bluuebunny/crossref_metadata_2025 huggingface dataset:
NEUTRINO NUCLEUS CROSS-SECTIONS
Authors: SAJJAD ATHAR M. , CHAUHAN S. , SINGH S. K. , VICENTE VACAS M. J.
Published: September 2009

We present the results of our calculation which has been performed to study the nuclear effects in the quasielastic, inelastic and deep inelastic scattering of neutrinos(antineutrinos) from nuclear targets. These calculations are done in the local density approximation. We take into account the effect of Pauli blocking, Fermi motion, Coulomb effect, renormalization of weak transition strengths in the nuclear medium in the case of the quasielastic reaction. The inelastic reaction leading to production of pions is calculated in a Δ-dominance model taking into account the renormalization of Δ properties in the nuclear medium and the final state interaction effects of the outgoing pions with the residual nucleus. We discuss the nuclear effects in the [Formula: see text] structure function in the deep inelastic neutrino(antineutrino) reaction using a relativistic framework to describe the nucleon spectral function in the nucleus.
ON FINITE GALOIS STABLE SUBGROUPS OF GLnIN SOME RELATIVE EXTENSIONS OF NUMBER FIELDS
Authors: BARTELS H.-J. , MALININ D. A.
Published: September 2009

Let K/ℚ be a finite Galois extension with maximal order [Formula: see text] and Galois group Γ. For finite Γ-stable subgroups [Formula: see text] it is known [4], that they are generated by matrices with coefficients in [Formula: see text], Kabthe maximal abelian subextension of K over ℚ. This note gives a contribution to the corresponding question in the case of a relative Galois extension K/R, where R is a finite extension of the rationals ℚ. It turns out, that in this relative situation the answer to the corresponding question depends heavily on the arithmetic of the number field R, more precisely on the ramification behavior of primes in K/R. Due to the possibility of unramified extensions of R for certain number fields R there exist examples of Galois stable linear groups [Formula: see text] which are not fixed elementwise by the commutator subgroup of Gal (K/R).
THE MOUFANG LAWS, GLOBAL AND LOCAL
Authors: PHILLIPS J. D.
Published: September 2009

There are many possible ways to define Moufang element. We show that the traditional definition is not the most felicitious — for instance, the set of all Moufang elements in an arbitrary loop, qua the traditional definition, need not form a subloop. We offer a new definition of Moufang element that ensures that the set of all Moufang elements in an arbitrary loop is a subloop. Moreover, this definition is "maximally algebraic" with respect to autotopisms. We also give an application of this new definition by showing that a flexible A-element in an inverse property loop is, in fact, a Moufang element, thus sharpening a well-known result of Kinyon, Kunen, and the present author [6]. Finally, we prove that divisible, Moufang groupoids are Moufang loops, thus sharpening a result of Kunen [9], one of the first computer-generated proofs in loop theory.
MULTIPLICATIVE JORDAN DECOMPOSITION IN GROUP RINGS OF 3-GROUPS
Authors: LIU CHIA-HSIN , PASSMAN D. S.
Published: September 2009

In this paper, we essentially classify those finite 3-groups G having integral group rings with the multiplicative Jordan decomposition property. If G is abelian, then it is clear that ℤ[G] satisfies MJD. Thus, we are only concerned with the nonabelian case. Here we show that ℤ[G] has the MJD property for the two nonabelian groups of order 33. Furthermore, we show that there are at most three other specific nonabelian groups, all of order 34, with ℤ[G] having the MJD property. Unfortunately, we are unable to decide which, if any, of these three satisfies the appropriate condition.
AN ALGORITHM FOR COMPUTING THE RATLIFF–RUSH CLOSURE
Authors: AL-AYYOUB IBRAHIM
Published: September 2009

Let I ⊂ K[x, y] be a 〈x, y〉-primary monomial ideal where K is a field. This paper produces an algorithm for computing the Ratliff–Rush closure Ĩ for the ideal I = 〈m0, …, mn〉 whenever mi is contained in the integral closure of the ideal 〈xan, yb0〉. This generalizes of the work of Crispin [2]. Also, it provides generalizations and answers for some questions given in [6], and enables us to construct infinite families of Ratliff–Rush ideals.
THE HOPF ALGEBRAS OF SYMMETRIC FUNCTIONS AND QUASI-SYMMETRIC FUNCTIONS IN NON-COMMUTATIVE VARIABLES ARE FREE AND CO-FREE
Authors: BERGERON NANTEL , ZABROCKI MIKE
Published: September 2009

We uncover the structure of the space of symmetric functions in non-commutative variables by showing that the underlined Hopf algebra is both free and co-free. We also introduce the Hopf algebra of quasi-symmetric functions in non-commutative variables and define the product and coproduct on the monomial basis of this space and show that this Hopf algebra is free and co-free. In the process of looking for bases which generate the space we define orders on the set partitions and set compositions which allow us to define bases which have simple and natural rules for the product of basis elements.
ROTA–BAXTER OPERATORS ON GENERALIZED POWER SERIES RINGS
Authors: GUO LI , LIU ZHONGKUI
Published: September 2009

An important instance of Rota–Baxter algebras from their quantum field theory application is the ring of Laurent series with a suitable projection. We view the ring of Laurent series as a special case of generalized power series rings with exponents in an ordered monoid. We study when a generalized power series ring has a Rota–Baxter operator and how this is related to the ordered monoid.
Systematic and Biogeographical Patterns in the Reproductive Biology of Scleractinian Corals
Authors: Baird Andrew H. , Guest James R. , Willis Bette L.
Published: September 2009

