bluuebunny/crossref_metadata_2025 huggingface dataset:
Practical experience of using directly observed procedures, mini clinical evaluation examinations, and peer observation in pre-registration house officer (FY1) trainees
Authors: Morris A , Hewitt J , Roberts C M
Published: April 2006

This paper describes an eight month experience with three of the four main assessment tools that will be used to validate the successful completion of the FY1 placement. The practical issues around the implementation of these new tools is of great concern to all involved in the management of postgraduate training and it is hoped that this paper will contribute some of the practical elements so far unavailable from Department of Health sources.
Assessment of internet use and effects among healthcare professionals: a cross sectional survey
Authors: Podichetty V K , Booher J , Whitfield M , Biscup R S
Published: April 2006

Purpose

Several studies have explored the scientific platforms on patient use of the internet for health information. In contrast physicians' perspective on evolving internet environment is lacking. The purpose of this study is to assess and correlate the extent of internet use among healthcare professionals and examine its effects on clinical practice.

Methods

Cross sectional survey conducted in the USA using questionnaires distributed randomly to healthcare professionals attending distinct continuing medical education programmes between 2003 and 2004. Multiple choice and yes/no questions related to the trends of internet use and its effects on clinical practice were extracted and responses analysed. The main outcome measures are self reported rates of internet use, perceived effects, and the role of medical web sites in clinical practice.

Results

The overall response rate was 60%. A total of 277 survey respondents (97%) had internet access. Some 7% in private practice and 1% of group practice physicians did not have internet access. Most (71%) used the internet regularly for medical or professional updating and 62% (n = 178) felt the need for sharing web sites designed for healthcare professionals with patients. Some 27% of the physicians currently own established personal practice web sites. Sixty three per cent have recommended a web site to a patient for more information, matching the positive trust (>70%) on the general quality of selected medical web sites.

Conclusion

This cross sectional survey shows that internet use and web based medical information is widely popular among physicians and patients. About 23%–31% of the healthcare professionals report >80% interaction with web informed patients in their daily practice.
Prevalence of obesity in type 2 diabetes in secondary care: association with cardiovascular risk factors
Authors: Daousi C , Casson I F , Gill G V , MacFarlane I A , Wilding J P H , Pinkney J H
Published: April 2006

Aims

To determine the prevalence of overweight and obesity among patients with type 1 and type 2 diabetes mellitus attending a secondary care diabetes clinic in the United Kingdom, and to assess the impact of overweight and obesity on glycaemic control and cardiovascular risk factors in patients with type 2 diabetes.

Methods

3637 patients with diabetes were identified from the hospital electronic diabetes register, 916 with type 1 diabetes (mean (SD) age 40.4 (15.1) years, 496 male) and 2721 with type 2 diabetes (mean (SD) age 62.5 (11.8) years, 1436 male). Data on body mass index (BMI), glycaemic control, lipid profiles, and blood pressure were extracted.

Results

Of patients with type 1 diabetes, 55.3% were overweight (BMI ⩾25 kg/m2), 16.6% were obese (BMI ⩾30 kg/m2), and 0.4% had morbid obesity (BMI ⩾40 kg/m2). In contrast, 86% of patients with type 2 diabetes were overweight or obese, 52% were obese, and 8.1% had morbid obesity. Obese patients with type 2 diabetes were younger, had poorer glycaemic control, higher blood pressures, worse lipid profiles, and were more likely to be receiving antihypertensive and lipid lowering drugs compared with patients with BMI <30 kg/m2.

Conclusions

Obesity is the rule among patients attending this hospital diabetes clinic, with 86% of those with type 2 diabetes overweight or obese. Obesity is associated with significantly worse cardiovascular risk factors in this patient group, suggesting that more active interventions to control weight gain would be appropriate.
A NEW APPROACH TO THE ANALYSIS OF A NONCOMMUTATIVE CHERN–SIMONS THEORY
Authors: MUKHERJEE PRADIP , SAHA ANIRBAN
Published: April 2006

A novel approach to the analysis of a noncommutative Chern–Simons gauge theory with matter coupled in the adjoint representation has been discussed. The analysis is based on a recently proposed closed form Seiberg–Witten map which is exact in the noncommutative parameter.
THE BEHAVIOR OF THE SEXTIC COUPLING FOR THE SCALAR FIELD AT THE INTERMEDIATE AND STRONG COUPLING REGIME
Authors: AÑAÑOS GINO J.
Published: April 2006

We study the behavior of the renormalized sextic coupling at the intermediate and strong coupling regime for the φ4 theory defined in d = 2 dimensions. We found a good agreement with the results obtained by the field-theoretical renormalization-group in the Ising limit. In this work we use the lattice regularization method.
Sandstone-hosted concretions record evidence for syn-lithification seismicity, cavitation processes, and Palaeocene rapid burial of Lower Cretaceous deep-marine sandstones (Outer Moray Firth, UK North Sea)
Authors: Hendry James P. , Poulsom Andrew J.
Published: April 2006

Syn- and post-lithification cemented fractures are abundant in concretions formed during shallow burial of Hauterivian turbidites in the Outer Moray Firth. Early fractures are irregular, bifurcating, and contain entrained sand grains. They are confined to the concretion bodies, but commonly splay into narrower fracture swarms at the margins. Multiple, cross-cutting fills of calcite microspar have similar isotopic composition to adjacent concretionary cements, suggesting that rupture and cementation cycles occurred as host concretions lithified. Expulsion of cementing pore fluids from the fractures produced cement protrusions at concretion margins. A hydraulic fracture mechanism resulting from localized permeability heterogeneity and episodic seismic activity is proposed. Rapid seismic loading created high pore fluid pressures for fracture dilation in lithifying concretions and, through cavitation and CO
2
degassing, a trigger for rapid homogeneous nucleation of calcite. Many of the early structures were subsequently reactivated as brittle tensile fractures, and host a variety of mesogenetic cements. Reactivation probably occurred in response to stress amplification during rapid Palaeocene burial. By this time lithification of the concretions had dramatically changed their rheology and failure style. Minor permeability remained in the concretion cements adjacent to reactivated fractures, permitting invasion of intercrystalline voids by late diagenetic fluids.
Sequence stratigraphy and architectural variability in growth fault-bounded basin fills: a review of Plio-Pleistocene stratal units of the Crotone Basin, southern Italy
Authors: Zecchin Massimo , Mellere Donatella , Roda Cesare
Published: April 2006

Field examples from the Pliocene to Pleistocene succession of the Crotone Basin document the variability of stratal architecture in syntectonic units deposited in normal fault-bounded basins. Relatively thick trangressive intervals are common within these successions, as shown in the Zinga 2, Zinga 3 and Strongoli stratal units. Transgressive packages are formed by lagoonal mudstones that are abruptly overlain by shoreface sandstones. Aggradational highstand shallow-marine packages are typical of the lower Pliocene succession in half-graben basins. These deposits resulted from balanced conditions between the rate of sediment supply and the rate of creation of accommodation. Relatively thick forced regressive deposits are common within basins during phases where the accommodation–supply ratio is low (e.g. the middle Pleistocene San Mauro Sandstone). These deposits, influenced by growth faulting and folding, recorded base-level lowering linked to glacio-eustasy. A complex stratal architecture may be the consequence of the alternation between tectonic subsidence and uplift (e.g. the Serra Piani stratal unit). Such variations are thought to be related to the onset of an earliest mid-Pliocene transpressional tectonic phase. The studied deposits, therefore, show a marked tectonic control that strongly influenced their stratal architecture. These examples represent interesting cases of sequence-stratigraphic analysis in growth-faulted contexts.
Chaotic breccia along the Dent Fault, NW England: implosion or collapse of a fault void?
Authors: Woodcock N.H. , Omma J.E. , Dickson J.A.D.
Published: April 2006

A body of chaotic breccia along the reverse-oblique Dent Fault zone is ascribed to hanging-wall collapse into persistent voids created by geometric mismatch of fault walls, although some implosion into transient voids is a possibility. The breccia comprises a 20 m wide body of hanging-wall lithologies, with a chaotic clast-supported fabric that contrasts with the fitted-fabric breccias typical of the Dent Fault damage zone. The breccia body has crude bedding defined by clast shape and size contrasts. The void fill is cut by Variscan fault strands, which, together with its ferroan calcite and barite cement, prove its late Carboniferous rather than recent age. It is shown that any fault void, transient or persistent, had a smaller aperture than the final width of the breccia body, and no more than 5 m; a span that can be supported to depths of 2 or 3 km. However, cement zonation in the breccia fill suggests that the void opened in multiple increments, each of an aperture compatible with the maximum displacement in any one event along the Dent Fault. The Dent Fault example highlights the possible general importance of fault-void collapse but also the problems in distinguishing it from implosion processes.
Timing and kinematics of Eburnean tectonics in the central Reguibat Shield, Mauritania
Authors: Schofield D.I. , Horstwood M.S.A. , Pitfield P.E.J. , Crowley Q.G. , Wilkinson A.F. , Sidaty H.Ch.O.
Published: April 2006

The Reguibat Shield of north Mauritania comprises a western Archaean terrane dominated by gneisses and granitic rocks and an eastern Eburnean terrane largely made up of Palaeoproterozoic granitic and metasedimentary rocks. These were juxtaposed during the
c
. 2.1–2.0 Ga Eburnean Orogeny, which formed an approximately north-trending front contiguous with the Eburnean belt of the Leo Shield in equatorial West Africa. Geological surveying in the Sfariat region of the Reguibat Shield has shown that a metamorphosed Palaeoproterozoic continental margin succession has been intruded by and intercalated with synorogenic granitoids and transported SW onto the Archaean foreland during sinistral oblique collision preserved as strongly partitioned D
1
shortening and D
2
strike-slip-dominated transpression within the Sfariat Belt. This was subsequently affected by retrogressive dextral transcurrent deformation and the propagation of the en echelon Imarkene and Tmeimichat fault zones. Laser ablation and conventional thermal ionization mass spectrometry U–Pb geochronology were carried out on five samples of granitic rock and migmatitic gneiss from the region, which reveal that anatexis and sinistral transpression took place between
c
. 2117 and 2064 Ma. Timing and kinematics of the Eburnean event in the Reguibat Shield are similar to those for the Leo Shield, which underwent SW-directed sinistral transpression at this time.
Timing of deformation within Old Red Sandstone lithologies from the Dingle Peninsula, SW Ireland
Authors: Meere Patrick A. , Mulchrone Kieran F.
Published: April 2006

Finite strain analysis of deformed clastic sedimentary rocks below and above the Acadian unconformity on the Dingle Peninsula, SW Ireland, reveals that this boundary represents a significant bulk strain discontinuity. The Late Emsian Acadian event is primarily responsible for penetrative cleavage development and high strain in rocks below the unconformity and not, as previously held, the later Variscan event, which overprinted the peninsula with a weak and localized disjunctive cleavage. The presence of apparent anticlockwise transecting cleavage and implied dextral closure of the Dingle Basin during the Acadian event is compatible with northward convergence of Armorica with respect to Eastern Avalonia.
Subglacial bedrock welding associated with glacial earthquakes
Authors: Bestmann M. , Rice A.H.N. , Langenhorst F. , Grasemann B. , Heidelbach F.
Published: April 2006

A <3 mm thick, intensely brecciated layer associated with Marinoan (

c

. 635 Ma) glacial striations on a Neoproterozoic sandstone pavement is documented. Only instantaneous solidification could have preserved the breccia

in situ

. Glacier speeds of

c

. 0.3 m s
−1
would have induced peak flash temperatures sufficient (>1130 °C) to cause partial frictional welding of the deformed quartzitic bedrock beneath an ice-loaded clast. These results support suggestions that glacial seismicity is due to episodic very rapid shifts of large ice masses over the substrate (stick–slip movement). They also indicate that significant effective normal stresses occur at the base of glaciers.
Potential of fibroblasts to regulate the formation of three-dimensional vessel-like structures from endothelial cells in vitro
Authors: Kunz-Schughart Leoni A. , Schroeder Josef A. , Wondrak Marit , van Rey Frank , Lehle Karla , Hofstaedter Ferdinand , Wheatley Denys N.
Published: April 2006

The development of vessel-like structures in vitro to mimic as well as to realize the possibility of tissue-engineered small vascular networks presents a major challenge to cell biologists and biotechnologists. We aimed to establish a three-dimensional (3-D) culture system with an endothelial network that does not require artificial substrates or ECM compounds. By using human skin fibroblasts and endothelial cells (ECs) from the human umbilical vein (HUVECs) in diverse spheroid coculture strategies, we verified that fibroblast support and modulate EC migration, viability, and network formation in a 3-D tissue-like stromal environment. In mixed spheroid cultures consisting of human ECs and fibroblasts, a complex 3-D network with EC tubular structures, lumen formation, pinocytotic activity, and tight junction complexes has been identified on the basis of immunohistochemical and transmission electron microscopic imaging. Tubular networks with extensions up to 400 μm were achieved. When EC suspensions were used, EC migration and network formation were critically affected by the status of the fibroblast. However, the absence of EC migration into the center of 14-day, but not 3-day, precultured fibroblast spheroids could not be attributed to loss of F viability. In parallel, it was also confirmed that migrated ECs that entered cluster-like formations became apoptotic, whereas the majority of those forming vessel-like structures remained viable for >8 days. Our protocols allow us to study the nature of tubule formation in a manner more closely related to the in vivo situation as well as to understand the basis for the integration of capillary networks in tissue grafts and develop methods of quantifying the amount of angiogenesis in spheroids using fibroblast and other cells isolated from the same patient, along with ECs.
Polyunsaturated fatty acids mobilize intracellular Ca2+ in NT2 human teratocarcinoma cells by causing release of Ca2+ from mitochondria
Authors: Zhang Bin-Xian , Ma Xiuye , Zhang Wanke , Yeh Chih-Ko , Lin Alan , Luo Jian , Sprague Eugene A. , Swerdlow Russell H. , Katz Michael S.
Published: April 2006

In a variety of disorders, overaccumulation of lipid in nonadipose tissues, including the heart, skeletal muscle, kidney, and liver, is associated with deterioration of normal organ function, and is accompanied by excessive plasma and cellular levels of free fatty acids (FA). Increased concentrations of FA may lead to defects in mitochondrial function found in diverse diseases. One of the most important regulators of mitochondrial function is mitochondrial Ca2+ ([Ca2+]m), which fluctuates in coordination with intracellular Ca2+ ([Ca2+]i). Polyunsaturated FA (PUFA) have been shown to cause [Ca2+]i mobilization albeit by unknown mechanisms. We have found that PUFA but not monounsaturated or saturated FA cause [Ca2+]i mobilization in NT2 human teratocarcinoma cells. Unlike the [Ca2+]i response to the muscarinic G protein-coupled receptor agonist carbachol, PUFA-mediated [Ca2+]i mobilization in NT2 cells is independent of phospholipase C and inositol-1,4,5-trisphospate (IP3) receptor activation, as well as IP3-sensitive internal Ca2+ stores. Furthermore, PUFA-mediated [Ca2+]i mobilization is inhibited by the mitochondria uncoupler carboxyl cyanide m-chlorophenylhydrozone. Direct measurements of [Ca2+]m with X-rhod-1 and 45Ca2+ indicate that PUFA induce Ca2+ efflux from mitochondria. Further studies show that ruthenium red, an inhibitor of the mitochondrial Ca2+ uniporter, blocks PUFA-induced Ca2+ efflux from mitochondria, whereas inhibitors of the mitochondrial permeability transition pore cyclosporin A and bongkrekic acid have no effect. Thus PUFA-gated Ca2+ release from mitochondria, possibly via the Ca2+ uniporter, appears to be the underlying mechanism for PUFA-induced [Ca2+]i mobilization in NT2 cells.
Involvement of JAK2 and Src kinase tyrosine phosphorylation in human growth hormone-stimulated increases in cytosolic free Ca2+ and insulin secretion
Authors: Zhang Fan , Zhang Qimin , Tengholm Anders , Sjöholm Åke
Published: April 2006

We previously reported that human growth hormone (hGH) increases cytoplasmic Ca2+ concentration ([Ca2+]i) and proliferation in pancreatic β-cells (Sjöholm Å, Zhang Q, Welsh N, Hansson A, Larsson O, Tally M, and Berggren PO. J Biol Chem 275: 21033–21040, 2000) and that the hGH-induced rise in [Ca2+]i involves Ca2+-induced Ca2+ release facilitated by tyrosine phosphorylation of ryanodine receptors (Zhang Q, Kohler M, Yang SN, Zhang F, Larsson O, and Berggren PO. Mol Endocrinol 18: 1658–1669, 2004). Here we investigated the tyrosine kinases that convey the hGH-induced rise in [Ca2+]i and insulin release in BRIN-BD11 β-cells. hGH caused tyrosine phosphorylation of Janus kinase (JAK)2 and c-Src, events inhibited by the JAK2 inhibitor AG490 or the Src kinase inhibitor PP2. Although hGH-stimulated rises in [Ca2+]i and insulin secretion were completely abolished by AG490 and JAK2 inhibitor II, the inhibitors had no effect on insulin secretion stimulated by a high K+ concentration. Similarly, Src kinase inhibitor-1 and PP2, but not its inactive analog PP3, suppressed [Ca2+]i elevation and completely abolished insulin secretion stimulated by hGH but did not affect responses to K+. Ovine prolactin increased [Ca2+]i and insulin secretion to a similar extent as hGH, effects prevented by the JAK2 and Src kinase inhibitors. In contrast, bovine GH evoked a rise in [Ca2+]i but did not stimulate insulin secretion. Neither JAK2 nor Src kinase inhibitors influenced the effect of bovine GH on [Ca2+]i. Our study indicates that hGH stimulates rise in [Ca2+]i and insulin secretion mainly through activation of the prolactin receptor and JAK2 and Src kinases in rat insulin-secreting cells.
Caspase-dependent and -independent pathways for cadmium-induced apoptosis in cultured kidney proximal tubule cells
Authors: Lee Wing-Kee , Abouhamed Marouan , Thévenod Frank
Published: April 2006

The nephrotoxic metal cadmium at micromolar concentrations induces apoptosis of rat kidney proximal tubule (PT) cells within 3–6 h of exposure. The underlying cell death pathways remain poorly defined. Using Hoechst 33342/ethidium bromide nuclear staining and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cell death assays, 10–50 μM cadmium induced apoptosis of immortalized rat kidney cells derived from the S1-segment of PT at 6 and 24 h, but necrosis at 24 h only. Cadmium (10–50 μM) also caused mitochondrial cytochrome c (cyt. c)- and apoptosis-inducing factor release at 24 h, but not at 6 h, as measured by immunofluorescence imaging and immunoblotting. Caspases-9 and -3 were activated only by 10 μM cadmium for 24 h, and accordingly apoptosis was significantly reduced by the respective inhibitors (z-LEHD-fmk, z-DEVD-fmk; 10 μg/ml) at 24 h, but not at 6 h, without affecting necrosis. At 6 h, 10 μM cadmium increased the activity of the calcium-activated protease calpain, but not at 24 h, and calpain inhibitors (ALLN, PD 150606; 10–30 μM) blocked apoptosis by 10 μM cadmium at 3–6 h. However, PD-150606 also attenuated caspase-3 activity and apoptosis at 24 h, suggesting calpain-dependent caspase activation. Thus cadmium-induced apoptosis of PT cells involves a complex and sensitive interplay of signaling cascades involving mitochondrial proapoptotic factors, calpains and caspases, whose activation is also determined by cadmium concentration and the duration of cadmium exposure.
Ouabain modulation of endothelial calcium signaling in descending vasa recta
Authors: Pittner János , Rhinehart Kristie , Pallone Thomas L.
Published: April 2006

Using fura 2-loaded vessels, we tested whether ouabain modulates endothelial cytoplasmic calcium concentration ([Ca2+]CYT) in rat descending vasa recta (DVR). Over a broad range between 10−10and 10−4M, ouabain elicited biphasic peak and plateau [Ca2+]CYTelevations. Blockade of voltage-gated Ca2+entry with nifedipine did not affect the response to ouabain mitigating against a role for myo-endothelial gap junctions. Reduction of extracellular Na+concentration ([Na+]o) or Na+/Ca2+exchanger (NCX) inhibition with SEA-0400 (10−6M) elevated [Ca2+]CYT, supporting a role for NCX in the setting of basal [Ca2+]CYT. SEA-0400 abolished the [Ca2+]CYTresponse to ouabain implicating NCX as a mediator. The transient peak phase of [Ca2+]CYTelevation that followed either ouabain or reduction of [Na+]owas abolished by 2-aminoethoxydiphenyl borate (5 × 10−5M). Cation channel blockade with La3+(10 μM) or SKF-96365 (10 μM) also attenuated the ouabain-induced [Ca2+]CYTresponse. Ouabain pretreatment increased the [Ca2+]CYTelevation elicited by bradykinin (10−7M). We conclude that inhibition of ouabain-sensitive Na+-K+-ATPase enhances DVR endothelial Ca2+store loading and modulates [Ca2+]CYTsignaling through mechanisms that involve NCX, Ca2+release, and cation channel activation.
PTH(1–84)/PTH(7–84): a balance of power
Authors: Friedman Peter A. , Goodman William G.
Published: April 2006

