bluuebunny/crossref_metadata_2025 huggingface dataset:
Life-history plasticity in hosts (Lymnaea elodes) exposed to differing resources and parasitism
Authors: Sandland Gregory J , Minchella Dennis J
Published: January 2005

Assessing phenotypic expression across environments is essential for understanding the evolution of life histories, yet relatively few studies have empirically determined the role that multiple environmental factors play in altering animal phenotypes. We used a multifactorial approach to investigate the effects of both infection of Echinostoma revolutum (Frölich, 1802) and nutrient availability on phenotypic expressions in lines of the snail Lymnaea elodes (Say, 1821). Lines were initially established via selfing events followed by breeding (within lines) over the next four generations. Juveniles from each line were then size-matched and randomly exposed to parasite (exposed / sham-exposed) and diet (high protein / low protein) treatments, generating a 2 (line) × 2 (diet) × 2 (exposure) factorial design. Snail growth, reproduction, and survival were monitored over 5 weeks. Analyses revealed an interactive effect of host line and infection status on host growth. Main effects of both snail line and diet also significantly influenced host growth. Reproductive patterns differed between lines, with snails from one line producing egg masses and eggs in all treatments, and snails from the second line producing minimal eggs in only a single treatment. Snail survival remained similar between snail lines. Results from this study suggest that snail life-history traits can vary dramatically as a result of host genetics, the environment, and the interaction between these factors. Reasons for the occurrence and maintenance of this variability in life-history traits are discussed.
BIRTH OF CLOSED STRINGS AND DEATH OF OPEN STRINGS DURING TACHYON CONDENSATION
Authors: HASHIMOTO KOJI , HO PEI-MING , WANG JOHN E.
Published: January 2005

The tremendous progress achieved through the study of black holes and branes suggests that their time-dependent generalizations called Spacelike branes (S-branes) may prove similarly useful. An example of an established approach to S-branes is to include a string boundary interaction and we first summarize evidence for the death of open string degrees of freedom for the homogeneous rolling tachyon on a decaying brane. Then, we review how to extract the flat S-brane worldvolumes describing the homogeneous rolling tachyon and how large deformations correspond to creation of lower dimensional strings and branes. These S-brane worldvolumes are governed by S-brane actions which are on equal footing to D-brane actions, since they are derived by imposing conformality on the string worldsheet, as well as by analyzing fluctuations of time-dependent tachyon configurations. As further examples we generalize previous solutions of the S-brane actions so as to describe multiple decaying and nucleating closed fundamental strings. Conceptually S-brane actions are therefore different from D-brane actions and can provide a description of time-dependent strings/branes and possibly their interactions.
PRODUCTION OF π0 IN A STRONG, TIME-DEPENDENT MAGNETIC FIELD
Authors: DI PIAZZA ANTONINO , CALUCCI GIORGIO
Published: January 2005

The probability that a neutral meson π0 is produced from vacuum in the presence of a strong and time-varying magnetic field is calculated. Since the π0 has zero electric charge, the interaction with the external magnetic field occurs through the magnetic moment of the constituent quark–antiquark pairs. The phenomenological SU (6) quark model is used to build up perturbatively the one-particle neutral meson states in the presence of a static magnetic field. Then, the presence probability is obtained by means of the adiabatic perturbation theory. The mechanism proposed implies that the pion is produced together with another neutral meson. The final result is compared with the π-–π+ pair presence probability in the same time-varying magnetic field. The π± have almost the same mass of π0 but, unlike π0, are charged particle so the ratio of the two probabilities gives an order of magnitude of the relative strength of the two effective interactions with the external time depending magnetic field.
ANOTHER APPROACH TO LINEARIZED ELASTICITY AND A NEW PROOF OF KORN'S INEQUALITY
Authors: CIARLET PHILIPPE G. , CIARLET PATRICK
Published: January 2005

We describe and analyze an approach to the pure traction problem of three-dimensional linearized elasticity, whose novelty consists in considering the linearized strain tensor as the "primary" unknown, instead of the displacement itself as is customary. This approach leads to a well-posed minimization problem, constrained by a weak form of the St Venant compatibility conditions. Interestingly, it also provides a new proof of Korn's inequality.
TYPE-DEFINABILITY, COMPACT LIE GROUPS, AND o-MINIMALITY
Authors: PILLAY ANAND
Published: January 2005

We study type-definable subgroups of small index in definable groups, and the structure on the quotient, in first order structures. We raise some conjectures in the case where the ambient structure is o-minimal. The gist is that in this o-minimal case, any definable group G should have a smallest type-definable subgroup of bounded index, and that the quotient, when equipped with the logic topology, should be a compact Lie group of the "right" dimension. I give positive answers to the conjectures in the special cases when G is 1-dimensional, and when G is definably simple.
Subcellular redistribution of AQP5 by vasoactive intestinal polypeptide in the Brunner's gland of the rat duodenum
Authors: Parvin Most. Nahid , Kurabuchi Shingo , Murdiastuti Kwartarini , Yao Chenjuan , Kosugi-Tanaka Chisato , Akamatsu Tetsuya , Kanamori Norio , Hosoi Kazuo
Published: January 2005