A limited diversity of character states for reproductive traits and a robust phylogeny make scleractinian corals an ideal model organism with which to explore the evolution of life-history traits. Here, we explore systematic and biogeographical patterns in the reproductive biology of the Scleractinia within the context of a new molecular phylogeny and using reproductive traits from nearly 400 species. Our analyses confirm that coral sexuality is highly conserved, and mode of larval development is relatively plastic. An overabundance of species with autotrophic larvae in the eastern Pacific and Atlantic is most likely the result of increased capacity for long-distance dispersal conferred by vertical transmission of symbiotic zooxanthellae. Spawning records from diverse biogeographical regions indicate that multispecies spawning occurs in all speciose coral assemblages. A new quantitative index of spawning synchrony shows peaks at mid-tropical latitudes in the Indo-Pacific, influenced in part by two spawning seasons in many species on equatorial reefs.
The Role of Animal Pollination in Plant Speciation: Integrating Ecology, Geography, and Genetics
Authors: Kay Kathleen M. , Sargent Risa D.
Published: September 2009

Although animal pollination is often proposed as a major driver of floral divergence, questions remain about its importance in plant speciation. One issue is whether pollinator specialization, traditionally thought necessary for floral isolation, is prevalent enough to have played a major role in speciation. Furthermore, the ecological and geographic scenarios under which pollinator transitions occur are poorly understood, and the underlying genetic factors are just beginning to be uncovered for a few systems. Nevertheless, macroevolutionary studies consistently show that transitions to animal pollination are accompanied by an increase in diversification rate. Here we consider several models and diverse empirical data on how pollinators could influence speciation. We conclude that floral isolation is rarely, if ever, sufficient to cause speciation on its own, but that it acts synergistically with other isolating mechanisms. A more comprehensive approach is the key to an improved understanding of the role of pollinators in angiosperm speciation.
Stoichiometrically Explicit Food Webs: Feedbacks between Resource Supply, Elemental Constraints, and Species Diversity
Authors: Hall Spencer R.
Published: September 2009

A stoichiometrically explicit approach to food web ecology yields new insight into promotion and degradation of diversity, changes in species composition along environmental gradients, biomass partitioning among trophic levels, and limitation of primary production. These revelations emerge from food web modules that incorporate fundamental constraints imposed by mass balance and a key trait, stoichiometric body composition, into a species’ niche. These niche components involve a species’ requirements from its environment and its own impacts on its environment. More specifically, stoichiometric composition influences minimal nutrient requirements of consumers (perhaps especially grazers); this component becomes pertinent because large imbalances often arise between nutrient:carbon content of consumers relative to prey. Furthermore, these imbalances then modulate the impact of consumers on their own resources through nutrient recycling. Once these niche components become synthesized, their implications in shaping food webs provide powerful mechanisms linking changes in environmental gradients with community structure and ecosystem function.
Teaching the role of secretin in the regulation of gastric acid secretion using a classic paper by Johnson and Grossman
Authors: Walton Kristen L. W.
Published: September 2009

The regulation of gastric acid secretion has been the subject of investigation for over a century. Inhibition of gastrin-induced acid secretion by the intestine-derived hormone secretin provides a classic physiological example of negative feedback in the gastrointestinal tract. A classic paper by Leonard R. Johnson and Morton I. Grossman clearly shows the ability of secretin to negatively regulate gastric acid secretion, providing students with an example of this feedback loop. In addition, this article demonstrates the step forward in gastrointestinal endocrinology that occurred when pure preparations of secretin and other gastrointestinal hormones first became available. The comparison of the effects of exogenous, purified secretin to the physiological stimulus of acid in the duodenum is an important example of how newly available reagents allow scientists such as Johnson and Grossman to clarify the mechanisms behind previously established processes. One or more figures from this classic paper can be used to give students insight into the role of secretin in the regulation of the function of the gastrointestinal tract and will also give students a clear example of how the careful experimentation and clear interest in gastrointestinal physiology led Johnson and Grossman to advance the field.
Teaching the modes of Ca2+transport between the plasma membrane and endoplasmic reticulum using a classic paper by Kwan et al.
Authors: Liang Willmann
Published: September 2009

This teaching article uses the report by Kwan et al., “Effects of methacholine, thapsigargin, and La3+on plasmalemmal and intracellular Ca2+transport in lacrimal acinar cells,” where the effects of Ca2+-mobilizing agents in regulating Ca2+fluxes were examined under various conditions. Upper-level undergraduate and new graduate students in physiology are the targe audience. Teaching and learning points are put forth in this article to illustrate 1) the characteristics of methacholine- and thapsigargin-induced Ca2+responses, 2) the different endoplasmic reticulum Ca2+stores accessible to methacholine and thapsigargin, 3) the inhibitory effects of La3+on Ca2+extrusion and Ca2+influx, and 4) the facilitatory role of La3+on endoplasmic reticulum Ca2+recycling. Each of the above concepts is first explained with references to the figures adapted from the original article. A list of student learning questions then follows, where the answers are found in the teaching notes for the instructors. It is the objective of this article to make both teaching and learning Ca2+regulation a rewarding experience for all.
Cardiac structure and function in humans: a new cardiovascular physiology laboratory
Authors: Song Su , Burleson Paul D. , Passo Stanley , Messina Edward J. , Levine Norman , Thompson Carl I. , Belloni Francis L. , Recchia Fabio A. , Ojaimi Caroline , Kaley Gabor , Hintze Thomas H.
Published: September 2009

