bluuebunny/crossref_metadata_2025 huggingface dataset:
Fire and herbivory are not substitutable: evidence from regrowth patterns and changes in physical and chemical defences in Acacia seedlings
Authors: Hean Jeff W. , Ward David
Published: September 2011

Questions

What are the relative effects of burning and herbivory on regrowth and physical and chemical defences in Acacia seedlings? Are effects of herbivory consistent with predictions of the resource availability hypothesis? Do plants growing with adequate resources regrow lost material while those with low resource availability defend themselves to minimize effects of herbivory?

Location

Arboretum, Pietermaritzburg, South Africa.

Methods

We performed a two‐factor, completely randomized experiment on seven indigenous African Acacia (Acacia erioloba, A. haematoxylon, A. karroo, A. nilotica, A. robusta, A. sieberiana and A. xanthophloea) with simulated burning using a blowtorch and simulated herbivory by cutting at the first node. We measured seedling regrowth, thorn length and number, and tannin content.

Results

New stems were produced for all species. In all seven species, the control (no fire, no herbivory) produced longer stems than other treatments. Simulated herbivory increased thorn abundance among Acacia species, while burning often led to decreased overall thorn length. Tannin analysis revealed positive and negative responses of individual species to burning and herbivory.

Conclusions

We demonstrate that Acacia seedlings are tolerant of disturbance events such as herbivory and burning but these effects cannot be assumed to be substitutable. Importantly, there was a positive response to simulated herbivory and a negative response to fire in most species. The mechanisms behind these changes appear to be mediated by induction of defence responses (resulting in a positive response to herbivory) and a cost for root storage (resulting in reduced defences after fire). Only A. robusta displayed regrowth and defence responses consistent with predictions of the resource availability hypothesis. In contrast, the two arid‐adapted species invested heavily in regrowth but not in defence, while four of the five mesic species invested in increased defence.
Adult with sacral lipomyelomeningocele covered by an anomalous bone articulated with iliac bone: Computed tomography and magnetic resonance images
Authors: Lee Seung Hwa , Je Bo‐Kyung , Kim Sung‐Bum , Kim Baek Hyun
Published: September 2011

The present paper reports and discusses a case of sacral lipomyelomeningocele with an anomalous long bone articulating with the left iliac bone in a 40‐year‐old female. That patient had a monozygotic twin sister who had normal spine. The findings were incidental during an evaluation for a urinary tract infection. The computed tomography (CT) and magnetic resonance (MR) images revealed sacral dysraphism, lipomyelomeningocele, tethered spinal cord, and profound subcutaneous fat in the sacrococcygeal region. In addition, an anomalous bony strut was demonstrated on the posterior aspect of the sacrum, covering the sacral defect and the associated lipomyelomeningocele. The 3‐D CT images of the anomalous bone associated with the sacral lipomyelomeningocele and the putative embryologic process are presented with a review of the literature.
Testing the rate isomorphy hypothesis using five statistical methods
Authors: Kuang Xian‐Ju , Parajulee Megha N. , Shi Pei‐Jian , Ge Feng , Xue Fang‐Sen
Published: September 2011

Abstract  Organisms are said to be in developmental rate isomorphy when the proportions of developmental stage durations are unaffected by temperature. Comprehensive stage‐specific developmental data were generated on the cabbage beetle, Colaphellus bowringi Baly (Coleoptera: Chrysomelidae), at eight temperatures ranging from 16°C to 30°C (in 2°C increments) and five analytical methods were used to test the rate isomorphy hypothesis, including: (i) direct comparison of lower developmental thresholds with standard errors based on the traditional linear equation describing developmental rate as the linear function of temperature; (ii) analysis of covariance to compare the lower developmental thresholds of different stages based on the Ikemoto‐Takai linear equation; (iii) testing the significance of the slope item in the regression line of versus temperature, where p is the ratio of the developmental duration of a particular developmental stage to the entire pre‐imaginal developmental duration for one insect or mite species; (iv) analysis of variance to test for significant differences between the ratios of developmental stage durations to that of pre‐imaginal development; and (v) checking whether there is an element less than a given level of significance in the p‐value matrix of rotating regression line. The results revealed no significant difference among the lower developmental thresholds or among the aforementioned ratios, and thus convincingly confirmed the rate isomorphy hypothesis.
Modeling Fresh Water Lens Damage and Recovery on Atolls After Storm‐Wave Washover
Authors: Chui Ting Fong May , Terry James P.
Published: September 2011

The principal natural source of fresh water on scattered coral atolls throughout the tropical Pacific Ocean is thin unconfined groundwater lenses within islet substrates. Although there are many threats to the viability of atoll fresh water lenses, salinization caused by large storm waves washing over individual atoll islets is poorly understood. In this study, a mathematical modeling approach is used to examine the immediate responses, longer‐term behavior, and subsequent (partial) recovery of a Pacific atoll fresh water lens after saline damage caused by cyclone‐generated wave washover under different scenarios. Important findings include: (1) the saline plume formed by a washover event mostly migrates downward first through the top coral sand and gravel substrate, but then exits the aquifer to the ocean laterally through the more permeable basement limestone; (2) a lower water table position before the washover event, rather than a longer duration of storm washover, causes more severe damage to the fresh water lens; (3) relatively fresher water can possibly be found as a preserved horizon in the deeper part of an aquifer after disturbance, especially if the fresh water lens extends into the limestone under normal conditions; (4) post‐cyclone accumulation of sea water in the central depression (swamp) of an atoll islet prolongs the later stage of fresh water lens recovery.
Alcohol Consumption Among Urban, Suburban, and Rural Veterans Affairs Outpatients
Authors: Williams Emily C. , McFarland Lynne V. , Nelson Karin M.
Published: September 2011

Purpose: United States rural residents tend toward poorer health than urban residents. Although alcohol use is associated with multiple medical conditions and can be reduced via brief primary care‐based interventions, it is unknown whether alcohol consumption differs by rurality among primary care patients. We sought to describe alcohol consumption among urban, suburban, and rural Veterans Affairs (VA) outpatients.

