bluuebunny/crossref_metadata_2025 huggingface dataset:
Conjugated linoleic acid and atherosclerosis: studies in animal models
Authors: Mitchell Patricia L. , McLeod Roger S.
Published: August 2008

Conjugated linoleic acids (CLA) are isomeric forms of linoleic acid (LA) containing two conjugated sites of unsaturation. The most abundant dietary form of CLA is the cis-9,trans-11 (c-9,t-11) isomer that is found in the fatty tissues and milk of ruminant animals. CLA can also be acquired by ingestion of supplements, which are usually equimolar mixtures of the c-9,t-11 and t-10,c-12 CLA. For more than a decade, the potential for CLA to modify atherosclerosis in animal models has been examined. However, to date, the studies have failed to reach consensus on whether CLA can be effective in reducing the incidence or severity of atherosclerotic lesions, or whether or not plasma lipid and lipoprotein levels can be improved with CLA supplementation. This review will examine the evidence for and against a role for CLA in atherosclerosis, with a focus on the rabbit, the hamster, and the apoE-deficient mouse.
Tick vitellogenin receptor reveals critical role in oocyte development and transovarial transmission ofBabesiaparasite
Authors: Boldbaatar Damdinsuren , Battsetseg Badgar , Matsuo Tomohide , Hatta Takeshi , Umemiya-Shirafuji Rika , Xuan Xuenan , Fujisaki Kozo
Published: August 2008

A cDNA encoding the vitellogenin receptor of the ixodid tick, Haemaphysalis longicornis Neumann (HlVgR) was cloned and characterized. The full-length cDNA is 5631 bp, including an intact ORF encoding an expected protein with 1782 amino acids. The deduced amino acid sequence of the HlVgR cDNA revealed two ligand-binding domains with four class A cysteine-rich repeats in the first domain and eight in the second domain similar to those of insect VgRs. The immunoblot analysis detected ~197 kDa protein in both tick ovary and egg. The developmental expression profile demonstrated that HlVgR mRNA exists throughout the ovarian development, and the transcriptional level is especially high in the previtellogenic period. Immuno electron microscopy analysis demonstrated that the localization of HlVgR is detected on the external surface of oocyte plasma membrane. RNAi showed that eggs of HlVgR dsRNA-injected adult ticks had not developed into fully mature oocytes and laid abnormal eggs. The Babesia parasite DNA was not detected in the eggs of HlVgR dsRNA-injected tick that fed on Babesia gibsoni infected dog, whereas it was detected in the eggs of PBS-injected ticks and noninjected ticks. Expression of HlVgR was increased by the vitellogenic hormone 20-hydroxyecdysone. These results indicate that HlVgR, which is produced by the developing oocytes, is essential for Vg uptake, egg development in the H. longicornis tick, and transovarial transmission of Babesia parasites.
Keratin contribution to cellular mechanical stress response at focal adhesions as assayed by laser tweezers
Authors: Bordeleau François , Bessard Judicael , Sheng Yunlong , Marceau Normand
Published: August 2008

The ability of adherent cells to sense and adapt to a mechanical stress generated at focal adhesions (FAs) largely occurs through the integrin-mediated interaction between the cytoskeleton, namely actin microfilaments, and extracellular matrix elements, like fibronectin. Here we assessed the contribution of keratin 8 and 18 (K8/K18) intermediate filaments (IFs) in simple epithelial cells in response to a mechanical stress applied on integrins at FAs. To this end, we used monolayer cultures of K8-knockdown H4-II-E-C3 (shK8b1) rat hepatoma cells and their K8/K18-containing counterparts (H4ev). The stress was generated with a laser tweezers mediated force applied on a fibronectin-coated polystyrene bead attached to integrins α5/β1 forming FAs. Measurement of the bead displacement allowed assessment of the viscoelastic response at FAs and the associated surface membrane stiffness. Notably, the loss of K8/K18 IFs in shK8b1 cells revealed an immediate reduction in bead displacements characteristic of a sudden increased in the FA elastic stiffness, incompatible with the K8/K18 IF intrinsic viscoelastic features, but in line with an induced perturbation of the mechanotransduction signals triggered at integrins. In addition, actin microfilament disruption, and to a lesser extent microtubule disruption, led to prominent decreases in the elastic stiffness of FAs, thus identifying actin-MFs and MTs as modulators of the time-dependent FA stiffening in both H4ev cells and shK8b1 cells, in response to mechanical stress. On technical ground, the laser tweezers offer a tool of choice to delineate the K8/K18 IF-mediated modulation of cytoskeletal versus signaling activities at FAs in epithelial cells in response to mechanical stress.
Energy requirements of eastern coyotes
Authors: Pekins Peter J. , Mautz William W.
Published: August 2008

We used indirect respiration calorimetry to measure seasonal metabolism and lower critical temperatures (TLC) of eastern coyotes (Canis latrans var.). The yearly mean basal metabolic rate was 10.6 L O2∙kg−1∙d−1. No difference was found among seasonal BMRs. The TLC values were 10, 0, and 5 °C during summer, autumn, and spring, respectively. Metabolism increased linearly below the TLC values. Normal temperatures in New Hampshire were well within the seasonal thermoneutral zones of eastern coyotes. The average daily energy requirements of free-ranging eastern coyotes during winter were estimated as 163.5 kcal∙kg−1 (3 × BMR). A 15-kg coyote required three snowshoe hares (Lepus americanus) every 2 days to satisfy these energy needs. In northern forested habitats, where hare and white-tailed deer (Odocoileus virginianus) may represent the primary prey species, interrelationships of the energy requirements of eastern coyotes with coyote breeding activity, sociality, and snow conditions may favor predation of white-tailed deer during late winter, particularly if hare availability is low.
Growth, maturity, and sexual dimorphism in the wood turtle, Clemmys insculpta
Authors: Lovich Jeffrey E. , Ernst Carl H. , McBreen John F.
Published: August 2008

