bluuebunny/crossref_metadata_2025 huggingface dataset:
Microwave Heating of Cooked Pork Patties as a Function of Fat Content
Authors: Picouet P.A. , Fernández A. , Serra X. , Suñol J.J. , Arnau J.
Published: February 2007

ABSTRACT:  In this study, the parameters heating rate, dielectric factors, and specific heat capacity, which determine the heating profiles and the dissipation of energy during microwave heating, were obtained for precooked pork patties. The pork patties studied were lean meat, pure back fat, and several lean meat/back fat mixtures. Microwave heating at 798 W power was not sufficient to accelerate the heating rates in 100% lean meat compared to 415 W. However, samples were able to heat up faster and dissipate more energy at 798 W power as fat content increased and moisture content decreased. The recorded differences in the specific heat capacity of the studied materials as a function of temperature seemed not to be the key factor to explain the observed temperature rises. Temperature rise seemed to have more to do with the interactions of fat with the electromagnetic field, and with viscosity changes during phase transitions. Trends found for the dielectric properties over microwave heating of meat products agree with data from other authors, but the influence of parameters related to the sample composition and structure should be taken into account. The dissipation factors (ɛ″/ɛ′) provided a good approximation to the capacity of the samples containing lean meat and the lean meat/fat mixtures to transform the electromagnetic energy into heat. Neither the dielectric constant nor the loss or dissipation factors were able to clarify the high amount of energy transformed into heat in 100% back fat. Penetration depth and reflected power indicated that back fat allowed microwave energy to be repeatedly redirected to the material.
Physical Study of Minced Fish Muscle with a White‐Grape By‐Product Added as an Ingredient
Authors: Sánchez‐Alonso I. , Solas M.T. , Borderías A.J.
Published: February 2007

ABSTRACT:  Functional properties of a white grape dietary fiber concentrate (WGDF) obtained from wine industry residues were determined with a view to their use as potential functional ingredient in seafood products. The main features of interest of WGDF are that it is a natural product containing high concentrations of dietary fiber (DF) with a high‐soluble DF (sDF)/insoluble DF (iDF) ratio and associated bioactive compounds; as such it is considered potentially suitable for use as dietary fiber in the enrichment of foods. WGDF was therefore added to minced fish muscle (MFM) of horse mackerel (Trachurus trachurus) to take advantage of its technological properties, and also to enrich a food product that is a functional product in itself but does not contain dietary fiber. WGDF was added (2% and 4%) to MFM, which was stored for 6 mo at –20 °C, and a further lot was vacuum packed. Physical and mechanical properties, sensory and color analyses, microscopy, and electrophoretic profiles were all done in samples every month. The results indicate that WGDF had good functional properties, high water and oil retention capacity, and considerable swelling properties, which would make it useful as a natural ingredient in foods. The addition of WGDF to MFM augmented aggregation of myofibrillar proteins in the course of frozen storage, although electrophoretic profiles were very similar in samples with and without WGDF. The addition of WGDF to MFM made samples softer and less springy and cohesive. SEM showed good dispersion of WGDF in MFM but the matrix was more discontinuous than in the control. Water retention was significantly enhanced when WGDF was added, and the cooking yield improved. In sensory evaluation, samples containing 2% of WGDF scored highest in overall acceptance as compared with the control. Vacuum packing did not significantly affect the properties considered during frozen storage.
Biochemical evidence of myocardial fibrosis in veteran endurance athletes
Authors: Lindsay M Mitchell , Dunn Francis G
Published: February 2007

Background:Studies on exercise-induced left ventricular hypertrophy (LVH) in veteran athletes suggest the presence of abnormal diastolic filling and incomplete regression of LVH on cessation of exercise.

Hypothesis:Myocardial fibrosis occurs in exercise induced LVH in veteran athletes.

Aim:To document non-invasively the presence of fibrosis in veteran athletes

Design:Prospective case–control study.

Setting:City centre district general hospital.

Participants:45 normotensive elite veteran athletes and 45 normal sedentary subjects.

Interventions:Echocardiographic assessment was made of LV mass, LV systolic and LV diastolic function. Plasma carboxyterminal propeptide of collagen type I (PICP), carboxyterminal telopeptide of collagen type I (CITP) and tissue inhibitor of matrix metalloproteinase type I (TIMP-1) were measured as markers of collagen synthesis, degradation and inhibition of degradation, respectively.

Results:Veteran athletes had significant elevation in LV dimensions and calculated LV mass index (LVMI). Diastolic and systolic function was normal. Plasma PICP (259 vs 166 μg/l, p<0.001), CITP (5.4 vs 2.9 μg/l, p<0.001) and TIMP-1 (350 vs 253 ng/ml, p = 0.01) were elevated in the cohort of athletes. There was a further elevation of TIMP-1 in athletes with echocardiographic LVH, defined as an LVMI >130 g/m2(417 vs 266 ng/ml, p = 0.02).

