bluuebunny/crossref_metadata_2025 huggingface dataset:
Manipulation of Pituitary-Adrenal Activity Affects Neural Plasticity in Rodent Hippocampus
Authors: Foy Michael R. , Foy Judith G. , Levine Seymour , Thompson Richard F.
Published: April 2006

Hormones secreted from the pituitary-adrenal system during stress affect learning and memory processes. The phenomenon of long-term potentiation (LTP) is a robust example of neuronal plasticity and has become widely regarded as a possible physiological substrate for learning and memory in the mammalian brain. The current study supports our previous finding that stress impairs LTP in the in vitro hippocampal slice. In addition, manipulation of the pituitary-adrenal axis by dexamethasone (DEX), a synthetic glucocorticoid that blocks the pituitary-adrenal response to stress, appears to influence the temporal patterns of the development of the neuronal plastic changes which occur immediately after tetanus (post-tetanic potentiation period, or PTP). Since the stress-induced impairment of LTP occurs, regardless of DEX treatment, we suggest the action of DEX is to modulate the temporal pattern of the PTP/LTP interaction in response to stress.
Two Metabolites of [Leu]enkephalin, Tyr-Gly and Tyr-Gly-Gly-Phe, Impair Acquisition of an Active Avoidance Response in Mice
Authors: Martinez Joe L. , Weinberger Susan B. , Janak Patricia H. , Schulteis Gery
Published: April 2006

Two tyrosine-containing enkephalin metabolites, Tyr-Gly and Tyr-Gly-Gly-Phe, were found to impair acquisition of a one-way active avoidance response when administered intraperitoneally to mice. Prior studies demonstrated that the enkephalin metabolite Tyr-Gly-Gly also impairs avoidance acquisition, but that the tetrapeptide Gly-Gly-Phe-Leu is without similar effects. Since [leu]enkephalin also impairs acquisition of the avoidance response, these data are consistent with the suggestion that enkephalin metabolites containing an N-terminal tyrosine may be the active principals for the behavioral effects produced by [leu]enkephalin. Alternatively, these metabolites may represent a separate class of pharmacological agents that shares some behavioral effects with the enkephalins, but that produces effects on learning through a different mechanism.
Testosterone, Social Class, and Antisocial Behavior in a Sample of 4,462 Men
Authors: Dabbs James M. , Morris Robin
Published: April 2006

Two hypotheses have been offered to explain the relation between testosterone and antisocial behavior in delinquent and criminal populations. One is that testosterone leads directly to antisocial behavior. The other is that a constellation of dominance, competitiveness, and sensation seeking associated with testosterone leads to either antisocial or prosocial behavior, depending upon an individual's resources and background. Analysis of archival data from 4,462 U.S. military veterans supported the first hypothesis: Testosterone was correlated with a variety of antisocial behaviors among all individuals. However, socioeconomic status (SES) proved to be a moderating variable, with weaker testosterone-behavior relationships among high SES subjects.
Article Commentary: The Laboratory Animal Dilemma: A Solution in our Backyards
Authors: Devenport L.D. , Devenport J.A.
Published: April 2006

Despite external pressure, psychologists have not found an acceptable alternative to laboratory animals. While a strong defense of current practices may be the best policy for some, we question the assumption that the laboratory is the only or even the best setting for much behavioral research. Millions of domestic animals kept as pets are available for onsite experiments. We report that this subject pool is accessible, cost-effective, and produces reliable behavioral data. Using pets may even increase the scientific awareness of the public, improving the atmosphere for all animal research.
Attribution of Causality to Common and Distinctive Elements of Compound Stimuli
Authors: Wasserman Edward A.
Published: April 2006

Given the task of diagnosing the source of a patient's allergic reaction, college students judged the causal efficacy of common (X) and distinctive (A and B) elements of compound stimuli: AX and BX. As the differential correlation of AX and BX with the occurrence and nonoccurrence of the allergic reaction rose from .00 to 1.00, ratings of the distinctive A and B elements diverged; most importantly, ratings of the common X element fell. These causal judgments of humans closely parallel the conditioned responses of animals in associative learning studies, and clearly disclose that stimuli compete with one another for control over behavior.
Sensitivity to Three-Dimensional Orientation in Visual Search
Authors: Enns James T. , Rensink Ronald A.
Published: April 2006

Previous theories of early vision have assumed that visual search is based on simple two-dimensional aspects of an image, such as the orientation of edges and lines. It is shown here that search can also be based on three-dimensional orientation of objects in the corresponding scene, provided that these objects are simple convex blocks. Direct comparison shows that image-based and scene-based orientation are similar in their ability to facilitate search. These findings support the hypothesis that scene-based properties are represented at preattentive levels in early vision.
Individual Differences in Television Viewing in Early Childhood: Nature as Well as Nurture
Authors: Plomin Robert , Corley Robin , DeFries J.C. , Fulker D.W.
Published: April 2006