As the traditional cardiovascular control laboratory has disappeared from the first-year medical school curriculum, we have recognized the need to develop another “hands-on” experience as a vehicle for wide-ranging discussions of cardiovascular control mechanisms. Using an echocardiograph, an automatic blood pressure cuff, and a reclining bicycle, we developed protocols to illustrate the changes in cardiac and vascular function that occur with changes in posture, venous return, and graded exercise. We use medical student volunteers and a professional echocardiographer to generate and acquire data, respectively. In small-group sessions, we developed an interactive approach to discuss the data and to make a large number of calculations from a limited number of measurements. The sequence of cardiac events and cardiac structure in vivo were illustrated with the volunteers lying down, standing, and then with their legs raised passively above the heart to increase venous return. Volunteers were then asked to peddle the bicycle to achieve steady-state heart rates of 110 and 150 beats/min. Data were collected in all these states, and calculations were performed and used as the basis of a small-group discussion to illustrate physiological principles. Information related to a surprisingly large number of cardiovascular control mechanisms was derived, and its relevance to cardiovascular dysfunction was explored. This communication describes our experience in developing a new cardiovascular control laboratory to reinforce didactic material presented in lectures and small-group sessions.
The physiology and mechanics of undulatory swimming: a student laboratory exercise using medicinal leeches
Authors: Ellerby David J.
Published: September 2009

The medicinal leech is a useful animal model for investigating undulatory swimming in the classroom. Unlike many swimming organisms, its swimming performance can be quantified without specialized equipment. A large blood meal alters swimming behavior in a way that can be used to generate a discussion of the hydrodynamics of swimming, muscle mechanics, hydrostatic skeletons, and the physiological features that allow leeches to deal with the volume increase and osmotic load imposed by the meal. Analyses can be carried out at a range of levels tailored to suit a particular class.
A forgotten moment in physiology: the Lovelace Woman in Space Program (1960–1962)
Authors: Ryan Kathy L. , Loeppky Jack A. , Kilgore Donald E.
Published: September 2009

In 1959, Brigadier General Donald Flickinger and Dr. W. Randolph Lovelace II suggested that it would be more practical from an engineering standpoint to send women rather than men into space due to their lower body weights and oxygen requirements. When the Air Force decided not to pursue this project, Dr. Lovelace assumed leadership of the Woman in Space Program and began medical and physiological testing of a series of accomplished women aviators at the Lovelace Medical Clinic in Albuquerque, NM, in 1960. The tests that these women underwent were identical to those used to test the original Mercury astronauts, with the addition of gynecological examinations. Thirteen of the nineteen women tested passed these strenuous physiological exams (for comparison, 18 of 32 men tested passed); a subset of these pilots was further tested on a series of psychological exams that were similar to or, in some instances, more demanding than those given to male Mercury candidates. Despite these promising results, further testing was halted, and the Woman in Space Program was disbanded in 1962. Although the Woman in Space Program received a great deal of publicity at the time, the story of these women was somewhat lost until they were reunited at the 1999 launch of the shuttle Columbia, commanded by Colonel Eileen Collins.
VEGF autoregulates its proliferative and migratory ERK1/2 and p38 cascades by enhancing the expression of DUSP1 and DUSP5 phosphatases in endothelial cells
Authors: Bellou Sofia , Hink Mark A. , Bagli Eleni , Panopoulou Ekaterini , Bastiaens Philippe I. H. , Murphy Carol , Fotsis Theodore
Published: September 2009

Vascular endothelial growth factor (VEGF) is a key angiogenic factor that regulates proliferation and migration of endothelial cells via phosphorylation of extracellular signal-regulated kinase-1/2 (ERK1/2) and p38, respectively. Here, we demonstrate that VEGF strongly induces the transcription of two dual-specificity phosphatase (DUSP) genes DUSP1 and DUSP5 in endothelial cells. Using fluorescence microscopy, fluorescence lifetime imaging (FLIM), and fluorescence cross-correlation spectroscopy (FCCS), we found that DUSP1/mitogen-activated protein kinases phosphatase-1 (MKP-1) was localized in both the nucleus and cytoplasm of endothelial cells, where it existed in complex with p38 (effective dissociation constant, KDeff, values of 294 and 197 nM, respectively), whereas DUSP5 was localized in the nucleus of endothelial cells in complex with ERK1/2 ( KDeff 345 nM). VEGF administration affected differentially the KDeff values of the DUSP1/p38 and DUSP5/ERK1/2 complexes. Gain-of-function and lack-of-function approaches revealed that DUSP1/MKP-1 dephosphorylates primarily VEGF-phosphorylated p38, thereby inhibiting endothelial cell migration, whereas DUSP5 dephosphorylates VEGF-phosphorylated ERK1/2 inhibiting proliferation of endothelial cells. Moreover, DUSP5 exhibited considerable nuclear anchoring activity on ERK1/2 in the nucleus, thereby diminishing ERK1/2 export to the cytoplasm decreasing its further availability for activation.
Estradiol-mediated ERK phosphorylation and apoptosis in vascular smooth muscle cells requires GPR 30
Authors: Ding Qingming , Gros Robert , Limbird Lee E. , Chorazyczewski Jozef , Feldman Ross D.
Published: September 2009