This review considers many new basic and clinical aspects of parathyroid hormone (PTH). We focus especially on the identification of PTH fragments and how they may relate to renal failure, diagnosis, and treatment of secondary hyperparathyroidism and renal osteodystrophy. The biosynthesis and metabolism of PTH, measurement of circulating forms of PTH, the effects of PTH on receptor activation and turnover, the relationship between PTH levels and bone turnover in renal failure in humans, and the involvement of PTH in experimental models of renal failure are discussed. Despite these developments in understanding the etiology of renal failure and the availability of new assays for bioactive PTH, no adequate surrogate for bone biopsy and quantitative bone histomorphometry has been developed.
Effect of sodium delivery on superoxide and nitric oxide in the medullary thick ascending limb
Authors: Abe Michiaki , O'Connor Paul , Kaldunski Mary , Liang Mingyu , Roman Richard J. , Cowley Allen W.
Published: April 2006

Hypertension is associated with increased levels of oxidative stress and medullary renal injury. Previous studies have shown that elevations in renal perfusion pressure increase Na+ delivery to the medullary thick ascending limb (mTAL), and enhancement of NaCl transport in the outer medulla has been reported in many experimental forms of hypertension. This study examined the effects of increased Na+ and fluid delivery in mTAL perfused in vitro on the generation of superoxide. Osmolality was maintained constant between low- and high-Na+ perfusates by adjusting with choline Cl−. Real-time fluorescent microscopic techniques were used to determine the generation of superoxide and nitric oxide in individual mTAL cells using dihydroethidium and DAF-FM dyes, respectively. Increasing the Na+ concentration of the perfusate from 60 to 149 mM or luminal flow rate from 5 to 20 nl/min (with fixed Na+ concentration of 60 mM) significantly increased superoxide generation and decreased nitric oxide in mTAL. These effects were inhibited when active transport of Na+ was inhibited by ouabain. We conclude that increases in luminal Na+ concentration and/or flow rate can increase the generation of superoxide in mTAL and reduce nitric oxide bioavailability. This may lead to reduction in medullary blood flow and promote hypoxia and tubular necrosis within the renal medulla during in hypertension.
Aldosterone infusion with high-NaCl diet increases blood pressure in obese but not lean Zucker rats
Authors: Riazi S. , Khan Osman , Hu Xinqun , Ecelbarger Carolyn A.
Published: April 2006

Insulin-resistant, obese Zucker rats have blunted pressure natriuresis and are mildly hypertensive. This may involve inappropriate regulation of the renin-angiotensin-aldosterone system. To evaluate mechanisms underlying this defect, we employed the model of aldosterone escape. Male lean (L) and obese (O) Zucker rats were infused with aldosterone (2.8 μg/g body wt3/4) via osmotic minipump while being fed a 0.02% NaCl diet (LS). After 4 days, six rats of each type were switched to a high-NaCl (HS) diet (4%) for 4 additional days. Mean arterial blood pressure measured by radiotelemetry was significantly increased by the HS diet only in obese rats (final mean mmHg): 104 (LLS), 99 (LHS), 103 (OLS), and 115 (OHS). Obese rats had relatively increased renal cortical abundance of the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) and whole kidney α- and β-ENaC (epithelial sodium channel) relative to lean rats. However, band density for the thiazide-sensitive (Na-Cl) cotransporter (NCC) was similarly reduced by HS in lean and obese rats (∼50%). Obese rats had relatively reduced creatinine clearances and plasma renin activities, effects exacerbated by HS. Furthermore, HS resulted in a 129% increase in urinary nitrates plus nitrites excretion in lean rats and led to, in contrast, a 46% reduction in obese rats. Plasma sodium and potassium concentrations were increased by HS in obese but not lean rats. Thus we demonstrate an impaired response to aldosterone infusion in obese relative to lean Zucker rats. This impairment may involve increased sodium reabsorption via NKCC2 or ENaC, decreased glomerular filtration rate, and/or nitric oxide bioavailability.
Effect of flywheel-based resistance exercise on processes contributing to muscle atrophy during unloading in adult rats
Authors: Dupont-Versteegden Esther E. , Fluckey James D. , Knox Micheal , Gaddy Dana , Peterson Charlotte A.
Published: April 2006

Flywheel-based resistance exercise (RE) attenuates muscle atrophy during hindlimb suspension. We have previously shown that protein synthesis is elevated in response to RE, but the effect on protein degradation, cell proliferation, or apoptosis was not investigated. We hypothesized that, in addition to affecting protein synthesis, RE inhibits processes that actively contribute to muscle atrophy during hindlimb suspension. Male rats were housed in regular cages (control), tail suspended for 2 wk (HS), or HS with RE every other day for 2 wk (HSRE). Although RE attenuated soleus muscle atrophy during HS, the observed fivefold elevation in apoptosis and the 53% decrease in cell proliferation observed with HS were unaffected by RE. Expression of genes encoding components of the ubiquitin-proteasome pathway of protein degradation were elevated with HS, including ubiquitin, MAFbx, Murf-1, Nedd4, and XIAP, and proteasome subunits C2 and C9. Total ubiquitinated protein was increased with HS, but proteasome activity was not different from control. RE selectively altered the expression of different components of this pathway: MAFbx, Murf-1, and ubiquitin mRNA abundance were downregulated, whereas C2 and C9 subunits remained elevated. Similarly, Nedd4 and XIAP continued to be upregulated, potentially accounting for the observed augmentation in total ubiquitinated protein with RE. Thus a different constellation of proteins is likely ubiquitinated with RE due to altered ubiquitin ligase composition. In summary, the flywheel-based resistance exercise paradigm used in this study is associated with the inhibition of some mechanisms associated with muscle atrophy, such as the increase in MAFbx and Murf-1, but not with others, such as proteasome subunit remodeling, apoptosis, and decreased proliferation, potentially accounting for the inability to completely restore muscle mass. Identifying specific exercise parameters that affect these latter processes may be useful in designing effective exercise strategies in the elderly or during spaceflight.
Myogenic gene expression at rest and after a bout of resistance exercise in young (18–30 yr) and old (80–89 yr) women
Authors: Raue Ulrika , Slivka Dustin , Jemiolo Bozena , Hollon Chris , Trappe Scott
Published: April 2006

The purpose of this study was to investigate mRNA expression of several key skeletal muscle myogenic controllers; myogenic differentiation factor (MyoD), muscle regulatory factor 4 (MRF4), myogenic factor 5 (Myf5), myogenin, myostatin, and myocyte enhancer factor 2 (MEF2) at rest and 4 h after a single bout of resistance exercise (RE) in young and old women. Eight young women (YW; 23 ± 2 yr, 67 ± 5 kg) and six old women (OW; 85 ± 1 yr, 67 ± 4 kg) performed 3 sets of 10 repetitions of bilateral knee extensions at 70% of one repetition maximum. Muscle biopsies were taken from the vastus lateralis before and 4 h after RE. Using real-time RT PCR, mRNA from the muscle samples was amplified and normalized to GAPDH. At rest, OW expressed higher ( P < 0.05) levels of MyoD, MRF4, Myf5, myogenin, and myostatin compared with YW. In response to RE, there was a main time effect ( P < 0.05) for the YW and OW combined in the upregulation of MyoD (2.0-fold) and MRF4 (1.4-fold) and in the downregulation of myostatin (2.2-fold). There was a trend ( P = 0.08) for time × age interaction in MRF4. These data show that old women express higher myogenic mRNA levels at rest. The higher resting myogenic mRNA levels in old women may reflect an attempt to preserve muscle mass and function. When challenged with RE, old women appear to respond in a similar manner as young women.
Emergence of Hearing in the Chicken Embryo
Authors: Jones Timothy A. , Jones Sherri M. , Paggett Kristina C.
Published: April 2006

It is commonly held that hearing generally begins on incubation day 12 (E12) in the chicken embryo ( Gallus domesticus). However, little is known about the response properties of cochlear ganglion neurons for ages younger than E18. We studied ganglion neurons innervating the basilar papilla of embryos (E12–E18) and hatchlings (P13–P15). We asked first, when do primary afferent neurons begin to encode sounds? Second, when do afferents evidence frequency selectivity? Third, what range of characteristic frequencies (CFs) is represented in the late embryo? Finally, how does sound transfer from air to the cochlea affect responses in the embryo and hatchling? Responses to airborne sound were compared with responses to direct columella footplate stimulation of the cochlea. Cochlear ganglion neurons exhibited a profound insensitivity to sound from E12 to E16 (stages 39–42). Responses to sound and frequency selectivity emerged at about E15. Frequency selectivity matured rapidly from E16 to E18 (stages 42 and 44) to reflect a mature range of CFs (170–4,478 Hz) and response sensitivity to footplate stimulation. Limited high-frequency sound transfer from air to the cochlea restricted the response to airborne sound in the late embryo. Two periods of ontogeny are proposed. First is a prehearing period (roughly E12–E16) of endogenous cochlear signaling that provides neurotrophic support and guides normal developmental refinements in central binaural processing pathways followed by a period (roughly E16–E19) wherein the cochlea begins to detect and encode sound.
Sensorimotor Cortex Ablation Prevents H-Reflex Up-Conditioning and Causes a Paradoxical Response to Down-Conditioning in Rats
Authors: Chen Xiang Yang , Carp Jonathan S. , Chen Lu , Wolpaw Jonathan R.
Published: April 2006

Operant conditioning of the H-reflex, a simple model for skill acquisition, requires the corticospinal tract (CST) and does not require other major descending pathways. To further explore its mechanisms, we assessed the effects of ablating contralateral sensorimotor cortex (cSMC). In 22 Sprague–Dawley rats, the hindlimb area of left cSMC was ablated. EMG electrodes were implanted in the right soleus muscle and a stimulating cuff was placed around the right posterior tibial nerve. When EMG remained in a specified range, nerve stimulation just above the M response threshold elicited the H-reflex. In control mode, no reward occurred. In conditioning mode, reward occurred if H-reflex size was above (HRup mode) or below (HRdown mode) a criterion value. After exposure to the control mode for ≥10 days, each rat was exposed for another 50 days to the control mode, the HRup mode, or the HRdown mode. In control and HRup rats, final H-reflex size was not significantly different from initial H-reflex size. In contrast, in HRdown rats, final H-reflex size was significantly increased to an average of 136% of initial size. Thus like recent CST transection, cSMC ablation greatly impaired up-conditioning. However, unlike recent CST transection, cSMC produced a paradoxical response to down-conditioning: the H-reflex actually increased. These results confirm the critical role of cSMC in H-reflex conditioning and suggest that this role extends beyond producing essential CST activity. Its interactions with ipsilateral SMC or other areas contribute to the complex pattern of spinal and supraspinal plasticity that underlies H-reflex conditioning.
Oscillatory and Intrinsic Membrane Properties of Guinea Pig Nucleus Prepositus Hypoglossi Neurons In Vitro
Authors: Idoux Erwin , Serafin Mauro , Fort Patrice , Vidal Pierre-Paul , Beraneck Mathieu , Vibert Nicolas , Mühlethaler Michel , Moore L. E.
Published: April 2006