Although there has been a tremendous outpouring of research on the consequences of children's television viewing, little is known about the causes of individual differences in television viewing, which is one of the major activities of childhood. We present results from the first parent-offspring and sibling adoption analyses of individual differences in time spent watching television in early childhood, and we consider IQ and temperament as possible mechanisms of genetic influence. The sample consisted of over 220 adopted children studied at 3, 4, and 5 years of age, the complete sample of probands from the Colorado Adoption Project. Also assessed are the adoptees’ biological and adoptive parents, matched nonadoptive families, and younger adoptive and nonadoptive siblings. Both the parent-offspring and sibling adoption designs yielded evidence for significant genetic influence on individual differences in children's television viewing. Neither IQ nor temperament appear to be responsible for this genetic influence.
Neuronal Activity in the Rabbit Interpositus Nucleus during Classical NM-Conditioning with a Pontine-Nucleus-Stimulation CS
Authors: Steinmetz Joseph E.
Published: April 2006

The nictitating membranes of six rabbits were classically conditioned using a pontine-nucleus-stimulation conditioned stimulus with an air-puff unconditioned stimulus and a tone conditioned stimulus with an air-puff unconditioned stimulus. Multiple-unit neuronal activity in the cerebellar interpositus nucleus was monitored during the stimulation and tone training. Significant increases in the number of learned responses as well as increases in conditioning-related neuronal activity in the interpositus were observed during stimulation training. The number of conditioned nictitating-membrane responses and level of learning-related neuronal activity remained high during subsequent tone training. These data show that the cerebellum is activated in a similar manner when pontine stimulation or peripheral tones are used as a conditioned stimulus during classical nictitating-membrane conditioning.
The Role of Cohabitation in Remarriage
Authors: Xu Xiaohe , Hudspeth Clark D. , Bartkowski John P.
Published: April 2006

Using 3 subsamples of remarried respondents (n =1,583, 971, and 926) in the first wave of the National Survey of Families and Households, this study investigates how different types of cohabitation, especially postdivorce cohabitation, affect the timing and quality of remarriage in the United States. Ordinary Least Squares regression analysis indicates that postdivorce cohabitation in general and postdivorce cohabitation with multiple partners in particular delay remarriage. Furthermore, echoing previous research findings on the relationship between premarital cohabitation and relationship quality, the ordered logistic analysis shows that postdivorce cohabitation with a spouse is associated with lower levels of remarital happiness, and postdivorce cohabitation of all types tends to be associated with higher levels of remarital instability. Implications of these findings are briefly discussed.
Linked Lives: Adult Children’s Problems and Their Parents’ Psychological and Relational Well‐Being
Authors: Greenfield Emily A. , Marks Nadine F.
Published: April 2006

This study examined associations between adult children’s cumulative problems and their parents’ psychological and relational well‐being, as well as whether such associations are similar for married and single parents. Regression models were estimated using data from 1,188 parents in the 1995 National Survey of Midlife in the United States whose youngest child was at least 19 years old. Participants reporting children with more problems indicated moderately poorer levels of well‐being across all outcomes examined. Single parents reporting more problems indicated less positive affect than a comparable group of married parents, but married parents reporting more problems indicated poorer parent‐child relationship quality. Findings are congruent with the family life course perspective, conceptualizing parents and children as occupying mutually influential developmental trajectories.
Consumer knowledge and expectations of restaurant menus and their governing legislation: a qualitative assessment
Authors: Thomas Lionel , Mills Juline E.
Published: April 2006

Many consumers feel that it is the social responsibility of restaurants to inform them of the nutritional content of food items that may be detrimental to their health or contrary to their beliefs. Current legislation, through the Truth‐in‐Menu Law, protects consumers from misleading advertisements, but does not mandate that restaurant establishments provide nutritional information. This qualitative study aims to assess how much consumers really know about menu labeling legislation and what information they consider to be most important on restaurant menus. This study found that consumers feel consistency between item description and actual presentation, accuracy of claims, disclosure of ingredients, nutritional information, value and the availability of competent servers to explain any ambiguities were most important. The article concludes with recommendations on where legislation should go and what restaurants can do to provide menus that meet customer expectations.
Cell Division of
Giardia intestinalis
: Flagellar Developmental Cycle Involves Transformation and Exchange of Flagella between Mastigonts of a Diplomonad Cell
Authors: Nohýnková Eva , Tůmová Pavla , Kulda Jaroslav
Published: April 2006

Giardia intestinalis
is a binucleated diplomonad possessing four pairs of flagella of distinct location and function. Its pathogenic potential depends on the integrity of a complex microtubular cytoskeleton that undergoes a profound but poorly understood reorganization during cell division. We examined the cell division of
G. intestinalis
with the aid of light and electron microscopy and immunofluorescence methods and present here new observations on the reorganization of the flagellar apparatus in the dividing
Giardia
. Our results demonstrated the presence of a flagellar maturation process during which the flagella migrate, assume different position, and transform to different flagellar types in progeny until their maturation is completed. For each newly assembled flagellum it takes three cell cycles to become mature. The mature flagellum of
Giardia
is the caudal one that possesses a privileged basal body at which the microtubules of the adhesive disk nucleate. In contrast to generally accepted assumption that each of the two diplomonad mastigonts develops separately, we found that they are developmentally linked, exchanging their cytoskeletal components at the early phase of mitosis. The presence of the flagellar maturation process in a metamonad protist
Giardia
suggests that the basal body or centriole maturation is a universal phenomenon that may represent one of the core processes in a eukaryotic cell.
The Highly Conserved Family of
Tetrahymena thermophila
Chromosome Breakage Elements Contains an Invariant 10-Base-Pair Core
Authors: Hamilton Eileen P. , Williamson Sondra , Dunn Sandra , Merriam Virginia , Lin Cindy , Vong Linh , Russell-Colantonio Jessica , Orias Eduardo
Published: April 2006