Conclusion:There is biochemical evidence of disruption of the collagen equilibrium favouring fibrosis in veteran athletes with LVH. This may suggest that fibrosis occurs as part of the hypertrophic process in veteran athletes.
LAMB SHIFT AND STARK EFFECT IN SIMULTANEOUS SPACE–SPACE AND MOMENTUM–MOMENTUM NONCOMMUTATIVE QUANTUM MECHANICS AND θ-DEFORMED su(2) ALGEBRA
Authors: ALAVI S. A.
Published: February 2007

We study the spectrum of hydrogen atom, Lamb shift and Stark effect in the framework of simultaneous space–space and momentum–momentum (s-s, p-p) noncommutative quantum mechanics. The results show that the widths of Lamb shift due to noncommutativity is bigger than the one presented in Ref. 1. We also study the algebras of observables of systems of identical particles in s-s, p-p noncommutative quantum mechanics. We introduce θ-deformed su(2) algebra.
PARTON EVOLUTION IN THE FIXED FLAVOR FACTORIZATION SCHEME
Authors: GLÜCK M. , REYA E.
Published: February 2007

It is argued that while the scale dependence of the parton distributions in the fixed flavor factorization scheme is governed by three active flavors, the scale dependence of the running coupling should nevertheless be better governed by a variable number of active flavors.
FIRST-ORDER ACTIONS AND DUALITY
Authors: GAONA ALEJANDRO , GARCÍA J. ANTONIO
Published: February 2007

We consider some aspects of classical S-duality transformations in first-order actions taking into account the general covariance of the Dirac algorithm and the transformation properties of the Dirac bracket. By classical S-duality transformations we mean a field redefinition that interchanges the equations of motion and its associated Bianchi identities. By working from a first-order variational principle and performing the corresponding Dirac analysis we find that the standard electromagnetic duality can be reformulated as a canonical local transformation. The reduction from this phase space to the original phase space variables coincides with the well-known result about duality as a canonical nonlocal transformation. We have also applied our ideas to the bosonic string. These dualities are not canonical transformations for the Dirac bracket and relate actions with different kinetic terms in the reduced space.
DECAY OF SPIN-ONE PARTICLE INTO TWO PHOTONS IN PRESENCE OF UNIFORM EXTERNAL MAGNETIC FIELD
Authors: ANGOM DILIP , BHATTACHARYA KAUSHIK , RINDANI SAURABH D.
Published: February 2007

Yang's theorem states that an initial J = 1 state cannot decay into two photons. Because of this result some reactions relating to elementary particles or atomic transitions can be ruled out. The theorem is not valid in the presence of background electric or magnetic fields. In this work we show that the decay of a J = 1 particle into two photons is permitted by the Bose symmetry and rotational invariance when the background of the decay process is not pure vacuum but contains an external classical magnetic/electric field. We also discuss constraints on these amplitudes from the CP invariance.
STABILITY EQUATION AND TWO-COMPONENT EIGENMODE FOR DOMAIN WALLS IN A SCALAR POTENTIAL MODEL
Authors: DIAS G. S. , GRAÇA E. L. , DE LIMA RODRIGUES R.
Published: February 2007

The connection between the supersymmetric quantum mechanics involving two-component eigenfunctions and the stability equation associated with two classical configurations is investigated and a matrix superpotential is deduced. The question of stability is ensured for the Bogomol'nyi–Prasad–Sommerfield (BPS) states on two domain walls in a scalar potential model containing up to fourth-order powers in the fields, which is explicit demonstrated using the intertwining operators in terms of two-by-two matrix superpotential in the algebraic framework of supersymmetry in quantum mechanics. Also, a non-BPS state is found to be nonstable via the fluctuation Hessian matrix.
GAMMA RAYS FROM CLUSTERS OF GALAXIES
Authors: BLASI PASQUALE , GABICI STEFANO , BRUNETTI GIANFRANCO
Published: February 2007

Clusters of galaxies and the large scale filaments that connect neighboring clusters are expected to be sites of acceleration of charged particles and sources of non-thermal radiation from radio frequencies to gamma rays. Gamma rays are particularly interesting targets of investigation, since they may provide precious information on the nature and efficiency of the processes of acceleration and magnetic confinement of hadrons within clusters of galaxies. Here we review the status of viable scenarios that lead to the production of gamma rays from large scale structures and are compatible with the multifrequency observations that are already available. We also discuss the possibility of detection of gamma rays with space-borne telescopes such as GLAST and ground based Cherenkov telescopes, and the physical information that may be gathered from such observations.
FALL-RELATED ROTATOR CUFF TEARS
Authors: Lungren Matthew P. , Smith David , Carpenter James E. , Hughes Richard E.
Published: February 2007

Tears of the rotator cuff tendons may occur as a result of tendon degeneration or from a single traumatic event but commonly a combination of these factors are in play. Rotator cuff tendon degeneration and accidental falls are both known to increase in incidence with increasing age. No study to date has sought to investigate the characteristic of accidental falls as a significant cause of injury in the rotator cuff tear population. We developed a 25 multi-step item questionnaire to investigate the source of injury in sixty rotator cuff tear patients. The majority, 32/60 (53.3%), reported a fall associated with their rotator cuff tear. The tears nearly always occurred on the same side as the fall. Most falls resulting in cuff tears were to the side and front rather than backwards. Our findings highlight that falls are the leading cause of injury in the rotator cuff tear patient population and describe characteristics of the previously under-recognized fall-related rotator cuff tear population.
THE RELATIONSHIP BETWEEN HAND GRIP STRENGTH AND HAND BONE MINERAL DENSITY IN CHILDREN WITH INSULIN DEPENDENT DIABETES MELLITUS
Authors: Okumus Muyesser , Okumus Nurullah , Gokoglu Figen , Yorgancioglu Z. Rezan , Tasar M. Aysin , Dallar Yildiz
Published: February 2007

We thought that grip strength in patients with IDDM would be associated with hand BMD of patients and we thought that patients with IDDM have lower hand BMD than normal subjects.Therefore in this study, the evaluation of the relationship between hand grip strength and hand bone mineral density in healthy children and in children with insulin dependent diabetes mellitus was studied. The hand grip strength, hand and axial bone mineral density of patients were also compared to age-matched healthy controls.