Aquaporin (AQP)5, an exocrine-type water channel, was detected in the rat duodenum by Western blot analysis, and was localized by immunohistochemistry in the secretory granule membranes as well as in the apical and lateral aspects of the plasma membrane of Brunner's gland cells. Incubation of duodenal slices with vasoactive intestinal polypeptide (VIP) in vitro significantly increased the amount of AQP5 in the apical membrane fraction in a dose- and time-dependent manner with the amount reaching a plateau at 100 nM VIP and becoming near maximal after a 30-s incubation. Protein kinase inhibitors, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7, 50 μM), and N-[2-( p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89; PKA-specific, 1 μM) blocked this increase, but PKC-specific inhibitor calphostin C did not, implying the involvement of PKA but not PKC in this cellular event. Intravenous injection with VIP (40 μg/kg body wt) provoked dilation of the lumen of the Brunner's gland at 2 and 7 min and increased the staining intensity of AQP5 in the apical and lateral membranes. AQP1 (both nonglycosylated and glycosylated forms) was also found to localize in the apical and basolateral membranes of cells of Brunner's gland. VIP, however, did not provoke any significant change in the AQP1 level in the apical membrane, as judged from the results of the above in vitro and in vivo experiments. These results suggest that VIP induced the exocytosis of granule contents and simultaneously caused translocation of AQP5 but not of AQP1 to the apical membrane in Brunner's gland cells.
Temporal and spatial properties of cellular Ca2+flux in trout ventricular myocytes
Authors: Shiels Holly A. , White Ed
Published: January 2005

Confocal microscopy was used to investigate the temporal and spatial properties of Ca2+transients and Ca2+sparks in ventricular myocytes of the rainbow trout ( Oncorhynchus mykiss). Confocal imaging confirmed the absence of T tubules and the long (∼160 μm), thin (∼8 μm) morphology of trout myocytes. Line scan imaging of Ca2+transients evoked by electrical stimulation in cells loaded with fluo 4 revealed spatial inhomogeneities in the temporal properties of Ca2+transients across the width of the myocytes. The Ca2+wavefront initiated faster, rose faster, and reached larger peak amplitudes in the periphery of the myocyte compared with the center. These differences were exacerbated by stimulation with the L-type Ca2+channel agonist (−)BAY K 8644 or by sarcoplasmic reticulum (SR) inhibition with ryanodine and thapsigargin. Results reveal that the shape of the trout myocyte allows for rapid diffusion of Ca2+from the cell periphery to the cell center, with SR Ca2+release contributing to the cytosolic Ca2+rise in a time-dependent manner. Spontaneous Ca2+sparks were exceedingly rare in trout myocytes under control conditions (1 sparking cell from 238 cells examined). This is in marked contrast to the rat where a total of 56 spontaneous Ca2+sparks were observed in 9 of 11 myocytes examined. Ca2+sparklike events were observed in a very small number of trout myocytes (15 sparks from 9 of 378 cells examined) after stimulation with either (−)BAY K 8644 or high Ca2+(6 mM). Reducing temperature to 15°C in intact myocytes or permeabilizing myocytes to adjust intracellular conditions to favor Ca2+spark detection was without significant effects. Possible reasons for the rarity of Ca2+sparks in a cardiac myocyte with an active SR are discussed.
Chemical activation of pre-Bötzinger complex in vivo reduces respiratory network complexity
Authors: Chen Xinnian , Chon Ki H. , Solomon Irene C.
Published: January 2005

In the in vivo anesthetized adult cat model, multiple patterns of inspiratory motor discharge have been recorded in response to chemical stimulation and focal hypoxia of the pre-Bötzinger complex (pre-BötC), suggesting that this region may participate in the generation of complex respiratory dynamics. The complexity of a signal can be quantified using approximate entropy (ApEn) and multiscale entropy (MSEn) methods, both of which measure the regularity (orderliness) in a time series, with the latter method taking into consideration temporal fluctuations in the underlying dynamics. The current investigation was undertaken to examine the effects of pre-BötC-induced excitation of phasic phrenic nerve discharge, which is characterized by high-amplitude, rapid-rate-of-rise, short-duration bursts, on the complexity of the central inspiratory neural controller in the vagotomized, chloralose-anesthetized adult cat model. To assess inspiratory neural network complexity, we calculated the ApEn and MSEn of phrenic nerve bursts during eupneic (basal) discharge and during pre-BötC-induced excitation of phasic inspiratory bursts. Chemical stimulation of the pre-BötC using DL-homocysteic acid (DLH; 10 mM; 10–20 nl; n = 10) significantly reduced the ApEn from 0.982 ± 0.066 (mean ± SE) to 0.664 ± 0.067 ( P < 0.001) followed by recovery (∼1–2 min after DLH) of the ApEn to 1.014 ± 0.067; a slightly enhanced magnitude reduction in MSEn was observed. Focal pre-BötC hypoxia (induced by sodium cyanide; NaCN; 1 mM; 20 nl; n = 2) also elicited a reduction in both ApEn and MSEn, similar to those observed for the DLH-induced response. These observations demonstrate that activation of the pre-BötC reduces inspiratory network complexity, suggesting a role for the pre-BötC in regulation of complex respiratory dynamics.
Eicosapentaenoic fatty acid increases leptin secretion from primary cultured rat adipocytes: role of glucose metabolism
Authors: Pérez-Matute Patricia , Marti Amelia , Martínez J. Alfredo , Fernández-Otero M. P. , Stanhope Kimber L. , Havel Peter J. , Moreno-Aliaga María J.
Published: January 2005

