bluuebunny/crossref_metadata_2025 huggingface dataset:
Hibernation exhibit for Japanese black bear Ursus thibetanus japonicus at Ueno Zoological Gardens
Authors: ITOH K. , IDE K. , KOJIMA Y. , TERADA M.
Published: February 2010

In April 2006, a new bear exhibit was completed at Ueno Zoological Gardens, based on a concept whereby three bear species, from different climatic zones, would be exhibited alongside small mammal species from each zone. Visitors would be able to observe the hibernation of both the Japanese black bear Ursus thibetanus japonicus and other small mammals during the winter. The Japanese black bear, a subspecies distributed from China to south‐east Asia, is found on the Japanese islands of Honshu, Shikoku and Kyushu. This bear hibernates in tree hollows in winter and, during this time, pregnant ♀♀ deliver and rear their young. To observe bears in hibernation, air‐conditioning and illumination equipment were installed in the exhibit in order to create the environment of a mountainous habitat in winter. We first exhibited a Japanese black bear in hibernation in the winter of 2006/2007, when we observed induction to hibernation, hibernation and awakening from hibernation. We repeated this complete sequence in the winter of 2007/2008 and, as a result, we gained knowledge about behavioural changes and changes in physiological data for the Japanese black bear during hibernation. Meanwhile, the real‐time hibernation exhibit promoted understanding of hibernation among visitors to Ueno Zoological Gardens. It also generated a lot of media interest: between 2006 and 2007, the exhibit featured in 69 media reports, newspaper and magazine articles.
Effects of increasing days of exposure to prepartum transition diets on reproduction and health in dairy cows
Authors: DeGaris PJ , Lean IJ , Rabiee AR , Heuer C
Published: February 2010

Objective To evaluate the effect of the number of days exposure to a prepartum transition diet on reproduction and health in dairy cows.

Design A prospective cohort study.

Procedures We enrolled 1008 dairy cows from three herds to examine the effects on reproduction and health of increased days exposure to prepartum transition diets that included ryegrass pasture, ryegrass silage, cereal hay, grain, by‐products, oilseed meals, BioChlor®, rumen modifiers, minerals and vitamins. Diets provided 9.9 MJ metabolisable energy per kg dry matter (DM), a metabolisable protein balance of 286 g/day and a dietary cation anion difference of −150 meq/kg DM. Statistical models controlled for herd, calving day, age and gestation period.

Results In two of the three herds increased days exposure to prepartum transition diets increased the hazards of submission for breeding, conception and clinical mastitis, and decreased the hazard of cow removal. The odds of pregnancy by 6 and 21 weeks after the mating start date tended to increase with increasing days of exposure to prepartum transition diets.

Conclusions Increasing exposure to a prepartum transition diet improved the calving to conception interval, tended to improve the odds of pregnancy and reduced the risk of culling of cattle, but increased the hazard of clinical mastitis.
Mycobacterium ulcerans infections in two horses in south‐eastern Australia
Authors: Van Zyl A , Daniel J , Wayne J , McCowan C , Malik R , Jelfs P , Lavender CJ , Fyfe JA
Published: February 2010

Two horses were diagnosed as having Mycobacterium ulcerans infections. The first was a 21‐year‐old Quarterhorse‐cross mare living in Mallacoota (a coastal town near the border of New South Wales and Victoria, Australia) that presented with lichenification, hair‐loss and oedema on a fetlock, which subsequently ulcerated, as well as a non‐healing ulcer on the wither. The second horse was a 32 year‐old Standardbred gelding from Nicholson, near Bairnsdale, Victoria, that had an ulcerated lesion on its caudal thigh. Histologically, there were characteristic changes seen with M. ulcerans infections in other species, including extensive necrosis without associated granulomatous inflammation. The organisms were seen in Ziehl‐Neelsen‐stained smears or sections of the lesions from both horses and were isolated in culture from the first horse. A definitive diagnosis was provided by real‐time polymerase chain reaction targeting the M. ulcerans‐specific insertion sequence, IS2404. Delayed identification of the infectious agent in the first case led to the use of suboptimal antimicrobial therapy, resulting in failure to control the infection and the horse was subsequently euthanased. The second horse was successfully treated following surgical debulking of the centre of the lesion and one session of aggressive cryosurgery. Mycobacterium ulcerans should be considered in the differential diagnosis of unexplained lichenification with oedematous and ulcerated skin lesions in horses living in regions where this organism is endemic.
Rib osteomyelitis in three foals
Authors: Neil KM , Charman RE , Vasey JR
Published: February 2010

Three foals aged between 21 and 44 days were presented for evaluation of pyrexia and lameness. Each had subcutaneous abscessation associated with osteomyelitis of a rib at the costochondral junction and pathological fracture of the affected rib; one foal had more than one rib affected. Other localised sites of infection included other sites of osteomyelitis, omphalophlebitis, uveitis, enterocolitis, and calcaneal bursitis. The subcutaneous abscessation and rib osteomyelitis was treated surgically in two foals.Salmonella typhimuriumwas isolated from the subcutaneous abscess in one foal and from the faeces of another. Two of the three foals were euthanased. Ultrasonography was a more useful modality than radiography for establishing the diagnosis of costal osteomyelitis.
In this issue – March 2010
Authors: Jackson AE
Published: February 2010

Topical anaesthesia for castration and tail docking in lambs · Disease surveillance activities for saleyard pigs · Reproductive effects of time on prepartum transition diets in dairy cows · Bovine herpesvirus type 5 in bull semen · Rib osteomyelitis in three foals · Mycobacterium ulcerans in two horses · Nasal vascular hamartoma in a cat
Systematic review on the compatibility of Shuanghuanglian injection combined with western medical injections
Authors: Zhang Junhua , Shang Hongcai , Zheng Wenke , Hu Jing , Xu Hongjuan , Wang Hui , Zhang Li , Ren Ming , Zhang Boli
Published: February 2010

Objectives Shuanghuanglian injection (SHLI) is a typical Chinese herbal injection which has been used for more than 20 years. This study aims to investigate the compatibility of SHLI with western intravenous agents.