Growth in the wood turtle (Clemmys insculpta) is described using the von Bertalanffy growth model and nonlinear regression. Growth in both sexes is similar until about 160 mm plastron length. Males grew at a faster rate after this size. Males appear to mature at a larger size and later age than females, although age-specific body size is highly variable. Sexual size dimorphism, in carapace length, is pronounced, with males attaining mean body sizes significantly larger (1.07–1.10 times) than those of adult females. Plastron length is an inappropriate measure of sexual size dimorphism because of the development of plastral concavity in males. Females tend to predominate in samples, possibly owing to differential maturity of the sexes. The direction of sexual size dimorphism may be maintained by intrasexual competition among males for access to females. Data for several adults captured at intervals of from 9 to 20 years support the concept of indeterminate growth.
Some Echiniscidae (Tardigrada: Heterotardigrada) from Vancouver Island, British Columbia, Canada
Authors: Kathman R. Deedee , Dastych Hieronim
Published: August 2008

Eight species of tardigrades in the family Echiniscidae were observed: Echiniscus horningi, Echiniscus mauccii, Echiniscus quadrispinosus, Echiniscus wendti, Hypechiniscus gladiator, Pseudechiniscus goedeni, Pseudechiniscus suillus, and Testechiniscus laterculus. Of these, six are new to British Columbia and three are new to Canada. Two species that were previously collected in 1908 and 1910 in British Columbia have been recollected. All eight species are described and illustrated.
The entrainment role of photoperiod on hypoosmoregulatory and growth-related aspects of smolting in Atlantic salmon (Salmo salar)
Authors: Duston James , Saunders Richard L.
Published: August 2008

Potential yearling (1+) smolts were maintained under 8.25 h light: 15.75 h dark and constant temperature (10.0 °C) from late December. Groups were subjected to an abrupt increase to 16 h light: 8 h dark on December 31 (group A), February 1 (group B), March 1 (group C), or March 31 (group D). Group E was maintained under constant 8.25 h light: 15.75 h dark for the duration of the experiment and group LDN was maintained under a simulated natural photoperiod cycle (45°N). Plasma osmolality levels following 24-h, 29‰ salinity challenge tests indicated a photoperiod-independent development of hypoosmoregulatory mechanisms preceding completion of smoltification that was significantly correlated with fish body size. As judged by 96-h, 37.5‰ salinity tolerance tests and changes in condition factor, completion of smolting occurred in sequence; in groups A and B it was advanced to late February, while groups C and D completed smolting in mid-March and mid-April, respectively, compared with late May for group LDN. Group E, maintained under constant 8.25 h light: 15.75 h dark, developed salinity tolerance in late May, but unlike other groups exhibited no large reduction in condition factor. Following smolting, an increase in condition factor and a loss of salinity tolerance occurred in all groups. The results support the hypothesis that changes in photoperiod entrain an endogenous circannual rhythm involved in controlling the completion of smoltification and subsequent loss of some smolt characteristics.
Arctic ground squirrel predation on collared lemmings
Authors: Boonstra Rudy , Krebs Charles J. , Kanter Michelle
Published: August 2008

We document the first recorded evidence of predation of collared lemmings (Dicrostonyx kilangmiutak) by arctic ground squirrels (Spermophilus parryii). During an intensive study of lemming populations at Pearce Point, Northwest Territories, using livetrapping and radiotelemetry, we found one and six lemmings predated by arctic ground squirrels in 1987 and 1988, respectively. Predation involved some or all of the following: digging lemmings out of burrows, carrying them to temporary ground squirrel burrows, and partial or complete consumption. The best evidence was obtained during 1988, when a minimum of 4.5% (6/132) of radiotagged lemmings were killed by squirrels.
Tuned oscillations in the swimming scallop Pecten maximus
Authors: DeMont M. Edwin
Published: August 2008

Scallops swim by rythmic opening and closing of the valves. Water ejected from the mantle cavity during closing of the valves generates thrust that propels the animal. The closing phase is powered by contraction of adduction muscles, whereas refilling is powered by energy stored in elastic material (abductin) compressed during the closing phase. This paper examines the physics of these oscillations. A model is developed to represent the oscillations with a second-order linear differential equation with constant coefficients. Values for the constants are measured experimentally or estimated from simple engineering principles. The system is forced by a function that represents the contraction of the adductor muscle, in this case a Fourier series defining a half wave rectified sine wave. The response of the system shows that there is a resonance at a frequency that is within the range of frequencies at which the animals swim. This implies that scallops may swim at the resonant frequency of the shell–hinge system. Attempts are made to estimate the energetic advantages of the phenomenon.
The Impacts of Fisheries on Marine Ecosystems and the Transition to Ecosystem-Based Management
Authors: Crowder Larry B. , Hazen Elliott L. , Avissar Naomi , Bjorkland Rhema , Latanich Catherine , Ogburn Matthew B.
Published: August 2008