Eicosapentaenoic acid (EPA), one of the n-3 polyunsaturated fatty acids, has been shown to stimulate leptin mRNA expression and secretion in 3T3-L1 cells. However, other studies have reported inhibitory effects of EPA on leptin expression and secretion in vivo and in vitro. To determine the direct effects of EPA on basal and insulin-stimulated leptin secretion, isolated rat adipocytes were incubated with EPA in the absence and presence of insulin. EPA (10, 100, and 200 μM) increased basal leptin gene expression and secretion (+43.8%, P < 0.05; +71.1%, P < 0.01; and +73.7%, P < 0.01, respectively). EPA also increased leptin secretion in the presence of 1.6 nM insulin; however, the effect was less pronounced than in the absence of it. Because adipocyte glucose and lipid metabolism are involved in the regulation of leptin production, the metabolic effects of this fatty acid were also examined. EPA (200 μM) increased basal glucose uptake in isolated adipocytes (+50%, P < 0.05). Anaerobic metabolism of glucose, as assessed by lactate production and proportion of glucose metabolized to lactate, has been shown to be inversely correlated to leptin secretion and was decreased by EPA in both the absence and presence of insulin. EPA increased basal glucose oxidation as determined by the proportion of14C-labeled glucose metabolized to CO2. Lipogenesis (14C-labeled glucose incorporation into triglyceride) was decreased by EPA in the absence of insulin, whereas lipolysis (glycerol release) was unaffected. The EPA-induced increase of basal leptin secretion was highly correlated with increased glucose utilization ( r = +0.89, P < 0.01) and inversely related to the anaerobic glucose metabolism to lactate. EPA’s effect on insulin-stimulated leptin secretion was not related to increased glucose utilization but was inversely correlated with anaerobic glucose metabolism to lactate ( r = −0.84, P < 0.01). Together, the results suggest that EPA, like insulin, stimulates leptin production by increasing the nonanaerobic/oxidative metabolism of glucose.
Regulation of expression of two aquaporin homologs in the intestine of the European eel: effects of seawater acclimation and cortisol treatment
Authors: Martinez Anne-Sophie , Cutler Christopher P. , Wilson Gillian D. , Phillips Claire , Hazon Neil , Cramb Gordon
Published: January 2005

Complementary DNAs encoding homologs of the mammalian aquaglyceroporins (termed AQPe) and aquaporin-1 isoforms (termed AQP1) were isolated from the European eel. The AQP amino acid sequences share 35–54% identity with other known human AQPs. Although AQPe mRNA expression was approximately equivalent along the entire length of the gut, AQP1 expression was the highest in the posterior/rectal segment. Seawater (SW) acclimation increased AQP1 mRNA abundance by 5- and 17-fold in the anterior, 14- and 23-fold in the mid-, and 9- and 7-fold in the posterior/rectal gut regions of yellow and silver eels, respectively. SW acclimation had an effect on AQPe mRNA expression only in the midintestine of silver eels, where a small but significant 1.7-fold increase in abundance was measured. Western blots using an eel AQP1-specific antibody identified the presence of a major immunoreactive 28-kDa protein, primarily within the posterior/rectal segment. A 3-wk SW transfer induced an increase in AQP1 protein abundance in all intestinal segments, with the posterior/rectal region still expressing protein levels ∼40- and 8-fold higher than the anterior and midsegments, respectively. Strong AQP1 immunofluorescence was detected within the vascular endothelium in both freshwater (FW)- and SW-acclimated eels and in the epithelial apical brush border in the posterior/rectal gut regions of SW-acclimated eels. Cortisol infusion into FW eels had no effect on intestinal AQPe mRNA expression but induced increases in AQP1 mRNA and protein levels. These results provide evidence for the presence of a SW-induced and steroid-regulated AQP water channel pathway within the intestine of the European eel.
Induction of overlapping genes by fasting and a peroxisome proliferator in pigs: evidence of functional PPARα in nonproliferating species
Authors: Cheon Yewon , Nara Takayuki Y. , Band Mark R. , Beever Jonathan E. , Wallig Matthew A. , Nakamura Manabu T.
Published: January 2005

Peroxisome proliferator-activated receptor α (PPARα), a key regulator of fatty acid oxidation, is essential for adaptation to fasting in rats and mice. However, physiological functions of PPARα in other species, including humans, are controversial. A group of PPARα ligands called peroxisome proliferators (PPs) causes peroxisome proliferation and hepatocarcinogenesis only in rats and mice. To elucidate the role of PPARα in adaptation to fasting in nonproliferating species, we compared gene expressions in pig liver from fasted and clofibric acid (a PP)-fed groups against a control diet-fed group. As in rats and mice, fasting induced genes involved with mitochondrial fatty acid oxidation and ketogenesis in pigs. Those genes were also induced by clofibric acid feeding, indicating that PPARα mediates the induction of these genes. In contrast to rats and mice, little or no induction of genes for peroxisomal or microsomal fatty acid oxidation was observed in clofibric acid-fed pigs. Histology showed no significant hyperplasia or hepatomegaly in the clofibric acid-fed pigs, whereas it showed a reduction of glycogen by clofibric acid, an effect of PPs also observed in rats. Copy number of PPARα mRNA was higher in pigs than in mice and rats, suggesting that peroxisomal proliferation and hyperresponse of several genes to PPs seen only in rats and mice are unrelated to the abundance of PPARα. In conclusion, PPARα is likely to play a central role in adaptation to fasting in pig liver as in rats and mice.
New objective measures to quantify stress urinary incontinence in a novel durable animal model of intrinsic sphincter deficiency
Authors: Rodríguez Larissa V. , Chen Shinhong , Jack Gregory S. , de Almeida Fernando , Lee Kyo Won , Zhang Rong
Published: January 2005