We studied 31 consecutive outpatients with insulin dependent diabetes mellitus defined in accordance to the World Health Organization criteria, who attended to the diabetic outpatient clinic. Thirty two healthy children were included as control group.

There were no differences in the age, body mass index, bone age, serum Ca and P levels between the diabetic patients and the controls (p > 0.05). There were no significant differences between the groups in hand grip strength, total hand and axial bone mineral density (p > 0.05). There were significant correlations between hand grip strength and hand bone mineral density r = 0.824, p = 0.000), axial bone mineral density (r = 0.714, p = 0.000), bone age (r = 0.830, p = 0.000) and duration of insulin dependent diabetes mellitus in the diabetic group (r = 0.463, p = 0.009).

When linear multiple regression analysis was performed hand grip strength and bone age were independent predictors of hand BMD (p < 0.05).

We found that hand grip strength significantly correlated with the hand and axial bone mineral density in patients with insulin dependent diabetes mellitus. We suggest that strengthening exercises should be encouraged to increase bone mineral density in these patients.
Design patterns from biology for distributed computing
Authors: Babaoglu Ozalp , Canright Geoffrey , Deutsch Andreas , Caro Gianni A. Di , Ducatelle Frederick , Gambardella Luca M. , Ganguly Niloy , Jelasity Márk , Montemanni Roberto , Montresor Alberto , Urnes Tore
Published: February 2007

Recent developments in information technology have brought about important changes in distributed computing. New environments such as massively large-scale, wide-area computer networks and mobile ad hoc networks have emerged. Common characteristics of these environments include extreme dynamicity, unreliability, and large scale. Traditional approaches to designing distributed applications in these environments based on central control, small scale, or strong reliability assumptions are not suitable for exploiting their enormous potential. Based on the observation that living organisms can effectively organize large numbers of unreliable and dynamically-changing components (cells, molecules, individuals, etc.) into robust and adaptive structures, it has long been a research challenge to characterize the key ideas and mechanisms that make biological systems work and to apply them to distributed systems engineering. In this article we propose a conceptual framework that captures several basic biological processes in the form of a family of design patterns. Examples include plain diffusion, replication, chemotaxis, and stigmergy. We show through examples how to implement important functions for distributed computing based on these patterns. Using a common evaluation methodology, we show that our bio-inspired solutions have performance comparable to traditional, state-of-the-art solutions while they inherit desirable properties of biological systems including adaptivity and robustness.
Automated Facial Expression Classification and affect interpretation using infrared measurement of facial skin temperature variations
Authors: Khan Masood Mehmood , Ingleby Michael , Ward Robert D.
Published: February 2007

Machines would require the ability to perceive and adapt to affects for achieving artificial sociability. Most autonomous systems use Automated Facial Expression Classification (AFEC) and Automated Affect Interpretation (AAI) to achieve sociability. Varying lighting conditions, occlusion, and control over physiognomy can influence the real life performance of vision-based AFEC systems. Physiological signals provide complementary information for AFEC and AAI. We employed transient facial thermal features for AFEC and AAI. Infrared thermal images with participants' normal expression and intentional expressions of happiness, sadness, disgust, and fear were captured. Facial points that undergo significant thermal changes with a change in expression termed as Facial Thermal Feature Points (FTFPs) were identified. Discriminant analysis was invoked on principal components derived from the Thermal Intensity Values (TIVs) recorded at the FTFPs. The cross-validation and person-independent classification respectively resulted in 66.28% and 56.0% success rates. Classification significance tests suggest that (1) like other physiological cues, facial skin temperature also provides useful information about affective states and their facial expression; (2) patterns of facial skin temperature variation can complement other cues for AFEC and AAI; and (3) infrared thermal imaging may help achieve artificial sociability in robots and autonomous systems.
Cooperation through self-assembly in multi-robot systems
Authors: Tuci Elio , Groß Roderich , Trianni Vito , Mondada Francesco , Bonani Michael , Dorigo Marco
Published: February 2007

This article illustrates the methods and results of two sets of experiments in which a group of mobile robots, calleds-bots, are required to physically connect to each other, that is, to self-assemble, to cope with environmental conditions that prevent them from carrying out their task individually. The first set of experiments is a pioneering study on the utility of self-assembling robots to address relatively complex scenarios, such as cooperative object transport. The results of our work suggest that the s-bots possess hardware characteristics which facilitate the design of control mechanisms for autonomous self-assembly. The control architecture we developed proved particularly successful in guiding the robots engaged in the cooperative transport task. However, the results also showed that some features of the robots' controllers had a disruptive effect on their performances. The second set of experiments is an attempt to enhance the adaptiveness of our multi-robot system. In particular, we aim to synthesise an integrated (i.e., not-modular) decision-making mechanism which allows the s-bot to autonomously decide whether or not environmental contingencies require self-assembly. The results show that it is possible to synthesize, by using evolutionary computation techniques, artificial neural networks that integrate both the mechanisms for sensory-motor coordination and for decision making required by the robots in the context of self-assembly.
Signaling mechanisms for α2-adrenergic inhibition of PACAP-induced growth hormone secretion and gene expression grass carp pituitary cells
Authors: Wang Xinyan , Chu Mable M. S. , Wong Anderson O. L.
Published: February 2007