As a typical ciliate,
Tetrahymena thermophila
is a unicellular eukaryote that exhibits nuclear dimorphism: each cell contains a diploid, germ line micronucleus (MICN) and a polyploid, somatic macronucleus (MACN). During conjugation, when a new MACN differentiates from a mitotic descendant of the diploid fertilization nucleus, the five MICN chromosomes are site-specifically fragmented into 250 to 300 MACN chromosomes. The classic chromosome breakage sequence (CBS) is a 15-bp element (TAAACCAACCTCTTT) reported to be necessary and sufficient for chromosome breakage. To determine whether a CBS is present at every site of chromosome fragmentation and to assess the range of sequence variation tolerated, 31 CBSs were isolated without preconception as to the sequence of the chromosome breakage element. Additional CBS-related sequences were identified in the whole-genome sequence by their similarities to the classic CBS. Forty CBS elements behaved as authentic chromosome breakage sites. The CBS nucleotide sequence is more diverse than previously thought: nearly half of the CBS elements identified by unbiased methods have a variant of the classic CBS. Only an internal 10-bp core is completely conserved, but the entire 15-bp chromosome breakage sequence shows significant sequence conservation. Our results suggest that any one member of the CBS family provides a necessary and sufficient
cis
element for chromosome breakage. No chromosome breakage element totally unrelated to the classic CBS element was found; such elements, if they exist at all, must be rare.
Distinction between hereditary and sporadic breast cancer on the basis of clinicopathological data
Authors: van der Groep P , Bouter A , van der Zanden R , Siccama I , Menko F H , Gille J J P , van Kalken C , van der Wall E , Verheijen R H M , van Diest P J
Published: April 2006

Background:About 5% of all breast cancer cases are attributable to germline mutations in BRCA1 or BRCA2 genes. BRCA mutations in suspected carriers, however, may be missed, which hampers genetic counselling.

Materials and methods:Different clinicopathological features were compared between 22 breast cancers from carriers of proved BRCA1 mutations and 604 cancers from sporadic controls. In addition, 5 BRCA2-related breast cancers and 66 breast cancers of untested patients at intermediate risk and 19 breast cancers of untested patients at high risk of hereditary disease on the basis of family history were evaluated.

Results:A “probably sporadic” class (age ⩾54 years and epidermal growth factor receptor (EGFR) negative; 68% of cases) with a 0% chance of BRCA1-related breast cancer containing 79% of the sporadic cases was yielded by using a decision tree with age, Ki67 and EGFR. A 75% chance of BRCA1-related breast cancer was shown by the “probably BRCA1-related” class (age <54 years and Ki67 ⩾25%; 8% of cases) with 82% of the BRCA1-related cases but only 1.4% of the sporadic cases. Most cases at intermediate or high risk of hereditary disease on the basis of family history could be classified with high probability as either probably BRCA1 related or probably sporadic.

Conclusion:Breast carcinomas can be classified with a high level of certainty as sporadic or related to BRCA1 germline mutations by using a decision tree with age, Ki67 and EGFR. This can be clinically useful in mutation analysis in families with a borderline risk of hereditary disease.
Weight correction of MoM values: which method?
Authors: Reynolds T M , Vranken G , Van Nueten J
Published: April 2006

Background:Adjusting maternal serum markers for maternal weight is considered to be a standard practice when screening for pregnancies associated with Down’s syndrome. The choice of model for taking maternal weight into account is, however, rarely explicitly evaluated.

Method:The relationship between the maternal serum markers αfetoprotein (AFP), human chorionic gonadotropin (HCG) and unconjugated oestriol (uE3), determined with the Beckman Coulter access reagents and maternal weight was investigated in a cohort of 752 Belgian women being screened for pregnancy associated with Down’s syndrome. Two different models (the log–linear equation and the linear–reciprocal equation) were used to determine the relationship between the serum markers and maternal weight.

Results:A significant relationship between log10multiples of median (MoM) values and weight (kg) was obtained for all markers, and the log–linear model had higher coefficients of determination (r2) when compared with the linear–reciprocal model. Weight correction with either method achieved the optimum effect that the correction factor for a woman with a population median weight of 65.5 kg was not significantly different from 1. Simulated weight-corrected MoM values with the two approaches were compared and variation was estimated. The mean difference between the weight-corrected MoM values calculated by the two methods was 7.8% (SD 4.3%) for AFP, 14.0% (4.4%) for HCG and 5.9% (3.2%) for uE3. This resulted in a difference in risk estimate of 1.66–5.34% for Down’s syndrome owing to weight correction algorithm differences in women of median weight.