Numerous models of the oculomotor neuronal integrator located in the prepositus hypoglossi nucleus (PHN) involve both highly tuned recurrent networks and intrinsic neuronal properties; however, there is little experimental evidence for the relative role of these two mechanisms. The experiments reported here show that all PHN neurons (PHNn) show marked phasic behavior, which is highly oscillatory in ∼25% of the population. The behavior of this subset of PHNn, referred to as type D PHNn, is clearly different from that of the medial vestibular nucleus neurons, which transmit the bulk of head velocity-related sensory vestibular inputs without integrating them. We have investigated the firing and biophysical properties of PHNn and developed data-based realistic neuronal models to quantitatively illustrate that their active conductances can produce the oscillatory behavior. Although some individual type D PHNn are able to show some features of mathematical integration, the lack of robustness of this behavior strongly suggests that additional network interactions, likely involving all types of PHNn, are essential for the neuronal integrator. Furthermore, the relationship between the impulse activity and membrane potential of type D PHNn is highly nonlinear and frequency-dependent, even for relatively small-amplitude responses. These results suggest that some of the synaptic input to type D PHNn is likely to evoke oscillatory responses that will be nonlinearly amplified as the spike discharge rate increases. It would appear that the PHNn have specific intrinsic properties that, in conjunction with network interconnections, enhance the persistent neural activity needed for their function.
Thermogenic Mechanisms and Their Hormonal Regulation
Authors: Silva J. Enrique
Published: April 2006

Increased heat generation from biological processes is inherent to homeothermy. Homeothermic species produce more heat from sustaining a more active metabolism as well as from reducing fuel efficiency. This article reviews the mechanisms used by homeothermic species to generate more heat and their regulation largely by thyroid hormone (TH) and the sympathetic nervous system (SNS). Thermogenic mechanisms antecede homeothermy, but in homeothermic species they are activated and regulated. Some of these mechanisms increase ATP utilization (same amount of heat per ATP), whereas others increase the heat resulting from aerobic ATP synthesis (more heat per ATP). Among the former, ATP utilization in the maintenance of ionic gradient through membranes seems quantitatively more important, particularly in birds. Regulated reduction of the proton-motive force to produce heat, originally believed specific to brown adipose tissue, is indeed an ancient thermogenic mechanism. A regulated proton leak has been described in the mitochondria of several tissues, but its precise mechanism remains undefined. This leak is more active in homeothermic species and is regulated by TH, explaining a significant fraction of its thermogenic effect. Homeothermic species generate additional heat, in a facultative manner, when obligatory thermogenesis and heat-saving mechanisms become limiting. Facultative thermogenesis is activated by the SNS but is modulated by TH. The type II iodothyronine deiodinase plays a critical role in modulating the amount of the active TH, T3, in BAT, thereby modulating the responses to SNS. Other hormones affect thermogenesis in an indirect or permissive manner, providing fuel and modulating thermogenesis depending on food availability, but they do not seem to have a primary role in temperature homeostasis. Thermogenesis has a very high energy cost. Cold adaptation and food availability may have been conflicting selection pressures accounting for the variability of thermogenesis in humans.
Hypertension, Kidney, and Transgenics: A Fresh Perspective
Authors: Mullins Linda J. , Bailey Matthew A. , Mullins John J.
Published: April 2006

In this review, we outline the application and contribution of transgenic technology to establishing the genetic basis of blood pressure regulation and its dysfunction. Apart from a small number of examples where high blood pressure is the result of single gene mutation, essential hypertension is the sum of interactions between multiple environmental and genetic factors. Candidate genes can be identified by a variety of means including linkage analysis, quantitative trait locus analysis, association studies, and genome-wide scans. To test the validity of candidate genes, it is valuable to model hypertension in laboratory animals. Animal models generated through selective breeding strategies are often complex, and the underlying mechanism of hypertension is not clear. A complementary strategy has been the use of transgenic technology. Here one gene can be selectively, tissue specifically, or developmentally overexpressed, knocked down, or knocked out. Although resulting phenotypes may still be complicated, the underlying genetic perturbation is a starting point for identifying interactions that lead to hypertension. We recognize that the development and maintenance of hypertension may involve many systems including the vascular, cardiac, and central nervous systems. However, given the central role of the kidney in normal and abnormal blood pressure regulation, we intend to limit our review to models with a broadly renal perspective.
Nutrition and Aging: Changes in the Regulation of Energy Metabolism With Aging
Authors: Roberts Susan B. , Rosenberg Irwin
Published: April 2006

