responses to the problems associated with the evaluation of complex motivational trainings.
Power dynamics in the long‐term development of employee‐friendly flexible working
Authors: Nadeem Sadia , Hendry Chris
Published: March 2003

This paper focuses on the possibilities of the long‐term development of flexible working as a work‐life policy, through understanding the power dynamics between the individual and the organisation. The study presents a framework which summarises the factors influencing the employee‐employer power dynamics, and leads us to the research questions. The methodology involves triangulation in case studies in two organisations based on surveys of representative samples in each organisation (n= 243 andn= 128) and interviews with the management. Findings support the long‐term development of employee‐friendly flexible working. There is a strong desire, and a lack of polarisation of attitudes, among employees for greater flexibility. Certain employee groups with stronger negotiating power have initiated the work‐life debate, but in doing so, they have increased the power of all employees through lowering ideological barriers, and creating knowledge of new possibilities and aspirations. Favourable external pressures and changing business needs also improve the position of employees.
Pitavastatin-Induced Thrombomodulin Expression by Endothelial Cells Acts Via Inhibition of Small G Proteins of the Rho Family
Authors: Masamura Katsuhiko , Oida Koji , Kanehara Hideo , Suzuki Jinya , Horie Shuichi , Ishii Hidemi , Miyamori Isamu
Published: March 2003

Objective—

3-Hydroxyl-3-methyl coenzyme A reductase inhibitors (statins) can function to protect the vasculature in a manner that is independent of their lipid-lowering activity. The main feature of the antithrombotic properties of endothelial cells is an increase in the expression of thrombomodulin (TM) without induction of tissue factor (TF) expression. We investigated the effect of statins on the expression of TM and TF by endothelial cells.

Methods and Results—

The incubation of endothelial cells with pitavastatin led to a concentration- and time-dependent increase in cellular TM antigen and mRNA levels. In contrast, the expression of TF mRNA was not induced under the same conditions. A nuclear run-on study revealed that pitavastatin accelerates TM transcription rate. The stimulation of TM expression by pitavastatin was prevented by either mevalonate or geranylgeranylpyrophosphate. Specific inhibition of geranylgeranyltransferase-I and Rac/Cdc42 by GGTI-286 and
Clostridium sordellii
lethal toxin, respectively, enhanced TM expression, whereas inactivation of Rho by
Clostridium botulinum
C3 exoenzyme was ineffective.

Conclusions—

Statins regulate TM expression via inhibition of small G proteins of the Rho family; Rac/Cdc42. A statin-mediated increase in TM expression by endothelial cells may contribute to the beneficial effects of statins on endothelial function.
Enhancing effects of mustard oil on preneoplastic hepatic foci development in Wistar rats
Authors: Shukla Yogeshwer , Arora Annu
Published: March 2003

Dietary habits are known to be the major contributory factor in the development of cancer. Mustard oil, which is extensively used in India and elsewhere as a frying and cooking medium, is reported to induce an inflammatory response. The development of altered hepatic foci is an early carcinogenic change in rat liver in diethylnitrosamine (DEN)-induced hepatocarcinogenesis. In the present study, the development of preneoplastic lesions was observed following administration of mustard oil (0.5 mL/day for 8 weeks) in DEN-initiated and partially hepatomized Wistar rats. A significant decrease in the relative and absolute liver weight of mustard oil-exposed rats was recorded. The results revealed a significant increase in the number and area of placental glutathione S-transferase (GST-P) and g-glutamyl transpeptidase (GGT)-positive foci in mustard oil-administered animals. The GST-P and GGT-positive foci were more prominent in the animals given boiled (up to 3008C for 3 hours) mustard oil in comparison to the animals given fresh mustard oil. These results indicate the possible tumourigenic risk associated with mustard oil consumption.
Role of the Different Mitogen-Activated Protein Kinase Subfamilies in the Stimulation of Dog and Human Thyroid Epithelial Cell Proliferation by Cyclic Adenosine 5′-Monophosphate and Growth Factors
Authors: Vandeput Fabrice , Perpete Sandrine , Coulonval Katia , Lamy Françoise , Dumont Jacques E.
Published: March 2003

We have investigated the role of the different classes of MAPKs, i.e. ERKs, c-Jun N-terminal kinases (JNKs), and p38 MAPK in the proliferation of dog and human thyroid epithelial cells (thyrocytes) in primary cultures. In these cells, TSH, acting through cAMP, epidermal growth factor, hepatocyte growth factor (HGF), and phorbol 12-myristate 13-acetate induce DNA synthesis. With the exception of HGF, all of these factors require the presence of insulin for mitogenic effects to be expressed.

We found that TSH and forskolin are without effect on the phosphorylation and activity of the different classes of MAPKs. In contrast, all the cAMP-independent growth factors, whereas without effect on the phosphorylation and activity of JNKs and p38 MAPK, stimulated the ERKs. This effect was strong and sustained in response to HGF, epidermal growth factor and 12-myristate 13-acetate but weak and transient in response to insulin. Moreover, whereas in stimulated cells DNA synthesis was inhibited by PD 098059, an inhibitor of MAPK kinase 1 and consequently of ERKs, it was not modified by SB 203580, an inhibitor of p38 MAPK.

Taken together, these data 1) exclude a role of JNKs and p38 MAPK in the proliferation of dog and human thyrocytes; 2) suggest that the mitogenic action of the cAMP-independent agents requires a strong and sustained activation of both ERKs and phosphatidylinositol 3-kinase/protein kinase B as realized by HGF alone or by the other agents together with insulin; and 3) show that TSH and cAMP do not activate ERKs but that the weak activation of ERKs by insulin is nevertheless necessary for DNA synthesis to occur.