Conclusion:The log–linear weight correction approach was shown to be marginally more effective by a goodness-of-fit analysis. Differences in weight-corrected MoM values estimated with the two approaches are highly significant (p<0.0001, Wilcoxon’s paired sample test), but the effect on risk calculation was not significant. It was observed that the changes in risk became significant the more the MoM correction factors deviated from 1.
SUPERCRITICAL ISING MODEL ON THE LATTICE FRACTAL — THE SIERPINSKI CARPET
Authors: WANG JUN
Published: April 2006

The spectral gap of the Ising model on the lattice fractal (lattice Sierpinski carpet) with the plus boundary condition is considered. In the absence of an external field and at the supercritical condition, we show a lower bound of the spectral gap of the Ising model.
STABILIZATION OF UNSTABLE PERIODIC ORBITS FOR DISCRETE TIME CHAOTIC SYSTEMS BY USING PERIODIC FEEDBACK
Authors: MORGÜL ÖMER
Published: April 2006

We propose a periodic feedback scheme for the stabilization of periodic orbits for discrete time chaotic systems. We first consider one-dimensional discrete time systems and obtain some stability results. Then we extend these results to higher dimensional discrete time systems. The proposed scheme is quite simple and we show that any hyperbolic periodic orbit can be stabilized with this scheme. We also present some simulation results.
BINARY INFORMATION PROCESSING VIA PARAMETER-INDUCED STOCHASTIC RESONANCE IN THE PRESENCE OF MULTIPLICATIVE AND ADDITIVE COLORED NOISE WITH COLORED CROSS-CORRELATION
Authors: LI JIANLONG , XU BOHOU
Published: April 2006

In the presence of multiplicative and additive colored noise with colored cross-correlation, a method of parameter-induced aperiodic stochastic resonance (SR) for baseband binary pulse amplitude modulated (PAM) signal processing is investigated in detail. Firstly, the dynamic bit error rate (DBER) is defined by the nonstationary solution of the Fokker–Planck equation (FPE). Because the output probability densities of the nonlinear system are unsymmetrical, the decision level of the binary signal is decided by minimizing DBER. Then we take this minimal DBER (MDBER) as a quantity to optimize in the aperiodic SR problem by tuning the system parameters. With theoretical and numerical simulation methods, the effect of noise correlation times on MDBER is discussed. Finally, by comparison between theoretical and numerical simulation results, we find that the agreement is good for not so large noise correlation times.
DYNAMIC LINEAR LEVEL OCTREE-BASED VOLUME RENDERING METHODS FOR INTERACTIVE MICROSURGICAL SIMULATION
Authors: WANG ZHENLAN , CHUI CHEE-KONG , CAI YIYU , ANG CHUAN-HENG , TEOH SWEE-HIN
Published: April 2006

Microsurgery is a highly complex surgical procedure on small body parts performed by a dedicated surgical team. An operating microscope is typically used to obtain a precise view of the soft tissues. The complexity of the microsurgical procedure makes it a suitable application of virtual/augmented reality technology for training purpose. In this paper, we present an overview of our simulator and then describe in details the visualization work that reconstructs the magnified view of the operating area from medical images. The visualization component is based entirely on our newly proposed dynamic linear level octree (DLLO)-based volume rendering methods. In comparison with the conventional ray casting algorithms, our computational method achieves fast rendering speed, reduces hardware requirement and combines surface-volume rendering for realistic and interactive PC-based medical simulations. The new algorithms are suitable for rendering dynamic medical data which are increasingly popular clinically.
TEMPLATE-BASED ISOCONTOURING
Authors: LAKSHMIPATHY JAGANNATHAN , NOWINSKI WIESLAW L. , WERNERT ERIC A.
Published: April 2006

Different isocontour extraction methods use different cell types (tetrahedral, hexahedral, etc.) depending on the nature of the acquisition grids (structured, unstructured, etc.). The existing isocontouring methods have the following pre-steps for the actual extraction process: (a) identification of cell types, (b) identification of topologically independent instances for each cell type, (c) determination of surface primitives contained in the topologically independent instances and (d) generation of a lookup table such that the name of the entry is an instance of a cell and the entry is the triangle set for that instance. The extraction process outputs the triangles from the lookup table. In this paper we present a novel generic method that enables us to list topologically independent surface primitives called "templates" within any n-polytope cell namely tetrahedra, hexahedra etc. We have also modified the traditional lookup table such that name is the cell instance and the entry is face index representations of all template instances contained in that cell. To show an example, we have applied this approach on a hexahedron and listed the templates and subsequently we have showed how to construct a lookup table. Most modern graphics hardware render triangles faster if they are rendered collectively as triangle strips as opposed to individual triangles. With our modified lookup table approach we can identify triangles in the neighboring cell in a linear time and hence we are able to connect two triangle strips into a longer triangle strip on the fly during the extraction process. We have compared our approach with some existing methods. The following are some of the important features of the method: (1) Simplicity, (2) procedural triangulation and (3) face-index representation.
BIO-NATIVE SHAPE MODELING AND VIRTUAL REALITY FOR BIO EDUCATION
Authors: LU BAIFANG , FAN ZHAOWEI , ZHENG JIANMIN , LI LIN
Published: April 2006

Bio structural and functional research and education is playing an increasingly important role in today's post-genome era. Protein geometry and shape modeling is thus a fundamental issue for protein visualization. The number of protein structures determined by X-ray crystallography or Nuclear Magnetic Resonance (NMR) is expanding in an exponential rate. Recent technology advancement has also made it possible for the determination of larger and more complicated proteins structure. A generic and automatic shape modeling for protein structures is therefore highly desired for effective and efficient protein visualization. We propose a bio-native geometric modeling technique in this paper for constructing protein secondary structure. Our emphasis is placed on the shape compatibility with the protein conformation property. Efforts are also made to handle smooth sweeping for complex protein structures. We describe as well a Virtual Reality (VR) application for protein structure education based on our Bio-native shape modeling and visualization techniques developed in this work.
Mechanisms of Liver Injury. III. Oxidative stress in the pathogenesis of hepatitis C virus
Authors: Choi Jinah , James Ou J.-H.
Published: April 2006

Hepatitis C virus (HCV) is a major cause of viral hepatitis that can progress to hepatic fibrosis, steatosis, hepatocellular carcinoma, and liver failure. HCV infection is characterized by a systemic oxidative stress that is most likely caused by a combination of chronic inflammation, iron overload, liver damage, and proteins encoded by HCV. The increased generation of reactive oxygen and nitrogen species, together with the decreased antioxidant defense, promotes the development and progression of hepatic and extrahepatic complications of HCV infection. This review discusses the possible mechanisms of HCV-induced oxidative stress and its role in HCV pathogenesis.
Quantifying cardiac sympathetic and parasympathetic nervous activities using principal dynamic modes analysis of heart rate variability
Authors: Zhong Yuru , Jan Kung-Ming , Ju Ki Hwan , Chon Ki H.
Published: April 2006

The ratio between low-frequency (LF) and high-frequency (HF) spectral power of heart rate has been used as an approximate index for determining the autonomic nervous system (ANS) balance. An accurate assessment of the ANS balance can only be achieved if clear separation of the dynamics of the sympathetic and parasympathetic nervous activities can be obtained, which is a daunting task because they are nonlinear and have overlapping dynamics. In this study, a promising nonlinear method, termed the principal dynamic mode (PDM) method, is used to separate dynamic components of the sympathetic and parasympathetic nervous activities on the basis of ECG signal, and the results are compared with the power spectral approach to assessing the ANS balance. The PDM analysis based on the 28 subjects consistently resulted in a clear separation of the two nervous systems, which have similar frequency characteristics for parasympathetic and sympathetic activities as those reported in the literature. With the application of atropine, in 13 of 15 supine subjects there was an increase in the sympathetic-to-parasympathetic ratio (SPR) due to a greater decrease of parasympathetic than sympathetic activity ( P = 0.003), and all 13 subjects in the upright position had a decrease in SPR due to a greater decrease of sympathetic than parasympathetic activity ( P < 0.001) with the application of propranolol. The LF-to-HF ratio calculated by the power spectral density is less accurate than the PDM because it is not able to separate the dynamics of the parasympathetic and sympathetic nervous systems. The culprit is equivalent decreases in both the sympathetic and parasympathetic activities irrespective of the pharmacological blockades. These findings suggest that the PDM shows promise as a noninvasive and quantitative marker of ANS imbalance, which has been shown to be a factor in many cardiac and stress-related diseases.
Developmental changes in hemodynamics of uterine artery, utero- and umbilicoplacental, and vitelline circulations in mouse throughout gestation
Authors: Mu Junwu , Adamson S. Lee
Published: April 2006

In human pregnancy, abnormal placental hemodynamics likely contribute to the etiology of early-onset preeclampsia and fetal intrauterine growth restriction. The mouse is increasingly being deployed to study normal and abnormal mammalian placental development, yet the placental hemodynamics in normal pregnancy in mice is currently unknown. We used ultrasound biomicroscopy to noninvasively image and record Doppler blood velocity waveforms from the maternal and embryonic placental circulations in mice throughout gestation. In the uterine artery, peak systolic velocity (PSV) increased significantly from 23 ± 2 (SE) to 59 ± 3 cm/s, and end-diastolic velocity (EDV) increased from 7 ± 1 to 28 ± 2 cm/s in nonpregnant versus full-term females so that the uterine arterial resistance index (RI) decreased from 0.70 ± 0.02 to 0.53 ± 0.02. Velocities in the maternal arterial canal in the placenta were low and nearly steady and increased from 0.9 ± 0.03 cm/s at embryonic day 10.5 (E10.5) to 2.4 ± 0.07 cm/s at E18.5. PSV in the umbilical artery increased steadily from 0.8 ± 0.1 cm/s at E8.5 to 15 ± 0.6 cm/s at E18.5, whereas PSV in the vitelline artery increased from 0.6 ± 0.1 cm/s at E8.5 to 4 ± 0.2 cm/s at E13.5 and then remained stable to term. In the umbilical artery, the EDV detection rate was 0% at ≤E14.5 and 94% at E18.5, and the RI decreased from 1 to 0.82 ± 0.01 during this interval. We conclude that ultrasound biomicroscopy can be used to monitor placental hemodynamics during pregnancy in mice. These results provide novel information concerning the development of the vitelline and placental circulations in mice and reveal strong similarities in placental hemodynamics between mice and humans.
Myocardial protection by pioglitazone, atorvastatin, and their combination: mechanisms and possible interactions
Authors: Ye Yumei , Lin Yu , Atar Shaul , Huang Ming-He , Perez-Polo Jose R. , Uretsky Barry F. , Birnbaum Yochai
Published: April 2006