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent growth hormone (GH)-releasing factor in lower vertebrates. However, its functional interactions with other GH regulators have not been fully characterized. In fish models, norepinephrine (NE) inhibits GH release at the pituitary cell level, but its effects on GH synthesis have yet to be determined. We examined adrenergic inhibition of PACAP-induced GH secretion and GH gene expression using grass carp pituitary cells as a cell model. Through activation of pituitary α2-adrenoreceptors, NE or the α2-agonist clonidine reduced both basal and PACAP-induced GH release and GH mRNA expression. In carp pituitary cells, clonidine also suppressed cAMP production and intracellular Ca2+levels and blocked PACAP induction of these two second messenger signals. In GH3cells transfected with a reporter carrying the grass carp GH promoter, PACAP stimulation increased GH promoter activity, and this stimulatory effect could be abolished by NE treatment. In parallel experiments, clonidine reduced GH primary transcript and GH promoter activity without affecting GH mRNA stability, and these inhibitory actions were mimicked by inhibiting adenylate cyclase (AC), blocking protein kinase A (PKA), removing extracellular Ca2+in the culture medium, or inactivating L-type voltage-sensitive Ca2+channels (VSCC). Since our recent studies have shown that PACAP can induce GH secretion in carp pituitary cells through cAMP/PKA- and Ca2+/calmodulin-dependent mechanisms, these results, taken together, suggest that α2-adrenergic stimulation in the carp pituitary may inhibit PACAP-induced GH release and GH gene transcription by blocking the AC/cAMP/PKA pathway and Ca2+entry through L-type VSCC.
Glucagon-like peptide-1 accelerates the onset of insulin action on glucose disappearance in mice
Authors: Thomaseth K. , Pavan A. , Pacini G. , Ahrén B.
Published: February 2007

Glucagon-like peptide-1 (GLP-1) plays a significant role in glucose homeostasis through its incretin effect on insulin secretion. However, GLP-1 also exhibits extrapancreatic actions, and in particular its possible influences on insulin sensitivity are controversial. To study the dynamic action of GLP-1 on insulin sensitivity, we applied advanced statistical modeling methods to study glucose disappearance in mice that underwent intravenous glucose tolerance test with administration of GLP-1 at various dose levels. In particular, the minimal model of glucose disappearance was exploited within a population estimation framework for accurate detection of relationships between glucose disappearance parameters and GLP-1. Minimal model parameters were estimated from glucose and insulin data collected in 209 anesthetized normal mice after intravenous injection of glucose (1 g/kg) alone or with GLP-1 (0.03–100 nmol/kg). Insulin secretion markedly increased, as expected, with increasing GLP-1 dose. However, minimal model-derived indexes, i.e., insulin sensitivity and glucose effectiveness, did not significantly change with GLP-1 dose. Instead, fractional turnover rate of insulin action [P2 = 0.0207 ± 24.3% (min) at zero GLP-1 dose] increased steadily with administered GLP-1 dose, with significant differences at 10.4 nmol/kg (P2 = 0.040 ± 15.5%, P = 0.0046) and 31.2 nmol/kg (P2 = 0.050 ± 29.2%, P = 0.01). These results show that GLP-1 influences the dynamics of insulin action by accelerating insulin action following glucose challenge. This is a novel mechanism contributing to the glucose-lowering action of GLP-1.
Glycogenin protein and mRNA expression in response to changing glycogen concentration in exercise and recovery
Authors: Wilson Rhonda J. , Gusba Jenny E. , Robinson Deborah L. , Graham Terry E.
Published: February 2007

Glycogenin (GN-1) is essential for the formation of a glycogen granule; however, rarely has it been studied when glycogen concentration changes in exercise and recovery. It is unclear whether GN-1 is degraded or is liberated and exists as apoprotein (apo)-GN-1 (unglycosylated). To examine this, we measured GN-1 protein and mRNA level at rest, at exhaustion (EXH), and during 5 h of recovery in which the rate of glycogen restoration was influenced by carbohydrate (CHO) provision. Ten males cycled (65% V̇o2 max) to volitional EXH (117.8 ± 4.2 min) on two separate occasions. Subjects were administered carbohydrate (CHO; 1 g·kg−1·h−1Gatorlode) or water [placebo (PL)] during 5 h of recovery. Muscle biopsies were taken at rest, at EXH, and following 30, 60, 120, and 300 min of recovery. At EXH, total glycogen concentration was reduced ( P < 0.05). However, GN-1 protein and mRNA content did not change. By 5 h of recovery, glycogen was resynthesized to ∼60% of rest in the CHO trial and remained unchanged in the PL trial. GN-1 protein and mRNA level did not increase during recovery in either trial. We observed modest amounts of apo-GN-1 at EXH, suggesting complete degradation of some granules. These data suggest that GN-1 is conserved, possibly as very small, or nascent, granules when glycogen concentration is low. This would provide the ability to rapidly restore glycogen during early recovery.
Sex differences in abdominal, gluteal, and thigh LPL activity
Authors: Votruba Susanne B. , Jensen Michael D.
Published: February 2007

Lipoprotein lipase (LPL) activity is necessary for adipocytes to take up triglycerides from the circulation, and regional differences in LPL activity could help determine regional fat storage. LPL activity has been reported to increase as a function of fat cell size, but this issue has not been extensively evaluated in different depots comparing sexes. Our objective was to determine whether sex alters the relationship between LPL activity and fat cell size. Subcutaneous adipose tissue biopsies were taken from the abdomen and thigh after an overnight fast and 1 h after a meal in 65 females (BMI 25.4 ± 0.8, means ± SE) and 41 males (BMI 23.7 ± 0.3); gluteal adipose samples were obtained in 47 of the females and 27 of the males. Fat cell size was greater in females than males in thigh ( P < 0.005) and gluteal ( P < 0.05) regions but not in the abdomen. There was a relationship between fasting LPL activity/fat cell and fat cell size in females (abdomen r2= 0.52, P < 0.0001; gluteal r2= 0.23, P < 0.005; thigh r2= 0.19, P < 0.005). In males, this relationship was seen only in the abdomen ( r2= 0.51, P < 0.0001) and thigh ( r2= 0.17, P < 0.05). Males and females had a significantly different relationship in the thigh only in the fasted state. Similar results were found in the fed state, although the strength of the relationship decreased in the abdominal regions for females only. This suggests fundamental differences in the regulation of triglyceride uptake between males and females and adipose regions.
Rapid determination of renal filtration function using an optical ratiometric imaging approach
Authors: Yu Weiming , Sandoval Ruben M. , Molitoris Bruce A.
Published: February 2007

Glomerular filtration rate (GFR), which measures the amount of plasma filtered through the kidney within a given time, is an essential and clinically important indicator of kidney function. Here, we report a new ratiometric measurement technique based on intravital fluorescence microscopy that allows rapid evaluations of renal function in rodent models. By using this technique, plasma clearance rates of a fluorescent GFR marker can be measured in less than 5 min following a bolus infusion of a fluorescent dye mixture into the bloodstream. The plasma clearance kinetics of the GFR marker showed consistent values when measured in healthy animals at locations both in the kidney and from the skin. In addition, by using this technique, we were able to rapidly determine renal function with acute renal failure animal models and with other animal models where kidney filtration functions were altered. The measured plasma clearance kinetics using this technique correlated with expected changes in kidney function. We found this ratiometric approach offers improved accuracy and speed for quantifying renal function compared with the approach using single fluorescent probes, and the measurement can be done noninvasively from the skin. This approach also offers a high sensitivity for determining plasma clearance rate of a fluorescent compound. This feature is important for rapidly quantifying small differences in plasma clearance when kidney function is changing.
Mcl-1 is downregulated in cisplatin-induced apoptosis, and proteasome inhibitors restore Mcl-1 and promote survival in renal tubular epithelial cells
Authors: Yang Cheng , Kaushal Varsha , Shah Sudhir V. , Kaushal Gur P.
Published: February 2007

Mcl-1 is an antiapoptotic member of the Bcl-2 family that plays an important role in cell survival. We demonstrate that proteasome-dependent regulation of Mcl-1 plays a critical role in renal tubular epithelial cell injury from cisplatin. Protein levels of Mcl-1 rapidly declined in a time-dependent manner following cisplatin treatment of LLC-PK1cells. However, mRNA levels of Mcl-1 were not altered following cisplatin treatment. Expression of other antiapoptotic members of the Bcl-2 family such as Bcl-2 and BclxL was not affected by cisplatin treatment. Cisplatin-induced loss of Mcl-1 occurs at the same time as the mitochondrial release of cytochrome c, activation of caspase-3, and initiation of apoptosis. Treatment of cells with cycloheximide, a protein synthesis inhibitor, revealed rapid turnover of Mcl-1. In addition, treatment with cycloheximide in the presence or absence of cisplatin demonstrated that cisplatin-induced loss of Mcl-1 results from posttranslational degradation rather than transcriptional inhibition. Overexpression of Mcl-1 protected cells from cisplatin-induced caspase-3 activation and apoptosis. Preincubating cells with the proteasome inhibitor MG-132 or lactacystin not only restored cisplatin-induced loss of Mcl-1 but also resulted in an accumulation of Mcl-1 that exceeded basal levels; however, Bcl-2 and BclxL levels did not change in response to MG-132 or lactacystin. The proteasome inhibitors effectively blocked cisplatin-induced mitochondrial release of cytochrome c, caspase-3 activation, and apoptosis. These studies suggest that proteasome regulation of Mcl-1 is crucial in the cisplatin-induced apoptosis via the mitochondrial apoptotic pathway and that Mcl-1 is an important therapeutic target in cisplatin injury to renal tubular epithelial cells.
Aberrant Expression of X-Linked Genes RbAp46, Rsk4, and Cldn2 in Breast Cancer
Authors: Thakur Archana , Rahman KM Wahidur , Wu Jack , Bollig Aliccia , Biliran Hector , Lin Xiukun , Nassar Hind , Grignon David J. , Sarkar Fazlul H. , Liao Joshua D.
Published: February 2007

The consequence of activation status or gain/loss of an X-chromosome in terms of the expression of tumor suppressor genes or oncogenes in breast cancer has not been clearly addressed. In this study, we investigated the activation status of the X-chromosomes in a panel of human breast cancer cell lines, human breast carcinoma, and adjacent mammary tissues and a panel of murine mammary epithelial sublines ranging from low to high invasive potentials. Results show that most human breast cancer cell lines were homozygous, but both benign cell lines were heterozygous for highly polymorphic X-loci (IDS and G6PD). On the other hand, 60% of human breast carcinoma cases were heterozygous for either IDS or G6PD markers. Investigation of the activation status of heterozygous cell lines revealed the presence of only one active X-chromosome, whereas most heterozygous human breast carcinoma cases had two active X-chromosomes. Furthermore, we determined whether or not an additional active X-chromosome affects expression levels of tumor suppressor genes and oncogenes. Reverse transcription-PCR data show high expression of putative tumor suppressor genes Rsk4 and RbAp46 in 47% and 79% of breast carcinoma cases, respectively, whereas Cldn2 was down-regulated in 52% of breast cancer cases compared with normal adjacent tissues. Consistent with mRNA expression, immunostaining for these proteins also showed a similar pattern. In conclusion, our data suggest that high expression of RbAp46 is likely to have a role in the development or progression of human breast cancer. The activation status of the X-chromosome may influence the expression levels of X-linked oncogenes or tumor suppressor genes. (Mol Cancer Res 2007;5(2):171–81)
Induction of Tumorigenesis and Metastasis by the Murine Orthologue of Tumor Protein D52
Authors: Lewis Jennifer D. , Payton Laura A. , Whitford Jill G. , Byrne Jennifer A. , Smith David I. , Yang LiBang , Bright Robert K.
Published: February 2007

Expression studies have consistently identified tumor protein D52 (TPD52) overexpression in tumor cells. Murine TPD52 (mD52) shares 86% identity with the human orthologue. To study a possible role for TPD52 in transformation, 3T3 fibroblasts were transfected with the full-length cDNA for mD52. Expression of mD52 was confirmed by reverse transcription-PCR (RT-PCR), real-time PCR, and Western blot analysis compared with 3T3 and vector-transfected 3T3 (3T3.V), and the resultant cell line was designated 3T3.mD52. At 4 weeks, 3T3.mD52 gained a 2-fold increase in growth rate, lost contact inhibition, and exhibited a marked phenotype change. Further characterization revealed an acquired ability for anchorage-independent cell growth. To determine whether 3T3.mD52 had become tumorigenic, naïve, healthy, immunocompetent syngeneic mice were inoculated subcutaneously with varying cell doses. Tumors measuring >1 cm2 were detected 60 days postinoculation with 3T3.mD52, and a 50% subcutaneous tumor incidence was obtained with as few as 5 × 105 3T3.mD52 cells. Remarkably, when lungs from 3T3.mD52 tumor-bearing mice were analyzed, numerous tumor nodules were observed, ranging from nodules less than 10 to nodules too numerous to count (inoculation with 1 × 105 and 5 × 106 cells, respectively). Further support for the metastatic capacity of 3T3.mD52 was the demonstration that transforming growth factor (TGF)-βR1 (receptor) expression decreased and TGF-β1 secretion increased in 3T3.mD52 compared with 3T3 controls. cDNA microarray analysis showed a gene expression pattern that further supported mD52-induced transformation and metastasis. Together, these data suggest that mD52 expression in 3T3 cells initiated cellular transformation, tumorigenesis, and progression to metastasis. (Mol Cancer Res 2007;5(2):133–44)
Phosphatidylinositol-3-OH Kinase or RAS Pathway Mutations in Human Breast Cancer Cell Lines
Authors: Hollestelle Antoinette , Elstrodt Fons , Nagel Jord H.A. , Kallemeijn Wouter W. , Schutte Mieke
Published: February 2007

Constitutive activation of the phosphatidylinositol-3-OH kinase (PI3K) and RAS signaling pathways are important events in tumor formation. This is illustrated by the frequent genetic alteration of several key players from these pathways in a wide variety of human cancers. Here, we report a detailed sequence analysis of the PTEN, PIK3CA, KRAS, HRAS, NRAS, and BRAF genes in a collection of 40 human breast cancer cell lines. We identified a surprisingly large proportion of cell lines with mutations in the PI3K or RAS pathways (54% and 25%, respectively), with mutants for each of the six genes. The PIK3CA, KRAS, and BRAF mutation spectra of the breast cancer cell lines were similar to those of colorectal cancers. Unlike in colorectal cancers, however, mutational activation of the PI3K pathway was mutually exclusive with mutational activation of the RAS pathway in all but 1 of 30 mutant breast cancer cell lines (P = 0.001). These results suggest that there is a fine distinction between the signaling activators and downstream effectors of the oncogenic PI3K and RAS pathways in breast epithelium and those in other tissues. (Mol Cancer Res 2007;5(2):195–201)
Lysophosphatidic Acid Down-Regulates Stress Fibers and Up-Regulates Pro–Matrix Metalloproteinase-2 Activation in Ovarian Cancer Cells
Authors: Do Thuy-Vy , Symowicz Jay C. , Berman David M. , Liotta Lance A. , Petricoin Emanuel F. , Stack M. Sharon , Fishman David A.
Published: February 2007

Epithelial ovarian cancer (EOC) is asymptomatic at early stages and is often diagnosed late when tumor cells are highly metastatic. Lysophosphatidic acid (LPA) has been implicated in ovarian oncogenesis as levels of this lipid are elevated in patient ascites and plasma. Because the underlying mechanism governing LPA regulation of matrix metalloproteinase-2 (MMP-2) activation remains undefined, we investigated the relationship between LPA-induced changes in actin microfilament organization and MMP-2 enzymatic activity. We report that when cells were cultured at a high density, LPA mediated stress fiber and focal adhesion disassembly and significantly repressed RhoA activity in EOC cells. Inhibition of Rho-kinase/ROCK enhanced both LPA-stimulated loss of stress fibers and pro–MMP-2 activation. In contrast, expression of the constitutively active RhoA(G14V) mutant diminished LPA-induced pro–MMP-2 activation. LPA had no effects on membrane type 1–MMP or tissue inhibitor of metalloproteinase-2 expression, but up-regulated MMP-2 levels, contributing to the induction of MMP-2 activation. Interestingly, when cells were cultured at a low density, stress fibers were present after LPA stimulation, and ROCK activity was required for EOC cell migration. Collectively, these results were consistent with a model in which LPA stimulates the metastatic dissemination of EOC cells by initiating loss of adhesion and metalloproteinase activation. (Mol Cancer Res 2007;5(2):121–31)
Local Neurosteroid Production in the Hippocampus: Influence on Synaptic Plasticity of Memory
Authors: Mukai Hideo , Tsurugizawa Tomokazu , Ogiue-Ikeda Mari , Murakami Gen , Hojo Yasushi , Ishii Hirotaka , Kimoto Tetsuya , Kawato Suguru
Published: February 2007

In neuroendocrinology, it is believed that steroid hormones are synthesized in the gonads and/or adrenal glands, and reach the brain via the blood circulation. In contrast to this view, we are in progress of demonstrating that estrogens and androgens are also synthesized locally by cytochrome P450s in the hippocampus, and that these steroids act rapidly to modulate neuronal synaptic plasticity. We demonstrated that estrogens were locally synthesized in the adult hippocampal neurons. In the pathway of steroidogenesis, cholesterol is converted to pregnenolone (by P450scc), dehydroepiandrosterone [by P450(17α)], androstenediol (by 17β-hydroxysteroid dehydrogenase, 17β-HSD), testosterone (by 3β-HSD) and finally to estradiol (by P450arom) and dihydrotestosterone (by 5α-reductase). The basal concentration of estradiol in the hippocampus was approximately 1 nM, which was greater than that in blood plasma. Significant expression of mRNA for P450scc, P450(17α), P450arom, 17β-HSD, 3β-HSD and 5α-reductase was demonstrated by RT-PCR. Their mRNA levels in the hippocampus were 1/200–1/5,000 of those in the endocrine organs. Localization of P450(17α) and P450arom was observed in synapses in addition to endoplasmic reticulum of principal neurons using immunoelectron microscopy. Different from slow action of gonadal estradiol which reaches the brain via the blood circulation, hippocampal neuron-derived estradiol may act locally and rapidly within the neurons. For example, 1 nM 17β-estradiol rapidly enhanced the long-term depression (LTD) not only in CA1 but also in CA3 and dentate gyrus. The density of thin spines was selectively increased within 2 h upon application of 1 nM estradiol in CA1 pyramidal neurons. Only ERα agonist propyl-pyrazole-trinyl-phenol induced the same enhancing effect as estradiol on both LTD and spinogenesis in the CA1. ERβ agonist hydroxyphenyl-propionitrile suppressed LTD and did not affect spinogenesis. Localization of estrogen receptor ERα in spines in addition to nuclei of principal neurons implies that synaptic ERα can drive rapid modulation of synaptic plasticity by endogenous estradiol.
Stress in Pregnancy Activates Neurosteroid Production in the Fetal Brain
Authors: Hirst Jonathan J. , Yawno Tamara , Nguyen Phuong , Walker David W.
Published: February 2007

Neurosteroids such as allopregnanolone are potent agonists at the GABAA receptor and suppress the fetal CNS activity. These steroids are synthesized in the fetal brain either from cholesterol or from circulating precursors derived from the placenta. The concentrations of allopregnanolone are remarkably high in the fetal brain and rise further in response to acute hypoxic stress, induced by constriction of the umbilical cord. This response may result from the increased 5α-reductase and cytochrome P-450SCC expression in the brain. These observations suggest that the rise in neurosteroid concentrations in response to acute hypoxia may represent an endogenous protective mechanism that reduces excitotoxicity following hypoxic stress in the developing brain. In contrast to acute stress, chronic hypoxemia induces neurosteroidogenic enzyme expression without an increase in neurosteroid concentrations and, therefore, may pose a greater risk to the fetus. At birth, the allopregnanolone concentrations in the brain fall markedly, probably due to the loss of placental precursors; however, stressors, including hypoxia and endotoxin-induced inflammation, raise allopregnanolone concentrations in the newborn brain. This may protect the newborn brain from hypoxia-induced damage. However, the rise in allopregnanolone concentrations was also associated with increased sleep. This rise in sedative steroid levels may depress arousal and contribute to the risk of sudden infant death syndrome. Our recent findings indicate that acute hypoxic stress in pregnancy initiates a neurosteroid response that may protect the fetal brain from hypoxia-induced cell death, whereas the decline in allopregnanolone levels after birth may result in greater vulnerability to brain injury in neonates.
Central Nervous System Circuitry Involved in the Hyperinsulinism Syndrome
Authors: Lechin Fuad , van der Dijs Bertha
Published: February 2007

Raised plasma levels of insulin, glucose and glucagon are found in patients affected by ‘hyperinsulinism’. Obesity, hypertension, mammary plus ovary cysts and rheumatic symptoms are frequently observed in these patients. Sleep disorders and depression are also present in most subjects affected by this polysymptomatic disorder. The simultaneous increases of glucose, insulin and glucagon plasma levels seen in these patients indicate that the normal crosstalk between A cells, B cells and D cells is disrupted. With respect to this, it is well known that glucose excites B cells (which secrete insulin) and inhibits A cells (which secrete glucagon), which in turn excites D cells (which secrete somatostatin). Gastrointestinal hormones (incretins) modulate this crosstalk both directly and indirectly throughout pancreatic and hepatobiliary mechanisms. The above factors depend on autonomic nervous system mediation. For instance, acetylcholine released from parasympathetic nerves excites both B and A cells. Noradrenaline released from sympathetic nerves and adrenaline secreted from the adrenal glands inhibit B cells and excite A cells, which are crowded with β2- and α2-receptors, respectively. Noradrenaline released from sympathetic nerves also excites A cells by acting at α1-receptors located at this level. According to this, the excessive release of noradrenaline from these nerves should provoke an enhancement of glucagon secretion which will result in overexcitation of insulin secretion from B cells. That is the disorder seen in the so-called ‘hyperinsulinism’, in which raised plasma levels of glucose, insulin and glucagon coexist. Taking into account that neural sympathetic activity is positively correlated to the A5 noradrenergic nucleus and median raphe serotonergic neurons, and negatively correlated to the A6 noradrenergic, the dorsal raphe serotonergic and the C1 adrenergic neurons, we postulate that this unbalanced central nervous system circuitry is responsible for the hyperinsulinism syndrome.
Asistencia de pacientes con fibrosis quística
Authors: Strandvik Birgitta
Published: February 2007