Methods: Outpatients from 7 VA facilities responded to mailed surveys that included the validated Alcohol Use Disorders Identification Test Consumption (AUDIT‐C) screening questionnaire. The ZIP code approximation of the US Department of Agriculture's rural‐urban commuting area (RUCA) codes classified participants into urban, suburban, and rural areas. For each area, adjusted logistic regression models estimated the prevalence of past‐year abstinence among all participants and unhealthy alcohol use (AUDIT‐C ≥ 3 for women and ≥ 4 for men) among drinkers.

Findings: Among 33,883 outpatients, 14,967 (44%) reported abstinence. Among 18,916 drinkers, 8,524 (45%) screened positive for unhealthy alcohol use. The adjusted prevalence of abstinence was lowest in urban residents (43%, 95% CI 42%‐43%) with significantly higher rates in both suburban and rural residents [45% (44%‐46%) and 46% (45%‐47%), respectively]. No significant differences were observed in the adjusted prevalence of unhealthy alcohol use among drinkers.

Conclusions: Abstinence is slightly more common among rural and suburban than urban VA outpatients, but unhealthy alcohol use does not vary by rurality. As the VA and other health systems implement evidence‐based care for unhealthy alcohol use, more research is needed to identify whether preventive strategies targeted to high‐risk areas are needed.
Structure and function of a complex sensory synapse
Authors: Regus‐Leidig H. , Brandstätter J. H.
Published: September 2011

Vision is the most important of the senses for humans, and the retina is the first stage in the processing of light signals in the visual system. In the retina, highly specialized light‐sensing neurons, the rod and cone photoreceptors, convert light into neural signals. These signals are extensively processed and filtered in the subsequent retinal network before transmitted to the higher visual centres in the brain, where the perception of viewed objects and scenes is finally constructed. A key feature of signal processing in the mammalian retina is parallel processing. Visual information is segregated in parallel pathways already at the rod and cone photoreceptor terminals, which provide multiple output synapses for the faithful encoding and transfer of the visual signals to the post‐receptoral retinal network. This review aims at highlighting the current knowledge about the structural and functional pre‐ and post‐synaptic specializations of rod and cone photoreceptor ribbon synapses, which belong to the most complex chemical synapses in the central nervous system.
Toward an interdisciplinary science of consumption
Authors: Preston Stephanie D.
Published: September 2011

Scientific perspectives on the drive to consume were presented in Ann Arbor, Michigan, at the conference entitled “The Interdisciplinary Science of Consumption: Mechanisms of Allocating Resources Across Disciplines.” The meeting, which took place May 12–15, 2010 and was sponsored by Rackham Graduate School and the Department of Psychology at the University of Michigan, included presentations on human, primate, and rodent models and spanned multiple domains of consumption, including reward seeking, delay discounting, food‐sharing reciprocity, and the consumption and display of material possessions across the life span.
Platelet Cyclooxygenase Expression in Normal Dogs
Authors: Thomason J. , Lunsford K. , Mullins K. , Stokes J. , Pinchuk L. , Wills R. , Mclaughlin R. , Langston C. , Pruett S. , Mackin A.
Published: September 2011

Background:

Human platelets express both cyclooxygenase‐1 (COX‐1) and cyclooxygenase‐2 (COX‐2). Variation in COX‐2 expression could be a mechanism for variable response to aspirin.

Hypothesis/Objectives:

The hypotheses were that circulating canine platelets express COX‐1 and COX‐2, and that aspirin alters COX expression. The objective was to identify changes in platelet COX expression and in platelet function caused by aspirin administration to dogs.

Animals:

Eight female, intact hounds.

Methods:

A single population, repeated measures design was used to evaluate platelet COX‐1 and COX‐2 expression by flow cytometry before and after aspirin (10 mg/kg Q12h for 10 days). Platelet function was analyzed via PFA‐100® (collagen/epinephrine), and urine 11‐dehydro‐thromboxane B2 (11‐dTXB2) was measured and normalized to urinary creatinine. Differences in COX expression, PFA‐100® closure times, and urine 11‐dTXB2 : creatinine ratio were analyzed before and after aspirin administration.

Results:

Both COX‐1 and COX‐2 were expressed in canine platelets. COX‐1 mean fluorescent intensity (MFI) increased in all dogs, by 250% (range 63–476%), while COX‐2 expression did not change significantly (P = 0.124) after aspirin exposure, with large interindividual variation. PFA‐100® closure times were prolonged and urine 11‐dTXB2 concentration decreased in all dogs after aspirin administration.