Recent studies suggest that the rapid and nongenomic effects of estradiol may be mediated through the G protein-coupled receptor dubbed GPR30 receptor. The present study examines the role of GPR30 versus a classical estrogen receptor (ERα) in mediating the growth regulatory effects of estradiol. GPR30 is readily detectable in freshly isolated vascular tissue but barely detectable in cultured vascular smooth muscle cells (VSMC). In freshly isolated aortic tissue, estradiol stimulated extracellular signal-regulated kinases (ERK) phosphorylation. In contrast, in cultured VSMC, where GPR30 expression is significantly reduced, estradiol inhibits ERK phosphorylation. Transfer of the genes encoding GPR30 led to estradiol stimulation of ERK phosphorylation, which is opposite the effects of estradiol in the primary culture of VSMCs. Transduction of the mineralocorticoid receptor (MR) had no effect on estradiol effects on ERK. Estradiol-mediated stimulation of ERK subsequent to heterologous GPR30 expression was pertussis toxin sensitive and phosphoinositide 3-kinase (PI3 kinase) dependent; under these conditions, estradiol also inhibited protein kinase A (PKA). In contrast, in the absence of GPR30 expression in cultured VSMC, estradiol stimulated PKA activity and inhibited ERK phosphorylation. To determine the functional effect of GPR30 (vs. estrogen receptor expression), we assessed estradiol-mediated apoptosis. In the absence of GPR30 expression, estradiol inhibited apoptosis. This effect was enhanced with ERα expression. In contrast, with GPR30 expression, estradiol stimulated apoptosis in an ERK-dependent manner. Thus the effect of estradiol on vascular smooth muscle cell apoptosis is likely dependent on the balance between ER-mediated PKA activation and GPR30-mediated PKA inhibition and PI3 kinase activation. Taken together, we postulate that modulation of GPR30 expression or activity may be an important determinant of the effects of estradiol in the vasculature.
Loss of the apical V-ATPase a-subunit VHA-6 prevents acidification of the intestinal lumen during a rhythmic behavior in C. elegans
Authors: Allman Erik , Johnson David , Nehrke Keith
Published: September 2009

In Caenorhabditis elegans, oscillations of intestinal pH contribute to the rhythmic defecation behavior, but the acid-base transport mechanisms that facilitate proton movement are not well understood. Here, we demonstrate that VHA-6, an intestine-specific a-subunit of the H+-K+-ATPase complex (V-ATPase), resides in the apical membrane of the intestinal epithelial cells and is required for luminal acidification. Disruption of the vha-6 gene led to early developmental arrest; the arrest phenotype could be complemented by expression of a fluorescently labeled vha-6 transgene. To study the contribution of vha-6 to pH homeostasis in larval worms, we used a partial reduction of function through postembryonic single-generation RNA interference. We demonstrate that the inability to fully acidify the intestinal lumen coincides with a defect in pH recovery of the intestinal epithelial cells, suggesting that VHA-6 is essential for proton pumping following defecation. Moreover, intestinal dipeptide accumulation and fat storage are compromised by the loss of VHA-6, suggesting that luminal acidification promotes nutrient uptake in worms, as well as in mammals. Since acidified intracellular vesicles and autofluorescent storage granules are indistinguishable between the vha-6 mutant and controls, it is likely that the nutrient-restricted phenotype is due to a loss of plasma membrane V-ATPase activity specifically. These data establish a simple genetic model for proton pump-driven acidification. Since defecation occurs at 45-s intervals in worms, this model represents an opportunity to study acute regulation of V-ATPase activity on a short time scale and may be useful in the study of alternative treatments for acid-peptic disorders.
Hepatocyte nuclear factor 1 is essential for transcription of sodium-dependent vitamin C transporter protein 1
Authors: Michels Alexander J. , Hagen Tory M.
Published: September 2009

Transport and distribution of vitamin C is primarily regulated by the function of sodium-dependent vitamin C transporters (SVCTs). SVCT1 is expressed in the small intestine, liver, and kidney, organs that play a vital role in whole body vitamin C homeostasis. Despite the importance of this protein, little is known about regulation of the gene encoding SVCT1, Slc23a1. In this study, we present the first investigation of the transcriptional regulation of human Slc23a1, identifying transcription factors that may influence its expression. A 1,239-bp genomic DNA fragment corresponding to the 5′-flanking region of Slc23a1 was isolated from a human hepatocarcinoma cell line (HepG2) and sequenced. When cloned into a reporter gene construct, robust transcriptional activity was seen in this sequence, nearly 25-fold above the control vector. Deletion analysis of the SVCT1 reporter gene vector defined the minimal active promoter as a small 135-bp region upstream of the transcriptional start site. While several transcription factor binding sites were identified within this sequence, reporter constructs showed that basal transcription required the binding of hepatic nuclear factor 1 (HNF-1) to its cognate sequence. Furthermore, mutation of this HNF-1 binding site resulted in complete loss of luciferase expression, even in the context of the whole promoter. Additionally, small interfering RNA knockdown of both members of the HNF-1 family, HNF-1α and HNF-1β, resulted in a significant decline in SVCT1 transcription. Together, these data suggest that HNF-1α and/or HNF-1β binding is required for SVCT1 expression and may be involved in the coordinate regulation of whole body vitamin C status.
Inherent differences in morphology, proliferation, and migration in saphenous vein smooth muscle cells cultured from nondiabetic and Type 2 diabetic patients
Authors: Madi Haifa A. , Riches Kirsten , Warburton Philip , O'Regan David J. , Turner Neil A. , Porter Karen E.
Published: September 2009