Fishing remains one of the largest factors modifying marine ecosystems. Because fisheries constitute only one of many anthropogenic effects, management is shifting from single-species approaches toward ecosystem-based management. Interaction webs are a critical nexus to understand linkages, to model ecosystem change, and to apply management directives. Ecosystem-based management requires consideration of both direct and indirect effects of commercial fisheries. But it must also include impacts of bycatch, recreational fisheries, artisanal fisheries, and environmental change that can be large but unanticipated. Synergistic effects of fishing, environmental variation, and climate change increasingly threaten marine ecosystems and complicate management. Here we review the global effects of fisheries and propose an integrated framework for managing biophysical processes and human ecology. To incorporate the multitude of effects, this emerging approach focuses on the dynamics of interaction webs in a spatially explicit or place-based framework.
Marine Chemical Technology and Sensors for Marine Waters: Potentials and Limits
Authors: Moore Tommy S. , Mullaugh Katherine M. , Holyoke Rebecca R. , Madison Andrew S. , Yücel Mustafa , Luther George W.
Published: August 2008

A significant need exists for in situ sensors that can measure chemical species involved in the major processes of primary production (photosynthesis and chemosynthesis) and respiration. Some key chemical species are O2, nutrients (N and P), micronutrients (metals), pCO2, dissolved inorganic carbon (DIC), pH, and sulfide. Sensors need to have excellent detection limits, precision, selectivity, response time, a large dynamic concentration range, low power consumption, robustness, and less variation of instrument response with temperature and pressure, as well as be free from fouling problems (biological, physical, and chemical). Here we review the principles of operation of most sensors used in marine waters. We also show that some sensors can be used in several different oceanic environments to detect the target chemical species, whereas others are useful in only one environment because of various limitations. Several sensors can be used truly in situ, whereas many others involve water brought into a flow cell via tubing to the analyzer in the environment or aboard ship. Multi-element sensors that measure many chemical species in the same water mass should be targeted for further development.
Macro-Ecology of Gulf of Mexico Cold Seeps
Authors: Cordes Erik E. , Bergquist Derk C. , Fisher Charles R.
Published: August 2008

Shortly after the discovery of chemosynthetic ecosystems at deep-sea hydrothermal vents, similar ecosystems were found at cold seeps in the Gulf of Mexico. Over the past two decades, these sites have become model systems for understanding the physiology of the symbiont-containing megafauna and the ecology of seep communities worldwide. Symbiont-containing bivalves and siboglinid polychaetes dominate the communities, including five bathymodiolin mussel species and six vestimentiferan (siboglinid polychaete) species in the Gulf of Mexico. The mussels include the first described examples of methanotrophic symbiosis and dual methanotrophic/thiotrophic symbiosis. Studies with the vestimentiferans have demonstrated their potential for extreme longevity and their ability to use posterior structures for subsurface exchange of dissolved metabolites. Ecological investigations have demonstrated that the vestimentiferans function as ecosystem engineers and identified a community succession sequence from a specialized high-biomass endemic community to a low-biomass community of background fauna over the life of a hydrocarbon seep site.
Early mechanical dysfunction of the diaphragm in the muscular dystrophy with myositis (Ttnmdm) model
Authors: Lopez Michael A. , Pardo Patricia S. , Cox Gregory A. , Boriek Aladin M.
Published: August 2008

A complex rearrangement mutation in the mouse titin gene leads to an in-frame 83-amino acid deletion in the N2A region of titin. Autosomal recessive inheritance of the titin muscular dystrophy with myositis ( Ttn mdm/mdm) mutation leads to a severe early-onset muscular dystrophy and premature death. We hypothesized that the N2A deletion would negatively impact the force-generating capacity and passive mechanical properties of the mdm diaphragm. We measured in vitro active isometric contractile and passive length-tension properties to assess muscle function at 2 and 6 wk of age. Micro-CT, myosin heavy chain Western blotting, and histology were used to assess diaphragm structure. Marked chest wall distortions began at 2 wk and progressively worsened until 5 wk. The percentage of myofibers with centrally located nuclei in mdm mice was significantly ( P < 0.01) increased at 2 and 6 wk by 4% and 17%, respectively, compared with controls. At 6 wk, mdm diaphragm twitch stress was significantly ( P < 0.01) reduced by 71%, time to peak twitch was significantly ( P < 0.05) reduced by 52%, and half-relaxation time was significantly ( P < 0.05) reduced by 57%. Isometric tetanic stress was significantly ( P < 0.05) depressed in 2- and 6-wk mdm diaphragms by as much as 64%. Length-tension relationships of the 2- and 6-wk mdm diaphragms showed significantly ( P < 0.05) decreased extensibility and increased stiffness. Slow myosin heavy chain expression was aberrantly favored in the mdm diaphragm at 6 wk. Our data strongly support early contractile and passive mechanical aberrations of the respiratory pump in mdm mice.
Electron probe X-ray microanalysis of intact pathway for human aqueous humor outflow
Authors: McLaughlin Charles W. , Karl Mike O. , Zellhuber-McMillan Sylvia , Wang Zhao , Do Chi Wai , Leung Chi Ting , Li Ang , Stone Richard A. , Macknight Anthony D. C. , Civan Mortimer M.
Published: August 2008