La fibrosis quística (FQ), la enfermedad pediátrica hereditaria autosómica más corriente, ha dejado de estar limitada a la infancia desde que la terapia moderna ha proporcionado a los pacientes una mayor longevidad y una mejor calidad de vida. Cuando se identificó el gen, hace más de 16 años, y se descubrió la mutación más corriente, ΔF508, se suscitó la esperanza general de una rápida curación de la enfermedad. Aunque el descubrimiento acarreó un considerable impulso de la investigación sobre la fisiopatología, hasta la fecha las mejoras del tratamiento clínico se deben por completo a desarrollos en el contexto del tratamiento tradicional. Las mejorías del estado de los pacientes se vinculan a mejores aportes complementarios de enzimas pancreáticas y a un tratamiento nutricional más intensivo, incluyendo la atención debida al metabolismo anormal de los lípidos. El tratamiento pulmonar ha desembocado en una mejor conservación de la función pulmonar en la edad adulta, con acceso a toda una batería de antibióticos eficientes y al desarrollo de nuevas estrategias: agentes mucolíticos en combinación con el fomento de la actividad física a partir de una edad temprana, conjuntamente con modificaciones en la fisioterapia y mejores resultados en los trasplantes pulmonares como último recurso terapéutico. La hepatopatía goza de un mayor reconocimiento y se trata a menudo a largo plazo con ácido ursodesoxicólico, si bien su efecto en la prevención de la progresión de la hepatopatía no ha sido explorado en todos sus extremos. La detección sistemática neonatal se practica cada vez más, afrontando problemas a corto plazo, como los de naturaleza psicológica, cuando se descubren portadores o casos muy leves, y explorando los resultados a largo plazo para demostrar la mejoría del estado clínico y el incremento adicional de la supervivencia. Las limitaciones en la supervivencia, todavía presentes, parecen deberse principalmente al misterio que subyace a la colonización crónica de las vías respiratorias por microorganismos.
Wnt Signaling Pathway in Mammary Gland Development and Carcinogenesis
Authors: Turashvili Gulisa , Bouchal Jan , Burkadze George , Kolar Zdenek
Published: February 2007

The signaling pathway mediated by Wingless-type (Wnt) proteins is highly conserved in evolution. This pivotal pathway is known to regulate cell fate decisions, cell proliferation, morphology, migration, apoptosis, differentiation and stem cell self-renewal. It currently includes the canonical or Wnt/β-catenin pathway in which Wnt proteins bind to ‘frizzled’ receptors, which leads to downstream activation of gene transcription by β-catenin. Second, the noncanonical or β-catenin-independent pathways are now known to be mediated by three possible mechanisms: (1) the Wnt/Ca2+ pathway, (2) the Wnt/G protein signaling pathway, and (3) the Wnt/PCP or planar cell polarity pathway. Wnt signaling is implicated at several stages of mammary gland growth and differentiation, and possibly in the involution of mammary gland following lactation. Recent evidence suggests the role of Wnt signaling in human breast cancer involves elevated levels of nuclear and/or cytoplasmic β-catenin using immunohistochemistry, overexpression or downregulation of specific Wnt proteins, overexpression of CKII and sFRP4, downregulation of WIF-1 and sFRP1, as well as amplification of DVL-1. Further research is required to determine how Wnt signaling is involved in the development of different histological types of breast cancer and whether it promotes the viability of cancer stem cells or not.
Advanced Glycation End Product in Diabetic Rat Skeletal Muscle in vivo
Authors: Snow LeAnn M. , Lynner Christa B. , Nielsen Erin M. , Neu Hillari S. , Thompson LaDora V.
Published: February 2007

Background: Advanced glycation end products (AGEs) are implicated in the etiology of diabetic complications in the kidney, nerve and eye. Skeletal muscle contractile parameters have also been found to be altered in diabetes. Glycation has not been extensively studied in skeletal muscle, but AGE-modified proteins may influence contractility. Objective and Methods: The aim of this study was to use immunohistochemistry to identify distribution patterns of the AGE NΕ-(carboxymethyl)-lysine in plantaris muscle of diabetic rats. Results: Results revealed the presence of NΕ-(carboxymethyl)-lysine intracellularly and also at sites along the myofiber periphery. The number of myofibers immunolabeling for AGE in animals with diabetes was more than 4-fold greater than in control animals. Additionally, there was a greater proportion of slow + fast myosin heavy chain coexpression in the AGE-positive cells from diabetic animals than in AGE-positive fibers from control animals. No significant difference was present between cross-sectional areas of AGE-positive fibers and AGE-negative fibers within the respective experimental groups. Conclusions: AGE accumulation is greater in skeletal muscle in vivo from diabetic animals than in control animals. This AGE accumulation appears to be associated with fiber-type transformation rather than with myofiber size. Further study is needed to determine the identity of these AGE-modified proteins and to determine how they influence skeletal muscle function in diabetes.