Individuals with Type 2 diabetes mellitus (T2DM) are at increased risk of saphenous vein (SV) graft stenosis following coronary artery bypass. Graft stenosis is caused by intimal hyperplasia, a pathology characterized by smooth muscle cell (SMC) proliferation and migration. We hypothesized that SV-SMC from T2DM patients were intrinsically more proliferative and migratory than those from nondiabetic individuals. SV-SMC were cultured from nondiabetic and T2DM patients. Cell morphology (light microscopy, immunocytochemistry), S100A4 expression (real-time RT-PCR, immunoblotting), proliferation (cell counting), migration (Boyden chamber assay), and cell signaling (immunoblotting with phosphorylation state-specific antibodies) were studied. SV-SMC from T2DM patients were morphologically distinct from nondiabetic patients and exhibited a predominantly rhomboid phenotype, accompanied by disrupted F-actin cytoskeleton, disorganized α-smooth muscle actin network, and increased focal adhesion formation. However, no differences were observed in expression of the calcium-binding protein S100A4, a marker of rhomboid SMC phenotype, between the two cell populations. T2DM cells were less proliferative in response to fetal calf serum than nondiabetic cells, but both populations had similar proliferative responses to insulin plus PDGF. Under high glucose concentration conditions in the presence of insulin, migration of diabetic SV-SMC was greater than nondiabetic cells. Glucose concentration did not affect SV-SMC proliferation. No differences in insulin or PDGF-induced phosphorylation of ERK-1/2 or components of the Akt pathway (Akt-Ser473, Akt-Thr308, and GSK-3β) were apparent between the two populations. In conclusion, SV-SMC from T2DM patients differ from nondiabetic SV-SMC in that they exhibit a rhomboid phenotype and are more migratory, but less proliferative, in response to serum.
Site-specific attenuation of food intake but not the latency to eat after hypothalamic injections of neuropeptide Y in dehydrated-anorexic rats
Authors: Salter-Venzon Dawna , Watts Alan G.
Published: September 2009

Anorexia that accompanies cellular dehydration in rats (DE-anorexia) offers a relatively simple model for investigating the functional organization of neural mechanisms that can suppress feeding during dehydration. Previous studies strongly suggest that the inputs that drive ingestive behavior control neurons in the paraventricular nucleus of the hypothalamus (PVH) and lateral hypothalamic area (LHA) remain active during DE-anorexia. Here we examine whether these two regions retain their sensitivity to neuropeptide Y (NPY). NPY is an important component in two major feeding-related inputs from the arcuate nucleus and the hindbrain. We found that intake responses to NPY injections in the LHA and PVH were suppressed in DE-anorexia, but the PVH remained less sensitive to the effects of NPY than the LHA in DE-anorexic animals. Indeed the higher dose of NPY (238 pmol) completely overcame shorter periods of DE-anorexia when injected into the LHA but not the PVH. However, the latency to eat after NPY injections remained unchanged from control animals, regardless of NPY dose, injection location, or intensity of anorexia. Furthermore, the onset and size of the strong and rapidly induced compensatory feeding that follows the return of water to DE-anorexic animals was also unaffected by any NPY injections. These data support the hypothesis that DE-anorexia develops as a consequence of the premature termination of regularly initiated meals, which perhaps involves processes that alter the sensitivity of satiety mechanisms downstream to the PVH and LHA.
Proinsulin C-peptide reduces diabetes-induced glomerular hyperfiltration via efferent arteriole dilation and inhibition of tubular sodium reabsorption
Authors: Nordquist Lina , Brown Russell , Fasching Angelica , Persson Patrik , Palm Fredrik
Published: September 2009

C-peptide reduces diabetes-induced glomerular hyperfiltration in diabetic patients and experimental animal models. However, the mechanisms mediating the beneficial effect of C-peptide remain unclear. We investigated whether altered renal afferent-efferent arteriole tonus or alterations in tubular Na+transport (TNa) in response to C-peptide administration mediate the reduction of diabetes-induced glomerular hyperfiltration. Glomerular filtration rate, filtration fraction, total and cortical renal blood flow, total kidney O2consumption (Qo2), TNa, fractional Na+and Li+excretions, and tubular free-flow and stop-flow pressures were measured in anesthetized adult male normoglycemic and streptozotocin-diabetic Sprague-Dawley rats. The specific effect of C-peptide on transport-dependent Qo2was investigated in vitro in freshly isolated proximal tubular cells. C-peptide reduced glomerular filtration rate (−24%), stop-flow pressure (−8%), and filtration fraction (−17%) exclusively in diabetic rats without altering renal blood flow. Diabetic rats had higher baseline TNa(+40%), which was reduced by C-peptide. Similarly, C-peptide increased fractional Na+(+80%) and Li+(+47%) excretions only in the diabetic rats. None of these parameters was affected by vehicle treatments in either group. Baseline Qo2was 37% higher in proximal tubular cells from diabetic rats than controls and was normalized by C-peptide. C-peptide had no effect on ouabain-pretreated diabetic cells from diabetic rats. C-peptide reduced diabetes-induced hyperfiltration via a net dilation of the efferent arteriole and inhibition of tubular Na+reabsorption, both potent regulators of the glomerular net filtration pressure. These findings provide new mechanistic insight into the beneficial effects of C-peptide on diabetic kidney function.
Enhanced tubuloglomerular feedback in mice with vascular overexpression of A1adenosine receptors
Authors: Oppermann Mona , Qin Yan , Lai En Yin , Eisner Christoph , Li Lingli , Huang Yuning , Mizel Diane , Fryc Justyna , Wilcox Christopher S. , Briggs Josephine , Schnermann Jurgen , Castrop Hayo
Published: September 2009