Conclusions and Clinical Importance:

Canine platelets express both COX isoforms. After aspirin exposure, COX‐1 expression increased despite impairment of platelet function, while COX‐2 expression varied markedly among dogs. Variability in platelet COX‐2 expression should be explored as a potential mechanism for, or marker of, variable aspirin responsiveness.
Ultrasonographic examination of the distal podotrochlear apparatus of the horse: A transcuneal approach
Authors: Jacquet S. , Denoix J.‐M.
Published: September 2011

In the diagnostic work‐up of lameness originating from the foot, ultrasonographic examination is an essential complement to radiography for the detection of soft tissue lesions of the podotrochlear apparatus (PTA). The infrasesamoidean part of the deep digital flexor tendon, distal sesamoidean ligament and distal sesamoid bone can be accurately assessed using a transcuneal approach. This paper describes the ultrasonographic technique and presents normal and abnormal ultrasound images of the infrasesamoidean part of the PTA.
Proximal injuries of the accessory ligament of the deep digital flexor tendon in forelimbs and hindlimbs: 12 horses (2006–2010)
Authors: Dyson S.
Published: September 2011

There have been no detailed ultrasonographic descriptions of injuries of the accessory ligament of the deep digital flexor tendon (ALDDFT) in the carpal and proximal metacarpal and tarsal and proximal metatarsal regions. The aims of this study were to describe the: 1) normal ultrasonographic appearance of the proximal aspect of the ALDDFT in fore‐ and hindlimbs and 2) clinical and ultrasonographic features of proximal injuries of the ALDDFT in both fore‐ and hindlimbs. The proximal aspects of the ALDDFT of both fore‐ and hindlimbs of 10 horses free from lameness were examined ultrasonographically. Clinical records of 12 horses examined between January 2006 and December 2010 with proximal injuries of the ALDDFT were reviewed. All 4 horses with proximal lesions of the ALDDFT in a forelimb had no localising clinical signs and diagnostic analgesia was required to localise the source of pain. Eight horses with recent onset hindlimb lameness had oedematous swelling in the proximoplantaromedial aspect of the metatarsal region (n = 7) or more generalised thickening in the region of the proximal aspect of the ALDDFT (n = 1). Diagnosis was confirmed ultrasonographically in all horses. One horse was retired for unrelated reasons. One of 3 horses with forelimb lameness returned to full athletic function. Four of 6 horses with hindlimb lameness returned to work; the remaining 2 horses resumed work, but experienced recurrent injury of the ALDDFT. Proximal injuries of the ALDDFT should be considered as a cause of either fore‐ or hindlimb lameness, even in the absence of gross palpable abnormalities.
Experimental and Analytical Investigation of High Speed Turbocharger Ball Bearings
Authors: Ashtekar Ankur , Sadeghi Farshid
Published: August 2011

The objectives of this investigation were to design and construct a high speed turbocharger test rig (TTR) to measure dynamics of angular contact ball bearing rotor system, and to develop a coupled dynamic model for the ball bearing rotor system to corroborate the experimental and analytical results. In order to achieve the objectives of the experimental aspect of this study, a test rig was designed and developed to operate at speeds up to 70,000 rpm. The rotating components (i.e., turbine wheels) of the TTR were made to be dynamically similar to the actual turbocharger. Proximity sensors were used to record the turbine wheel displacements while accelerometers were used to monitor the rotor vibrations. The TTR was used to examine the dynamic response of the turbocharger under normal and extreme operating conditions. To achieve the objectives of analytical investigation, a discrete element ball bearing model was coupled through a set of interface points with a component mode synthesis rotor model to simulate the dynamics of the turbocharger test rig. Displacements of the rotor from the analytical model were corroborated with experimental results. The analytical and experimental results are in good agreement. The bearing rotor system model was used to examine the bearing component dynamics. Effects of preloading and imbalance were also found to have significant effects on turbocharger rotor and bearing dynamics.
Simulation Study of Advanced Variable Displacement Engine Coupled to Power-Split Hydraulic Hybrid Powertrain
Authors: Tavares Fernando , Johri Rajit , Filipi Zoran
Published: September 2011

The simulation based investigation of the variable displacement engine is motivated by a desire to enable unthrottled operation at part load, and hence eliminate pumping losses. The mechanism modeled in this work is derived from a Hefley engine concept. Other salient features of the proposed engine are turbocharging and cylinder deactivation. The cylinder deactivation combined with variable displacement further expands the range of unthrottled operation, whereas turbocharging increases the power density of the engine and allows downsizing without the loss of performance. Although the proposed variable displacement turbocharged engine (VDTCE) concept enables operations in a very wide range, running near idle is impractical. Therefore, the VDTCE is integrated with a hybrid powertrain to mitigate issues with engine transients and mode transitions. The engine model is developed in AMESim using physics based models, such as thermodynamic cycle simulation, filling and emptying of manifolds, and turbulent flame entrainment combustion. A predictive model of the power-split hydraulic hybrid driveline is created in SIMULINK, thus facilitating integration with the engine. The integrated simulation tool is utilized to address design and control issues, before determining the fuel economy potential of the powertrain comprising a VDTCE engine and a hydraulic hybrid driveline.
Mystery Pioneer Anomaly Is Real But Still a Mystery
Authors: Kerr Richard A.
Published: September 2011