Methods An extensive literature search was executed to identify all experimental tests and clinical reports on the topics. Data on the types of infusion solutions and western medical injections, usage and dosage, outcome measures for physical and chemical properties, and changes of drug effect were searched for. The included data was analyzed and described by the category of included western drugs. Compatibility was tested through integrating the evaluations of physical properties, chemical composition, drug metabolism, and safety.

Results Sixty articles (38 experimental tests and 22 clinical reports) were included after screening. Fifty–three western medical injections were identified from all the included articles. Most of the research was about the compatibility of SHLI with different types of antibiotics, including β‐lactam, aminoglycoside, and quinolone etc. Thirty‐one western medical injections were not recommended to be combined with SHLI. The quality of the experimental test design was low because of unbalanced evaluation indicators: more attention to physical changes than drug metabolism, effect, and safety.

Conclusions A broad incompatibility existed in the combination of SHLI with western medical injections. Some results were still uncertain, but the combinations should still be avoided until researched clearly. The compatibility and interaction of Chinese herbal injections and western medicines is still a weak area. The pharmaceutical sector should strengthen post‐market research to update evidence and improve its distribution.
Toxicants Exposures as Novel Zoonoses: Reflections on Sustainable Development, Food Safety and Veterinary Public Health
Authors: Frazzoli C. , Mantovani A.
Published: February 2010

The modern concept of zoonosis considers any detriment to the health and/or quality of human life resulting from relationships with (other) vertebrate or edible or toxic invertebrate animals. Whereas exposure to toxicants through foods of animal origin (a.o.) is a well‐established issue, hereby we discuss it as novel zoonoses, from the standpoints of health implications as well as similarities and differences with classical zoonoses caused by biological agents. Novel toxicant‐related zoonoses are linked with new issues in food safety, such as the environment‐feed‐food chain. In fact, the potential effect of the combined and repeated exposure to dietary toxicants is generally long‐term and not readily discernible. Endocrine disrupting chemicals in staple foods of a.o. are discussed as a telling example of a food safety issue summing up critical points covered by the definition of sustainable development, also implicating health risks for generations to come. We suggest some critical points to implement the veterinary public health action in sustainable food safety, such as enhancement of Hazard Analysis and Critical Control Points systems for toxicological risk management.
Diagnosis of Bovine‐Associated Parapoxvirus Infections in Humans: Molecular and Epidemiological Evidence
Authors: MacNeil A. , Lederman E. , Reynolds M. G. , Ragade N. J. , Talken R. , Friedman D. , Hall W. , Shwe T. , Li Y. , Zhao H. , Smith S. , Davidson W. , Hughes C. , Damon I. K.
Published: February 2010

Orf virus, pseudocowpox virus and bovine papular stomatitis virus, are parapoxviruses, associated with domestic ruminants, which are capable of causing cutaneous infections in humans. Owing to virtually identical appearances in humans, clinical differentiation of these viruses is difficult. We discuss three recent occurrences of parapoxvirus infection, involving contact with domestic bovine and use a combination of molecular and epidemiological data in the diagnosis. These cases underscore the utility of modern diagnostic tools, along with species‐specific contact information in acquiring a definitive diagnosis, in the case of suspected parapoxvirus infection.
Tularaemia in Minnesota: Case Report and Brief Epidemiology
Authors: Scheftel J. M. , Griffith J. M. , Leppke B. A. , Pantlin G. C. , Snippes P. M. , Wünschmann A.
Published: February 2010

The 2008 case presented here of tularaemia in a cat and its owner occurred in an urban setting and was associated with animal contact, a relatively rare mode of transmission in Minnesota in recent years. Response to this case exemplified a ‘One Health’ approach involving pre‐existing relationships, cooperation between multiple disciplines and laboratory infrastructure that facilitated information sharing.
A Method to Generate Propulsor Side Forces
Authors: Huyer Stephen A. , Dropkin Amanda , Dick James , Beal David
Published: February 2010

A computational study was performed to investigate a method to generate vehicle maneuvering forces from a propulsor alone. A ducted, preswirl propulsor was configured with an upstream stator row and downstream rotor. During normal operation, the upstream stator blades are all situated at the same pitch angle and preswirl the flow into the propulsor while generating a roll moment to counter the moment produced by the rotor. By varying the pitch angles of the stator blade about the circumference, it is possible to both generate a mean stator side force and subsequently vary the axial velocity and swirl that is ingested into the propulsor. The rotor then generates a side force in response to the inflow. Both potential flow and fully viscous 3D Reynolds averaged Navier–Stokes (RANS) computations were used to predict the stator forces, velocity field, and rotor response. Potential flow methods were used for initial examination of a wide variety of stator configurations. The most promising were then modeled using RANS. The RANS inflow was then computed and used as velocity boundary conditions during rotor blade design using potential flow methods. Blade parameters including blade number, rake, skew, and a combination of the two were varied to characterize their effects. RANS was used to then validate the final propulsor design. Computations demonstrated that total side force coefficients on the order of 0.1 and moment coefficients about the stator leading edge of 0.066 could be generated by the propulsor alone. This translates to an additional 50% control authority at 3 kn for current Navy 21″ unmanned undersea vehicles.
Thermodynamic Effect on a Cavitating Inducer—Part I: Geometrical Similarity of Leading Edge Cavities and Cavitation Instabilities
Authors: Franc Jean-Pierre , Boitel Guillaume , Riondet Michel , Janson Éric , Ramina Pierre , Rebattet Claude
Published: February 2010