Adenosine 1 receptors (A1AR) in the kidney are expressed in the vasculature and the tubular system. Pharmacological inhibition or global genetic deletion of A1AR causes marked reductions or abolishment of tubuloglomerular feedback (TGF) responses. To assess the function of vascular A1AR in TGF, we generated transgenic mouse lines in which A1AR expression in smooth muscle was augmented by placing A1AR under the control of a 5.38-kb fragment of the rat smooth muscle α-actin promoter and first intron ( 12 ). Two founder lines with highest expression in the kidney [353 ± 42 and 575 ± 43% compared with the wild type (WT)] were used in the experiments. Enhanced expression of A1AR at the expected site in these lines was confirmed by augmented constrictor responses of isolated afferent arterioles to administration of the A1AR agonist N6-cyclohexyladenosine. Maximum TGF responses (0–30 nl/min flow step) were increased from 8.4 ± 0.9 mmHg in WT ( n = 21) to 14.2 ± 0.7 mmHg in A1AR-transgene (tg) 4 ( n = 22; P < 0.0001), and to 12.6 ± 1.2 mmHg in A1AR-tg7 ( n = 12; P < 0.02). Stepwise changes in perfusion flow caused greater numerical TGF responses in A1AR-tg than WT in all flow ranges with differences reaching levels of significance in the intermediate flow ranges of 7.5–10 and 10–15 nl/min. Proximal-distal single-nephron glomerular filtration rate (SNGFR) differences (free-flow micropuncture) were also increased in A1AR-tg, averaging 6.25 ± 1.5 nl/min compared with 2.6 ± 0.51 nl/min in WT ( P = 0.034). Basal plasma renin concentrations as well as the suppression of renin secretion after volume expansion were similar in A1AR-tg and WT mice, suggesting lack of transgene expression in juxtaglomerular cells. These data indicate that A1AR expression in vascular smooth muscle cells is a critical component for TGF signaling and that changes in renal vascular A1AR expression may determine the magnitude of TGF responses.
PKC-dependent superoxide production by the renal medullary thick ascending limb from diabetic rats
Authors: Yang Jing , Lane Pascale H. , Pollock Jennifer S. , Carmines Pamela K
Published: September 2009

Type 1 diabetes (T1D) is a state of oxidative stress accompanied by PKC activation in many tissues. The primary site of O2•−production by the normal rat kidney is the medullary thick ascending limb (mTAL). We hypothesized that T1D increases O2•−production by the mTAL through a PKC-dependent mechanism involving increased expression and translocation of one or more PKC isoforms. mTAL suspensions were prepared from rats with streptozotocin-induced T1D (STZ mTALs) and from normal or sham rats (normal/sham mTALs). O2•−production by STZ mTALs was fivefold higher than normal/sham mTALs ( P < 0.05). PMA (30 min) mimicked the effect of T1D on O2•−production. Exposure to calphostin C or chelerythrine (PKC inhibitors), Gö6976 (PKCα/β inhibitor), or rottlerin (PKCδ inhibitor) decreased O2•−production to <20% of untreated baseline in both normal/sham and STZ mTALs. PKCβ inhibitors had no effect. PKC activity was increased in STZ mTALs ( P < 0.05 vs. normal/sham mTALs) and was unaltered by antioxidant exposure (tempol). PKCα protein levels were increased by 70% in STZ mTALs, with a ∼30% increase in the fraction associated with the membrane (both P < 0.05 vs. sham). PKCβ protein levels were elevated by 29% in STZ mTALs ( P < 0.05 vs. sham) with no change in the membrane-bound fraction. Neither PKCδ protein levels nor its membrane-bound fraction differed between groups. Thus STZ mTALs display PKC activation, upregulation of PKCα and PKCβ protein levels, increased PKCα translocation to the membrane, and accelerated O2•−production that is eradicated by inhibition of PKCα or PKCδ (but not PKCβ). We conclude that increased PKCα expression and activity are primarily responsible for PKC-dependent O2•−production by the mTAL during T1D.
Pulmonary responses to subacute ozone exposure in obese vs. lean mice
Authors: Shore Stephanie A. , Lang Jason E. , Kasahara David I. , Lu Frank L. , Verbout Norah G. , Si Huiqing , Williams Erin S. , Terry Raya D. , Lee Anna , Johnston Richard A.
Published: September 2009