Long-forgotten Pioneer records confirm that the spacecraft have been slowing more than they should as they headed out of the solar system and reveal for the first time that the anomaly has actually been shrinking.
Comparison of Performance of the Novel Chromogenic Spectra VRE Agar to That of Bile Esculin Azide and Campylobacter Agars for Detection of Vancomycin-Resistant Enterococci in Fecal Samples
Authors: Jenkins S. G. , Raskoshina L. , Schuetz A. N.
Published: September 2011

A total of 142 stool specimens were evaluated for vancomycin-resistant enterococcus (VRE). Twenty-four-hour sensitivities and specificities, respectively, were 98% and 95% for Spectra VRE chromogenic agar (Remel, Lenexa, KS), 86% and 92% for bile esculin azide with vancomycin (BEAV; Remel), and 96.5% and 92% for
Campylobacter
agar (CAMPY; Remel). Spectra VRE and CAMPY are significantly more sensitive at 24 h than BEAV.
Canada's First Case of a Multidrug-Resistant Corynebacterium diphtheriae Strain, Isolated from a Skin Abscess
Authors: Mina Neil V. , Burdz Tamara , Wiebe Deborah , Rai Jagtar S. , Rahim Tazim , Shing Fern , Hoang Linda , Bernard Kathryn
Published: September 2011

A toxigenicCorynebacterium diphtheriaebiovar mitis sequence type 136 (ST136) strain was recovered from a toe infection of an unvaccinated patient recently returned from India. The isolate was resistant to clindamycin, erythromycin (ermXpositive), tetracycline, and trimethoprim-sulfamethoxazole, intermediate to ceftriaxone and cefotaxime, and had high MICs for telithromycin and chloramphenicol but was sensitive to other drugs.
The Latency-Associated UL138 Gene Product of Human Cytomegalovirus Sensitizes Cells to Tumor Necrosis Factor Alpha (TNF-α) Signaling by Upregulating TNF-α Receptor 1 Cell Surface Expression
Authors: Montag Christina , Wagner Jutta Annabella , Gruska Iris , Vetter Barbara , Wiebusch Lüder , Hagemeier Christian
Published: September 2011

Many viruses antagonize tumor necrosis factor alpha (TNF-α) signaling in order to counteract its antiviral properties. One way viruses achieve this goal is to reduce TNF-α receptor 1 (TNFR1) on the surface of infected cells. Such a mechanism is also employed by human cytomegalovirus (HCMV), as recently reported by others and us. On the other hand, TNF-α has also been shown to foster reactivation of HCMV from latency. By characterizing a new variant of HCMV AD169, we show here that TNFR1 downregulation by HCMV only becomes apparent upon infection of cells with HCMV strains lacking the so-called ULb′ region. This region contains genes involved in regulating viral immune escape, cell tropism, or latency and is typically lost from laboratory strains but present in low-passage strains and clinical isolates. We further show that although ULb′-positive viruses also contain the TNFR1-antagonizing function, this activity is masked by a dominant TNFR1 upregulation mediated by the ULb′ gene product UL138. Isolated expression of UL138 in the absence of viral infection upregulates TNFR1 surface expression and can rescue both TNFR1 reexpression and TNF-α responsiveness of cells infected with an HCMV mutant lacking the UL138-containing transcription unit. Given that the UL138 gene product is one of the few genes recognized to be expressed during HCMV latency and the known positive effects of TNF-α on viral reactivation, we suggest that via upregulating TNFR1 surface expression UL138 may sensitize latently infected cells to TNF-α-mediated reactivation of HCMV.
Bayesian integrated survey-based assessments: an example applied to North Sea herring (Clupea harengus) survey data
Authors: Hillary Richard
Published: August 2011

Stock assessments that use only fisheries independent data have been developed from a number of different standpoints over the last 15 years. While the ability of such stock assessments to avoid the use of potentially compromised or hard to interpret commercial data or making certain assumptions that are common to traditional assessments has been established, little has been made of their potential for detecting and estimating complex mortality trends over time or their potential utility in survey-based management procedures. Using North Sea herring ( Clupea harengus ) data as an example, a Bayesian survey-based assessment method that is able to estimate all the key population variables is detailed. However, survival probability, and not fishing mortality that is conditional on natural mortality, is the key parameter. Reversible jump Markov chain Monte Carlo routines were developed to explore the range of ages over which survival separates into year and age effects (a common assumption in many stock assessments). Post hoc estimates of natural mortality suggest that changes over years and ages may have occurred in relativity to historic levels. The derivation of reference points based on survival probability and surplus biomass production are detailed as proxies for more common F-based reference points. The potential role for the outputs of such assessments in a management procedure sense is discussed.
Phenotypic plasticity in physiological status at emergence from nests as a response to temperature in Atlantic salmon (Salmo salar)
Authors: Skoglund Helge , Einum Sigurd , Forseth Torbjørn , Barlaup Bjørn Torgeir
Published: August 2011

Successful transitions from relying on yolk to exogenous feeding may be strongly influenced by temperature conditions experienced both during embryonic development, through effects on juvenile phenotype, and during initiation of feeding. Here we simultaneously assess these two effects of temperature treatments (2, 5, 8, and 12 °C) in Atlantic salmon ( Salmo salar ). Fry emerging from low incubation temperatures were smaller and had metabolized more energy prior to emergence, but had larger yolk sacs and higher mass specific energy levels, than those experiencing higher temperatures. After emergence, activity, feeding, and growth increased significantly with increasing temperature, but fry were able to initiate feeding and maintain positive growth at all four temperatures. Larger energy stores may provide an advantage when emerging at cold temperatures with a low potential for feeding activity, whereas having a large body size, which is primarily of importance in competitive interactions, may be less important owing to cryptic feeding and sheltering at low temperatures. However, the adaptive significance of the observed phenotypic response to incubation temperature remains untested.
A new method to reconstruct fish diet and movement patterns from δ13C values in otolith amino acids
Authors: McMahon Kelton W. , Fogel Marilyn L. , Johnson Beverly J. , Houghton Leah A. , Thorrold Simon R.
Published: August 2011

Fish ecologists have used geochemical values in otoliths to examine habitat use, migration, and population connectivity for decades. However, it remains difficult to determine an unambiguous dietary δ13C signature from bulk analysis of otolith. Studies to date have focused on the aragonite component of otoliths with less attention paid to the organic fraction. We describe the application of compound-specific stable isotope analysis (SIA) to analyze amino acid (AA) δ13C values from small amounts (<1 mg) of otolith powder. We examined δ13C values of otolith and muscle AAs from a reef-associated snapper (Lutjanus ehrenbergii (Peters, 1869)) collected along a carbon isotope gradient (isoscape) from seagrass beds to coral reefs. Carbon isotope values in otolith and muscle samples were highly correlated within and among coastal habitats. Moreover, δ13C values of otolith AAs provided a purely dietary record that avoided dilution from dissolved inorganic carbon. Otolith AAs served as a robust tracer of δ13C values at the base of the food web, making compound-specific SIA a powerful tool for dietary reconstructions and tracking the movement of fishes across isoscapes.
Application of a method for estimating effective population size and admixture using diagnostic single nucleotide polymorphisms (SNPs): implications for conservation of threatened Paiute cutthroat trout (Oncorhynchus clarkii seleniris) in Silver King Creek, California
Authors: Finger Amanda J. , Anderson Eric C. , Stephens Molly R. , May Bernard P.
Published: August 2011

The threatened Paiute cutthroat trout ( Oncorhynchus clarkii seleniris , PCT) is endemic to Silver King Creek, California, USA, which was stocked with non-native trout beginning in 1930. Single nucleotide polymorphism (SNP) and microsatellite data reveal that the trout population in Silver King Creek is weakly structured and composed of introgressed California golden trout ( Oncorhynchus mykiss aguabonita , CAGT), hatchery rainbow trout ( Oncorhynchus mykiss , RT), and some native PCT. Two SNP groups were analyzed: (i) one mitochondrial and five autosomal SNPs, diagnostic between Lahontan cutthroat trout ( Oncorhynchus clarkii henshawi ) or PCT and CAGT or RT and (ii) one mitochondrial and five autosomal SNPs nearly diagnostic between CAGT and RT. The five autosomal cutthroat–rainbow SNPs were used to jointly estimate the cutthroat trout mixing proportion in Silver King Creek and effective population size (Ne) of the admixed population, using a coalescent-based maximum likelihood method. Given the stocking history of Silver King Creek, there are two different scenarios that bound the range of expected point estimates for Ne. We obtain point estimates of Ne = 150 and Ne = 750 for Silver King Creek under these two scenarios. This method will be useful in cases with differentiated taxa and in prioritizing conservation and restoration programs where the populations of concern are introgressed.
SPIN-DEPENDENT BEATS CREATED BY IRRADIATION OF MICROWAVE FIELD THROUGH A QUANTUM DOT
Authors: TAGANI M. BAGHERI , SOLEIMANI H. RAHIMPOUR
Published: August 2011

We study spin-dependent transport through a quantum dot with Zeeman split levels coupled to ferromagnetic leads and under influence of microwave irradiation. Current polarization, spin current, spin accumulation and tunneling magnetoresistance are analyzed using nonequilibrium Green's function formalism and rate equations. Spin-dependent beats in spin resolved currents are observed. The effects of magnetic field, temperature and Coulomb interaction on these beats are studied.
Lithium reduces aquaporin-2 transcription independent of prostaglandins
Authors: Kortenoeven Marleen L. A. , Schweer Horst , Cox Rik , Wetzels Jack F. M. , Deen Peter M. T.
Published: September 2011

Vasopressin (AVP)-stimulated translocation and transcription of aquaporin-2 (AQP2) water channels in renal principal cells is essential for urine concentration. Twenty percent of patients treated with lithium develop nephrogenic diabetes insipidus (NDI), a disorder in which the kidney is unable to concentrate urine. In vivo and in mouse collecting duct (mpkCCD) cells, lithium treatment coincides with decreased AQP2 abundance and inactivation of glycogen synthase kinase (Gsk) 3β. This is paralleled in vivo by an increased renal cyclooxygenase 2 (COX-2) expression and urinary prostaglandin PGE2 excretion. PGE2 reduces AVP-stimulated water reabsorption, but its precise role in lithium-induced downregulation of AQP2 is unclear. Using mpkCCD cells, we here investigated whether prostaglandins contribute to lithium-induced downregulation of AQP2. In these cells, lithium application reduced AQP2 abundance, which coincided with Gsk3β inactivation and increased COX-2 expression. Inhibition of COX by indomethacin, leading to reduced PGE2 and PGF2α levels, or dexamethasone-induced downregulation of COX-2 both increased AQP2 abundance, while PGE2 addition reduced AQP2 abundance. However, lithium did not change the prostaglandin levels, and indomethacin and dexamethasone did not prevent lithium-induced AQP2 downregulation. Further analysis revealed that lithium decreased AQP2 protein abundance, mRNA levels and transcription, while PGE2 reduced AQP2 abundance by increasing its lysosomal degradation, but not by reducing AQP2 gene transcription. In conclusion, our data reveal that in mpkCCD cells, prostaglandins decrease AQP2 protein stability by increasing its lysosomal degradation, indicating that in vivo paracrine-produced prostaglandins might have a role in lithium-induced NDI via this mechanism. However, lithium affects also AQP2 gene transcription, which is prostaglandin independent.
New approaches in small animal echocardiography: imaging the sounds of silence
Authors: Ram Rashmi , Mickelsen Deanne M. , Theodoropoulos Catherine , Blaxall Burns C.
Published: August 2011

Systolic and diastolic dysfunction of the left ventricle (LV) is a hallmark of most cardiac diseases. In vivo assessment of heart function in animal models, particularly mice, is essential to refining our understanding of cardiovascular disease processes. Ultrasound echocardiography has emerged as a powerful, noninvasive tool to serially monitor cardiac performance and map the progression of heart dysfunction in murine injury models. This review covers current applications of small animal echocardiography, as well as emerging technologies that improve evaluation of LV function. In particular, we describe speckle-tracking imaging-based regional LV analysis, a recent advancement in murine echocardiography with proven clinical utility. This sensitive measure enables an early detection of subtle myocardial defects before global dysfunction in genetically engineered and rodent surgical injury models. Novel visualization technologies that allow in-depth phenotypic assessment of small animal models, including perfusion imaging and fetal echocardiography, are also discussed. As imaging capabilities continue to improve, murine echocardiography will remain a critical component of the investigator's armamentarium in translating animal data to enhanced clinical treatment of cardiovascular diseases.
Circadian integration of sleep-wake and feeding requires NPY receptor-expressing neurons in the mediobasal hypothalamus
Authors: Wiater M. F. , Mukherjee S. , Li A.-J. , Dinh T. T. , Rooney E. M. , Simasko S. M. , Ritter S.
Published: September 2011

Sleep and feeding rhythms are highly coordinated across the circadian cycle, but the brain sites responsible for this coordination are unknown. We examined the role of neuropeptide Y (NPY) receptor-expressing neurons in the mediobasal hypothalamus (MBH) in this process by injecting the targeted toxin, NPY-saporin (NPY-SAP), into the arcuate nucleus (Arc). NPY-SAP-lesioned rats were initially hyperphagic, became obese, exhibited sustained disruption of circadian feeding patterns, and had abnormal circadian distribution of sleep-wake patterns. Total amounts of rapid eye movement sleep (REMS) and non-REMS (NREMS) were not altered by NPY-SAP lesions, but a peak amount of REMS was permanently displaced to the dark period, and circadian variation in NREMS was eliminated. The phase reversal of REMS to the dark period by the lesion suggests that REMS timing is independently linked to the function of MBH NPY receptor-expressing neurons and is not dependent on NREMS pattern, which was altered but not phase reversed by the lesion. Sleep-wake patterns were altered in controls by restricting feeding to the light period, but were not altered in NPY-SAP rats by restricting feeding to either the light or dark period, indicating that disturbed sleep-wake patterns in lesioned rats were not secondary to changes in food intake. Sleep abnormalities persisted even after hyperphagia abated during the static phase of the lesion. Results suggest that the MBH is required for the essential task of integrating sleep-wake and feeding rhythms, a function that allows animals to accommodate changeable patterns of food availability. NPY receptor-expressing neurons are key components of this integrative function.
The “other” respiratory effect of opioids: suppression of spontaneous augmented (“sigh”) breaths
Authors: Bell Harold J. , Azubike Elizabeth , Haouzi Philippe
Published: August 2011

The purpose of this study was to examine the effects of a clinically relevant opioid on the production of augmented breaths (ABs) in unanesthetized animals breathing normal room air, using a dosage which does not depress breathing. To do this we monitored breathing noninvasively, in unrestrained animals before and after subcutaneous injection of either morphine, or a saline control. The effect of ketamine/xylazine was also studied to determine the potential effect of an alternative sedative agent. Last, the effect of naloxone was studied to determine the potential influence of endogenous opioids in regulating the normal incidence of ABs. Morphine (5 mg/kg) had no depressive effect on breathing, but completely eliminated ABs in all animals in room air ( P = 0.027). However, when animals breathed hypoxic air (10% O2), animals did express ABs, although their incidence was still reduced by morphine ( P < 0.001). This was not a result of sedation per se, as ABs continued at their normal rate in room air during sedation with ketamine. Naloxone had no effect on breathing or AB production, and so endogenous opioids are not likely involved in regulating their rate of production under normal conditions. Our results show that in unanesthetized animals breathing normal room air, a clinically relevant opioid eliminates ABs, even at a dose that does not cause respiratory depression. Despite this, hypoxia-induced stimulation of breathing can facilitate the production of ABs even with the systemic opioid present, indicating that peripheral chemoreceptor stimulation provides a potential means of overcoming the opioid-induced suppression of these respiratory events.
Low-volume high-intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes
Authors: Little Jonathan P. , Gillen Jenna B. , Percival Michael E. , Safdar Adeel , Tarnopolsky Mark A. , Punthakee Zubin , Jung Mary E. , Gibala Martin J.
Published: August 2011

Low-volume high-intensity interval training (HIT) is emerging as a time-efficient exercise strategy for improving health and fitness. This form of exercise has not been tested in type 2 diabetes and thus we examined the effects of low-volume HIT on glucose regulation and skeletal muscle metabolic capacity in patients with type 2 diabetes. Eight patients with type 2 diabetes (63 ± 8 yr, body mass index 32 ± 6 kg/m2, HbA1C6.9 ± 0.7%) volunteered to participate in this study. Participants performed six sessions of HIT (10 × 60-s cycling bouts eliciting ∼90% maximal heart rate, interspersed with 60 s rest) over 2 wk. Before training and from ∼48 to 72 h after the last training bout, glucose regulation was assessed using 24-h continuous glucose monitoring under standardized dietary conditions. Markers of skeletal muscle metabolic capacity were measured in biopsy samples (vastus lateralis) before and after (72 h) training. Average 24-h blood glucose concentration was reduced after training (7.6 ± 1.0 vs. 6.6 ± 0.7 mmol/l) as was the sum of the 3-h postprandial areas under the glucose curve for breakfast, lunch, and dinner (both P < 0.05). Training increased muscle mitochondrial capacity as evidenced by higher citrate synthase maximal activity (∼20%) and protein content of Complex II 70 kDa subunit (∼37%), Complex III Core 2 protein (∼51%), and Complex IV subunit IV (∼68%, all P < 0.05). Mitofusin 2 (∼71%) and GLUT4 (∼369%) protein content were also higher after training (both P < 0.05). Our findings indicate that low-volume HIT can rapidly improve glucose control and induce adaptations in skeletal muscle that are linked to improved metabolic health in patients with type 2 diabetes.
Improved V̇O2 uptake kinetics and shift in muscle fiber type in high-altitude trekkers
Authors: Doria C. , Toniolo L. , Verratti V. , Cancellara P. , Pietrangelo T. , Marconi V. , Paoli A. , Pogliaghi S. , Fanò G. , Reggiani C. , Capelli C.
Published: August 2011

The study investigated the effect of prolonged hypoxia on central [i.e., cardiovascular oxygen delivery (Q̇aO2)] and peripheral (i.e., O2 utilization) determinants of oxidative metabolism response during exercise in humans. To this aim, seven male mountaineers were examined before and immediately after the Himalayan Expedition Interamnia 8000–Manaslu 2008, lasting 43 days, among which, 23 days were above 5,000 m. The subjects showed a decrease in body weight ( P < 0.05) and of power output during a Wingate Anaerobic test ( P < 0.05) and an increase of thigh cross-sectional area ( P < 0.05). Absolute maximal O2 uptake (V̇O2max) did not change. The mean response time of V̇O2 kinetics at the onset of step submaximal cycling exercise was reduced significantly from 53.8 s ± 10.9 to 39.8 s ± 10.9 ( P < 0.05), whereas that of Q̇aO2 was not. Analysis of single fibers dissected from vastus lateralis biopsies revealed that the expression of slow isoforms of both heavy and light myosin subunits increased, whereas that of fast isoforms decreased. Unloaded shortening velocity of fibers was decreased significantly. In summary, independent findings converge in indicating that adaptation to chronic hypoxia brings about a fast-to-slow transition of muscle fibers, resulting in a faster activation of the mitochondrial oxidative metabolism. These results indicate that a prolonged and active sojourn in hypoxia may induce muscular ultrastructural and functional changes similar to those observed after aerobic training.
TMS of the right angular gyrus modulates priming of pop-out in visual search: combined TMS-ERP evidence
Authors: Taylor Paul C. J. , Muggleton Neil G. , Kalla Roger , Walsh Vincent , Eimer Martin
Published: September 2011

During priming of pop-out, performance at discriminating a pop-out feature target in visual search is affected by whether the target on the previous trial was defined by the same feature as on the upcoming trial. Recent studies suggest that priming of pop-out relies on attentional processes. With the use of simultaneous, combined transcranial magnetic stimulation and event-related potential recording (TMS-ERP), we tested for any critical role of the right angular gyrus (rANG) and left and right frontal eye fields (FEFs)—key attentional sites—in modulating both performance and the ERPs evoked by such visual events. Intertrial TMS trains were applied while participants discriminated the orientation of a color pop-out element in a visual search array. rANG TMS disrupted priming of pop-out, reducing reaction time costs on switch trials and speeding responses when the color of the pop-out target switched. rANG TMS caused a negativity in the ERP elicited in response to the visual stimulus array, starting 210 ms after stimulus onset. Both behavioral and ERP effects were apparent only after rANG TMS, on switch trials, and when the target in the visual search array was presented in the left visual field, with no effects after left or right FEF TMS. These results provide evidence for an attentional reorienting mechanism, which originates in the rANG and is modulated by the implicit memory of the previous trial. The rANG plays a causal role on switch trials during priming of pop-out by interacting with visual processing, particularly in the ipsilateral hemisphere representing the contralateral hemifield.
Taking into account latency, amplitude, and morphology: improved estimation of single-trial ERPs by wavelet filtering and multiple linear regression
Authors: Hu L. , Liang M. , Mouraux A. , Wise R. G. , Hu Y. , Iannetti G. D.
Published: September 2011

Across-trial averaging is a widely used approach to enhance the signal-to-noise ratio (SNR) of event-related potentials (ERPs). However, across-trial variability of ERP latency and amplitude may contain physiologically relevant information that is lost by across-trial averaging. Hence, we aimed to develop a novel method that uses 1) wavelet filtering (WF) to enhance the SNR of ERPs and 2) a multiple linear regression with a dispersion term (MLRd) that takes into account shape distortions to estimate the single-trial latency and amplitude of ERP peaks. Using simulated ERP data sets containing different levels of noise, we provide evidence that, compared with other approaches, the proposed WF+MLRdmethod yields the most accurate estimate of single-trial ERP features. When applied to a real laser-evoked potential data set, the WF+MLRdapproach provides reliable estimation of single-trial latency, amplitude, and morphology of ERPs and thereby allows performing meaningful correlations at single-trial level. We obtained three main findings. First, WF significantly enhances the SNR of single-trial ERPs. Second, MLRdeffectively captures and measures the variability in the morphology of single-trial ERPs, thus providing an accurate and unbiased estimate of their peak latency and amplitude. Third, intensity of pain perception significantly correlates with the single-trial estimates of N2 and P2 amplitude. These results indicate that WF+MLRdcan be used to explore the dynamics between different ERP features, behavioral variables, and other neuroimaging measures of brain activity, thus providing new insights into the functional significance of the different brain processes underlying the brain responses to sensory stimuli.
Release from the cone ribbon synapse under bright light conditions can be controlled by the opening of only a few Ca2+ channels
Authors: Bartoletti Theodore M. , Jackman Skyler L. , Babai Norbert , Mercer Aaron J. , Kramer Richard H. , Thoreson Wallace B.
Published: September 2011

Light hyperpolarizes cone photoreceptors, causing synaptic voltage-gated Ca2+ channels to open infrequently. To understand neurotransmission under these conditions, we determined the number of L-type Ca2+ channel openings necessary for vesicle fusion at the cone ribbon synapse. Ca2+ currents ( ICa) were activated in voltage-clamped cones, and excitatory postsynaptic currents (EPSCs) were recorded from horizontal cells in the salamander retina slice preparation. Ca2+ channel number and single-channel current amplitude were calculated by mean-variance analysis of ICa. Two different comparisons—one comparing average numbers of release events to average ICa amplitude and the other involving deconvolution of both EPSCs and simultaneously recorded cone ICa—suggested that fewer than three Ca2+ channel openings accompanied fusion of each vesicle at the peak of release during the first few milliseconds of stimulation. Opening fewer Ca2+ channels did not enhance fusion efficiency, suggesting that few unnecessary channel openings occurred during strong depolarization. We simulated release at the cone synapse, using empirically determined synaptic dimensions, vesicle pool size, Ca2+ dependence of release, Ca2+ channel number, and Ca2+ channel properties. The model replicated observations when a barrier was added to slow Ca2+ diffusion. Consistent with the presence of a diffusion barrier, dialyzing cones with diffusible Ca2+ buffers did not affect release efficiency. The tight clustering of Ca2+ channels, along with a high-Ca2+ affinity release mechanism and diffusion barrier, promotes a linear coupling between Ca2+ influx and vesicle fusion. This may improve detection of small light decrements when cones are hyperpolarized by bright light.
A Role for Bone Morphogenetic Protein-4 in Lymph Node Vascular Remodeling and Primary Tumor Growth
Authors: Farnsworth Rae H. , Karnezis Tara , Shayan Ramin , Matsumoto Masataka , Nowell Cameron J. , Achen Marc G. , Stacker Steven A.
Published: August 2011

Lymph node metastasis, an early and prognostically important event in the progression of many human cancers, is associated with expression of VEGF-D. Changes to lymph node vasculature that occur during malignant progression may create a metastatic niche capable of attracting and supporting tumor cells. In this study, we sought to characterize molecules expressed in lymph node endothelium that could represent therapeutic or prognostic targets. Differential mRNA expression profiling of endothelial cells from lymph nodes that drained metastatic or nonmetastatic primary tumors revealed genes associated with tumor progression, in particular bone morphogenetic protein-4 (BMP-4). Metastasis driven by VEGF-D was associated with reduced BMP-4 expression in high endothelial venules, where BMP-4 loss could remodel the typical high-walled phenotype to thin-walled vessels. VEGF-D expression was sufficient to suppress proliferation of the more typical BMP-4–expressing high endothelial venules in favor of remodeled vessels, and mechanistic studies indicated that VEGF receptor-2 contributed to high endothelial venule proliferation and remodeling. BMP-4 could regulate high endothelial venule phenotype and cellular function, thereby determining morphology and proliferation responses. Notably, therapeutic administration of BMP-4 suppressed primary tumor growth, acting both at the level of tumor cells and tumor stromal cells. Together, our results show that VEGF-D–driven metastasis induces vascular remodeling in lymph nodes. Furthermore, they implicate BMP-4 as a negative regulator of this process, suggesting its potential utility as a prognostic marker or antitumor agent. Cancer Res; 71(20); 6547–57. ©2011 AACR.