The thermodynamic effect on a cavitating inducer is investigated from joint experiments in cold water and Refrigerant 114. The analysis is focused on leading edge cavitation and cavitation instabilities, especially on alternate blade cavitation and supersynchronous rotating cavitation. The cavity length along cylindrical cuts at different radii between the hub and casing is analyzed with respect to the local cavitation number and angle of attack. The similarity in shape of the cavity closure line between water and R114 is examined and deviation caused by thermodynamic effect is clarified. The influence of rotation speed on cavity length is investigated in both fluids and analyzed on the basis of a comparison of characteristic times, namely, the transit time and a thermal time. Thermodynamic delay in the development of leading edge cavities is determined and temperature depressions within the cavities are estimated. Thresholds for the onset of cavitation instabilities are determined for both fluids. The occurrence of cavitation instabilities is discussed with respect to the extent of leading edge cavitation. The thermodynamic delay affecting the occurrence of cavitation instabilities is estimated and compared with the delay on cavity development.
Abundance of Ribosomal RNA Gene Copies Maintains Genome Integrity
Authors: Ide Satoru , Miyazaki Takaaki , Maki Hisaji , Kobayashi Takehiko
Published: February 2010

Protective Abundance

Massively repeated sequences are generally dangerous to genomes because they promote recombination and, potentially, genome instability. Eukaryotic ribosomal RNA genes (rDNA), which are highly transcribed, are organized into large arrays of repeats and have a system that actively maintains these large arrays. In getting to the bottom of this apparent contradiction,

Ide
et al.

(p.
693
) found that reducing the number of rDNA repeats in yeast resulted in a marked sensitivity to DNA damage, owing to heavy rDNA transcription preventing repair of compromised DNA replication forks. It appears that the additional copies of rDNA both reduce the ability of transcription to interfere with DNA repair and provide, through the action of condensin, templates for the recombination-based repair of replication-induced damage.
Comment on “Unexpected Epoxide Formation in the Gas-Phase Photooxidation of Isoprene”
Authors: Claeys Magda
Published: February 2010

Paulot
et al
. (Reports, 7 August 2009, p. 730) reported that the photooxidation of isoprene under low–nitrogen oxides (NO
x
) conditions produces epoxides that can facilitate the formation of secondary organic aerosol (SOA). However, another pathway involving the formation of methyl-butenediol intermediates can also lead to isoprene-derived SOA formation. Further research is needed to clarify the fate of isoprene in the atmosphere.
Cryo-EM Model of the Bullet-Shaped Vesicular Stomatitis Virus
Authors: Ge Peng , Tsao Jun , Schein Stan , Green Todd J. , Luo Ming , Zhou Z. Hong
Published: February 2010

VSV in 3D

Rhabdoviruses are a family of negative-stranded RNA viruses that includes rabies virus, which have a characteristic bullet shape. Though structures of individual rhabdovirus proteins have been reported, how these are organized into a bullet shape has remained unclear. Now,

Ge
et al.

(p.
689
) report a cryo-electron microscopy structure of a model rhabdovirus, vesicular stomatitis virus. The structural data and examination of mutants allows modeling of virion assembly.
Conformational Spread as a Mechanism for Cooperativity in the Bacterial Flagellar Switch
Authors: Bai Fan , Branch Richard W. , Nicolau Dan V. , Pilizota Teuta , Steel Bradley C. , Maini Philip K. , Berry Richard M.
Published: February 2010

Complex Cooperativity

Cooperativity in multisubunit protein complexes is classically understood in terms of either a concerted model, in which all subunits switch conformation simultaneously, or a sequential model, in which a subunit switches conformation whenever a ligand binds. More recently, a “conformational spread” model has suggested that a conformational coupling between subunits and between subunit and ligand is probabilistic. Using high-resolution optical microscopy,

Bai
et al.

(p.
685
; see the Perspective by

Hilser

) observed multistate switching of the bacterial flagellar switch complex that was previously understood in terms of a concerted allosteric model. The conformational spread model gives quantitative agreement with the data.
Optimal Localization by Pointing Off Axis
Authors: Yovel Yossi , Falk Ben , Moss Cynthia F. , Ulanovsky Nachum
Published: February 2010

Detection Versus Localization

Active-sensing systems allow an animal some control over the information acquired from the environment. For example, echolocating bats are known to control many aspects of their sonar signal design. However, their sensory data-acquisition strategies are still not fully understood.

Yovel
et al.