We assessed 1) whether pretreatment before ischemia with pioglitazone (Pio) limits infarct size (IS) and whether this protective effect is due to nitric oxide synthase (NOS) and/or prostaglandin production, as has been shown for atorvastatin (ATV); and 2) whether Pio and ATV have synergistic effects on myocardial protection. Sprague-Dawley rats received oral ATV (10 mg·kg−1·day−1), Pio (10 mg·kg−1·day−1), their combination (Pio + ATV), or water alone for 3 days. Additional rats received Pio (10 mg·kg−1·day−1) for 3 days and intravenous SC-58125 [a cyclooxygenase-2 (COX-2) inhibitor] or SC-560 (a COX-1 inhibitor) 15 min before ischemia. Rats underwent 30 min of myocardial ischemia and 4 h of reperfusion, or hearts were harvested for analysis. IS in the Pio and in the ATV groups was significantly smaller than in the sham-treated group. IS in the Pio + ATV group was smaller than in all other groups ( P < 0.001 vs. each group). The protective effect of Pio was abrogated by SC-58125 but not by SC-560. Pio, ATV, and Pio + ATV increased the expression and activity of cytosolic phospholipase A2 (cPLA2) and COX-2. ATV increased phosphorylated-Akt, phosphorylated-endothelial NOS (P-eNOS), inducible NOS, and COX-2 levels. In contrast, Pio caused an insignificant increase in myocardial levels of phosphorylated-Akt but did not change P-eNOS and iNOS expression. In conclusion, the IS-limiting effects of Pio and ATV involve COX-2. However, the upstream steps differ. ATV induced eNOS phosphorylation and iNOS, cPLA2, and COX-2 expression, whereas Pio induced mainly the expression and activity of cPLA2. The effects of Pio and ATV were additive.
Sex-related dimorphic response of HIF-1α expression in myocardial ischemia
Authors: Zampino Manuela , Yuzhakova Milana , Hansen James , McKinney Ronald D. , Goldspink Paul H. , Geenen David L. , Buttrick Peter M.
Published: April 2006

Hypoxia-inducible factor-1α (HIF-1α) plays a role in a number of cell-protective pathways after ischemia. There are clear sex-related differences in the remodeling process, and hearts from males tend to dilate in response to pathological loads and ischemia to a greater degree than do hearts from females. Thus we hypothesized that there would be a sex-related dimorphic response of HIF-1α to an ischemic event. Male and female rats were euthanized 5 and 24 h after coronary ligation (M-MI and F-MI; MI, myocardial ischemia), and HIF-1α expression was determined by immunohistochemistry, Western blot, and quantitative RT-PCR. Sham-operated male and female animals served as controls (M-SH and F-SH). In the ischemic area, histochemical analysis at 5 h showed that HIF was expressed in 33% of cell nuclei in M-MI and in 55% in F-MI. At 24 h, HIF expression increased to 49% in M-MI and to 82% in F-MI ( P < 0.05 vs. SH and also M-MI vs. F-MI). This difference was not only statistically significant between the two sexes at 24 h but also within each sex at 5 and 24 h after ligation. Western blots confirmed that, at 24 h after ischemia, HIF protein increased significantly in both male and female hearts relative to sham-operated animals but that the increase in females was 60% greater than that seen in males. mRNA expression of HIF was significantly increased at 24 h in F-MI versus M-MI and sham-operated animals. Expression of downstream HIF target genes (heme oxygenase and brain natriuretic peptide) was increased in proportion to the levels of HIF expression. These data suggest a novel cellular mechanism to explain the sex-related dimorphic response to ischemia and also the possibility that exogenous modulation of HIF might represent a new therapeutic approach to preventing left ventricular remodeling.
Caveolin-1 and regulation of cellular cholesterol homeostasis
Authors: Frank Philippe G. , Cheung Michelle W.-C. , Pavlides Stephanos , Llaverias Gemma , Park David S. , Lisanti Michael P.
Published: April 2006

Caveolae are 50- to 100-nm cell surface plasma membrane invaginations present in terminally differentiated cells. They are characterized by the presence of caveolin-1, sphingolipids, and cholesterol. Caveolin-1 is thought to play an important role in the regulation of cellular cholesterol homeostasis, a process that needs to be properly controlled to limit and prevent cholesterol accumulation and eventually atherosclerosis. We have recently generated caveolin-1-deficient [Cav-1(−/−)] mice in which caveolae organelles are completely eliminated from all cell types, except cardiac and skeletal muscle. In the present study, we examined the metabolism of cholesterol in wild-type (WT) and Cav-1(−/−) mouse embryonic fibroblasts (MEFs) and mouse peritoneal macrophages (MPMs). We observed that Cav-1(−/−) MEFs are enriched in esterified cholesterol but depleted of free cholesterol compared with their wild-type counterparts. Similarly, Cav-1(−/−) MPMs also contained less free cholesterol and were enriched in esterified cholesterol on cholesterol loading. In agreement with this finding, caveolin-1 deficiency was associated with reduced free cholesterol synthesis but increased acyl-CoA:cholesterol acyl-transferase (ACAT) activity. In wild-type MPMs, we observed that caveolin-1 was markedly upregulated on cholesterol loading. Despite these differences, cellular cholesterol efflux from MEFs and MPMs to HDL was not affected in the Cav-1-deficient cells. Neither ATP-binding cassette transporter G1 (ABCG1)- nor scavenger receptor class B type I (SR-BI)-mediated cholesterol efflux was affected. Cellular cholesterol efflux to apolipoprotein A-I was not significantly reduced in Cav-1(−/−) MPMs compared with wild-type MPMs. However, ABCA1-mediated cholesterol efflux was clearly more sensitive to the inhibitory effects of glyburide in Cav-1(−/−) MPMs versus WT MPMs. Taken together, these findings suggest that caveolin-1 plays an important role in the regulation of intracellular cholesterol homeostasis and can modulate the activity of other proteins that are involved in the regulation of intracellular cholesterol homeostasis.
Abdominal aortic hemodynamics in young healthy adults at rest and during lower limb exercise: quantification using image-based computer modeling
Authors: Tang Beverly T. , Cheng Christopher P. , Draney Mary T. , Wilson Nathan M. , Tsao Philip S. , Herfkens Robert J. , Taylor Charles A.
Published: April 2006

Localization of atherosclerotic lesions in the abdominal aorta has been previously correlated to areas of adverse hemodynamic conditions, such as flow recirculation, low mean wall shear stress, and high temporal oscillations in shear. Along with its many systemic benefits, exercise is also proposed to have local benefits in the vasculature via the alteration of these regional flow patterns. In this work, subject-specific models of the human abdominal aorta were constructed from magnetic resonance angiograms of five young, healthy subjects, and computer simulations were performed under resting and exercise (50% increase in resting heart rate) pulsatile flow conditions. Velocity fields and spatial variations in mean wall shear stress (WSS) and oscillatory shear index (OSI) are presented. When averaged over all subjects, WSS increased from 4.8 ± 0.6 to 31.6 ± 5.7 dyn/cm2 and OSI decreased from 0.22 ± 0.03 to 0.03 ± 0.02 in the infrarenal aorta between rest and exercise. WSS significantly increased, whereas OSI decreased between rest and exercise at the supraceliac, infrarenal, and suprabifurcation levels, and significant differences in WSS were found between anterior and posterior sections. These results support the hypothesis that exercise provides localized benefits to the cardiovascular system through acute mechanical stimuli that trigger longer-term biological processes leading to protection against the development or progression of atherosclerosis.
Regulation of myocardial substrate metabolism during increased energy expenditure: insights from computational studies
Authors: Zhou Lufang , Cabrera Marco E. , Okere Isidore C. , Sharma Naveen , Stanley William C.
Published: April 2006

In response to exercise, the heart increases its metabolic rate severalfold while maintaining energy species (e.g., ATP, ADP, and Pi) concentrations constant; however, the mechanisms that regulate this response are unclear. Limited experimental studies show that the classic regulatory species NADH and NAD+ are also maintained nearly constant with increased cardiac power generation, but current measurements lump the cytosol and mitochondria and do not provide dynamic information during the early phase of the transition from low to high work states. In the present study, we modified our previously published computational model of cardiac metabolism by incorporating parallel activation of ATP hydrolysis, glycolysis, mitochondrial dehydrogenases, the electron transport chain, and oxidative phosphorylation, and simulated the metabolic responses of the heart to an abrupt increase in energy expenditure. Model simulations showed that myocardial oxygen consumption, pyruvate oxidation, fatty acids oxidation, and ATP generation were all increased with increased energy expenditure, whereas ATP and ADP remained constant. Both cytosolic and mitochondrial NADH/NAD+ increased during the first minutes (by 40% and 20%, respectively) and returned to the resting values by 10–15 min. Furthermore, model simulations showed that an altered substrate selection, induced by either elevated arterial lactate or diabetic conditions, affected cytosolic NADH/NAD+ but had minimal effects on the mitochondrial NADH/NAD+, myocardial oxygen consumption, or ATP production. In conclusion, these results support the concept of parallel activation of metabolic processes generating reducing equivalents during an abrupt increase in cardiac energy expenditure and suggest there is a transient increase in the mitochondrial NADH/NAD+ ratio that is independent of substrate supply.
Role of Phosphophoryn in Dentin Mineralization
Authors: George Anne , Hao Jianjun
Published: April 2006

Mineral deposition is essential for the development of hard tissues like bone and teeth. In matrix-mediated mechanisms responsible for dentin formation, type I collagen defines the framework for mineral deposition and by itself is not sufficient to support nucleation of hydroxyapatite. However, in the presence of non-collagenous proteins, nucleation sites have been identified within the hole regions of the fibrils, and at these sites, mineral crystals can grow and propagate. Non-collagenous proteins constitute 5–10% of the total extracellular matrix proteins. They are embedded within the mineral deposits, suggesting a possible interaction with the mineral phase. During dentin formation, phosphophoryn (PP), an abundant macromolecule in the extracellular matrix, can initiate mineral deposition in localized regions by matrix-mediated mineralization mechanism. In our work, we have demonstrated that PP, due to its highly phosphorylated post-translational modification, can bind calcium ions with high affinity and at the same time aggregate collagen fibrils at the mineralization front. Molecular modeling has further demonstrated that the spacing of the carboxyl and phosphate groups present on PP might be essential for dictating the crystal orientation relative to the collagen substrate. Thus, PP may provide the interface linkage between mineral crystal and collagen fibrils.
Defining the Roots of Cementum Formation
Authors: Popowics T. , Foster B.L. , Swanson E.C. , Fong H. , Somerman M.J.
Published: April 2006