Intraocular pressure (IOP) is regulated by the resistance to outflow of the eye's aqueous humor. Elevated resistance raises IOP and can cause glaucoma. Despite the importance of outflow resistance, its site and regulation are unclear. The small size, complex geometry, and relative inaccessibility of the outflow pathway have limited study to whole animal, whole eye, or anterior-segment preparations, or isolated cells. We now report measuring elemental contents of the heterogeneous cell types within the intact human trabecular outflow pathway using electron-probe X-ray microanalysis. Baseline contents of Na+, K+, Cl−, and P and volume (monitored as Na+K contents) were comparable to those of epithelial cells previously studied. Elemental contents and volume were altered by ouabain to block Na+-K+-activated ATPase and by hypotonicity to trigger a regulatory volume decrease (RVD). Previous results with isolated trabecular meshwork (TM) cells had disagreed whether TM cells express an RVD. In the intact tissue, we found that all cells, including TM cells, displayed a regulatory solute release consistent with an RVD. Selective agonists of A1 and A2 adenosine receptors (ARs), which exert opposite effects on IOP, produced similar effects on juxtacanalicular (JCT) cells, previously inaccessible to functional study, but not on Schlemm's canal cells that adjoin the JCT. The results obtained with hypotonicity and AR agonists indicate the potential of this approach to dissect physiological mechanisms in an area that is extremely difficult to study functionally and demonstrate the utility of electron microprobe analysis in studying the cellular physiology of the human trabecular outflow pathway in situ.
Directing osteogenic and myogenic differentiation of MSCs: interplay of stiffness and adhesive ligand presentation
Authors: Rowlands Andrew S. , George Peter A. , Cooper-White Justin J.
Published: August 2008

The mechanical properties of the extracellular matrix (ECM) can exert significant influence in determining cell fate. Human mesenchymal stem cells (MSCs) grown on substrates with varying stiffness have been shown to express various cell lineage markers, without the use of toxic DNA demethylation agents or complex cocktails of expensive growth factors. Here we investigated the myogenic and osteogenic potential of various polyacrylamide gel substrates that were coated with covalently bound tissue-specific ECM proteins (collagen I, collagen IV, laminin, or fibronectin). The gel-protein substrates were shown to support the growth and proliferation of MSCs in a stiffness-dependent manner. Higher stiffness substrates encouraged up to a 10-fold increase in cell number over lower stiffness gels. There appears to be definitive interplay between substrate stiffness and ECM protein with regard to the expression of both osteogenic and myogenic transcription factors by MSCs. Of the 16 gel-protein combinations investigated, osteogenic differentiation was found to occur significantly only on collagen I-coated gels with the highest modulus gel tested (80 kPa). Myogenic differentiation occurred on all gel-protein combinations that had stiffnesses >9 kPa but to varying extents as ascertained by MyoD1 expression. Peak MyoD1 expression was seen on gels with a modulus of 25 kPa coated in fibronectin, with similar levels of expression observed on 80-kPa collagen I-coated gels. The modulation of myogenic and osteogenic transcription factors by various ECM proteins demonstrates that substrate stiffness alone does not direct stem cell lineage specification. This has important implications in the development of tailored biomaterial systems that more closely mimic the microenvironment found in native tissues.
Role of Krüppel-like factor 6 in transforming growth factor-β1-induced epithelial-mesenchymal transition of proximal tubule cells
Authors: Holian John , Qi Weier , Kelly Darren J. , Zhang Yuan , Mreich Ellein , Pollock Carol A. , Chen Xin-Ming
Published: August 2008

Krüppel-like factor 6 (KLF6) is a DNA-binding protein containing a triple zinc-fingered motif and plays a key role in the regulation of cell proliferation, differentiation, and development. More recently it has been implicated in hepatic fibrosis via its binding to the transforming growth factor (TGF)-β control element. In the kidney, epithelial-mesenchymal transition (EMT) is a major contributor to the pathogenesis of renal fibrosis, with TGF-β1 being a key mediator of EMT. The present study aimed to determine the role of KLF6 and TGF-β1 in EMT in proximal tubule cells. To determine the relevance in clinical disease, KLF6 was measured in kidneys of streptozotocin-induced diabetic Ren-2 rats and in cells exposed to high (30 mM) glucose. TGF-β1 was confirmed to induce EMT by morphological change, loss of E-cadherin, and gain in vimentin expression. KLF6 mRNA expression was concomitantly measured. To determine the role of KLF6 in EMT, the above markers of EMT were determined in KLF6-silenced (small interfering RNA) and KLF6-overexpressing proximal tubule cells. KLF6 overexpression significantly promoted a phenotype consistent with EMT. High glucose induced KLF6 in proximal tubule cells ( P < 0.05). This increase in KLF6 in response to high glucose was TGF-β1 mediated. In an in vivo model of diabetic nephropathy KLF6 increased at week 8 ( P < 0.05). KLF6 plays a permissive role in TGF-β1-induced EMT in proximal tubule cells. Its upregulation in in vivo models of diabetic nephropathy suggests it as a potential therapeutic target.
Periostin induces proliferation of human autosomal dominant polycystic kidney cells through αV-integrin receptor
Authors: Wallace Darren P. , Quante Megan T. , Reif Gail A. , Nivens Emily , Ahmed Farhana , Hempson Scott J. , Blanco Gustavo , Yamaguchi Tamio
Published: August 2008

Progressive renal enlargement due to the growth of innumerable fluid-filled cysts is a central pathophysiological feature of autosomal dominant polycystic kidney disease (ADPKD). These epithelial neoplasms enlarge slowly and damage noncystic parenchyma by mechanisms that have not been clearly defined. In a microarray analysis of cultured human ADPKD cyst epithelial cells, periostin mRNA was overexpressed 15-fold compared with normal human kidney (NHK) cells. Periostin, initially identified in osteoblasts, is not expressed in normal adult kidneys but is expressed transiently during renal development. We found periostin in cyst-lining cells in situ in the extracellular matrix adjacent to the cysts and within cyst fluid. ADPKD cells secreted periostin across luminal and basolateral plasma membranes. Periostin increased proliferation of cyst epithelial cells 27.9 ± 3.1% ( P < 0.001) above baseline and augmented in vitro cyst growth but did not affect proliferation of normal renal cells. Expression of αV-integrin, a periostin receptor, was ninefold higher in ADPKD cells compared with NHK cells, and antibodies that block αV-integrin inhibited periostin-induced cell proliferation. We conclude that periostin is a novel autocrine mitogen secreted by mural epithelial cells with the potential to accelerate cyst growth and promote interstitial remodeling in ADPKD.
Complement activation by tubular cells is mediated by properdin binding
Authors: Gaarkeuken Hilde , Siezenga Machiel A. , Zuidwijk Kim , van Kooten Cees , Rabelink Ton J. , Daha Mohamed R. , Berger Stefan P.
Published: August 2008

Activation of filtered complement products on the brush border of the tubular epithelium is thought to be a key factor underlying proteinuria-induced tubulointerstitial injury. However, the mechanism of tubular complement activation is still unclear. Recent studies on mechanisms of complement activation indicate a key role for properdin in the initiation of an alternative pathway. We hypothesized that properdin serves as a focal point for complement activation on the tubulus. We observed a strong staining for properdin on the luminal surface of the tubules in kidney biopsies from patients with proteinuric renal disease. In vitro experiments revealed dose-dependent binding of properdin to proximal tubular epithelial cells (PTEC), whereas no significant binding to endothelial cells was detected. Exposure of PTEC with normal human serum as a source of complement resulted in complement activation with deposition of C3 and generation of C5b-9. These effects were virtually absent with properdin-deficient serum. Preincubation of PTEC with properdin before addition of properdin-depleted serum fully restored complement activation on the cells, strongly suggesting a key role for properdin in the activation of complement at the tubular surface. In proteinuric renal disease, filtered properdin may bind to PTEC and act as a focal point for alternative pathway activation. We propose that this contribution of properdin is pivotal in tubular complement activation and subsequent damage. Interference with properdin binding to tubular cells may provide an option for the treatment of proteinuric renal disease.
Low-Frequency Envelope Sensitivity Produces Asymmetric Binaural Tuning Curves
Authors: Agapiou John P. , McAlpine David
Published: August 2008

Neurons in the auditory midbrain are sensitive to differences in the timing of sounds at the two ears—an important sound localization cue. We used broadband noise stimuli to investigate the interaural-delay sensitivity of low-frequency neurons in two midbrain nuclei: the inferior colliculus (IC) and the dorsal nucleus of the lateral lemniscus. Noise-delay functions showed asymmetries not predicted from a linear dependence on interaural correlation: a stretching along the firing-rate dimension ( rate asymmetry), and a skewing along the interaural-delay dimension ( delay asymmetry). These asymmetries were produced by an envelope-sensitive component to the response that could not entirely be accounted for by monaural or binaural nonlinearities, instead indicating an enhancement of envelope sensitivity at or after the level of the superior olivary complex. In IC, the skew-like asymmetry was consistent with intermediate-type responses produced by the convergence of ipsilateral peak-type inputs and contralateral trough-type inputs. This suggests a stereotyped pattern of input to the IC. In the course of this analysis, we were also able to determine the contribution of time and phase components to neurons' internal delays. These findings have important consequences for the neural representation of interaural timing differences and interaural correlation—cues critical to the perception of acoustic space.
Effects of Gait Variations on Grip Force Coordination During Object Transport
Authors: Gysin Priska , Kaminski Terry R. , Hass Chris J. , Grobet Cécile E. , Gordon Andrew M.
Published: August 2008

In object transport during unimpeded locomotion, grip force is precisely timed and scaled to the regularly paced sinusoidal inertial force fluctuations. However, it is unknown whether this coupling is due to moment-to-moment predictions of upcoming inertial forces or a longer, generalized time estimate of regularly paced inertial forces generated during the normal gait cycle. Eight subjects transported a grip instrument during five walking conditions, four of which altered the gait cycle. The variations included changes in step length (taking a longer or shorter step) or stepping on and over a stable (predictable) or unstable (unpredictable support surface) obstacle within a series of baseline steps, which resulted in altered frequencies and magnitudes of the inertial forces exerted on the transported object. Except when stepping on the unstable obstacle, a tight temporal coupling between the grip and inertial forces was maintained across gait variations. Precision of this timing varied slightly within the time window for anticipatory grip force control possibly due to increased attention demands related to some of the step alterations. Furthermore, subjects anticipated variations in inertial force when the gait cycle was altered with increases or decreases in grip force, relative to the level of the inertial force peaks. Overall the maintenance of force coupling and scaling across predictable walking conditions suggests that the CNS is able to anticipate changes in inertial forces generated by gait variations and to efficiently predict the grip force needed to maintain object stability on a moment-to-moment basis.
Molecular Identity and Functional Properties of a Novel T-Type Ca2+ Channel Cloned From the Sensory Epithelia of the Mouse Inner Ear
Authors: Nie Liping , Zhu Jun , Gratton Michael Anne , Liao Amy , Mu Karen J. , Nonner Wolfgang , Richardson Guy P. , Yamoah Ebenezer N.
Published: August 2008