(p.
701
) found that Egyptian fruit bats (
Rousettus aegyptiacus
) did not aim their sonar beams directly on target in a standard localization task. Instead, the bats pointed the main lobe of their sonar beam off-axis. Bats approaching the target emitted sounds to the left and right of its localization, in an alternating manner, so that the maximum slope of the change in intensity of the sonar beam was often positioned close to the target. This echolocation strategy is ideal for target localization but occurs at the cost of target detection.
Effect of Ocean Acidification on Iron Availability to Marine Phytoplankton
Authors: Shi Dalin , Xu Yan , Hopkinson Brian M. , Morel François M. M.
Published: February 2010

Ironed Out

In large regions of the ocean, low levels of the essential nutrient, iron, limits primary productivity. Iron's chemistry and bioavailability are highly dependent on pH. Rising concentrations of atmospheric CO
2
is leading to the acidification of the ocean.

Shi
et al.

(p.
676
, published online 14 January; see the Perspective by

Sunda

) show that the bioavailable fraction of iron dissolved in the ocean may decline as a result of the decrease in ocean pH, which affects the rate of iron uptake by diatoms and coccolithophores. Unless iron input to the oceans increases, these changes may lead to an increase in the iron stress of phytoplankton.
Visualizing Critical Correlations Near the Metal-Insulator Transition in Ga
1-

x

Mn

x

As
Authors: Richardella Anthony , Roushan Pedram , Mack Shawn , Zhou Brian , Huse David A. , Awschalom David D. , Yazdani Ali
Published: February 2010

Metal-Insulator Transition

At near-zero temperatures, some materials undergo a metal-insulator transition and their electronic properties change from conducting to insulating. In the dilute magnetic semiconductor Ga

1−
x

Mn

x

As, a promising spintronics material, the metal-insulator transition is driven by the substitution of Ga atoms with Mn. While disorder clearly plays a key role in this transition, the influence of electron-electron correlations has been far from clear.

Richardella
et al.

(p.
665
; see the Perspective by

Fiete and de Lozanne

) used scanning tunneling microscopy to study the electronic states of this system. The autocorrelation function of the local density of states exhibited a power law (rather than an exponential) decay at Fermi energy. Thus, electron-electron interactions are indeed crucial for understanding dilute magnetic semiconductors.
Splitting Spin States on a Chip
Authors: Burkard Guido
Published: February 2010

Controlling electron spins on semiconductor quantum dots with help from nuclear spins may speed up fundamental steps in quantum computing.
The Trouble with Trees
The New Foundations of Evolution
On the Tree of Life

by
Jan Sapp

Oxford University Press, New York, 2009. 445 pp. $99, £54. ISBN 9780195388497. Paper, $39.95, £27.50. ISBN 9780195388503.
Authors: Hanage W. P.
Published: February 2010

Sapp explores how molecular methods have changed our understanding of microbial genetics and genomics and the large-scale relationships among microbes.
Seeing Quantum Fractals
Authors: Fiete Gregory A. , de Lozanne Alex
Published: February 2010

Scanning tunneling microscopy reveals indications of fractal electronic structure in a magnetic semiconductor.
Iron and the Carbon Pump
Authors: Sunda William G.
Published: February 2010

Ocean acidification may reduce the biological availability of iron, affecting the ocean's ability to absorb more carbon dioxide.
Ensuring Integrity in Science
Authors: Cicerone Ralph J.
Published: February 2010

Hacked Electronic Records of Climate Scientists at the University of East Anglia's Climate Research Unit (UEA/CRU) led to worldwide publicity during the December 2009 Copenhagen climate change convention. UEA is conducting a formal investigation to determine whether UEA scientists manipulated or suppressed data or otherwise acted unprofessionally. My reading of the vast scientific literature on climate change is that our understanding is undiminished by this incident; but it has raised concern about the standards of science and has damaged public trust in what scientists do.
Science Spared From Domestic Spending Freeze—for Now
Authors: Mervis Jeffrey
Published: February 2010

Despite his pledge to freeze domestic discretionary spending in an attempt to shrink a $1.6 trillion deficit, President Barack Obama has asked Congress to boost science spending next year across the federal government.
Evaluation of Standard Chemotherapy in the Guinea Pig Model of Tuberculosis
Authors: Ordway Diane J. , Shanley Crystal A. , Caraway Megan L. , Orme Eileen A. , Bucy Daniel S. , Hascall-Dove Laurel , Henao-Tamayo Marcela , Harton Marisa R. , Shang Shaobin , Ackart David , Kraft Susan L. , Lenaerts Anne J. , Basaraba Randall J. , Orme Ian M.
Published: February 2010

The purpose of this study was 2-fold. First, we evaluated standard chemotherapy in the guinea pig model of tuberculosis to determine if this animal species could productively be used for this purpose. Second, given the similarities of the pathology of disease in guinea pigs and humans, we wished to evaluate additional parameters, including magnetic resonance imaging, microscopy, and cytokine expression and lymphocyte phenotypes, in response to an infection treated with drug therapy. This study shows that conventional rifampin-isoniazid-pyrazinamide chemotherapy significantly decreased the numbers of the highly virulent Erdman K01 strain of
Mycobacterium tuberculosis
, with most of the bacilli being eliminated in a month. Despite this result, bacteria could still be detected in the lungs and other tissues for at least another 3 to 4 months. Resolution of the nonnecrotic granulomas in the lungs and lymph nodes could be clearly visualized by magnetic resonance imaging at the macroscopic level. Microscopically, the majority of the pulmonary and extrapulmonary inflammation resolved spontaneously, leaving residual lesions composed of dystrophic calcification and fibrosis marking the site of necrosis of the primary lesion. Residual calcified lesions, which were also associated with pulmonary lymphangitis, contained acid-fast bacilli even following aggressive chemotherapy. The presence of intact extracellular bacilli within these lesions suggests that these could serve as the primary sites of disease reactivation. The chemotherapy reduced the level of T-cell influx into infected tissues and was accompanied by a large and sustained increase in TH1 cytokine expression. Chemotherapy also prevented the emergence in lung tissues of high levels of interleukin-10 and Foxp3-positive cells, known markers of regulatory T cells.
Efflux Pumps Are Involved in the Defense of Gram-Negative Bacteria against the Natural Products Isobavachalcone and Diospyrone
Authors: Kuete Victor , Ngameni Bathélémy , Tangmouo Jean G. , Bolla Jean-Michel , Alibert-Franco Sandrine , Ngadjui Bonaventure T. , Pagès Jean-Marie
Published: February 2010