Significant progress has been seen in research aimed at regeneration of the disease-damaged periodontium. Our own strategy has been to approach periodontal tissue development (i.e. root, cementum, periodontal ligament, and bone) as a source for the identification of key regulators of cellular processes that may be applicable to periodontal tissue repair. Specifically, enamel-like molecules, bone morphogenetic proteins (BMPs), and phosphates have been investigated for their role in altering gene expression and cell functions in follicle cells, periodontal ligament cells, and cementoblasts. Amelogenin, leucine-rich amelogenin peptide, and tyrosine-rich amelogenin peptide have been found to similarly affect cementoblast gene expression and cementoblast-mediated mineralization in vitro; however, these enamel-like factors do not increase cell proliferation as has been observed in cells treated with Emdogain® (Biora AB, Malmö, Sweden), an enamel matrix derivative. BMP-2 has been found to promote differentiation of follicle cells into a cementoblast/osteoblast phenotype, and BMP-3 is being investigated as a negative regulator of mineralization. The increased ratio of phosphate to pyrophosphate in the local region during root development has been found to significantly enhance the extent of cementum formation in animal models. Furthermore, phosphate has been identified as a regulator of cementoblast SIBLING (small integrin-binding ligand N-linked glycoprotein) gene expression in vitro. These investigations of candidate factors for periodontal regeneration have uncovered mechanisms regulating gene expression and cell function in cells controlling the behavior of periodontal tissues (i.e. follicle cells, periodontal cells, and cementoblasts) and offer new directions to consider for clinical repair of periodontal defects.
Hormonal Regulation of Fetal Growth
Authors: Gicquel C. , Le Bouc Y.
Published: April 2006

Fetal growth is a complex process depending on the genetics of the fetus, the availability of nutrients and oxygen to the fetus, maternal nutrition and various growth factors and hormones of maternal, fetal and placental origin. Hormones play a central role in regulating fetal growth and development. They act as maturational and nutritional signals in utero and control tissue development and differentiation according to the prevailing environmental conditions in the fetus. The insulin-like growth factor (IGF) system, and IGF-I and IGF-II in particular, plays a critical role in fetal and placental growth throughout gestation. Disruption of the IGF1, IGF2 or IGF1R gene retards fetal growth, whereas disruption of IGF2R or overexpression of IGF2 enhances fetal growth. IGF-I stimulates fetal growth when nutrients are available, thereby ensuring that fetal growth is appropriate for the nutrient supply. The production of IGF-I is particularly sensitive to undernutrition. IGF-II plays a key role in placental growth and nutrient transfer. Several key hormone genes involved in embryonic and fetal growth are imprinted. Disruption of this imprinting causes disorders involving growth defects, such as Beckwith-Wiedemann syndrome, which is associated with fetal overgrowth, or Silver-Russell syndrome, which is associated with intrauterine growth retardation. Optimal fetal growth is essential for perinatal survival and has long-term consequences extending into adulthood. Given the high incidence of intrauterine growth retardation and the high risk of metabolic and cardiovascular complications in later life, further clinical and basic research is needed to develop accurate early diagnosis of aberrant fetal growth and novel therapeutic strategies.
Perinatal Nutrition and Hormone-Dependent Programming of Food Intake
Authors: Plagemann A.
Published: April 2006

It is increasingly accepted that alterations of the intrauterine and early postnatal nutritional, metabolic and hormonal environment may predispose individuals to development of diseases in later life. Results from studies of the offspring of diabetic mothers strongly support this hypothesis. It has also been suggested that being light at birth leads to an increased risk of the metabolic syndrome (Syndrome X) in later life (the Barker hypothesis). The pathophysiological mechanisms that underlie this programming are unclear. However, hormones are important environment-dependent organizers of the developing neuroendocrine-immune network, which regulates all the fundamental processes of life. Hormones can act as ‘endogenous functional teratogens’ when present in non-physiological concentrations, induced by alterations in the intrauterine or neonatal environment during critical periods of perinatal life. Perinatal hyperinsulinism is pathognomic in offspring of diabetic mothers. Early hyperinsulinism also occurs as a result of early postnatal overfeeding. In rats, endogenous hyperinsulinism, as well as peripheral or intrahypothalamic insulin treatment during perinatal development, may lead to ‘malprogramming’ of the neuroendocrine systems regulating body weight, food intake and metabolism. This results in an increased disposition to become obese and to develop diabetes throughout life. Similar malprogramming may occur due to perinatal hypercortisolism and hyperleptinism. With regard to ‘small baby syndrome’ and the thrifty phenotype hypothesis, we propose that early postnatal overfeeding of underweight newborns may substantially contribute to their long-term risk of obesity and diabetes. In summary, a complex malprogramming of the central regulation of body weight and metabolism may provide a general aetiopathogenetic concept, explaining perinatally acquired disposition to later disease and, thereby, opening a wide field for primary prevention.