Changes in energy regulation occur during normal aging and contribute to the common phenomenon of weight and fat losses late in life. This review synthesizes data on aging-related changes in energy intake and energy expenditure and on the regulation of energy intake and expenditure. The ability of older adults to accurately regulate energy intake is impaired, with a number of possible explanations including delayed rate of absorption of macronutrients secondary to reductions in taste and smell acuity and numerous hormonal and metabolic mediators of energy regulation that change with aging. There are also changes in patterns of dietary intake and a reduction in the variety of foods consumed in old age that are thought to further reduce energy intake. Additionally, all components of energy expenditure decrease with aging, in particular energy expenditure for physical activity and basal metabolic rate, and the ability of energy expenditure to increase or decrease to attenuate energy imbalance during overeating or undereating also decreases. Combined, these changes result in an increased susceptibility to energy imbalance (both positive and negative) in old age that is associated with deteriorations in health. Practical interventions for prevention of weight and fat fluctuations in old age are anticipated here based on emerging knowledge of the role of such factors as dietary variety, taste, and palatability in late-life energy regulation.
Role of Ubiquitylation in Cellular Membrane Transport
Authors: Staub Olivier , Rotin Daniela
Published: April 2006

Ubiquitylation of membrane proteins has gained considerable interest in recent years. It has been recognized as a signal that negatively regulates the cell surface expression of many plasma membrane proteins both in yeast and in mammalian cells. Moreover, it is also involved in endoplasmic reticulum-associated degradation of membrane proteins, and it acts as a sorting signal both in the secretory pathway and in endosomes, where it targets proteins into multivesicular bodies in the lumen of vacuoles/lysosomes. In this review we discuss the progress in understanding these processes, achieved during the past several years.
Transcriptional Regulation of Metabolism
Authors: Desvergne Béatrice , Michalik Liliane , Wahli Walter
Published: April 2006

Our understanding of metabolism is undergoing a dramatic shift. Indeed, the efforts made towards elucidating the mechanisms controlling the major regulatory pathways are now being rewarded. At the molecular level, the crucial role of transcription factors is particularly well-illustrated by the link between alterations of their functions and the occurrence of major metabolic diseases. In addition, the possibility of manipulating the ligand-dependent activity of some of these transcription factors makes them attractive as therapeutic targets. The aim of this review is to summarize recent knowledge on the transcriptional control of metabolic homeostasis. We first review data on the transcriptional regulation of the intermediary metabolism, i.e., glucose, amino acid, lipid, and cholesterol metabolism. Then, we analyze how transcription factors integrate signals from various pathways to ensure homeostasis. One example of this coordination is the daily adaptation to the circadian fasting and feeding rhythm. This section also discusses the dysregulations causing the metabolic syndrome, which reveals the intricate nature of glucose and lipid metabolism and the role of the transcription factor PPARγ in orchestrating this association. Finally, we discuss the molecular mechanisms underlying metabolic regulations, which provide new opportunities for treating complex metabolic disorders.
Microphysical and Geometrical Controls on the Pattern of Orographic Precipitation
Authors: Roe Gerard H. , Baker Marcia B.
Published: April 2006

Patterns of orographic precipitation can vary significantly both in time and space, and such variations must ultimately be related to mountain geometry, cloud microphysics, and synoptic conditions. Here an extension of the classic upslope model is presented, which incorporates an explicit representation in the vertical dimension, represents the finite growth time of hydrometeors, their downwind advection by the prevailing wind, and also allows for evaporation. For a simple mountain geometry the authors derive an analytical solution for the precipitation rate, which can be understood in terms of four nondimensional parameters. The finite growth time and slanting hydrometeor trajectories give rise to some interesting possibilities: a precipitation rate that maximizes at intermediate values of the horizontal wind speed, localized precipitation efficiencies in excess of 100%, and a reverse rain shadow with more precipitation falling on the leeward flank than on the windward flank.
The Role of the North American Topography on the Maintenance of the Great Plains Summer Low-Level Jet*
Authors: Ting Mingfang , Wang Hailan
Published: April 2006

Summer precipitation over the central United States depends strongly on the strength of the Great Plains low-level jet (LLJ). The Geophysical Fluid Dynamics Laboratory’s new generation of the atmospheric general circulation model (GCM) and the linear and nonlinear stationary wave models are used in this study to examine the role of North American topography in maintaining the Great Plains summer mean LLJ and precipitation. Atmospheric GCM experiments were first performed with and without the North American topography and with prescribed climatological sea surface temperatures. Results show that the Great Plains LLJ disappears completely in the experiment when the North American topography is removed, while the summer seasonal mean LLJ is well simulated in the experiment with full earth topography. In the absence of the North American topography, the summer precipitation is significantly reduced over the central United States and increased along the Gulf States and northeast Mexico.

Linear and nonlinear stationary wave models are used to determine the physical mechanisms through which the North American topography maintains the Great Plains time mean LLJ. Possible mechanisms include the physical blocking of the topography and the induced flow over and around the mountains, the thermal effect due to the elevation of the topography, and the transient thermal and vorticity forcing due to the modification of transient eddy activities in the presence of the topography. The linear and nonlinear model results indicate that the dominant mechanism for maintaining the time mean Great Plains LLJ is through the nonlinear effect of the trade wind along the southern flank of the North Atlantic subtropical high encountering the east slope of the Sierra Oriental and causing the flow to turn northward. As the flow turns north along the east slope of the North American topography, it obtains anticyclonic shear vorticity and thus the LLJ. The effect of the thermal forcing is negligible, while the effect of transient forcing is only important in extending the jet farther northward and eastward. The results suggest that variations in the strength of the North Atlantic subtropical anticyclone and the associated trade wind over the Caribbean Sea and the Gulf of Mexico may be important for understanding the interannual variation of the Great Plains LLJ and U.S. precipitation.