The activities of two naturally occurring compounds, isobavachalcone and diospyrone, against documented strains and multidrug-resistant (MDR) Gram-negative bacterial isolates were evaluated. The results indicated that the two compounds exhibited intrinsic antibacterial activity against several Gram-negative bacteria, and their activities were significantly improved in the presence of an efflux pump inhibitor (MIC values decreased to below 10 μg/ml). In addition, the activities of isobavachalcone and diospyrone against various strains exhibiting deletions of the major efflux pump components (AcrAB, TolC) were significantly increased. The overall results indicate that isobavachalcone and diospyrone could be candidates for the development of new drugs against MDR strains and that their use in combination with efflux pump inhibitors reinforces their activity.
Sequence Analysis and Characterization of a Transferable Hybrid Plasmid Encoding Multidrug Resistance and Enabling Zoonotic Potential for Extraintestinal
Escherichia coli
Authors: Johnson Timothy J. , Jordan Dianna , Kariyawasam Subhashinie , Stell Adam L. , Bell Nathan P. , Wannemuehler Yvonne M. , Alarcón Claudia Fernández , Li Ganwu , Tivendale Kelly A. , Logue Catherine M. , Nolan Lisa K.
Published: February 2010

ColV plasmids of extraintestinal pathogenic
Escherichia coli
(ExPEC) encode a variety of fitness and virulence factors and have long been associated with septicemia and avian colibacillosis. These plasmids are found significantly more often in ExPEC, including ExPEC associated with human neonatal meningitis and avian colibacillosis, than in commensal
E. coli
. Here we describe pAPEC-O103-ColBM, a hybrid RepFIIA/FIB plasmid harboring components of the ColV pathogenicity island and a multidrug resistance (MDR)-encoding island. This plasmid is mobilizable and confers the ability to cause septicemia in chickens, the ability to cause bacteremia resulting in meningitis in the rat model of human disease, and the ability to resist the killing effects of multiple antimicrobial agents and human serum. The results of a sequence analysis of this and other ColV plasmids supported previous findings which indicated that these plasmid types arose from a RepFIIA/FIB plasmid backbone on multiple occasions. Comparisons of pAPEC-O103-ColBM with other sequenced ColV and ColBM plasmids indicated that there is a core repertoire of virulence genes that might contribute to the ability of some ExPEC strains to cause high-level bacteremia and meningitis in a rat model. Examination of a neonatal meningitis
E. coli
(NMEC) population revealed that approximately 58% of the isolates examined harbored ColV-type plasmids and that 26% of these plasmids had genetic contents similar to that of pAPEC-O103-ColBM. The linkage of the ability to confer MDR and the ability contribute to multiple forms of human and animal disease on a single plasmid presents further challenges for preventing and treating ExPEC infections.
A new antidiabetic compound attenuates inflammation and insulin resistance in Zucker diabetic fatty rats
Authors: Lu Min , Patsouris David , Li Pingping , Flores-Riveros Jaime , Frincke James M. , Watkins Steve , Schenk Simon , Olefsky Jerrold M.
Published: February 2010

Tissue macrophage inflammatory pathways contribute to obesity-associated insulin resistance. Here, we have examined the efficacy and mechanisms of action of a novel anti-inflammatory compound (HE3286) in vitro and in vivo. In primary murine macrophages, HE3286 attenuates LPS- and TNFα-stimulated inflammation. In Zucker diabetic fatty rats, inflammatory cytokine/chemokine expression was downregulated in liver and adipose tissue by HE3286 treatment, as was macrophage infiltration into adipose tissue. In line with reduced inflammation, HE3286 treatment normalized fasting and fed glucose levels, improved glucose tolerance, and enhanced skeletal muscle and liver insulin sensitivity, as assessed by hyperinsulinemic euglycemic clamp studies. In phase 2 clinical trials, HE3286 treatment led to an enhancement in insulin sensitivity in humans. Gluconeogenic capacity was also reduced by HE3286 treatment, as evidenced by a reduced glycemic response during pyruvate tolerance tests and decreased basal hepatic glucose production (HGP) rates. Since serum levels of gluconeogenic substrates were decreased by HE3286, it indicates that the reduction of both intrinsic gluconeogenic capacity and substrate availability contributes to the decrease in HGP. Lipidomic analysis revealed that HE3286 treatment reduced liver cholesterol and triglyceride content, leading to a feedback elevation of LDL receptor and HMG-CoA reductase expression. Accordingly, HE3286 treatment markedly decreased total serum cholesterol. In conclusion, HE3286 is a novel anti-inflammatory compound, which displays both glucose-lowering and cholesterol-lowering effects.
Expression and response of acid-sensing ion channels in urinary bladder to cyclophosphamide-induced cystitis
Authors: Corrow Kimberly , Girard Beatrice M. , Vizzard Margaret A.
Published: February 2010