The purpose of this study was to determine whether obesity affects pulmonary responses following a 3-day ozone exposure. Obese db/ db and lean wild-type mice were exposed to ozone (0.3 ppm) for 72 h. In wild-type mice, ozone exposure caused pulmonary injury and inflammation, and these events were associated with reduced pulmonary compliance. In db/ db mice, ozone-induced neutrophil recruitment to the lung was reduced and no reduction in compliance was observed. Similar results were obtained in obese Cpe fat mice, indicating that loss of leptin signaling in db/ db mice does not account for these obesity-related changes. To examine the role of interleukin (IL)-6 in this obesity-related difference in ozone responsiveness, wild-type and IL-6-deficient mice were raised on 10% or 60% fat diets. Compared with 10% fat-fed mice, wild-type 60% fat-fed mice were obese and had reduced neutrophil recruitment following ozone. IL-6 deficiency reduced ozone-induced neutrophil recruitment in 10% fat-fed mice. In contrast, in obese mice, no effect of IL-6 deficiency on neutrophil recruitment was observed. Obesity-related differences in the effect of ozone on compliance were observed in both wild-type and IL-6-deficient mice. Obesity-related differences in serum IL-6 were observed and may account for obesity-related differences in the effect of IL-6 deficiency on neutrophil recruitment. In summary, the neutrophilic inflammation induced by prolonged low level ozone exposure was attenuated in obese mice and appeared to result from an absence of IL-6-dependent neutrophil recruitment in the obese mice.
Functional Properties of Cutaneous A- and C-Fibers 1–15 Months After a Nerve Lesion
Authors: Gorodetskaya Natalia , Grossmann Lydia , Constantin Cristina , Jänig Wilfrid
Published: September 2009

The functional properties of cutaneous afferent fibers were investigated 1–15 mo after nerve lesions, which allowed regeneration into denervated skin. After crushing or transection and resuturing the rat sural nerve, ongoing activity and responses to cold, heat, and mechanical stimuli presented to the denervated skin or to the nerve distal to the lesion were examined in 273 A-fibers and 211 C-fibers. Reinnervation of skin by A-fibers was largely complete by 1–4 mo after crushing but incomplete after transection and resuturing. A few A-fibers could be activated from the nerve trunk, even after 10–15 mo. Almost all regenerated A-fibers were mechanosensitive and about 6% were cold- or heat-sensitive. A few A-fibers had ongoing activity after nerve crush. Only 15–35% of C-fibers could be activated at 1–4 mo, but 60% were excited from the skin at 10–15 mo, when many also had receptive fields within the lesioned nerve. The remaining C-fibers had receptive fields only within the nerve trunk. Responses of both intraneural and intradermal endings of C-fibers could be classified into functional groups similar to those of C-fibers in control nerves to cutaneous stimuli. The frequency of afferent C-fibers with ongoing activity that were not highly cold sensitive was 45%. We conclude that the functional characteristics of afferent A- and C-fibers are expressed by regenerating nerve endings, even when they do not reinnervate their target tissue. The reinnervation of skin by afferent C-fibers is extremely slow and may never recover to normal.
Postural Feedback Scaling Deficits in Parkinson's Disease
Authors: Kim Seyoung , Horak Fay B. , Carlson-Kuhta Patricia , Park Sukyung
Published: September 2009

Many differences in postural responses have been associated with age and Parkinson's disease (PD), but until now there has been no quantitative model to explain these differences. We developed a feedback control model of body dynamics that could reproduce the postural responses of young subjects, elderly subjects, and subjects with PD, and we investigated whether the postural impairments of subjects with PD can be described as an abnormal scaling of postural feedback gain. Feedback gains quantify how the nervous system generates compensatory joint torques based on kinematic responses. Seven subjects in each group experienced forward postural perturbations to seven different backward support surface translations ranging from 3- to 15-cm amplitudes and with a constant duration of 275 ms. Ground reaction forces and joint kinematics were measured to obtain joint torques from inverse dynamics. A full-state feedback controller with a two-segment body dynamic model was used to simulate joint kinematics and kinetics in response to perturbations. Results showed that all three subject groups gradually scaled postural feedback gains as a function of perturbation amplitudes, and the scaling started even before the maximum allowable ankle torque was reached. This result implies that the nervous system takes body dynamics into account and adjusts postural feedback gains to accommodate biomechanical constraints. PD subjects showed significantly smaller than normal ankle feedback gain with low scaling and larger hip feedback gain, which led to an early violation of the flat-foot constraint and unusually small (bradykinetic) postural responses. Our postural feedback control model quantitatively described the postural abnormality of the patients with PD as abnormal feedback gains and reduced ability to modify postural feedback gain with changes in postural challenge.
On the Open-Loop and Feedback Processes That Underlie the Formation of Trajectories During Visual and Nonvisual Locomotion in Humans
Authors: Pham Quang-Cuong , Hicheur Halim
Published: September 2009

We investigated the nature of the control mechanisms at work during goal-oriented locomotion. In particular, we tested the effects of vision, locomotor speed, and the presence of via points on the geometric and kinematic properties of locomotor trajectories. We first observed that the average trajectories recorded in visual and nonvisual locomotion were highly comparable, suggesting the existence of vision-independent processes underlying the formation of locomotor trajectories. Then by analyzing and comparing the variability around the average trajectories across different experimental conditions, we were able to demonstrate the existence of on-line feedback control in both visual and nonvisual locomotion and to clarify the relations between visual and nonvisual control strategies. Based on these insights, we designed a model in which maximum-smoothness and optimal feedback control principles account, respectively, for the open-loop and feedback processes. Taken together, the experimental and modeling findings provide a novel understanding of the nature of the motor, sensory, and “navigational” processes underlying goal-oriented locomotion.
Locomotor Adaptation and Aftereffects in Patients With Reduced Somatosensory Input Due to Peripheral Neuropathy
Authors: Bunday Karen L. , Bronstein Adolfo M.
Published: September 2009

We studied 12 peripheral neuropathy patients (PNP) and 13 age-matched controls with the “broken escalator” paradigm to see how somatosensory loss affects gait adaptation and the release and recovery (“braking”) of the forward trunk overshoot observed during this locomotor aftereffect. Trunk displacement, foot contact signals, and leg electromyograms (EMGs) were recorded while subjects walked onto a stationary sled (BEFORE trials), onto the moving sled (MOVING or adaptation trials), and again onto the stationary sled (AFTER trials). PNP were unsteady during the MOVING trials, but this progressively improved, indicating some adaptation. During the after trials, 77% of control subjects displayed a trunk overshoot aftereffect but over half of the PNP (58%) did not. The PNP without a trunk aftereffect adapted to the MOVING trials by increasing distance traveled; subsequently this was expressed as increased distance traveled during the aftereffect rather than as a trunk overshoot. This clear separation in consequent aftereffects was not seen in the normal controls suggesting that, as a result of somatosensory loss, some PNP use distinctive strategies to negotiate the moving sled, in turn resulting in a distinct aftereffects. In addition, PNP displayed earlier than normal anticipatory leg EMG activity during the first after trial. Although proprioceptive inputs are not critical for the emergence or termination of the aftereffect, somatosensory loss induces profound changes in motor adaptation and anticipation. Our study has found individual differences in adaptive motor performance, indicative that PNP adopt different feed-forward gait compensatory strategies in response to peripheral sensory loss.
Maintenance of Thalamic Epileptiform Activity Depends on the Astrocytic Glutamate-Glutamine Cycle
Authors: Bryant Astra S. , Li Bojia , Beenhakker Mark P. , Huguenard John R.
Published: September 2009

The generation of prolonged neuronal activity depends on the maintenance of synaptic neurotransmitter pools. The astrocytic glutamate-glutamine cycle is a major mechanism for recycling the neurotransmitters GABA and glutamate. Here we tested the effect of disrupting the glutamate-glutamine cycle on two types of neuronal activity patterns in the thalamus: sleep-related spindles and epileptiform oscillations. In recording conditions believed to induce glutamine scarcity, epileptiform oscillations showed a progressive reduction in duration that was partially reversible by the application of exogenous glutamine (300 μM). Blocking uptake of glutamine into neurons with α-(methylamino) isobutyric acid (5 mM) caused a similar reduction in oscillation duration, as did blocking neuronal GABA synthesis with 3-mercaptoproprionic acid (10 μM). However, comparable manipulations did not affect sleep spindles. Together, these results support a crucial role for the glutamate-glutamine cycle in providing the neurotransmitters necessary for the generation of epileptiform activity and suggest potential therapeutic approaches that selectively reduce seizure activity but maintain normal neuronal activity.
Differential Activation of Projection Neurons by Two Sensory Pathways Contributes to Motor Pattern Selection
Authors: Hedrich Ulrike B. S. , Smarandache Carmen R. , Stein Wolfgang
Published: September 2009

Sensorimotor integration is known to occur at the level of motor circuits as well as in upstream interneurons that regulate motor activity. Here we show, using the crab stomatogastric nervous system (STNS) as a model, that different sensory systems affect the same set of projection neurons. However, they have qualitatively different effects on their activities (excitation vs. inhibition), and these differences contribute to the selection of motor patterns from multifunctional circuits. We compare the actions of the proprioceptive anterior gastric receptor (AGR) and the inferior ventricular (IV) neurons, which relay chemosensory information from the brain to the STNS, on modulatory commissural neurons 1 and 5 (MCN1 and MCN5) and commissural projection neuron 2 (CPN2) and their resulting actions on the gastric mill central pattern generating circuit in the stomatogastric ganglion. When stimulated, AGR and the IV neurons affect all three projection neurons but elicit distinct gastric mill rhythms. The effects of both sensory pathways on the projection neurons differ in the type of excitation provided to CPN2 and MCN5 (electrical vs. chemical) and the effect on MCN1 (direct inhibition by AGR vs. polysynaptic excitation by the IV neurons). The latter is functionally important because a restoration of MCN1 activity during the AGR rhythm made it more similar to that elicited by IV neuron stimulation. Our results thus support the hypothesis that sensory pathways activate different combinations of projection neurons to select distinct outputs from the same neuronal circuit.
Adaptation to Visuomotor Rotation Through Interaction Between Posterior Parietal and Motor Cortical Areas
Authors: Tanaka Hirokazu , Sejnowski Terrence J. , Krakauer John W.
Published: September 2009

Studying how motor adaptation to visuomotor rotation for one reach direction generalizes to other reach directions can provide insight into how visuomotor maps are represented and learned in the brain. Previous psychophysical studies have concluded that postadaptation generalization is restricted to a narrow range of directions around the training direction. A population-coding model that updates the weights between narrow Gaussian-tuned visual units and motor units on each trial reproduced experimental trial-by-trial learning curves for rotation adaptation and the generalization function measured postadaptation. These results suggest that the neurons involved in rotation adaptation have a relatively narrow directional tuning width (∼23°). Population coding models with units having broader tuning functions (such as cosine tuning in motor cortex and Gaussian sum in the cerebellum) could not reproduce the narrow single-peaked generalization pattern. Visually selective neurons with narrow Gaussian tuning curves have been identified in posterior parietal cortex, making it a possible site of adaptation to visuomotor rotation. We propose that rotation adaptation proceeds through changes in synaptic weights between neurons in posterior parietal cortex and motor cortex driven by a prediction error computed by the cerebellum.