Existing animal models of stress urinary incontinence (SUI) are limited because of the low rate of incontinence seen in the animals and to their relatively low durability. In addition, most methods described to measure incontinence are operator-dependent. The aim of this study was to develop a new durable animal model of SUI and establish objective measures to quantify SUI. We subjected female rats to transabdominal urethrolysis. At baseline and at 1, 4, 8, 12, and 24 wk after intervention, animals underwent cystometry and evaluation with abdominal leak point pressure (ALPP). Urethral resistance was evaluated by retrograde urethral perfusion pressure (RUPP). Tissues were obtained for histology and immunohistochemistry. Normal female rats had an average ALPP of 19.4 cmH2O and RUPP of 22.6 cmH2O at baseline. More than 93% of the animals had significantly decreased ALPP and RUPP after the procedure. The mean ALPP and RUPP decreased to 9.8 cmH2O and 11.2 cmH2O, respectively, by 1 wk after urethrolysis. These changes were maintained for up to 24 wk. Changes seen in urethral resistance and ALPP appear to be mediated by apoptosis, decreased neuronal mass, and smooth muscle atrophy. These results indicate that transabdominal urethrolysis is a reliable method of achieving durable decreased urethral resistance in a SUI model. RUPP and ALPP are objective and reproducible methods of assessing urethral resistance. Changes in continence and urethral resistance appear to be mediated by denervation and smooth muscle atrophy, which are seen in both elderly incontinent patients and in patients with intrinsic sphincter dysfunction.
Effect of contractile duration on intracellular Po2kinetics inXenopussingle skeletal myocytes
Authors: Kindig Casey A. , Howlett Richard A. , Hogan Michael C.
Published: January 2005

It has been suggested that skeletal muscle O2uptake (V̇o2) kinetics follow a first-order control model. Consistent with that, V̇o2should show both 1) similar onset kinetics and 2) an on-off symmetry across submaximal work intensities regardless of the metabolic perturbation. To date, consensus on this issue has not been reached in whole body studies due to numerous confounding factors associated with O2availability and fiber-type recruitment. To test whether single myocytes demonstrate similar intracellular Po2(PiO2) on- and off-transient kinetics at varying work intensities, we studied Xenopus laevis single myocyte ( n = 8) PiO2via phosphorescence quenching during two bouts of electrically induced isometric muscle contractions of 200 (low)- and 400 (high)-ms contraction duration (1 contraction every 4 s, 15 min between trials, order randomized). The fall in PiO2, which is inversely proportional to the net increase in V̇o2, was significantly greater ( P < 0.05) during the high (24.1 ± 3.2 Torr) vs. low (17.4 ± 1.6 Torr) contraction bout. However, the mean response time (MRT; time to 63% of the overall change) for the fall in PiO2from resting baseline to end contractions was not different (high, 77.8 ± 11.5 vs. low, 76.1 ± 13.6 s; P > 0.05) between trials. The initial rate of change at contraction onset, defined as ΔPiO2/MRT, was significantly greater ( P < 0.05) in high compared with low. PiO2off-transient MRT from the end of the contraction bout to initial baseline was unchanged (high, 83.3 ± 18.3 vs. low, 80.4 ± 21.6 s; P > 0.05) between high and low trials. These data revealed that PiO2dynamics in frog isolated skeletal myocytes were invariant despite differing contraction durations and, by inference, metabolic demands. Thus these findings demonstrate that mitochondria can respond more rapidly at the initial onset of contractions when challenged with an augmented metabolic stimulus in accordance with an apparent first-order rate law.
Cyr61 mediates the expression of VEGF, αv-integrin, and α-actin genes through cytoskeletally based mechanotransduction mechanisms in bladder smooth muscle cells
Authors: Zhou Dongming , Herrick David J. , Rosenbloom Joel , Chaqour Brahim
Published: January 2005

Application of cyclic strain to bladder smooth muscle (SM) cells results in profound alterations of the histomorphometry, phenotype, and function of the cells. The onset of this process is characterized by the activation of a cascade of signaling events coupled to progressive and, perhaps, interdependent changes of gene expression. In particular, externally applied cyclic stretch to cultured bladder SM cells results in the transient expression of the Cyr61 gene that encodes a cysteine-rich heparin-binding protein originally described as a proangiogenic factor capable of altering the gene programs for angiogenesis, adhesion, and extracellular matrix synthesis. In this study, we investigated the effects of mechanical stretch-induced Cyr61 on the expression of potential mechanosensitive Cyr61 target genes and the signaling pathways involved. We showed that suppression of Cyr61 expression with an adenoviral vector encoding an antisense oligonucleotide reduced mechanical strain-induced VEGF, αv-integrin, and SM α-actin gene expression but had no effect on the myosin heavy chain isoforms SM-1 and SM-2. Signaling pathways involving RhoA GTPase, phosphatidyl inositol 3-kinase, and cytoskeletal actin dynamics altered stretch-induced Cyr61 and Cyr61 target genes. Reciprocally, adenovirus-mediated overexpression of Cyr61 in cells cultured under static conditions increased the expression of VEGF, αv-integrin, and SM α-actin, as well as that of SM-1 and SM-2 isoforms, suggesting that the effects of a sustained expression of Cyr61 extend to SM specific contractile function. These effects were dependent on integrity of the actin cytoskeleton. Together, these results indicate that Cyr61 is an important determinant of the genetic reprogramming that occurs in mechanically challenged cells.
Capsaicin administration inhibits the abducent branch but excites the thyroarytenoid branch of the recurrent laryngeal nerves in the rat
Authors: Lu I-Jung , Lee Kun-Ze , Lin Jin-Tun , Hwang Ji-Chuu
Published: January 2005

Our recent study showed that both inspiratory and expiratory activities of the recurrent laryngeal nerve (RLN) were enhanced by capsaicin administration in the rat (Lu IJ, Ku LC, Lin JT, Lee KZ, and Hwang JC. Chin J Physiol 45: 143–154, 2002). There are two intralaryngeal branches of the RLN: one innervates the thyroarytenoid (TA) muscle and the other innervates the abductor (Abd) muscles. To examine whether these two intralaryngeal branches respond similarly to capsaicin administration, their discharges as well as activities of the phrenic nerve (PNA) and the superior laryngeal nerve (SLNA) were monitored in anesthetized and ventilated rats at normocapnia in hyperoxia. The low dose of capsaicin (0.625 μg/kg) produced a cardiopulmonary chemoreflex, showing apnea, a decrease in PNA, hypotension, and bradycardia, and significant decreases in SLNA and the activity of the Abd branch. Concurrently, there was an increase in the intralaryngeal TA activity during both apnea and the recovery from apnea. The high dose of capsaicin (1.25 μg/kg) evoked larger chemoreflexive responses and laryngeal nerve activities. In addition, both doses of capsaicin initiated a similar delay in the onset of Abd activity and SLNA but an earlier onset for the TA branch to commence during inspiration. A bilateral vagotomy abolished the laryngeal responses to capsaicin administration. However, PNA and blood pressure were enhanced with capsaicin administration after the vagotomy. These results suggest that laryngeal adduction in response to capsaicin administration is vagal afferent dependent and that it may also represent reflexive protection for the airway and lungs.
Physiological Characterization of Synaptic Inputs to Inhibitory Burst Neurons From the Rostral and Caudal Superior Colliculus
Authors: Sugiuchi Y. , Izawa Y. , Takahashi M. , Na J. , Shinoda Y.
Published: January 2005

The caudal superior colliculus (SC) contains movement neurons that fire during saccades and the rostral SC contains fixation neurons that fire during visual fixation, suggesting potentially different functions for these 2 regions. To study whether these areas might have different projections, we characterized synaptic inputs from the rostral and caudal SC to inhibitory burst neurons (IBNs) in anesthetized cats. We recorded intracellular potentials from neurons in the IBN region and identified them as IBNs based on their antidromic activation from the contralateral abducens nucleus and short-latency excitation from the contralateral caudal SC and/or single-cell morphology. IBNs received disynaptic inhibition from the ipsilateral caudal SC and disynaptic inhibition from the rostral SC on both sides. Stimulation of the contralateral IBN region evoked monosynaptic inhibition in IBNs, which was enhanced by preconditioning stimulation of the ipsilateral caudal SC. A midline section between the IBN regions eliminated inhibition from the ipsilateral caudal SC, but inhibition from the rostral SC remained unaffected, indicating that the latter inhibition was mediated by inhibitory interneurons other than IBNs. A transverse section of the brain stem rostral to the pause neuron (PN) region eliminated inhibition from the rostral SC, suggesting that this inhibition is mediated by PNs. These results indicate that the most rostral SC inhibits bilateral IBNs, most likely via PNs, and the more caudal SC exerts monosynaptic excitation on contralateral IBNs and antagonistic inhibition on ipsilateral IBNs via contralateral IBNs. The most rostral SC may play roles in maintaining fixation by inhibition of burst neurons and facilitating saccadic initiation by releasing their inhibition.
Histamine Contributes to Ischemia-Related Activation of Cardiac Spinal Afferents: Role of H1 Receptors and PKC
Authors: Fu Liang-Wu , Schunack Walter , Longhurst John C.
Published: January 2005

Myocardial ischemia activates cardiac spinal afferents that transmit the nociceptive information leading to chest pain and elicit excitatory cardiovascular reflexes. Previous studies have shown that histamine is increased in coronary sinus blood during myocardial ischemia and that this autacoid stimulates abdominal visceral afferents. The present investigation evaluated the role of endogenous histamine in stimulation of ischemically sensitive cardiac spinal afferents. Nerve activity of single-unit cardiac afferents was recorded from the left sympathetic chain or rami communicans (T2–T5) in anesthetized cats. Sixty-four cardiac afferents were identified. Injection (5–30 μg/kg) of histamine into the left atrium (LA) stimulated 7 ischemically sensitive cardiac afferents resulting in a significant increase in their activity in a dose-dependent manner. Also, LA injection of histamine (10 μg/kg) stimulated 7 of 8 ischemically insensitive cardiac spinal afferents. Administrations of 2-(3-chlorophenyl)histamine (250 μg/kg, LA), a specific H1 receptor agonist and histamine (10 μg/kg, LA), stimulated 9 other ischemically sensitive cardiac afferents (0.48 ± 0.10 to 1.40 ± 0.20 imp/s). In contrast, dimaprit (500 μg/kg, LA), an H2 receptor agonist, stimulated only one of the 9 afferents and thus did not alter their overall activity (0.40 ± 0.09 to 0.54 ± 0.09 imp/s). ( R)α-Methyl-histamine (500 μg/kg, LA), an H3 receptor agonist, did not stimulate any of the 9 afferents. Pyrilamine (300 μg/kg, iv), a selective H1 receptor antagonist, attenuated the activity of 8 afferents during 5 min of ischemia from 3.32 ± 0.38 to 1.87 ± 0.28 imp/s and abolished the response of 9 other cardiac afferents to histamine. Finally, administration of PKC-(19–36) (30 μg/kg, iv), a selective inhibitor of protein kinase C, attenuated the response of 8 cardiac afferents to histamine by 32%. These data indicate that endogenous histamine contributes to activation of cardiac sympathetic afferents during myocardial ischemia through H1 receptors and that the action of histamine on these cardiac afferents is partially dependent on the intracellular PKC pathway.
Dynamic Multiphoton Imaging: A Live View from Cells to Systems
Authors: Stutzmann Grace E. , Parker Ian
Published: January 2005

Leaps in scientific technology often occur at the interface of seemingly disparate disciplines. This holds true with the recent application of multiphoton microscopy to the biological sciences, leading to a new generation of imaging-based studies extending from the tracking of individual molecules within living cells to the observation of whole organisms.
Single-Molecule Fluorescence Spectroscopy: New Probes of Protein Function and Dynamics
Authors: Johnson Carey K. , Osborn Kenneth D. , Allen Michael W. , Slaughter Brian D.
Published: January 2005

Single-molecule fluorescence methods provide new tools for the study of biological systems. Single-pair fluorescence resonance energy transfer has provided detailed information about dynamics and structure of the Ca2+-signaling protein calmodulin. Single-molecule polarization modulation spectroscopy has probed the mechanism by which calmodulin activates the plasma membrane Ca2+ pump.
Molecular Control of Cytoskeletal Mechanics by Hemodynamic Forces
Authors: Helmke Brian P.
Published: January 2005

The endothelium at the interface between blood and tissue acts as a primary transducer of local hemodynamic forces into signals that maintain physiological function or initiate pathological processes in vessel walls. Rapid intracellular spatial gradients of structural dynamics and signaling molecule activity suggest that mechanical cues at the molecular level guide cellular mechanotransduction and adaptation to shear stress profiles.
Broca’s Region: From Action to Language
Authors: Nishitani Nobuyuki , Schürmann Martin , Amunts Katrin , Hari Riitta
Published: January 2005

Broca’s region, classically considered a motor speech-production area, is involved in action understanding and imitation. It also seems to help in sequencing of actions. Broca’s region might have evolved for interindividual communication, both by gestures and speech.
A Role for the Wilms’ Tumor Protein WT1 in Organ Development
Authors: Scholz Holger , Kirschner Karin M.
Published: January 2005

Wilms’ tumor (nephroblastoma) represents a unique example of an aberrant kidney formation that can result from mutations in a tumor suppressor gene, Wilms’ tumor 1 ( WT1). Targeted gene inactivation in mice testifies that WT1 is a master switch for the development of the genitourinary system and other organs.
Regulation of Vascular Smooth Muscle Cell Proliferation and Migration by Human Sprouty 2
Authors: Zhang Chunxiang , Chaturvedi Deepti , Jaggar Laura , Magnuson Debra , Lee John M. , Patel Tarun B.
Published: January 2005

Objectives—

To determine whether the human sprouty 2 (hSPRY2) protein, an inhibitor of receptor tyrosine kinase actions, regulates vascular smooth muscle cell (VSMC) proliferation, migration, and neointima formation in injured carotid artery.

Methods and Results—

The hSPRY2 protein or green fluorescent protein (GFP; control) was transduced into VSMCs by placing an N-terminal TAT epitope on the proteins. The transduction of TAT-tagged hSPRY2 (TAT-hSPRY2) but not TAT-GFP inhibited the ability of serum and different growth factors to stimulate migration of VSMCs. Likewise, TAT-hSPRY2 also inhibited VSMC proliferation in response to serum. The hSPRY2 microtubule association (amino acids 123–177) and membrane translocation (amino acids 178–194) domains were necessary for the biological actions of hSPRY2. In the rat carotid artery injury model, exposure of the injured vessel for 1 hour to TAT-hSPRY2, but not TAT-GFP, markedly inhibited growth of the neointima over the 28-day postangioplasty period as well as VSMC proliferation. The exogenously applied TAT-hSPRY2 was retained in the carotid arteries for at least 3 days after injury, and endogenous SPRY2 expression was maximized around day 14 after injury. The latter is perhaps a compensatory mechanism to regulate neointima formation.

Conclusions—

We conclude that TAT-tagged proteins are efficiently transduced into VSMCs in vitro and in vivo, that hSPRY2 inhibits growth and migration of VSMCs, and that this protein can decrease neointimal growth after blood vessel injury.
Carotid Plaque Composition Differs Between Ethno-Racial Groups
Authors: Saam T. , Cai J.M. , Cai Y.Q. , An N.Y. , Kampschulte A. , Xu D. , Kerwin W.S. , Takaya N. , Polissar N.L. , Hatsukami T.S. , Yuan C.
Published: January 2005

Objective—

Ethnicity-based research may identify new clues to the pathogenesis of atherosclerotic disease. Therefore, we sought to determine whether carotid lesions differ between 20 Chinese and 20 Caucasian Americans by MRI.

Methods and Results—

Inclusion criteria were >50% stenosis as measured by duplex ultrasound and recent symptoms attributed to carotid artery disease. The patients were imaged in 2 centers (Beijing, China and Seattle, Wash) using a standardized protocol. Both carotid arteries were reviewed quantitatively (lumen, wall, outer wall, tissue components) and morphologically (lesion types, fibrous cap status). Significant differences between the Chinese and Americans were found for the mean size of the lipid/necrotic core (13.6 versus 7.8 mm
2
;
P
=0.002), percentage of slices with calcified type VII lesions (1.6 versus 12.4%;
P
=0.03), and percentage of slices with early type III lesions (19.3 versus 9.3%;
P
=0.02). Furthermore, the mean outer wall area in the common carotid artery was larger in the Chinese population (
P
=0.007).

Conclusions—

This pilot study suggests that composition and morphology of atherosclerotic lesions in symptomatic carotid disease differ between ethno-racial groups. Quantitative MRI-based review of carotid atherosclerosis comparing plaque morphology and composition between ethno-racial groups is feasible, and future MRI studies may improve our understanding of the pathophysiology of this disease.
Cystatin C Deficiency Increases Elastic Lamina Degradation and Aortic Dilatation in Apolipoprotein E–Null Mice
Authors: Sukhova Galina K. , Wang Bing , Libby Peter , Pan Jie-Hong , Zhang Yaou , Grubb Anders , Fang Kenneth , Chapman Harold A. , Shi Guo-Ping
Published: January 2005

The pathogenesis of atherosclerosis and abdominal aortic aneurysm involves substantial proteolysis of the arterial extracellular matrix. The lysosomal cysteine proteases can exert potent elastolytic and collagenolytic activity. Human atherosclerotic plaques have increased cysteine protease content and decreased levels of the endogenous inhibitor cystatin C, suggesting an imbalance that would favor matrix degradation in the arterial wall. This study tested directly the hypothesis that impaired expression of cystatin C alters arterial structure. Cystatin C–deficient mice (Cyst C
−/−
) were crossbred with apolipoprotein E–deficient mice (ApoE
−/−
) to generate cystatin C and apolipoprotein E–double deficient mice (Cyst C
−/−
ApoE
−/−
). After 12 weeks on an atherogenic diet, cystatin C deficiency yielded significantly increased tunica media elastic lamina fragmentation, decreased medial size, and increased smooth muscle cell and collagen content in aortic lesions of ApoE
−/−
mice. Cyst C
−/−
ApoE
−/−
mice also showed dilated thoracic and abdominal aortae compared with control ApoE
−/−
mice, although atheroma lesion size, intimal macrophage accumulation, and lipid core size did not differ between these mice. These findings demonstrate directly the importance of cysteine protease/protease inhibitor balance in dysregulated arterial integrity and remodeling during experimental atherogenesis.
Restenosis After Carotid Angioplasty, Stenting, or Endarterectomy in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS)
Authors: McCabe Dominick J.H. , Pereira Anthony C. , Clifton Andrew , Bland J. Martin , Brown Martin M.
Published: January 2005

Background and Purpose—

Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) patients with carotid stenosis were randomized between endovascular treatment and endarterectomy. The rates of residual severe stenosis and restenosis and their contribution to recurrent symptoms was unclear.

Methods—

Endovascular patients were treated by balloon angioplasty alone (88%) or stenting (22%). Patches were used in 63% of endarterectomy patients. Carotid stenosis was categorized as mild (0% to 49%), moderate (50% to 69%), severe (70% to 99%), or occluded, using standardized Doppler ultrasound criteria at the examination closest to 1 month (n=283) and 1 year (n=347) after treatment. Recurrent cerebrovascular symptoms during follow-up were analyzed.

Results—

More patients had ≥70% stenosis of the ipsilateral carotid artery 1 year after endovascular treatment than after endarterectomy (18.5% versus 5.2%,
P
=0.0001). Residual severe stenosis was present in 6.5% of patients at 1 month after endovascular treatment. Between 1 month and 1 year, restenosis to ≥70% stenosis occurred in 10.5% of the endovascular group. After endarterectomy, 1.7% had residual severe stenosis at 1 month, and 2.5% developed severe restenosis. The results were significantly better after stenting compared with angioplasty alone at 1 month (
P
<0.001) but not at 1 year. Recurrent ipsilateral symptoms were more common in endovascular patients with severe stenosis (5/32 [15.6%]) compared with lesser degrees of stenosis at 1 year (11/141 [7.8%],
P
=0.02), but most were transient ischemic attacks and none were disabling or fatal strokes. There were no recurrent symptoms in the 9 endarterectomy patients with ≥70% stenosis at 1 year.

Conclusions—

Carotid stenosis 1 year after endovascular treatment is partly explained by poor initial anatomical results and partly by restenosis. The majority of patients were treated by angioplasty without stenting. Further randomized studies are required to determine whether newer carotid stenting techniques are associated with a lower risk of restenosis. The low rate of recurrent stroke in both endovascular and endarterectomy patients suggests that treatment of restenosis should be limited to patients with recurrent symptoms, but long term follow up data are required.
Preference-Based Quality of Life in Patients With Cerebral Aneurysms
Authors: King Joseph T. , Tsevat Joel , Roberts Mark S.
Published: January 2005

Background and Purpose—

Functional outcome scales are typically used to measure quality of life (QOL) and outcomes in patients with cerebral aneurysms; however, these instruments only examine a limited number of domains that contribute to QOL. An alternative are preference-based QOL methods, which integrate all factors contributing to QOL and provide a comprehensive individualized measure of how patients value their current health state. An additional advantage of preference-based QOL values is that they can be incorporated into decision analyses and cost-effectiveness analyses.

Methods—

We used 4 preference-based QOL methods to measure QOL in 176 outpatients with cerebral aneurysms: (1) standard gamble; (2) time trade-off; (3) visual analogue scale; and (4) willingness to pay. We measured functional status with the Glasgow Outcome Scale (GOS), Rankin Scale, and Barthel Index. We then built multivariate linear regression models to examine the relationships between preference-based QOL, functional status, and patient characteristics.

Results—

Preference-based QOL was moderately diminished in the aneurysm patients. Mean values were: standard gamble, 0.78; time trade-off, 0.79; visual analogue scale, 0.67; and willingness to pay, $121 000. Preference-based QOL was not well-explained by functional status or patient characteristics, as shown by regression models that accounted for <15% of the variation in preference-based QOL (
R
2
<0.15).