The expression of acid-sensing ion channel (ASIC) isoforms, ASIC1, ASIC2a, and ASIC3, was examined in the urinary bladder after cyclophosphamide (CYP)-induced cystitis of varying duration (4 h, 48 h, and chronic). Immunohistochemical, Western blot, and quantitative PCR approaches were used to evaluate channel expression and effects of CYP-induced cystitis in whole urinary bladder and split-bladder preparations from control (no inflammation) and CYP-treated rats. Quantitative PCR demonstrated significant ( P ≤ 0.01) increases in ASIC2a and ASIC3 transcripts with CYP-induced cystitis (48 h and chronic) in the urothelium but no changes (e.g., ASIC3) or modest changes (e.g., ASIC2a) in detrusor smooth muscle. ASIC1 mRNA expression in the urothelium or detrusor was not affected by CYP-induced cystitis. Immunohistochemistry for ASIC2a and ASIC3 protein expression revealed significant ( P ≤ 0.01) increases in ASIC immunoreactivity in the urothelium and suburothelial plexus with CYP-induced cystitis at all time points examined. Western blotting for ASIC2a and ASIC3 protein expression was complementary and revealed significant ( P ≤ 0.01) increases in ASIC immunoreactivity. For the first time, these studies demonstrate that CYP-induced cystitis alters ASIC2a and ASIC3 expression in the urinary bladder; ASIC1 transcript expression is not altered by CYP-induced cystitis. Future studies are necessary to determine ASIC isoform contributions to micturition reflexes in control and inflamed urinary bladder.
Thiazolidinediones alter growth and epithelial cell integrity, independent of PPAR-γ and MAPK activation, in mouse M1 cortical collecting duct cells
Authors: Nasrallah Rania , Clark Jordan , Corinaldi Jaime , Paris Geneviève , Miura Pedro , Jasmin Bernard J. , Hébert Richard L.
Published: February 2010

Peroxisome proliferator-activated receptor (PPAR)-γ is highly expressed in the collecting duct (CD), yet little is known about the effects of PPAR-γ ligands, thiazolidinediones (TZDs), on CD cell structure and function. M1 mouse cortical CD cells were treated with 5 μM troglitazone (TRO) and rosiglitazone (ROSI). First, growth was measured by [3H]thymidine and [3H]leucine incorporation, as well as analysis of cyclin D1 and the CDK inhibitor p27 by Western blot. [3H]thymidine incorporation was reduced by 56 and 24% by TRO and ROSI at 6 h, and [3H]leucine by 21 and 10%. A similar growth inhibition was also observed after 24 h for thymidine, but leucine was reduced by 48 and 24%, respectively. Likewise, cyclin D1 was diminished 60% by TRO, and p27 was elevated 1.6- and 1.7-fold in response to TRO and ROSI. Next, epithelial cell integrity was assessed by measuring different markers by Western blot analysis. While fibronectin and α-smooth muscle actin levels were unchanged, by 24 h E-cadherin was decreased by 50%, and β-catenin levels were reduced 2- and 1.5-fold in response to TRO and ROSI, respectively. GW9662, a PPAR-γ antagonist, did not reverse any of the TZD responses in M1 cells. Of interest, phosho-p38 levels were also elevated 2-fold in response to TRO and 2.3-fold to ROSI, but MAPK inhibition by PD98059 or SB203580 caused an additive inhibition of cell growth and did not alter E-cadherin or β-catenin in response to TZDs. Finally, apoptotic death was assessed by Western blot, but cleaved caspase-3 levels were unchanged from 15 min to 24 h in response to TZDs, and TRO did not affect cell viability or reactive oxygen species generation. Our data suggest that TZDs cause a disruption of M1 cell integrity that is preceded by an inhibition of cell growth. This response is independent of p38 or PPAR-γ activation.
Response Properties of Neurons in Primary Somatosensory Cortex of Owl Monkeys Reflect Widespread Spatiotemporal Integration
Authors: Reed Jamie L. , Qi Hui-Xin , Zhou Zhiyi , Bernard Melanie R. , Burish Mark J. , Bonds A. B. , Kaas Jon H.
Published: February 2010

Receptive fields of neurons in somatosensory area 3b of monkeys are typically described as restricted to part of a single digit or palm pad. However, such neurons are likely involved in integrating stimulus information from across the hand. To evaluate this possibility, we recorded from area 3b neurons in anesthetized owl monkeys with 100-electrode arrays, stimulating two hand locations with electromechanical probes simultaneously or asynchronously. Response magnitudes and latencies of single- and multiunits varied with stimulus conditions, and multiunit responses were similar to single-unit responses. The mean peak firing rate for single neurons stimulated within the preferred location was estimated to be ∼26 spike/s. Simultaneous stimulation with a second probe outside the preferred location slightly decreased peak firing rates to ∼22 spike/s. When the nonpreferred stimulus preceded the preferred stimulus by 10–500 ms, peak firing rates were suppressed with greatest suppression when the nonpreferred stimulus preceded by 30 ms (∼7 spike/s). The mean latency for single neurons stimulated within the preferred location was ∼23 ms, and latency was little affected by simultaneous paired stimulation. However, when the nonpreferred stimulus preceded the preferred stimulus by 10 ms, latencies shortened to ∼16 ms. Response suppression occurred even when stimuli were separated by long distances (nonadjacent digits) or long times (500 ms onset asynchrony). Facilitation, though rare, occurred most often when the stimulus onsets were within 0–30 ms of each other. These findings quantify spatiotemporal interactions and support the hypothesis that area 3b is involved in widespread stimulus integration.
Voluntary Control of Multisaccade Gaze Shifts During Movement Preparation and Execution
Authors: Ramakrishnan Arjun , Chokhandre Snehal , Murthy Aditya
Published: February 2010

