bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzymatic properties of Staphylococcus aureus adenosine synthase (AdsA)
Authors: Thammavongsa Vilasack , Schneewind Olaf , Missiakas Dominique M
Published: November 2011

Background

Staphylococcus aureus is a human pathogen that produces extracellular adenosine to evade clearance by the host immune system, an activity attributed to the 5'-nucleotidase activity of adenosine synthase (AdsA). In mammals, conversion of adenosine triphosphate to adenosine is catalyzed in a two-step process: ecto-nucleoside triphosphate diphosphohydrolases (ecto-NTDPases) hydrolyze ATP and ADP to AMP, whereas 5'-nucleotidases hydrolyze AMP to adenosine. NTPDases harbor apyrase conserved regions (ACRs) that are critical for activity.

Results

NTPDase ACR motifs are absent in AdsA, yet we report here that recombinant AdsA hydrolyzes ADP and ATP in addition to AMP. Competition assays suggest that hydrolysis occurs following binding of all three substrates at a unique site. Alanine substitution of two amino acids, aspartic acid 127 and histidine 196 within the 5'-nucleotidase signature sequence, leads to reduced AMP or ADP hydrolysis but does not affect the binding of these substrates.

Conclusion

Collectively, these results provide insight into the unique ability of AdsA to produce adenosine through the consecutive hydrolysis of ATP, ADP and AMP, thereby endowing S. aureus with the ability to modulate host immune responses.
The Fur regulon in anaerobically grown Salmonella enterica sv. Typhimurium: identification of new Fur targets
Authors: Troxell Bryan , Fink Ryan C , Porwollik Steffen , McClelland Michael , Hassan Hosni M
Published: November 2011

Background

The Ferric uptake regulator (Fur) is a transcriptional regulator that controls iron homeostasis in bacteria. Although the regulatory role of Fur inEscherichia coliis well characterized, most of the studies were conducted under routine culture conditions, i.e., in ambient oxygen concentration. To reveal potentially novel aspects of the Fur regulon inSalmonella entericaserovar Typhimurium under oxygen conditions similar to that encountered in the host, we compared the transcriptional profiles of the virulent wild-type strain (ATCC 14028s) and its isogenic Δfurstrain under anaerobic conditions.

Results

Microarray analysis of anaerobically grown Δfur S. Typhimurium identified 298 differentially expressed genes. Expression of several genes controlled by Fnr and NsrR appeared to be also dependent on Fur. Furthermore, Fur was required for the activity of the cytoplasmic superoxide disumutases (MnSOD and FeSOD). The regulation of FeSOD gene,sodB, occurred via small RNAs (i.e., theryhBhomologs,rfrAandrfrB) with the aid of the RNA chaperone Hfq. The transcription ofsodAwas increased in Δfur;however, the enzyme was inactive due to the incorporation of iron instead of manganese in SodA. Additionally, in Δfur, the expression of the gene coding for the ferritin-like protein (ftnB) was down-regulated, while the transcription of the gene coding for the nitric oxide (NO·) detoxifying flavohemoglobin (hmpA) was up-regulated. The promoters offtnBandhmpAdo not contain recognized Fur binding motifs, which indicated their probable indirect regulation by Fur. However, Fur activation offtnBwas independent of Fnr. In addition, the expression of the gene coding for the histone-like protein, H-NS (hns) was increased in Δfur. This may explain the observed down-regulation of thetdcoperon, responsible for the anaerobic degradation of threonine, andftnBin Δfur.

Conclusions

This study determined that Fur is a positive factor inftnBregulation, while serving to repress the expression ofhmpA. Furthermore, Fur is required for the proper expression and activation of the antioxidant enzymes, FeSOD and MnSOD. Finally, this work identified twenty-six new targets of Fur regulation, and demonstrates that H-NS repressed genes are down-regulated in Δfur.
Acute infarct of the corpus callosum presenting as alien hand syndrome: evidence of diffusion weighted imaging and magnetic resonance angiography
Authors: Yuan Jun Liang , Wang Shuang Kun , Guo Xiao Juan , Hu Wen Li
Published: November 2011

Background

Infarcts of the corpus callosum are rare and have not been well documented previously. As for a variety of signs and symptoms presented, alien hand syndrome (AHS) can be easily overlooked.

Case presentation

In this report, we present a patient with a mixed types of AHS coexistence secondary to the corpus callosum infarction, including a motor type of AHS by intermanual conflict (callosal type AHS) and a sensory type of AHS by alien hand and left hemianesthesia (posterior AHS).

Conclusions

Our case may contribute to the early recognition of AHS and to explore the abnormal neural mechanism of AHS. To our knowledge, rare reports have ever documented such mixed AHS coexisting secondary to the callosal lesion, based on advanced neuroimaging methods as in our case.
Overexpression of hepatoma-derived growth factor in melanocytes does not lead to oncogenic transformation
Authors: Sedlmaier Angela , Wernert Nicolas , Gallitzendörfer Rainer , Abouzied Mekky M , Gieselmann Volkmar , Franken Sebastian
Published: November 2011

Background

HDGF is a growth factor which is overexpressed in a wide range of tumors. Importantly, expression levels were identified as a prognostic marker in some types of cancer such as melanoma.

Methods

To investigate the presumed oncogenic/transforming capacity of HDGF, we generated transgenic mice overexpressing HDGF in melanocytes. These mice were bred with mice heterozygous for a defective copy of the Ink4a tumor suppressor gene and were exposed to UV light to increase the risk for tumor development both genetically and physiochemically. Mice were analyzed by immunohistochemistry and Western blotting. Furthermore, primary melanocytes were isolated from different strains created.

Results

Transgenic animals overexpressed HDGF in hair follicle melanocytes. Interestingly, primary melanocytes isolated from transgenic animals were not able to differentiate in vitro whereas cells isolated from wild type and HDGF-deficient animals were. Although, HDGF-/-/Ink4a+/- mice displayed an increased number of epidermoid cysts after exposure to UV light, no melanomas or premelanocytic alterations could be detected in this mouse model.

Conclusions

The results therefore provide no evidence that HDGF has a transforming capacity in tumor development. Our results in combination with previous findings point to a possible role in cell differentiation and suggest that HDGF promotes tumor progression after secondary upregulation and may represent another protein fitting into the concept of non-oncogene addiction of tumor tissue.
Isolation and characterization of novel bacterial strains exhibiting ligninolytic potential
Authors: Bandounas Luaine , Wierckx Nick JP , de Winde Johannes H , Ruijssenaars Harald J
Published: November 2011

Background

To expand on the range of products which can be obtained from lignocellulosic biomass, the lignin component should be utilized as feedstock for value-added chemicals such as substituted aromatics, instead of being incinerated for heat and energy. Enzymes could provide an effective means for lignin depolymerization into products of interest. In this study, soil bacteria were isolated by enrichment on Kraft lignin and evaluated for their ligninolytic potential as a source of novel enzymes for waste lignin valorization.

Results

Based on 16S rRNA gene sequencing and phenotypic characterization, the organisms were identified as Pandoraea norimbergensis LD001, Pseudomonas sp LD002 and Bacillus sp LD003. The ligninolytic capability of each of these isolates was assessed by growth on high-molecular weight and low-molecular weight lignin fractions, utilization of lignin-associated aromatic monomers and degradation of ligninolytic indicator dyes. Pandoraea norimbergensis LD001 and Pseudomonas sp. LD002 exhibited best growth on lignin fractions, but limited dye-decolourizing capacity. Bacillus sp. LD003, however, showed least efficient growth on lignin fractions but extensive dye-decolourizing capacity, with a particular preference for the recalcitrant phenothiazine dye class (Azure B, Methylene Blue and Toluidene Blue O).

Conclusions

Bacillus sp. LD003 was selected as a promising source of novel types of ligninolytic enzymes. Our observations suggested that lignin mineralization and depolymerization are separate events which place additional challenges on the screening of ligninolytic microorganisms for specific ligninolytic enzymes.
Development of quality indicators for monitoring outcomes of frail elderly hospitalised in acute care health settings: Study Protocol
Authors: Brand Caroline A , Martin-Khan Melinda , Wright Olivia , Jones Richard N , Morris John N , Travers Catherine M , Tropea Joannne , Gray Leonard C
Published: November 2011

Background

Frail older people admitted to acute care hospitals are at risk of a range of adverse outcomes, including geriatric syndromes, although targeted care strategies can improve health outcomes for these patients. It is therefore important to assess inter-hospital variation in performance in order to plan and resource improvement programs.

Clinical quality outcome indicators provide a mechanism for identifying variation in performance over time and between hospitals, however to date there has been no routine use of such indicators in acute care settings.

A barrier to using quality indicators is lack of access to routinely collected clinical data. The interRAI Acute Care (AC) assessment system supports comprehensive geriatric assessment of older people within routine daily practice in hospital and includes process and outcome data pertaining to geriatric syndromes.

This paper reports the study protocol for the development of aged care quality indicators for acute care hospitals.

Methods/Design

The study will be conducted in three phases:

Development of a preliminary inclusive set of quality indicators set based on a literature review and expert panel consultation,

A prospective field study including recruitment of 480 patients aged 70 years or older across 9 Australian hospitals. Each patient will be assessed on admission and discharge using the interRAI AC, and will undergo daily monitoring to observe outcomes. Medical records will be independently audited, and

Analysis and compilation of a definitive quality indicator set, including two anonymous voting rounds for quality indicator inclusion by the expert panel.

Discussion

The approach to quality indicators proposed in this protocol has four distinct advantages over previous efforts: the quality indicators focus on outcomes; they can be collected as part of a routinely applied clinical information and decision support system; the clinical data will be robust and will contribute to better understanding variations in hospital care of older patients; The quality indicators will have international relevance as they will be built on the interRAI assessment instrument, an internationally recognised clinical system.
The roles of testicular nuclear receptor 4 (TR4) in male fertility-priapism and sexual behavior defects in TR4 knockout mice
Authors: Collins Loretta L , Lee Yi-Fen , Ting Huei-Ju , Lin Wen-Jye , Liu Ning-Chun , Meshul Charles K , Uno Hideo , Bao Bo-Ying , Chen Yen-Ta , Chang Chawnshang
Published: November 2011

Background

Successful reproductive efforts require the establishment of a situation favorable for reproduction that requires integration of both behavior and internal physiological events. TR4 nuclear receptor is known to be involved in male fertility via controlling spermatogenesis, yet its roles in regulating other biological events related to reproduction have not been completely revealed.

Methods

Male TR4 knockout (TR4-/-) and wild type mice were used for the sexual behavior and penile dysfunction studies. Mice were sacrificed for histological examination and corresponding genes profiles were analyzed by quantitative RT-PCR. Reporter gene assays were performed.

Results

We describe an unexpected finding of priapism in TR4-/- mice. As a transcriptional factor, we demonstrated that TR4 transcriptionally modulates a key enzyme regulating penis erection and neuronal nitric oxide synthese NOS (nNOS). Thereby, elimination of TR4 results in nNOS reduction in both mRNA and protein levels, consequently may lead to erectile dysfunction. In addition, male TR4-/- mice display defects in sexual and social behavior, with increased fear or anxiety, as well as reduced mounting, intromission, and ejaculation. Reduction of ER alpha, ER beta, and oxytocin in the hypothalamus may contribute to defects in sexual behavior and stress response.

Conclusions

Together, these results provide in vivo evidence of important TR4 roles in penile physiology, as well as in male sexual behavior. In conjunction with previous finding, TR4 represents a key factor that controls male fertility via regulating behavior and internal physiological events.
Investigating a TELEmedicine solution to improve MEDication adherence in chronic Heart Failure (TELEMED-HF): study protocol for a randomized controlled trial
Authors: Kessing Dionne , Denollet Johan , Widdershoven Jos , Kupper Nina
Published: November 2011

Background

Frequent rehospitalisations and poorer survival chances in heart failure (HF) patients may partly be explained by poor medication adherence. There are multiple medication-related reasons for suboptimal adherence, but psychological reasons may also be important. A novel TELEmonitoring device may improve MEDication adherence in HF patients (TELEMED-HF). TELEMED-HF is a randomized, controlled clinical intervention trial designed to examine (1) the efficacy and cost-efficiency of an electronic medication adherence support system in improving and monitoring HF patients' medication adherence; (2) the effect of medication adherence on hospitalizations and health care consumption; as well as on (3) clinical characteristics, and Quality of Life (QoL); and (4) clinical, sociodemographic, and psychological determinants of medication adherence.

Methods/Design

Consecutive patients with chronic, systolic HF presenting to the outpatient clinic of the TweeSteden Hospital, The Netherlands, will be approached for study participation and randomly assigned (1:1) following blocked randomization procedures to the intervention (n = 200) or usual care arm (n = 200). Patients in the intervention arm use the medication support device for six months in addition to usual care. Post-intervention, patients return to usual care only and all patients participate in four follow-up occasions over 12 months. Primary endpoints comprise objective and subjective medication adherence, healthcare consumption, number of hospitalizations, and cost-effectiveness. Secondary endpoints include disease severity, physical functioning, and QoL.

Discussion

The TELEMED-HF study will provide us a comprehensive understanding of medication adherence in HF patients, and will show whether telemonitoring is effective and cost-efficient in improving adherence and preventing hospitalization in HF patients.

Trial registration number

NCT01347528.
A missed injury leading to delayed diagnosis and postoperative infection of an unstable thoracic spine fracture - case report of a potentially preventable complication
Authors: Yoshihara Hiroyuki , VanderHeiden Todd F , Stahel Philip F
Published: November 2011

Background

Patients suffering from polytrauma often present with altered mental status and have varying levels of examinability. This makes evaluation difficult. Physicians are often required to rely on advanced imaging techniques to make prompt and accurate diagnoses. Occasionally, injury detection on advanced imaging studies can be challenging given the subtle findings associated with certain conditions, such as diffuse idiopathic skeletal hyperostosis (DISH). Delayed or missed diagnoses in the setting of spinal fracture can lead to catastrophic neurological injury.

Case presentation

A man struck by a motor vehicle suffered multiple traumatic injuries including numerous rib fractures, a mechanically unstable pelvic fracture, and also had suspicion for an aortic injury. Unfortunately, the upper thoracic segment (T1-5) was only visualized with axial images based on the electronic data. Several days later, a contrast CT scan obtained to check the status of suspected aortic injury revealed T3-T4 subluxation indicative of an unstable extension-type fracture in the setting of DISH. Due to the missed injury and delay in diagnosis, surgery was not performed until eight days after the injury. At surgery, the patient was found to have left T3-T4 facet joint infection as well as infected hematoma surrounding a left T4 transverse process fracture and a traumatic T4 costo-transverse joint fracture-subluxation. Despite presence of infection, an instrumented posterior spinal fusion from T1-T6 was performed and the patient recovered well after antibiotic treatment.

Conclusion

A T3-T4 unstable DISH extension-type fracture was initially missed in a polytrauma patient due to inadequate imaging acquisition, which caused a delay in treatment and bacterial seeding of fracture hematoma. Complete imaging is especially needed in obtunded patients that cannot be thoroughly examined.
Simultaneous active and passive seismic monitoring of steam-assisted heavy oil production
Authors: Forgues E. , Schisselé E. , Cotton J.
Published: November 2011

The world-class heavy oil reserves of Canada represent a significant resource for North America which is free from the geopolitical uncertainty currently affecting conventional oil supplies in some parts of the world. Energy security and the current sustained oil prices make heavy oil extraction an attractive proposition.
Joint transmission and reflection traveltime tomography in imaging permafrost and thermokarst lakes in Northwest Territories, Canada
Authors: Huang Jun-Wei , Bellefleur Gilles
Published: November 2011

We propose an application of joint tomographic inversion using both transmitted and reflected arrivals to map velocity structures in thick permafrost areas of the Mackenzie Delta, Northwest Territories of Canada. Our tomography algorithm combines a grid-based solver of the eikonal equation, Huygens' principle, and the adjoint method. The grid-based solver assigns a traveltime to each grid point and avoids the shadow-zone problem in classical ray tracing and is well-adapted for parallelization. The adjoint method used in the inversion provides the gradient of a given objective function without explicitly estimating the Fréchet derivative matrix. When combined with Huygens' principle, the tomographic inversion can simultaneously use first and later arrivals to optimize a final velocity model. We first demonstrate the performance of the joint tomography algorithm on a two-dimensional synthetic model with velocity variations typical of permafrost. The method is then applied to a 2D seismic survey covering over 20 km with offsets up to 4 km, acquired in the Mackenzie Delta. The subsurface at that location is characterized by a thick permafrost (600 m) comprising high-velocity and low-velocity areas associated with thermokarst lakes. Our results show the potential of the joint tomography in characterizing multiscale heterogeneous velocity structures within the permafrost.
Lack of Overt FGF21 Resistance in Two Mouse Models of Obesity and Insulin Resistance
Authors: Hale Clarence , Chen Michelle M. , Stanislaus Shanaka , Chinookoswong Narumol , Hager Todd , Wang Minghan , Véniant Murielle M. , Xu Jing
Published: November 2011

Circulating levels of fibroblast growth factor 21 (FGF21), a metabolic regulator of glucose, lipid, and energy homeostasis, are elevated in obese diabetic subjects, raising questions about potential FGF21 resistance. Here we report tissue expression changes in FGF21 and its receptor components, and we describe the target-organ and whole-body responses to FGF21 in ob/ob and diet-induced obese (DIO) mice. Plasma FGF21 concentrations were elevated 8- and 16-fold in DIO and ob/ob mice, respectively, paralleling a dramatic increase in hepatic FGF21 mRNA expression. Concurrently, expression levels of βKlotho, FGF receptor (FGFR)-1c, and FGFR2c were markedly down-regulated in the white adipose tissues (WAT) of ob/ob and DIO mice. However, dose-response curves of recombinant human FGF21 (rhFGF21) stimulation of ERK phosphorylation in the liver and WAT were not right shifted in disease models, although the magnitude of induction in ERK phosphorylation was partially attenuated in DIO mice. Whole-body metabolic responses were preserved in ob/ob and DIO mice, with disease models being more sensitive and responsive than lean mice to the glucose-lowering and weight-loss effects of rhFGF21. Endogenous FGF21 levels, although elevated in diseased mice, were below the half-maximal effective concentrations of rhFGF21, suggesting a state of relative deficiency. Hepatic and WAT FGF21 mRNA expression levels declined after rhFGF21 treatment in the absence of the increased expression levels of βKlotho and FGFR. We conclude that overt FGF21 resistance was not evident in the disease models, and increased hepatic FGF21 expression as a result of local metabolic changes is likely a major cause of elevated circulating FGF21 levels.
Kisspeptin Signaling Is Indispensable for Neurokinin B, but not Glutamate, Stimulation of Gonadotropin Secretion in Mice
Authors: García-Galiano David , van Ingen Schenau Dorette , Leon Silvia , Krajnc-Franken Magda A. M. , Manfredi-Lozano Maria , Romero-Ruiz Antonio , Navarro Victor M. , Gaytan Francisco , van Noort Paula I. , Pinilla Leonor , Blomenröhr Marion , Tena-Sempere Manuel
Published: November 2011

Kisspeptins (Kp), products of the Kiss1 gene that act via Gpr54 to potently stimulate GnRH secretion, operate as mediators of other regulatory signals of the gonadotropic axis. Mouse models of Gpr54 and/or Kiss1 inactivation have been used to address the contribution of Kp in the central control of gonadotropin secretion; yet, phenotypic and hormonal differences have been detected among the transgenic lines available. We report here a series of neuroendocrine analyses in male mice of a novel Gpr54 knockout (KO) model, generated by heterozygous crossing of a loxP-Gpr54/Protamine-Cre double mutant line. Gpr54-null males showed severe hypogonadotropic hypogonadism but retained robust responsiveness to GnRH. Gonadotropic responses to the agonist of ionotropic glutamate receptors, N-methyl-d-aspartate, were attenuated, but persisted, in Gpr54-null mice. In contrast, LH secretion after activation of metabotropic glutamate receptors was totally preserved in the absence of Gpr54 signaling. Detectable, albeit reduced, LH responses were also observed in Gpr54 KO mice after intracerebroventricular administration of galanin-like peptide or RF9, putative antagonist of neuropeptide FF receptors for the mammalian ortholog of gonadotropin-inhibiting hormone. In contrast, the stimulatory effect of senktide, agonist of neurokinin B (NKB; cotransmitter of Kiss1 neurons), was totally abrogated in Gpr54 KO males. Lack of Kp signaling also eliminated feedback LH responses to testosterone withdrawal. However, residual but sustained increases of FSH were detected in gonadectomized Gpr54 KO males, in which testosterone replacement failed to fully suppress circulating FSH levels. In sum, our study provides novel evidence for the relative importance of Kp-dependent vs. -independent actions of several key regulators of GnRH secretion, such as glutamate, galanin-like peptide, and testosterone. In addition, our data document for the first time the indispensable role of Kp signaling in mediating the stimulatory effects of NKB on LH secretion, thus supporting the hypothesis that NKB actions on GnRH neurons are indirectly mediated via its ability to regulate Kiss1 neuronal output.
The inotropic effects of ammonia on isolated perfused rat hearts and the mechanisms involved
Authors: Zhang Quanxi , Meng Ziqiang
Published: November 2011

Ammonia (NH3) is a common exogenous gas in the atmosphere, as well as an endogenous chemical produced by amino acid catabolism and other pathways in vivo. Physiological and pathophysiological roles of NH3 in the nervous system have been studied. Recently, endogenous NH3 has been suggested to be a gas transmitter. However, so far the role of NH3 in cardiovascular functions has not been reported. The present study was designed to investigate the inotropic effects of NH3 on isolated perfused rat hearts and the possible mechanisms involved in these effects. The results showed that NH3 had a positive inotropic effect in a concentration-dependent manner and produced a higher positive effect than NaOH and NH4Cl. At low concentrations, the effect of NH3 on cardiac function was caused by NH3 molecules; at high concentrations, the effect of NH3 on hearts may be partly correlated with a change of pH value, but was mainly caused by NH3 molecules. The mechanisms involved in the NH3-induced positive inotropic effect may be related to the ATP-sensitive K+ (KATP) channel and the nitric oxide (NO)–cyclic GMP (cGMP) signaling pathway. In addition, at a concentration of 1.5 mmol l–1, NH3 significantly increased the activity of creatine kinase (CK) and lactate dehydrogenase (LDH) in the coronary perfusate and decreased the activity of Na+,K+-ATPase and Ca2+,Mg2+-ATPase in the hearts. These results indicate that NH3 at physiological or low concentrations may play a modulatory role in heart function, but at high concentrations had a damaging effect on isolated rat hearts.
Changes in cardiac performance during hypoxic exposure in the grass shrimpPalaemonetes pugio
Authors: Guadagnoli Jutta A. , Tobita Kimimasa , Reiber Carl L.
Published: November 2011

In hearts of higher invertebrates as well as vertebrates, the work performed by the ventricle is a function of both rate and contractility. Decapod crustaceans experience a hypoxia-induced bradycardia that is thought to result in an overall reduction in cardiac work; however, this hypothesis has not yet been tested and is the primary purpose of this study. In the grass shrimp Palaemonetes pugio, cardiac pressure and area data were obtained simultaneously, and in vivo, under normoxic (20.2 kPa O2) and hypoxic (6.8 or 2.2 kPa O2) conditions and integrated to generate pressure–area (P–A) loops. The area enclosed by the P–A loop provides a measure of stroke work and, when multiplied by the heart rate, provides an estimate of both cardiac work and myocardial O2 consumption. Changes in intra-cardiac pressure (dp/dt) are correlated to the isovolemic contraction phase and provide an indication of stroke work. At both levels of hypoxic exposure, intra-cardiac pressure, dp/dt, stroke work and cardiac work fell significantly. The significant decrease in intra-cardiac pressure provides the primary mechanism for the decrease in stroke work, and, when coupled with the hypoxia-induced bradycardia, it contributes to an overall fall in cardiac work. Compared with normoxic P–A loops, hypoxic P–A loops (at both levels of hypoxia) become curvilinear, indicating a fall in peripheral resistance (which might account for the reduction in intra-cardiac pressure), which would reduce both stroke work and cardiac work and ultimately would serve to reduce myocardial O2 consumption. This is the most direct evidence to date indicating that the hypoxia-induced bradycardia observed in many decapod crustaceans reduces cardiac work and is therefore energetically favorable during acute exposure to conditions of low oxygen.
Flea infestation does not cause a long-term increase in energy metabolism in Gerbillus nanus
Authors: Kam Michael , Khokhlova Irina S. , Krasnov Boris R. , Degen A. Allan
Published: November 2011

Fleas can increase the metabolic rate of their hosts. It has been suggested that a constitutive response, in which the host constantly maintains a relatively high level of energy metabolism to combat the parasite, is advantageous for hosts with high parasite infestation, while an induced response, in which the host increases energy metabolism in response to a parasite attack, is advantageous with low parasite infestation. As free-living Gerbillus nanus show a relatively low flea infestation, we hypothesized that this host uses an induced strategy and, consequently, flea infestation would not impose a long-term effect on energy metabolism. In a previous study in spring, higher field metabolic rate (FMR) was found in free-living parasitized than in non-parasitized G. nanus. In this study, G. nanus were captured at Hazeva in spring; some had fleas (N=14) and some did not (N=10). We brought them to the laboratory, removed the fleas from those that were infested and, after 3 weeks, measured average daily metabolic rate (ADMR) of all rodents. ADMR averaged 8.68±0.95 kJ g–0.54 day–1 for all rodents and was similar between previously parasitized and non-parasitized G. nanus while free living. Thus, the hypothesis that flea infestation does not have a long-term effect on energy metabolism was supported, as was the idea of an induced over a constitutive immune response by G. nanus in combating parasites.
Urotensin II and its receptor in the killifish gill: regulators of NaCl extrusion
Authors: Evans David H. , Hyndman Kelly A. , Cornwell Emily , Buchanan Patrick
Published: November 2011

The peptide urotensin II (UII) and its receptor (UT) mediate cardiovascular and renal effects in both mammals and fishes. In both groups, vasopressor and diuretic responses predominate, although, in mammals, some secondary vasodilatation is found, mediated by secondary release of nitric oxide or prostacyclin. In fishes, gill extrusion of NaCl is inhibited by UII, but a single study has determined that UT is expressed in gill vasculature, not on the epithelium that mediates the transport. To begin to clarify the pathways involved in UII inhibition of gill transport, we have cloned the cDNA encoding UII and UT from the euryhaline killifish (Fundulus heteroclitus L.) gill and spinal cord, quantified UT mRNA expression in various tissues and measured relative expression in gill tissue from fish acclimated to seawater (SW) vs fresh water (FW). We have also localized UT in the gill epithelium, and measured the effect of UII on ion transport across the opercular epithelium. We found that both UII and UT are synthesized in the gill of F. heteroclitus and that gill UT mRNA levels are ∼80% higher in SW- vs FW-acclimated individuals. In addition, UII inhibits NaCl transport across the opercular epithelium in a concentration-dependent manner, and this inhibition is at least partially mediated by both nitric oxide and a prostanoid.
Generation of Brønsted Acid Sites on Alumina-supported Tantalum(V) Oxide Calcined at 1223 K
Authors: Kitano Tomoyuki , