bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential control of the scapulothoracic muscles in humans
Authors: Alexander C. , Miley R. , Stynes S. , Harrison P. J.
Published: January 2007

The control of the scapulothoracic muscles trapezius (Tr) and serratus anterior (SA) has been examined in normal human subjects. Electromyographic recordings were made from the SA and Tr muscles (upper trapezius UTr, lower trapezius LTr) using surface electrodes placed bilaterally. Magnetic stimulation of the motor cortex and electrical stimulation of peripheral nerves were used to examine their descending and reflex control. The average optimal site of cortical stimulation was found to be the same for SA, UTr and LTr (an approximate centre of gravity of −0.6 cm, 3.7 cm where the centre of gravity is expressed as the mean anterio‐posterior position, the mean medio‐lateral position). Some asymmetry in the cortical representation of UTr was found in each individual tested. Magnetic stimulation evoked bilateral MEPs in Tr (latency contralateral (c) UTr 8.5 ± 1.6 ms, ipsilateral (i) UTr 19.0 ± 2.7 ms) but only contralateral responses were evoked in SA (11.2 ± 2.6 ms). Electrical stimulation of the long thoracic nerve at two sites was used to examine homonymous and heteronymous reflexes of SA, while electrical stimulation of cervical nerve of C3/4 was used to examine the heteronymous reflexes of Tr. Ipsilateral SA H reflexes were evoked at a latency of 9.9 ± 0.8 ms (proximal site) and 10.8 ± 1.2 ms (distal site). No group I reflexes were evoked from SA to its contralateral homologue. No group I reflexes were evoked between Tr and SA. Finally, cross‐correlation of activity from the Tr muscle pairs and the SA muscle pair revealed that the motoneurones of the Tr muscles share some common presynaptic input whereas there was no detectable common presynaptic input to the SA muscle pair. This study extends and consolidates knowledge regarding the neural control of trapezius and for the first time explores the neural control of SA. The study demonstrates a contrasting bilateral control of Tr and SA. These patterns of connections are discussed in relation to the contrasting bilateral functional roles of these muscles.
Finding the Curie Temperature for Ferromagnetic Materials
Authors: Kizowski Czesław , Budzik Sylwia , Cebulski Józef
Published: January 2007

The laboratory exercise described in this paper is based on a well-known qualitative demonstration of Curie temperature.1 A long ferromagnetic wire, in the form of a spiral, is attracted to a strong permanent magnet placed near its midpoint (see Fig. 1). The temperature of the wire is increased by passing a current through it. When the temperature reaches the Curie point, the wire becomes paramagnetic and is no longer strongly attracted to the magnet. We have developed this demonstration into a quantitative experiment by providing an accurate way to determine the temperature at which the ferromagnetic-paramagnetic transition occurs.
Making Light Rays Visible in 3-D
Authors: Logiurato F. , Gratton L. M. , Oss S.
Published: January 2007

Students become deeply involved in physics classes when spectacular demonstrations take over from abstract and formal presentations. In this paper we propose a simple experimental setup in which the wave behavior of light can be made spectacularly evident along the whole path of the light beam in a practically unlimited number of configurations.1 The idea is simply that of adopting a fog-making machine to show, by means of light scattering along its path, that diffraction and interference are effective processes, i.e., they do not “switch on” just at the detection screen, as one could somehow be tempted to imagine in a more conventional setup. In our experiment, an ultrasonic mist maker is used to produce a small, homogeneous volume of water vapor fog (see Fig. 1). The fog is produced through water fragmentation caused by the mechanical action of a ceramic electrode that oscillates at ultrasonic frequency.2
Magnetic Force in an Electrolyte
Authors: Kireš Marián , Ješková Zuzana
Published: January 2007

Various ways of demonstrating the magnetic force on moving charged particles have been described in the physics teaching literature.1–4 Here we describe a simple experiment to demonstrate the magnetic force in an electrolyte. All you need for this experiment is a glass dish (d ≈ 8 cm), two copper ring electrodes (d1 ≈ 2 cm, d2 ≈ 7.5 cm), a solenoid with an iron core (ours has N = 600 turns, R ≈ 9 Ω, rated for 2 A), a dc power supply, copper sulfate solution (approximately 20 g of copper sulfate/100 ml of water), connecting wires, and an overhead projector. A similar experimental setup was developed5 by E. Morgan using a salt solution and a bar magnet with zinc or copper electrodes. The setup we describe is both very simple and easily viewed using an overhead projector.
Developing an Inquiry Lesson
Authors: Blanton Patricia
Published: January 2007

I recently attended the North Carolina Science Teachers' Association's Professional Development Institute and would like to share an activity with you for your consideration. At one particular session were teachers who have been involved in developing support documents to help beginning teachers understand what is meant by the state-mandated curriculum objectives, as well as to give examples as to how these objectives might be most effectively presented to students. Science as Inquiry is found as a core strand in both North Carolina's science curriculum and in the National Science Education Standards, http://www.nap.edu/readingroom/books/nses/6a.html#sis, yet many teachers think that all “hands-on” activities are “inquiry” activities. The focus of this particular session dealt with an activity involving observations, activities, and discussion.
Proteasome-Independent Functions of Ubiquitin in Endocytosis and Signaling
Authors: Mukhopadhyay Debdyuti , Riezman Howard
Published: January 2007

Ubiquitination is a reversible posttranslational modification of cellular proteins, in which a 76–amino acid polypeptide, ubiquitin, is primarily attached to the ϵ-amino group of lysines in target proteins. Ubiquitination is a major player in regulating a broad host of cellular processes, including cell division, differentiation, signal transduction, protein trafficking, and quality control. Aberrations in the ubiquitination system are implicated in pathogenesis of some diseases, certain malignancies, neurodegenerative disorders, and pathologies of the inflammatory immune response. Here, we discuss the proteasome-independent roles of ubiquitination in signaling and endocytosis.
Comment on "A Common Genetic Variant Is Associated with Adult and Childhood Obesity"
Authors: Rosskopf Dieter , Bornhorst Alexa , Rimmbach Christian , Schwahn Christian , Kayser Alexander , Krüger Anne , Tessmann Grietje , Geissler Ingrid , Kroemer Heyo K. , Völzke Henry
Published: January 2007

Contrary to the findings of Herbert
et al
. (Reports, 14 April 2006, p. 279), homozygous carriers of the C allele of the rs7566605 variant near the
INSIG2
gene did not exhibit a significantly increased risk for obesity in a large population-based cross-sectional German study. A subgroup analysis, however, revealed that this allele significantly increased the risk for obesity in already overweight individuals.
Physiological Proteomics of the Uncultured Endosymbiont of
Riftia pachyptila
Authors: Markert Stephanie , Arndt Cordelia , Felbeck Horst , Becher Dörte , Sievert Stefan M. , Hügler Michael , Albrecht Dirk , Robidart Julie , Bench Shellie , Feldman Robert A. , Hecker Michael , Schweder Thomas
Published: January 2007

The bacterial endosymbiont of the deep-sea tube worm
Riftia pachyptila
has never been successfully cultivated outside its host. In the absence of cultivation data, we have taken a proteomic approach based on the metagenome sequence to study the metabolism of this peculiar microorganism in detail. As one result, we found that three major sulfide oxidation proteins constitute ∼12% of the total cytosolic proteome, which highlights the essential role of these enzymes for the symbiont's energy metabolism. Unexpectedly, the symbiont uses the reductive tricarboxylic acid cycle in addition to the previously identified Calvin cycle for CO
2
fixation.
Regulation of γδ Versus αß T Lymphocyte Differentiation by the Transcription Factor SOX13
Authors: Melichar Heather J. , Narayan Kavitha , Der Sandy D. , Hiraoka Yoshiki , Gardiol Noemie , Jeannet Gregoire , Held Werner , Chambers Cynthia A. , Kang Joonsoo
Published: January 2007

αβ and γδ T cells originate from a common, multipotential precursor population in the thymus, but the molecular mechanisms regulating this lineage-fate decision are unknown. We have identified
Sox13
as a γδ-specific gene in the immune system. Using
Sox13
transgenic mice, we showed that this transcription factor promotes γδ T cell development while opposing αβ T cell differentiation. Conversely, mice deficient in
Sox13
expression exhibited impaired development of γδ T cells but not αβ T cells. One mechanism of SOX13 function is the inhibition of signaling by the developmentally important Wnt/T cell factor (TCF) pathway. Our data thus reveal a dominant pathway regulating the developmental fate of these two lineages of T lymphocytes.
Improved Oxygen Reduction Activity on Pt
3
Ni(111) via Increased Surface Site Availability
Authors: Stamenkovic Vojislav R. , Fowler Ben , Mun Bongjin Simon , Wang Guofeng , Ross Philip N. , Lucas Christopher A. , Marković Nenad M.
Published: January 2007

The slow rate of the oxygen reduction reaction (ORR) in the polymer electrolyte membrane fuel cell (PEMFC) is the main limitation for automotive applications. We demonstrated that the Pt
3
Ni(111) surface is 10-fold more active for the ORR than the corresponding Pt(111) surface and 90-fold more active than the current state-of-the-art Pt/C catalysts for PEMFC. The Pt
3
Ni(111) surface has an unusual electronic structure (
d
-band center position) and arrangement of surface atoms in the near-surface region. Under operating conditions relevant to fuel cells, its near-surface layer exhibits a highly structured compositional oscillation in the outermost and third layers, which are Pt-rich, and in the second atomic layer, which is Ni-rich. The weak interaction between the Pt surface atoms and nonreactive oxygenated species increases the number of active sites for O
2
adsorption.
Picobiliphytes: A Marine Picoplanktonic Algal Group with Unknown Affinities to Other Eukaryotes
Authors: Not Fabrice , Valentin Klaus , Romari Khadidja , Lovejoy Connie , Massana Ramon , Töbe Kerstin , Vaulot Daniel , Medlin Linda K.
Published: January 2007

Environmental sequencing has revealed unimagined diversity among eukaryotic picoplankton. A distinct picoplanktonic algal group, initially detected from 18
S
ribosomal DNA (rDNA) sequences, was hybridized with rRNA λ-targeted (rRNA-targeted) probes, detected by tyramide signal amplification–fluorescent in situ hybridization, and showed an organelle-like body with orange fluorescence indicative of phycobilins. Using this fluorescence signal, cells were sorted by flow cytometry and probed. Hybridized cells contained a 4′,6′-diamidino-2-phenylindole–stained organelle resembling a plastid with a nucleomorph. This suggests that they may be secondary endosymbiotic algae. Pending the isolation of living cells and their formal description, these algae have been termed picobiliphytes.
An H-NS-like Stealth Protein Aids Horizontal DNA Transmission in Bacteria
Authors: Doyle Marie , Fookes Maria , Ivens Al , Mangan Michael W. , Wain John , Dorman Charles J.
Published: January 2007

The Sfh protein is encoded by self-transmissible plasmids involved in human typhoid and is closely related to the global regulator H-NS. We have found that Sfh provides a stealth function that allows the plasmids to be transmitted to new bacterial hosts with minimal effects on their fitness. Introducing the plasmid without the
sfh
gene imposes a mild H-NS
–
phenotype and a severe loss of fitness due to titration of the cellular pool of H-NS by the A+T-rich plasmid. This stealth strategy seems to be used widely to aid horizontal DNA transmission and has important implications for bacterial evolution.
Use of Novel Boronic Acid Transition State Inhibitors To Probe Substrate Affinity in SHV-Type Extended-Spectrum β-Lactamases
Authors: Thomson Jodi M. , Prati Fabio , Bethel Christopher R. , Bonomo Robert A.
Published: January 2007

Boronic acid transition state inhibitors (BATSIs) with R1 side chains of cefotaxime and ceftazidime were assayed against SHV-1, SHV-2, SHV-5, D104K, and D104K G238S β-lactamases. The D104K variant was the most susceptible to inhibition by the ceftazidime BATSI (

K
i

, 730 ± 80 nM), while the D104K G238S variant was the most susceptible to the cefotaxime BATSI (

K
i

, 1.1 ± 0.2 μM).
Evaluation of Genetic Markers and Molecular Typing Methods for Prediction of Sources of
Campylobacter jejuni
and
C. coli
Infections
Authors: Kärenlampi Rauni , Rautelin Hilpi , Hänninen Marja-Liisa
Published: January 2007

Campylobacter jejuni
and
C. coli
isolates from poultry, cattle, and humans were studied using pulsed-field gel electrophoresis (PFGE) and PCR of candidate livestock-associated marker genes. Human isolates showed 5.7 and 61% overlap with cattle and poultry isolates, respectively, by use of PFGE. No unambiguous association was found between marker genes (the Cj1321 and Cj1324 genes) and livestock-associated isolates.
Viral Determinants of Resistance to Treatment in Patients with Hepatitis C
Authors: Wohnsland Anette , Hofmann Wolf Peter , Sarrazin Christoph
Published: January 2007

Chronic hepatitis C virus (HCV) infection affects more than 170 million persons worldwide and is responsible for the development of liver cirrhosis in many cases. Standard treatment with pegylated alpha interferon (IFN-α) in combination with the nucleoside analogue ribavirin leads to a sustained virologic response in approximately half of the patients. IFN-α is classified as an indirect treatment, as it interacts with the host's immune response. The mechanism of action of ribavirin is still unknown. The benefit of triple therapy by adding other antiviral agents, e.g., amantadine, is controversial. Currently, new direct antiviral drugs (HCV protease/polymerase inhibitors) are being evaluated in phase 1/phase 2 trials. Phenotypic resistance to antiviral therapy has been attributed to amino acid variations within distinct regions of the HCV polyprotein. While sensitivity to IFN-α-based antiviral therapy in vivo is clearly correlated with the number of mutations within the HCV NS5A protein, the underlying functional mechanisms for this association are unknown. In turn, in vitro, several mechanisms to circumvent the host immune defense or to block treatment-induced antiviral activities have been described for different HCV proteins. By the introduction of direct antiviral drugs, hepatitis C therapy now is entering a new era in which the development of resistance may become the most important parameter for treatment success or failure.
Rat Bite Fever andStreptobacillus moniliformis
Authors: Elliott Sean P.
Published: January 2007

Rat bite fever, caused byStreptobacillus moniliformis, is a systemic illness classically characterized by fever, rigors, and polyarthralgias. If left untreated, it carries a mortality rate of 10%. Unfortunately, its nonspecific initial presentation combined with difficulties in culturing its causative organism produces a significant risk of delay or failure in diagnosis. The increasing popularity of rats and other rodents as pets, together with the risk of invasive or fatal disease, demands increased attention to rat bite fever as a potential diagnosis. The clinical and biological features of rat bite fever andStreptobacillus moniliformisare reviewed, providing some distinguishing features to assist the clinician and microbiologist in diagnosis.
Molecular Epidemiology of Malaria
Authors: Conway David J.
Published: January 2007

Malaria persists as an undiminished global problem, but the resources available to address it have increased. Many tools for understanding its biology and epidemiology are well developed, with a particular richness of comparative genome sequences. Targeted genetic manipulation is now effectively combined with in vitro culture assays on the most important human parasite,
Plasmodium falciparum
, and with in vivo analysis of rodent and monkey malaria parasites in their laboratory hosts. Studies of the epidemiology, prevention, and treatment of human malaria have already been influenced by the availability of molecular methods, and analyses of parasite polymorphisms have long had useful and highly informative applications. However, the molecular epidemiology of malaria is currently undergoing its most substantial revolution as a result of the genomic information and technologies that are available in well-resourced centers. It is a challenge for research agendas to face the real needs presented by a disease that largely exists in extremely resource-poor settings, but it is one that there appears to be an increased willingness to undertake. To this end, developments in the molecular epidemiology of malaria are reviewed here, emphasizing aspects that may be current and future priorities.
Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem
Authors: Pfaller M. A. , Diekema D. J.
Published: January 2007

Invasive candidiasis (IC) is a leading cause of mycosis-associated mortality in the United States. We examined data from the National Center for Health Statistics and reviewed recent literature in order to update the epidemiology of IC. IC-associated mortality has remained stable, at approximately 0.4 deaths per 100,000 population, since 1997, while mortality associated with invasive aspergillosis has continued to decline.
Candida albicans
remains the predominant cause of IC, accounting for over half of all cases, but
Candida glabrata
has emerged as the second most common cause of IC in the United States, and several less common
Candida
species may be emerging, some of which can exhibit resistance to triazoles and/or amphotericin B. Crude and attributable rates of mortality due to IC remain unacceptably high and unchanged for the past 2 decades. Nonpharmacologic preventive strategies should be emphasized, including hand hygiene; appropriate use, placement, and care of central venous catheters; and prudent use of antimicrobial therapy. Given that delays in appropriate antifungal therapy are associated with increased mortality, improved use of early empirical, preemptive, and prophylactic therapies should also help reduce IC-associated mortality. Several studies have now identified important variables that can be used to predict risk of IC and to help guide preventive strategies such as antifungal prophylaxis and early empirical therapy. However, improved non-culture-based diagnostics are needed to expand the potential for preemptive (or early directed) therapy. Further research to improve diagnostic, preventive, and therapeutic strategies is necessary to reduce the considerable morbidity and mortality associated with IC.
RR06 Activates Transcription of spr1996 andcbpAinStreptococcus pneumoniae
Authors: Ma Zhuo , Zhang Jing-Ren
Published: January 2007

Streptococcus pneumoniaecolonizes at the nasopharynx of humans and is able to disseminate and cause various infections. The hallmark of pneumococcal disease is rapid bacterial replication in different tissue sites leading to intense inflammation. The genetic basis of pneumococcal adaptation to different host niches remains sketchy. In this study, we investigated the regulatory effect of RR06, a response regulator protein, on gene expression ofS. pneumoniae.Microarray and Northern blot analyses showed that RR06 is specifically required for transcription of spr1996 andcbpA. While the function of Spr1996 is unknown, CbpA has been well characterized as a surface-exposed protective antigen and a virulence factor ofS. pneumoniae. A recombinant form of RR06 was able to bind to a 19-bp conserved sequence shared by the spr1996 andcbpApromoter regions. Furthermore, inactivation ofrr06resulted in loss of CbpA expression as detected by antibody staining and bacterial adhesion. CbpA expression was restored intransby the intactrr06gene. However, a mutant, RR06(D51A), with a point mutation in the aspartate residue at position 51 (a predicted major phosphorylation site) of RR06, completely abolished the CbpA expression, suggesting that RR06 phosphorylation is required for transcriptional activation of spr1996 andcbpA.Finally, inactivation ofrr06in additional pneumococcal strains also led to the loss of CbpA expression. These data implicate that RR06 activates the expression of spr1996 andcbpAin many other pneumococcal strains.
Isolated tumour cells in pathological node-negative lymph nodes adversely affect prognosis in cancer of the oesophagus or oesophagogastric junction
Authors: MacGuill Martin J , Barrett Ciara , Ravi Narayanasamy , MacDonald George , Reynolds John V
Published: January 2007

Aims:

To determine the prevalence of isolated tumour cells (ITC) in lymph nodes of patients with pathological node-negative (pN0) tumours and to assess their impact on disease-free and overall survival.

Methods:

Paraffin embedded lymph nodes from oesophagogastrectomy specimens were examined immunohistochemically using monoclonal anti-cytokeratin antibody (MNF118). Clinical and pathological features were summarised and overall and relapse-free survival were estimated.

Results:

Isolated tumour cells were detected in 12 of 146 patients (8%), and 24 of 1694 (1%) lymph nodes. With a median follow-up time of 28 months (range 0–160 months), both relapse-free and overall survival were significantly (p<0.05) associated with the presence of ITC in pN0 lymph nodes. There was no significant difference in the prevalence of ITC between patients who underwent multimodal therapy and those treated with surgery alone.

Conclusions:

ITC in pN0 lymph nodes may be less frequent than previously considered, but their presence is associated with poorer outcomes compared with true node negative disease.
ASPECTS OF SPINORIAL GEOMETRY
Authors: GRAN U. , GUTOWSKI J. , PAPADOPOULOS G. , ROEST D.
Published: January 2007

We review some aspects of the spinorial geometry approach to the classification of supersymmetric solutions of supergravity theories. In particular, we explain how spinorial geometry can be used to express the Killing spinor equations in terms of a linear system for the fluxes and the geometry of spacetime. The solutions of this linear system express some of the fluxes in terms of the spacetime geometry and determine the conditions on the spacetime geometry imposed by supersymmetry. We also present some of the recent applications like the classification of maximally supersymmetric G-backgrounds in IIB, this includes the most general pp-wave solution preserving 1/2 supersymmetry, and the classification of N = 31 backgrounds in ten and eleven dimensions.
A PERTURBATIVE TREATMENT FOR THE ENERGY LEVELS OF NEUTRAL ATOMS
Authors: IKHDAIR SAMEER M. , SEVER RAMAZAN
Published: January 2007

Energy levels of neutral atoms have been reexamined by applying an alternative perturbative scheme in solving the Schrödinger equation for the Yukawa potential model with a modified screening parameter. The predicted shell binding energies are found to be quite accurate over the entire range of the atomic number Z up to 84 and compare very well with those obtained within the framework of hypervirial-Padé scheme and the method of shifted large-N expansion. It is observed that the new perturbative method may also be applied to the other areas of atomic physics.
AXIAL ANOMALY: THE MODERN STATUS
Authors: IOFFE B. L.
Published: January 2007

The modern status of the problem of axial anomaly in QED and QCD is reviewed. Two methods of the derivation of the axial anomaly are presented: (1) by splitting of coordinates in the expression for the axial current and (2) by calculation of triangle diagrams, where the anomaly arises from the surface terms in momentum space. It is demonstrated, that the equivalent formulation of the anomaly can be given, as a sum rule for the structure function in dispersion representation of three point function of AVV interaction. It is argued, that such integral representation of the anomaly has some advantages in the case of description of the anomaly by contribution of hadronic states in QCD. The validity of the 't Hooft consistency condition is discussed. A few examples of the physical application of the axial anomaly are given.
Regulation of Cellular and Humoral Immune Responses by the SLAM and SAP Families of Molecules
Authors: Ma Cindy S. , Nichols Kim E. , Tangye Stuart G.
Published: January 2007

SAP (SLAM-associated protein) was identified in 1998 as an adaptor molecule involved in the intracellular signaling pathways elicited through the cell surface receptor SLAM and as the protein defective in the human immunodeficiency X-linked lymphoproliferative disease (XLP). During the past eight years, it has been established that the SLAM family of cell surface receptors (SLAM, 2B4, NTB-A, Ly9, CD84) and the SAP family of adaptors (SAP, EAT-2, ERT) play critical roles in lymphocyte development, differentiation, and acquisition of effector functions. Studies of these proteins have shown unexpected roles in cytokine production by T cells and myeloid cells, T cell–dependent humoral immune responses, NK cell–mediated cytotoxicity, and NKT cell development. This review highlights recent findings that have improved our understanding of the roles of the SLAM and SAP families of molecules in immune regulation and discusses how perturbations in the signaling pathways involving these proteins can result in different disease states.
Schizophrenia: New Pathological Insights and Therapies
Authors: Jarskog L. Fredrik , Miyamoto Seiya , Lieberman Jeffrey A.
Published: January 2007

The neurodevelopmental hypothesis of schizophrenia posits an interaction between multiple susceptibility genes and one or more environmental insults in early life, resulting in altered brain development and the emergence of psychosis in early adulthood. Based on this framework, it has been argued that most neuropathological deficits observed in post mortem and neuroimaging studies of schizophrenia represent one or more lesions that originated in early life and remained static thereafter. However, recent longitudinal neuroimaging studies demonstrate a progressive component to the neuropathology of new-onset schizophrenia. This opens the possibility that the functional decline seen in many patients following the onset of illness may be halted or slowed. This review provides an update on developments in research on the neuropathology of schizophrenia and discusses recent advances in antipsychotic treatment and the potential impact on long-term outcomes.
End-Stage Renal Disease Measures of Quality
Authors: Himmelfarb Jonathan , Kliger Alan S.
Published: January 2007

During the past 35 years, there has been a geometric expansion of the population of patients receiving chronic dialysis therapy in the United States. As the size and associated costs of the dialysis population have grown, there has been a consistent and evolving emphasis on measuring and improving the quality of dialysis care. These efforts, aided by robust data collection vehicles, have translated into defined clinical performance measures; nevertheless, morbidity and mortality rates remain high for the dialysis population. Recently, attention has focused on whether improved outcomes could be obtained by paying physicians and dialysis providers on the basis of quality metrics. The feasibility, value, pitfalls, and appropriate quality metrics in a “payment-for-quality” program for dialysis care are currently under vigorous discussion.
Mechanisms underlying nutrient-induced segmentation in isolated guinea pig small intestine
Authors: Gwynne R. M. , Bornstein J. C.
Published: January 2007

Mechanisms underlying nutrient-induced segmentation within the gut are not well understood. We have shown that decanoic acid and some amino acids induce neurally dependent segmentation in guinea pig small intestine in vitro. This study examined the neural mechanisms underlying segmentation in the circular muscle and whether the timing of segmentation contractions also depends on slow waves. Decanoic acid (1 mM) was infused into the lumen of guinea pig duodenum and jejunum. Video imaging was used to monitor intestinal diameter as a function of both longitudinal position and time. Circular muscle electrical activity was recorded by using suction electrodes. Recordings from sites of segmenting contractions showed they are always associated with excitatory junction potentials leading to action potentials. Recordings from sites oral and anal to segmenting contractions revealed inhibitory junction potentials that were time locked to those contractions. Slow waves were never observed underlying segmenting contractions. In paralyzed preparations, intracellular recording revealed that slow-wave frequency was highly consistent at 19.5 (SD 1.4) cycles per minute (c/min) in duodenum and 16.6 (SD 1.1) c/min in jejunum. By contrast, the frequencies of segmenting contractions varied widely (duodenum: 3.6–28.8 c/min, median 10.8 c/min; jejunum: 3.0–27.0 c/min, median 7.8 c/min) and sometimes exceeded slow-wave frequencies for that region. Thus nutrient-induced segmentation contractions in guinea pig small intestine do not depend on slow-wave activity. Rather they result from a neural circuit producing rhythmic localized activity in excitatory motor neurons, while simultaneously activating surrounding inhibitory motor neurons.
α1-Adrenoceptor-dependent vascular hypertrophy and remodeling in murine hypoxic pulmonary hypertension
Authors: Faber James E. , Szymeczek Caroline L. , Cotecchia Susanna , Thomas Steven A. , Tanoue Akito , Tsujimoto Gozoh , Zhang Hua
Published: January 2007

Excessive proliferation of vascular wall cells underlies the development of elevated vascular resistance in hypoxic pulmonary hypertension (PH), but the responsible mechanisms remain unclear. Growth-promoting effects of catecholamines may contribute. Hypoxemia causes sympathoexcitation, and prolonged stimulation of α1-adrenoceptors (α1-ARs) induces hypertrophy and hyperplasia of arterial smooth muscle cells and adventitial fibroblasts. Catecholamine trophic actions in arteries are enhanced when other conditions favoring growth or remodeling are present, e.g., injury or altered shear stress, in isolated pulmonary arteries from rats with hypoxic PH. The present study examined the hypothesis that catecholamines contribute to pulmonary vascular remodeling in vivo in hypoxic PH. Mice genetically deficient in norepinephrine and epinephrine production [dopamine β-hydroxylase−/−(DBH−/−)] or α1-ARs were examined for alterations in PH, cardiac hypertrophy, and vascular remodeling after 21 days exposure to normobaric 0.1 inspired oxygen fraction (FiO2). A decrease in the lumen area and an increase in the wall thickness of arteries were strongly inhibited in knockout mice (order of extent of inhibition: DBH−/−= α1D-AR−/−> α1B-AR−/−). Distal muscularization of small arterioles was also reduced (DBH−/−> α1D-AR−/−> α1B-AR−/−mice). Despite these reductions, increases in right ventricular pressure and hypertrophy were not attenuated in DBH−/−and α1B-AR−/−mice. However, hematocrit increased more in these mice, possibly as a consequence of impaired cardiovascular activation that occurs during reduction of FiO2. In contrast, in α1D-AR−/−mice, where hematocrit increased the same as in wild-type mice, right ventricular pressure was reduced. These data suggest that catecholamine stimulation of α1B- and α1D-ARs contributes significantly to vascular remodeling in hypoxic PH.
p22phox in the macula densa regulates single nephron GFR during angiotensin II infusion in rats
Authors: Nouri Pouneh , Gill Pritmohinder , Li Min , Wilcox Christopher S. , Welch William J.
Published: January 2007

Angiotensin II (ANG II) infusion increases renal superoxide (O2−) and enhances renal vasoconstriction via macula densa (MD) regulation of tubuloglomerular feedback, but the mechanism is unclear. We targeted the p22 phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) with small-interfering RNA (siRNA) to reduce NADPH oxidase activity and blood pressure response to ANG II in rats. We compared single nephron glomerular filtration rate (SNGFR) in samples collected from the proximal tubule (PT), which interrupts delivery to the MD, and from the distal tubule (DT), which maintains delivery to the MD, to assess MD regulation of GFR. SNGFR was measured in control and ANG II-infused rats (200 ng·kg−1·min−1 for 7 days) 2 days after intravenous injection of vehicle or siRNA directed to p22 phox to test the hypothesis that p22 phox mediates MD regulation of SNGFR during ANG II. The regulation of SNGFR by MD, determined by PT SNGFR-DT SNGFR, was not altered by siRNA in control rats (control + vehicle, 13 ± 1, n = 8; control + siRNA, 12 ± 2 nl/min, n = 8; not significant) but was reduced by siRNA in ANG II-treated rats (ANG II + vehicle, 13 ± 2, n = 7; ANG II + siRNA, 7 ± 1 nl/min, n = 8; P < 0.05). We conclude that p22 phox and NADPH oxidase regulate the SNGFR during ANG II infusion via MD-dependent mechanisms.
Targeted gene transfer increases contractility and decreases oxygen cost of contractility in normal rat hearts
Authors: Sakata Susumu , Lebeche Djamel , Sakata Naoya , Sakata Yuri , Chemaly Elie R. , Liang Li Fan , Takewa Yoshiaki , Jeong Dongtak , Park Woo Jin , Kawase Yoshiaki , Hajjar Roger J.
Published: January 2007

The aim of this study was to examine how global cardiac gene transfer of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) can influence left ventricular (LV) mechanical and energetic function, especially in terms of O2 cost of LV contractility, in normal rats. Normal rats were randomized to receive an adenovirus carrying the SERCA2a (SERCA) or β-galactosidase (β-Gal) gene or saline by a catheter-based technique. LV mechanical and energetic function was measured in cross-circulated heart preparations 2–3 days after the infection. The end-systolic pressure-volume relation was shifted upward, end-systolic pressure at 0.1 ml of intraballoon water volume was higher, and equivalent maximal elastance, i.e., enhanced LV contractility, was higher in the SERCA group than in the normal, β-Gal, and saline groups. Moreover, the LV relaxation rate was faster in the SERCA group. There was no significant difference in myocardial O2 consumption per beat-systolic pressure-volume area relation among the groups. Finally, O2 cost of LV contractility was decreased to subnormal levels in the SERCA group but remained unchanged in the β-Gal and saline groups. This lowered O2 cost of LV contractility in SERCA hearts indicates energy saving in Ca2+ handling during excitation-contraction coupling. Thus overexpression of SERCA2a transformed the normal energy utilization to a more efficient state in Ca2+ handling and superinduced the supranormal contraction/relaxation due to enhanced Ca2+ handling.
Rho kinase activation plays a major role as a mediator of irreversible injury in reperfused myocardium
Authors: Hamid Shabaz A. , Bower Hugo S. , Baxter Gary F.
Published: January 2007

Intracellular signal transduction events in reperfusion following ischemia influence myocardial infarct development. Here we investigate the role of Rho kinase (ROCK) activation as a specific injury signal during reperfusion via attenuation of the reperfusion injury salvage kinase (RISK) pathway phosphatidylinositol 3-kinase (PI3K)/Akt/endothelial nitric oxide (NO) synthase (eNOS). Rat isolated hearts underwent 35 min of left coronary artery occlusion and 120 min of reperfusion. Phosphorylation of the ROCK substrate protein complex ezrin-radixin-moesin, assessed by immunoblotting and immunofluorescence, was used as a marker of ROCK activation. Infarct size was determined by tetrazolium staining, and terminal dUTP nick-end labeling (TUNEL) positivity was used as an index of apoptosis. The ROCK inhibitors fasudil or Y-27632 given 10 min before ischemia until 10 min after reperfusion reduced infarct size (control, 34.1 ± 3.8%; 5 μM fasudil, 18.2 ± 3.1%; 0.3 μM Y-27632, 19.4 ± 4.4%; 5 μM Y-27632, 9.2 ± 2.9%). When 5 μM Y-27632 was targeted specifically during early reperfusion, robust infarct limitation was observed (14.2 ± 2.6% vs. control 33.4 ± 4.4%, P < 0.01). The protective action of Y-27632 given at reperfusion was attenuated by wortmannin (29.2 ± 6.1%) and Nω-nitro-l-arginine methyl ester (30.4 ± 5.7%), confirming a protective mechanism involving PI3K/Akt/NO. Ezrin-radixin-moesin phosphorylation in risk zone myocardium confirmed early and sustained ROCK activation during reperfusion and its inhibition by Y-27632. Inhibition of ROCK activation at reperfusion reduced the proportion of TUNEL-positive nuclei in the infarcted region. In conclusion, ROCK activation occurs specifically during early reperfusion. Inhibition of ROCK at reperfusion onset limits infarct size through an Akt/eNOS-dependent mechanism, suggesting that ROCK activation at reperfusion may be deleterious through suppression of the RISK pathway.
Protective effect of orally administered carnosine on bleomycin-induced lung injury
Authors: Cuzzocrea Salvatore , Genovese Tiziana , Failla Marco , Vecchio Graziella , Fruciano Mary , Mazzon Emanuela , Di Paola Rosanna , Muià Carmelo , La Rosa Cristina , Crimi Nunzio , Rizzarelli Enrico , Vancheri Carlo
Published: January 2007

Carnosine is an endogenously synthesized dipeptide composed of β-alanine and l-histidine. It acts as a free radical scavenger and possesses antioxidant properties. Carnosine reduces proinflammatory and profibrotic cytokines such as transforming growth factor-β (TGF-β), IL-1, and TNF-α in different experimental settings. In the present study, we investigated the efficacy of carnosine on the animal model of bleomycin-induced lung injury. Mice were subjected to intratracheal administration of bleomycin and were assigned to receive carnosine daily by an oral bolus of 150 mg/kg. One week after fibrosis induction, bronchoalveolar lavage (BAL) cell counts and TGF-β levels, lung histology, and immunohistochemical analyses for myeloperoxidase, TGF-β, inducible nitric oxide synthase, nitrotyrosine, and poly(ADP-ribose) polymerase were performed. Finally, apoptosis was quantified by terminal deoxynucleotidyltransferase-mediated UTP end-labeling assay. After bleomycin administration, carnosine-treated mice exhibited a reduced degree of lung damage and inflammation compared with wild-type mice, as shown by the reduction of 1) body weight, 2) mortality rate, 3) lung infiltration by neutrophils (myeloperoxidase activity and BAL total and differential cell counts), 4) lung edema, 5) histological evidence of lung injury and collagen deposition, 6) lung myeloperoxidase, TGF-β, inducible nitric oxide synthase, nitrotyrosine, and poly(ADP-ribose) polymerase immunostaining, 7) BAL TGF-β levels, and 8) apoptosis. Our results indicate that orally administered carnosine is able to prevent bleomycin-induced lung injury likely through its direct antioxidant properties. Carnosine is already available for human use. It might prove useful as an add-on therapy for the treatment of fibrotic disorders of the lung where oxidative stress plays a role, such as for idiopathic pulmonary fibrosis, a disease that still represents a major challenge to medical treatment.
Human bronchial epithelial cell transcriptome: gene expression changes following acute exposure to whole cigarette smoke in vitro
Authors: Maunders Heather , Patwardhan Sudhanshu , Phillips Jeremy , Clack Aaron , Richter Audrey
Published: January 2007

Cigarette smoke is a complex mixture of more than 4,000 constituents. Its effects on cell biology are poorly understood, partly because whole smoke exposure in vitro is technically challenging. To investigate the effects of smoke on cell signaling and function, a three-dimensional air-liquid interface model of tracheobronchial epithelium, grown from primary human lung epithelial cells, was exposed to air or whole mainstream cigarette smoke for 1 h in a purpose-designed chamber. Gene expression profiles were then determined at 1, 6, and 24 h postexposure using Affymetrix HGU133-2 Plus microarrays. Cells from three different donors were used in the study, and the experiment was performed in triplicate for each donor. Genes significantly regulated by smoke, compared with the air control, in all experiments were determined. Genes exhibiting differential expression were assigned to functional categories and mapped to signaling pathways. Effects were observed on many cellular processes including xenobiotic metabolism, oxidant/antioxidant balance, and DNA damage and repair. Notably, there was marked downregulation of the transforming growth factor-β pathway, which has not been previously reported. This study provides important data on the acute effects of whole cigarette smoke on mucociliary epithelium and may be used to gain a greater understanding of smoke toxicity.
Acute alcohol intoxication increases interleukin-18-mediated neutrophil infiltration and lung inflammation following burn injury in rats
Authors: Li Xiaoling , Kovacs Elizabeth J. , Schwacha Martin G. , Chaudry Irshad H. , Choudhry Mashkoor A.
Published: January 2007