Although the nature of gaze control regulating single saccades is relatively well documented, how such control is implemented to regulate multisaccade gaze shifts is not known. We used highly eccentric targets to elicit multisaccade gaze shifts and tested the ability of subjects to control the saccade sequence by presenting a second target on random trials. Their response allowed us to test the nature of control at many levels: before, during, and between saccades. Although the saccade sequence could be inhibited before it began, we observed clear signs of truncation of the first saccade, which confirmed that it could be inhibited in midflight as well. Using a race model that explains the control of single saccades, we estimated that it took about 100 ms to inhibit a planned saccade but took about 150 ms to inhibit a saccade during its execution. Although the time taken to inhibit was different, the high subject-wise correlation suggests a unitary inhibitory control acting at different levels in the oculomotor system. We also frequently observed responses that consisted of hypometric initial saccades, followed by secondary saccades to the initial target. Given the estimates of the inhibitory process provided by the model that also took into account the variances of the processes as well, the secondary saccades (average latency ∼215 ms) should have been inhibited. Failure to inhibit the secondary saccade suggests that the intersaccadic interval in a multisaccade response is a ballistic stage. Collectively, these data indicate that the oculomotor system can control a response until a very late stage in its execution. However, if the response consists of multiple movements then the preparation of the second movement becomes refractory to new visual input, either because it is part of a preprogrammed sequence or as a consequence of being a corrective response to a motor error.
Neurophysiological Correlates of Nociceptive Heterosynaptic Long-Term Potentiation in Humans
Authors: van den Broeke Emanuel N. , van Rijn Clementina M. , Biurrun Manresa José A. , Andersen Ole K. , Arendt-Nielsen Lars , Wilder-Smith Oliver H. G.
Published: February 2010

Long-term potentiation (LTP) is a cellular model of synaptic plasticity and reflects an increase of synaptic strength. LTP is also present in the nociceptive system and is believed to be one of the key mechanisms involved in the manifestations of chronic pain. LTP manifested as an increased response in pain perception can be induced in humans using high-frequency electrical stimulation (HFS). The aim of this study was to induce spinal heterosynaptic LTP using HFS and investigate its heterotopic effects on event-related potentials (ERPs) to repeated nonpainful cutaneous stimuli as a possible electrophysiological cortical correlate of sensitization. Twenty-two healthy subjects were randomly assigned to one of the two experimental conditions: HFS and control stimulation. Before and after the stimulation, both conditions received heterotopic mechanical (pinprick) and paired nonpainful electrical test stimuli to quantify and confirm the effects of HFS on the behavioral level. ERPs to paired nonpainful electrical stimulation were measured simultaneously. Conditioning HFS resulted in significant heterotopic effects after 30 min, including increased perceived intensity in response to (pinprick) mechanical and paired nonpainful electrical stimulation compared with control. The paired nonpainful electrical stimuli were accompanied by significantly enhanced responses regarding the ERP N1-P2 peak-to-peak and P300 amplitude compared with control. These findings suggest that HFS is capable of producing heterosynaptic spinal LTP that can be measured not only behaviorally but also using ERPs.
Macaque Pontine Omnipause Neurons Play No Direct Role in the Generation of Eye Blinks
Authors: Schultz K. P. , Williams C. R. , Busettini C.
Published: February 2010

We recorded the activity of pontine omnipause neurons (OPNs) in two macaques during saccadic eye movements and blinks. As previously reported, we found that OPNs fire tonically during fixation and pause about 15 ms before a saccadic eye movement. In contrast, for blinks elicited by air puffs, the OPNs paused <2 ms before the onset of the blink. Thus the burst in the agonist orbicularis oculi motoneurons (OOMNs) and the pause in the antagonist levator palpabrae superioris motoneurons (LPSMNs) necessarily precede the OPN pause. For spontaneous blinks there was no correlation between blink and pause onsets. In addition, the OPN pause continued for 40–60 ms after the time of the maximum downward closing of the eyelids, which occurs around the end of the OOMN burst of firing. LPSMN activity is not responsible for terminating the OPN pause because OPN resumption was very rapid, whereas the resumption of LPSMN firing during the reopening phase is gradual. OPN pause onset does not directly control blink onset, nor does pause offset control or encode the transition between the end of the OOMN firing and the resumption of the LPSMNs. The onset of the blink-related eye transients preceded both blink and OPN pause onsets. Therefore they initiated while the saccadic short-lead burst neurons were still fully inhibited by the OPNs and cannot be saccadic in origin. The abrupt dynamic change of the vertical eye transients from an oscillatory behavior to a single time constant exponential drift predicted the resumption of the OPNs.
Inhibitory Effect of Gamma-Irradiated Chitosan on the Growth of Denitrifiers
Authors: Vilcáez Javier , Watanabe Tomohide
Published: February 2010

In order to find an environmentally benign substitute to hazardous inhibitory agents, the inhibitory effect of -irradiated chitosans against a mixed culture of denitrifying bacteria was experimentally evaluated. Unlike other studies using pure aerobic cultures, the observed effect was not a complete inhibition but a transient inhibition reflected by prolonged lag phases and reduced growth rates. Raw chitosan under acid conditions (pH 6.3) exerted the strongest inhibition followed by the 100 kGy and 500 kGy irradiated chitosans, respectively. Therefore, because the molecular weight of chitosan decreases with the degree of -irradiation, the inhibitory properties of chitosan due to its high molecular weight were more relevant than the inhibitory properties gained due to the modification of the surface charge and/or chemical structure by -irradiation. High dosage of -irradiated appeared to increase the growth of mixed denitrifying bacteria in acid pH media. However, in neutral pH media, high dosage of -irradiation appeared to enhance the inhibitory effect of chitosan.
The Retinal Pigment Epithelium: Something More than a Constituent of the Blood-Retinal Barrier—Implications for the Pathogenesis of Diabetic Retinopathy
Authors: Simó Rafael , Villarroel Marta , Corraliza Lídia , Hernández Cristina , Garcia-Ramírez Marta
Published: February 2010

The retinal pigment epithelium (RPE) is an specialized epithelium lying in the interface between the neural retina and the choriocapillaris where it forms the outer blood-retinal barrier (BRB). The main functions of the RPE are the following: (1) transport of nutrients, ions, and water, (2) absorption of light and protection against photooxidation, (3) reisomerization of all-trans-retinal into 11-cis-retinal, which is crucial for the visual cycle, (4) phagocytosis of shed photoreceptor membranes, and (5) secretion of essential factors for the structural integrity of the retina. An overview of these functions will be given. Most of the research on the physiopathology of diabetic retinopathy has been focused on the impairment of the neuroretina and the breakdown of the inner BRB. By contrast, the effects of diabetes on the RPE and in particular on its secretory activity have received less attention. In this regard, new therapeutic strategies addressed to modulating RPE impairment are warranted.
Epidermal Growth Factor (EGF) Treatment on Multipotential Stromal Cells (MSCs). Possible Enhancement of Therapeutic Potential of MSC
Authors: Tamama Kenichi , Kawasaki Haruhisa , Wells Alan
Published: February 2010

Adult bone marrow multipotential stromal cells (MSCs) hold great promise in regenerative medicine and tissue engineering. However, due to their low numbers upon harvesting, MSCs need to be expanded in vitro without biasing future differentiation for optimal utility. In this concept paper, we focus on the potential use of epidermal growth factor (EGF), prototypal growth factor for enhancing the harvesting and/or differentiation of MSCs. Soluble EGF was shown to augment MSC proliferation while preserving early progenitors within MSC population, and thus did not induce differentiation. However, tethered form of EGF was shown to promote osteogenic differentiation. Soluble EGF was also shown to increase paracrine secretions including VEGF and HGF from MSC. Thus, soluble EGF can be used not only to expand MSC in vitro, but also to enhance paracrine secretion through drug-releasing MSC-encapsulated scaffolds in vivo. Tethered EGF can also be utilized to direct MSC towards osteogenic lineage both in vitro and in vivo.
Emerging Carbon Nanotube Electronic Circuits, Modeling, and Performance
Authors: Xu Yao , Srivastava Ashok , Sharma Ashwani K.
Published: February 2010

Current transport and dynamic models of carbon nanotube field-effect transistors are presented. A model of single-walled carbon nanotube as interconnect is also presented and extended in modeling of single-walled carbon nanotube bundles. These models are applied in studying the performances of circuits such as the complementary carbon nanotube inverter pair and carbon nanotube as interconnect. Cadence/Spectre simulations show that carbon nanotube field-effect transistor circuits can operate at upper GHz frequencies. Carbon nanotube interconnects give smaller delay than copper interconnects used in nanometer CMOS VLSI circuits.
An RNA Interference Screen Identifies Metabolic Regulators NR1D1 and PBP as Novel Survival Factors for Breast Cancer Cells with the ERBB2 Signature
Authors: Kourtidis Antonis , Jain Ritu , Carkner Richard D. , Eifert Cheryl , Brosnan M. Julia , Conklin Douglas S.
Published: February 2010

Overexpression of the adverse prognostic marker ERBB2 occurs in 30% of breast cancers; however, therapies targeting this gene have not proved to be as effective as was initially hoped. Transcriptional profiling meta-analyses have shown that there are ∼150 genes co-overexpressed with ERBB2, suggesting that these genes may represent alternative factors influencing ERBB2-positive tumors. Here we describe an RNA interference–based analysis of these genes that identifies transcriptional regulators of fat synthesis and storage as being critical for the survival of these cells. These transcription factors, nuclear receptor subfamily 1, group D, member 1 (NR1D1) and peroxisome proliferator activated receptor γ binding protein (PBP), both reside on ERBB2-containing 17q12-21 amplicons and are part of the ERBB2 expression signature. We show that NR1D1 and PBP act through a common pathway in upregulating several genes in the de novo fatty acid synthesis network, which is highly active in ERBB2-positive breast cancer cells. Malate dehydrogenase 1 and malic enzyme 1, enzymes that link glycolysis and fatty acid synthesis, are also regulated by NR1D1. The resulting high-level fat production from increased expression of these genes likely contributes to an abnormal cellular energy metabolism based on aerobic glycolysis. Together, these results show that the cells of this aggressive form of breast cancer are genetically preprogrammed to depend on NR1D1 and PBP for the energy production necessary for survival. Cancer Res; 70(5); 1783–92