The molecular identity of non-Cav1.3 channels in auditory and vestibular hair cells has remained obscure, yet the evidence in support of their roles to promote diverse Ca2+-dependent functions is indisputable. Recently, a transient Cav3.1 current that serves as a functional signature for the development and regeneration of hair cells has been identified in the chicken basilar papilla. The Cav3.1 current promotes spontaneous activity of the developing hair cell, which may be essential for synapse formation. Here, we have isolated and sequenced the full-length complementary DNA of a distinct isoform of Cav3.1 in the mouse inner ear. The channel is derived from alternative splicing of exon14, exon25A, exon34, and exon35. Functional expression of the channel in Xenopus oocytes yielded Ca2+ currents, which have a permeation phenotype consistent with T-type channels. However, unlike most multiion channels, the T-type channel does not exhibit the anomalous mole fraction effect, possibly reflecting comparable permeation properties of divalent cations. The Cav3.1 channel was expressed in sensory and nonsensory epithelia of the inner ear. Moreover, there are profound changes in the expression levels during development. The differential expression of the channel during development and the pharmacology of the inner ear Cav3.1 channel may have contributed to the difficulties associated with identification of the non-Cav1.3 currents.
Cholinergic Responses in Crossed Tecto-Reticular Neurons of Rat Superior Colliculus
Authors: Sooksawate Thongchai , Isa Kaoru , Isa Tadashi
Published: August 2008

Neurons in the intermediate gray layer (SGI) of mammalian superior colliculus (SC) receive cholinergic innervation from the brain stem parabrachial region, which seems to modulate the signal processing in the SC. To clarify its role particularly in orienting behaviors, we studied cholinergic effects on the major output neuron group of the SGI, crossed tecto-reticular neurons (cTRNs), identified by retrograde labeling from the contralateral brain stem gaze center in SC slices obtained from rats (PND 17–22) by whole cell patch-clamp techniques. Bath application of carbachol induced either 1) nicotinic inward (nIN) + muscarinic inward (mIN) (11/24) or 2) nIN + mIN + muscarinic outward (mOUT) (13/24) current responses. Transient pressure application of 1 mM acetylcholine elicited nIN in all neurons tested ( n = 58). In a majority of these neurons (52/58), the nIN was completely suppressed by dihydro-β-erythroidine, a specific antagonist for α4β2 nicotinic receptor subtype. The remaining 6/58 neurons exhibited not only the slower α4β2 receptor-mediated component but also a faster component that was inhibited by a specific antagonist for α7 nicotinic receptor, α-bungarotoxin. cTRNs expressing α7 nicotinic receptors tended to be smaller in size than those lacking α7 receptors. Bath application of muscarine induced two response patterns: mIN only (17/38) and mIN+ mOUT (21/38). The mIN and mOUT were mediated by M3 (plus M1) and M2 muscarinic receptors, respectively. These results suggest that a major response to cholinergic inputs to cTRNs is excitatory. This would indicate the facilitatory role of the brain stem cholinergic system in the execution of orienting behaviors including saccadic eye movements.
Machine Learning of the Reactor Core Loading Pattern Critical Parameters
Authors: Trontl Krešimir , Pevec Dubravko , Šmuc Tomislav
Published: August 2008

The usual approach to loading pattern optimization involves high degree of engineering judgment, a set of heuristic rules, an optimization algorithm, and a computer code used for evaluating proposed loading patterns. The speed of the optimization process is highly dependent on the computer code used for the evaluation. In this paper, we investigate the applicability of a machine learning model which could be used for fast loading pattern evaluation. We employ a recently introduced machine learning technique, support vector regression (SVR), which is a data driven, kernel based, nonlinear modeling paradigm, in which model parameters are automatically determined by solving a quadratic optimization problem. The main objective of the work reported in this paper was to evaluate the possibility of applying SVR method for reactor core loading pattern modeling. We illustrate the performance of the solution and discuss its applicability, that is, complexity, speed, and accuracy.
The Role of PPARγ in the Cyclooxygenase Pathway in Lung Cancer
Authors: Hazra Saswati , Peebles Katherine A. , Sharma Sherven , Mao Jenny T. , Dubinett Steven M.
Published: August 2008