In this study, we examined whether IL-18 plays a role in lung inflammation following alcohol (EtOH) and burn injury. Male rats (∼250 g) were gavaged with EtOH to achieve a blood EtOH level of ∼100 mg/dl before burn or sham injury (∼12.5% total body surface area). Immediately after injury, rats were treated with vehicle, caspase-1 inhibitor AC-YVAD-CHO to block IL-18 production or with IL-18 neutralizing anti-IL-18 antibodies. In another group, rats were treated with anti-neutrophil antiserum ∼16 h before injury to deplete neutrophils. On day 1 after injury, lung tissue IL-18, neutrophil chemokines (CINC-1/CINC-3), ICAM-1, neutrophil infiltration, MPO activity, and water content (i.e., edema) were significantly increased in rats receiving a combined insult of EtOH and burn injury compared with rats receiving either EtOH intoxication or burn injury alone. Treatment of rats with caspase-1 inhibitor prevented the increase in lung tissue IL-18, CINC-1, CINC-3, ICAM-1, MPO activity, and edema following EtOH and burn injury. The increase in lung IL-18, MPO, and edema was also prevented in rats treated with anti-IL-18 antibodies. Furthermore, administration of anti-neutrophil antiserum also attenuated the increase in lung MPO activity and edema, but did not prevent the increase in IL-18 levels following EtOH and burn injury. These findings suggest that acute EtOH intoxication before burn injury upregulates IL-18, which in turn contributes to increased neutrophil infiltration. Furthermore, the presence of neutrophils appears to be critical for IL-18-meditaed increased lung tissue edema following a combined insult of EtOH and burn injury.
Influence of preexercise muscle glycogen content on transcriptional activity of metabolic and myogenic genes in well-trained humans
Authors: Churchley Emmanuel G. , Coffey Vernon G. , Pedersen David J. , Shield Anthony , Carey Kate A. , Cameron-Smith David , Hawley John A.
Published: January 2007

To determine whether preexercise muscle glycogen content influences the transcription of several early-response genes involved in the regulation of muscle growth, seven male strength-trained subjects performed one-legged cycling exercise to exhaustion to lower muscle glycogen levels (Low) in one leg compared with the leg with normal muscle glycogen (Norm) and then the following day completed a unilateral bout of resistance training (RT). Muscle biopsies from both legs were taken at rest, immediately after RT, and after 3 h of recovery. Resting glycogen content was higher in the control leg (Norm leg) than in the Low leg (435 ± 87 vs. 193 ± 29 mmol/kg dry wt; P < 0.01). RT decreased glycogen content in both legs ( P < 0.05), but postexercise values remained significantly higher in the Norm than the Low leg (312 ± 129 vs. 102 ± 34 mmol/kg dry wt; P < 0.01). GLUT4 (3-fold; P < 0.01) and glycogenin mRNA abundance (2.5-fold; not significant) were elevated at rest in the Norm leg, but such differences were abolished after exercise. Preexercise mRNA abundance of atrogenes was also higher in the Norm compared with the Low leg [atrogin: ∼14-fold, P < 0.01; RING (really interesting novel gene) finger: ∼3-fold, P < 0.05] but decreased for atrogin in Norm following RT ( P < 0.05). There were no differences in the mRNA abundance of myogenic regulatory factors and IGF-I in the Norm compared with the Low leg. Our results demonstrate that 1) low muscle glycogen content has variable effects on the basal transcription of select metabolic and myogenic genes at rest, and 2) any differences in basal transcription are completely abolished after a single bout of heavy resistance training. We conclude that commencing resistance exercise with low muscle glycogen does not enhance the activity of genes implicated in promoting hypertrophy.
Estradiol replacement reverses ovariectomy-induced muscle contractile and myosin dysfunction in mature female mice
Authors: Moran Amy L. , Nelson Steven A. , Landisch Rachel M. , Warren Gordon L. , Lowe Dawn A.
Published: January 2007

Skeletal muscle contractility and myosin function decline following ovariectomy in mature female mice. In the present study we tested the hypothesis that estradiol replacement can reverse those declines. Four-month-old female C57BL/6 mice ( n = 69) were ovariectomized (OVX) or sham operated. Some mice were treated immediately with placebo or 17β-estradiol (OVX + E2) while other mice were treated 30 days postsurgery. Thirty or sixty days postsurgery, soleus muscles were assessed in vitro for contractile function and susceptibility to eccentric contraction-induced injury. Myosin structural dynamics was analyzed in extensor digitorum longus (EDL) muscles by electron paramagnetic resonance spectroscopy. Maximal isometric tetanic force was affected by estradiol status ( P < 0.001) being ∼10% less in soleus muscles from OVX compared with sham-operated mice [168 mN (SD 16.7) vs. 180 mN (SD 14.4)] and was restored in OVX + E2mice [187 mN (SD 17.6)]. The fraction of strong-binding myosin during contraction was also affected ( P = 0.045) and was ∼15% lower in EDL muscles from OVX compared with OVX + E2mice [0.263 (SD 0.034) vs. 0.311 (SD 0.022)]. Plasma estradiol levels were correlated with maximal isometric tetanic force ( r = 0.458; P < 0.001) and active stiffness ( r = 0.329; P = 0.044), indicating that circulating estradiol influenced muscle and myosin function. Estradiol was not effective in protecting muscle against an acute eccentric contraction-induced injury ( P ≥ 0.401) but did restore ovariectomy-induced increases in muscle wet mass caused by fluid accumulation. Collectively, estradiol had a beneficial effect on female mouse skeletal muscle.