Conclusions—

Preference-based QOL instruments capture components of QOL in patients with cerebral aneurysms not assessed by functional status measures or patient characteristics. Studies of patients with cerebral aneurysms should consider incorporating preference-based QOL measures for a fuller evaluation of the impact of aneurysmal disease and its treatment on QOL.
CpG stimulation of precursor B-lineage acute lymphoblastic leukemia induces a distinct change in costimulatory molecule expression and shifts allogeneic T cells toward a Th1 response
Authors: Reid Gregor S. D. , She Kevin , Terrett Luke , Food Michael R. , Trudeau Jacqueline D. , Schultz Kirk R.
Published: January 2005

Immunostimulatory DNA containing unmethylated cytosine-phosphate-guanosine (CpG) induces the development of T helper 1 (Th1) immune responses. The response of B cells to CpG stimulation involves increased proliferation, cytokine production, and costimulatory molecule expression. Similar effects have been observed following CpG stimulation of a variety of malignant B cells. Pediatric precursor B acute lymphoblastic leukemia (B-ALL) cells express low levels of costimulatory molecules and are generally poor stimulators of T-cell responses. In this study, we evaluated the impact of CpG stimulation on precursor B-ALL cell lines and pediatric patient-derived samples. The ability to respond to CpG oligodeoxynucleotides was determined by the level of Toll-like receptor 9 (TLR9) expression. In contrast to both nonleukemic B-cell precursors and mature B cells, the response of precursor B-ALL cells was characterized by increased CD40 expression but only small changes in CD86 levels and no induction of CD80 expression. CpG stimulation of ALL blasts produced increased levels of interleukin-6 (IL-6), IL-8, and IL-10 but no detectable IL-12p70 and led to a skewing of allogeneic T cells, with enhanced interferon γ (IFN-γ) production and reduced secretion of IL-5. These results demonstrate the functional relevance of CpG stimulation of precursor B-ALL cells and provide a rational basis for study of these agents for use in treatment of this disease.
In vitro digestion and lactase treatment influence uptake of quercetin and quercetin glucoside by the Caco-2 cell monolayer
Authors: Boyer Jeanelle , Brown Dan , Liu Rui Hai
Published: January 2005

Background

Quercetin and quercetin glycosides are widely consumed flavonoids found in many fruits and vegetables. These compounds have a wide range of potential health benefits, and understanding the bioavailability of flavonoids from foods is becoming increasingly important.

Methods

This study combined an in vitro digestion, a lactase treatment and the Caco-2 cell model to examine quercetin and quercetin glucoside uptake from shallot and apple homogenates.

Results

The in vitro digestion alone significantly decreased quercetin aglycone recovery from the shallot digestate (p < 0.05), but had no significant effect on quercetin-3-glucoside recovery (p > 0.05). Digestion increased the Caco-2 cell uptake of shallot quercetin-4'-glucoside by 2-fold when compared to the non-digested shallot. Despite the loss of quercetin from the digested shallot, the bioavailability of quercetin aglycone to the Caco-2 cells was the same in both the digested and non-digested shallot. Treatment with lactase increased quercetin recovery from the shallot digestate nearly 10-fold and decreased quercetin-4'-glucoside recovery by more than 100-fold (p < 0.05), but had no effect on quercetin recovery from apple digestates. Lactase treatment also increased shallot quercetin bioavailability to the Caco-2 cells approximately 14-fold, and decreased shallot quercetin-4'-glucoside bioavailability 23-fold (p < 0.05). These Caco-2 cells had lactase activity similar to that expressed by a lactose intolerant human.

Conclusions

The increase in quercetin uptake following treatment with lactase suggests that dietary supplementation with lactase may increase quercetin bioavailability in lactose intolerant humans. Combining the digestion, the lactase treatment and the Caco-2 cell culture model may provide a reliable in vitro model for examining flavonoid glucoside bioavailability from foods.
A case study of type 2 diabetes self-management
Authors: Wu Hsin-i
Published: January 2005

Background

It has been established that careful diabetes self-management is essential in avoiding chronic complications that compromise health. Disciplined diet control and regular exercise are the keys for the type 2 diabetes self-management. An ability to maintain one's blood glucose at a relatively flat level, not fluctuating wildly with meals and hypoglycemic medical intervention, would be the goal for self-management. Hemoglobin A1c (HbA1c or simply A1c) is a measure of a long-term blood plasma glucose average, a reliable index to reflect one's diabetic condition. A simple regimen that could reduce the elevated A1c levels without altering much of type 2 diabetic patients' daily routine denotes a successful self-management strategy.

Methods

A relatively simple model that relates the food impact on blood glucose excursions for type 2 diabetes was studied. Meal is treated as a bolus injection of glucose. Medical intervention of hypoglycaemic drug or injection, if any, is lumped with secreted insulin as a damping factor. Lunch was used for test meals. The recovery period of a blood glucose excursion returning to the pre-prandial level, the maximal reach, and the area under the excursion curve were used to characterize one's ability to regulate glucose metabolism. A case study is presented here to illustrate the possibility of devising an individual-based self-management regimen.

Results

Results of the lunch study for a type 2 diabetic subject indicate that the recovery time of the post-prandial blood glucose level can be adjusted to 4 hours, which is comparable to the typical time interval for non-diabetics: 3 to 4 hours. A moderate lifestyle adjustment of light supper coupled with morning swimming of 20 laps in a 25 m pool for 40 minutes enabled the subject to reduce his A1c level from 6.7 to 6.0 in six months and to maintain this level for the subsequent six months.

Conclusions

The preliminary result of this case study is encouraging. An individual life-style adjustment can be structured from the extracted characteristics of the post-prandial blood glucose excursions. Additional studies are certainly required to draw general applicable guidelines for lifestyle adjustments of type 2 diabetic patients.