Decreased expression of peroxisome proliferator activated receptor‐γ (PPARγ) and high levels of the proinflammatory enzyme cyclooxygenase‐2 (COX‐2) have been observed in many tumor types. Both reduced (PPARγ) expression and elevated COX‐2 within the tumor are associated with poor prognosis in lung cancer patients, and recent work has indicated that these signaling pathways may be interrelated. Synthetic (PPARγ) agonists such as the thiazolidinedione (TZD) class of anti‐diabetic drugs can decrease COX‐2 levels, inhibit growth of non‐small‐cell lung cancer (NSCLC) cells in vitro, and block tumor progression in xenograft models. TZDs alter the expression of COX‐2 and consequent production of the protumorigenic inflammatory molecule prostaglandin E2 (PGE2) through both (PPARγ) dependent and independent mechanisms. Certain TZDs also reduce expression of PGE2 receptors or upregulate the PGE2 catabolic enzyme 15‐prostaglandin dehydrogenase. As several COX‐2 enzymatic products have antitumor properties and specific COX‐2 inhibition has been associated with increased risk of adverse cardiac events, directly reducing the effects or concentration of PGE2 may provide a more safe and effective strategy for lung cancer treatment. Understanding the mechanisms underlying these effects may be helpful for designing anticancer therapies. This article summarizes recent research on the relationship between (PPARγ), TZDs, and the COX‐2/PGE2 pathways in lung cancer.
Chemokines and Transplant Vasculopathy
Authors: Belperio John A , Ardehali Abbas
Published: August 2008

Transplant vasculopathy (TV) remains the leading cause of late death among heart transplant recipients. Transplant vasculopathy is characterized by progressive neointimal proliferation, leading to ischemic failure of the allograft. Multiple experimental and clinical studies have shown that injury to the graft at various stages of transplantation can be a risk factor for development of transplant vasculopathy. The hallmark of cardiac allograft injury is the infiltration of leukocytes. Recruitment of leukocytes requires intercellular communication between infiltrating cells, endothelium, parenchymal cells, and components of extracellular matrix. These events are mediated via the generation of adhesion molecules, cytokines, and chemokines. The chemokines, by virtue of their specific cell receptor expression, can selectively mediate the local recruitment/activation of distinct leukocytes/cells, allowing for migration across the endothelium and beyond the vascular compartment. This report provides a comprehensive review of the chemokines that participate in the development of transplant vasculopathy.
Pacific Climate Change and ENSO Activity in the Mid-Holocene
Authors: Chiang J. C. H. , Fang Y. , Chang P.
Published: August 2008

The authors argue that a reduction to the stochastic forcing of the El Niño–Southern Oscillation (ENSO) wrought by Pacific-wide climate changes in response to mid-Holocene (6000 BP) orbital forcing is a viable hypothesis for the observed reduction of ENSO activity during that time. This conclusion is based on comprehensive analysis of an intermediate coupled model that achieves significant reduction to ENSO variance in response to mid-Holocene orbital forcing. The model’s excellent simulation of the tropical Pacific interannual variability lends credibility to the results.

Idealized simulations demonstrate that the mid-Holocene influence is communicated to the tropical Pacific largely via climate changes outside of the tropical Pacific, rather than from insolation changes directly on the tropical Pacific. This is particularly true for changes to the ENSO, but also with changes to the cold tongue annual cycle. Previously proposed mechanisms for teleconnected mid-Holocene ENSO changes, including forcing of ENSO by a strengthened Asian summer monsoon and an increase in the annual cycle forcing on the tropical Pacific leading to a reduction in ENSO activity by frequency entrainment, do not appear to occur in these simulations. Rather, the authors show that the modeled mid-Holocene climate exhibits a pronounced reduction in Pacific meridional mode activity that has been recently shown to be a forcing on ENSO, though the reasons for this reduction are still to be explained.

The contrasting nature of the results compared to previous studies highlights the effect of the prevailing ENSO paradigm on this problem. By showing that an externally forced ENSO model is equally capable of explaining mid-Holocene ENSO reduction as its nonlinear, weakly chaotic counterpart, it is demonstrated that the mid-Holocene ENSO data point cannot yet discriminate between these two paradigms of ENSO.
Investigation of a Severe Downburst Storm near Phoenix, Arizona, as Seen by a Mobile Doppler Radar and the KIWA WSR-88D
Authors: Vasiloff Steven V. , Howard Kenneth W.
Published: August 2008

A Shared Mobile Atmospheric Research and Teaching Radar (SMART-R) was deployed near Phoenix, Arizona, during the summer of 2004. The goal was to capture a severe microburst at close range to understand the low-altitude wind structure and evolution. During the evening of 27 July, a severe storm formed along the Estrella Mountains south of Phoenix and moved south of the SMART-R as well as the National Weather Service’s (NWS) Weather Surveillance Radar-1988 Doppler (WSR-88D) in Phoenix (KIWA). Several microburst–downburst pulses were observed by radar and a surface wind gust of 67 mi h−1 was reported. The radar data illustrate the finescale structure of the microburst pulses, with the SMART-R’s higher-resolution data showing Doppler velocities 3–4 m s−1 greater than the KIWA radar. SMART-R wind shear values were 2–3 times greater with the finer resolution of the SMART-R revealing smaller features in the surface outflow wind structure. Asymmetric outflow may have been a factor as well in the different divergence values. The evolution of the outflow was very rapid with the 5-min KIWA scan intervals being too course to sample the detailed evolution. The SMART-R scans were at 3–5-min intervals and also had difficulty resolving the event. The storm environment displayed characteristics of both moderate-to-high-reflectivity microbursts, typical of the high plains of Colorado.
A Micromechanical Damage Model for Carbon Fiber Composites at Reduced Temperatures
Authors: Peterson Edward C. , Patil Ranjit R. , Kallmeyer Alan R. , Kellogg Kenneth G.
Published: August 2008

Fiber-reinforced composites are seeing increased use in civil infrastructure applications where they may be exposed to moisture, sub-ambient temperatures (below —40°C in northern regions), and reduced-temperature (freeze— thaw) thermal cycling. These environments may induce internal damage in the composite due to residual stresses caused by mismatches in coefficients of thermal expansion between the constituents. In this study, a micromechanical damage model is presented for the prediction of matrix crack development in a unidirectional carbon/epoxy composite resulting from exposure to sub-ambient temperatures. Two thermal loadings are considered: cool-down from the cure temperature of the composite (121°C) to 25°C (▵T= -96°C) and to -50°C (▵T=-171°C). A finite element model is utilized to determine the internal stresses due to differences in the CTE of the constituents, and a shear-lag model is developed to predict subsequent crack spacing in the matrix. The influence of fiber spacing (or fiber volume fraction) is addressed. Model predictions indicate that, at 25°C, the internal stresses are not large enough to cause matrix cracking in this composite. However, at -50°C, the longitudinal tensile stress in the matrix exceeds the strength of the epoxy at most typical fiber volume fractions, which will result in matrix cracking. The shear-lag model was used to predict the subsequent crack spacing, and demonstrated a strong dependence on service temperature and fiber spacing. The model predictions provide good qualitative agreement with experimental observations, and indicate that the development of damage in a composite should be considered in the design of composite structures for reduced temperature environments.
Ibero-American observatories in the sectors of information, communication and culture: a brief history
Authors: Albornoz Luis A. , Herschmann Micael
Published: August 2008

This commentary provides an overview of the recent phenomenon of Ibero-American observatories which work on issues related to information, communication and culture. It also shows the results of some research under way which seeks to analyse the diversity of 61 observatories regarding their geographical location, key research themes and area of operations.
Variability and seasonality of North Atlantic climate during the early Holocene: evidence from Faroe Island lake sediments
Authors: Jessen Catherine A. , Rundgren Mats , Björck Svante , Andresen Camilla S. , Conley Daniel J.
Published: August 2008

Based on their position in relation to major ocean currents, palaeoclimatic archives in the Faroe Islands are expected to be sensitive recorders of variations in North Atlantic circulation. The multiproxy analysis (magnetic susceptibility, total carbon, nitrogen and sulphur, biogenic silica, grains >255 µm) of a lacustrine record with both winter and summer climate indicators illustrates the variability of Faroese climate during the early Holocene ( c. 11 300—10 240 cal. yr BP) and allows comparison with other records in the region. Our high-resolution record suggests a period of predominantly winter cooling and increased storminess centred at c. 11 150 cal. yr BP followed by a period of stability between c. 11 000 and 10 680 cal. yr BP, which correlates with a time when the North Atlantic was particularly free of meltwater incursions. After c. 10 680 cal. yr BP, both winter and summer indicators show an increase in variability broadly synchronous with increased variability at other North Atlantic sites. Within this time period, a predominantly winter cooling centred at c. 10 600 cal. yr BP, a winter/summer cooling centred at c. 10 450 cal. yr BP and a winter/summer cooling centred at c. 10 300 cal. yr BP are recorded. These distinctive coolings correspond to periods of ice core δ18O inferred lowered atmospheric temperatures over Greenland and the reoccurrence of meltwater outbursts at c. 10 600, 10 500 and 10 350 cal. yr BP.
Holocene history of the River Seine, Paris, France: bio-chronostratigraphic and geomorphological evidence from the Quai-Branly
Authors: Chaussé Christine , Leroyer Chantal , Girardclos Olivier , Allenet Gisèle , Pion Patrick , Raymond Pascal
Published: August 2008

Bio-chronostratigraphic observations compiled from Quai-Branly in Paris (France) and their comparison with previous studies in the Paris Basin allow documentation of the morphodynamic evolution of the River Seine during the middle and late Holocene. This history begins in the Boreal (between 9500 and 8850 cal. BP), with the deposition of tufa, expressing a stabilized river bed. During the second part of the sub-Boreal the water-table was low. At the beginning of the sub-Atlantic (towards 2800/2700 cal. BP), alluvial dynamics increase, as is recorded elsewhere throughout the Paris Basin. At the beginning of the second part of the sub-Atlantic (around 2000 cal. BP), flood dynamics persisted at a lower intensity. Human occupation occurred from the fifth century AD. Before or around the beginning of the seventeenth century AD, a natural levee was built, indicating the progressive attachment of the Quai-Branly area to the floodplain. The hydrodynamic evolution of the River Seine observed at the Quai-Branly site is similar to that recorded in other river valley floors of the Paris Basin. This evolution appears to be in response to global climatic changes rather than to variations induced by human activities.
Analysis of short DNA fragments from Holocene peatmoss samples
Authors: Suyama Y. , Gunnarsson U. , Parducci L.
Published: August 2008

This paper describes our recent attempt to isolate and analyse DNA from old plant remains of the common peatmoss Sphagnum fuscum retrieved from a peat core collected in the mire Fuglmyra, in central Norway. DNA was recoverable and usable from subfossilized (10—450 years old) plant remains of the peatmoss. A chloroplast ( trnL) and two nuclear (ITS2 and RAPDf) regions were co-amplified from 80 samples of different ages. The RAPDf region was the only variable one with three different haplotypes found among five samples. Comparison of the ancient sequences with modern sequences found in the extant population occurring at the same site ascertained a genetic link between modern and fossil samples of this species. This retrieval of ancient DNA from subfossilized moss remains isolated from peat cores has important implications for the palaeoecology of peatmosses by allowing direct estimates of plant population dynamics in space and time.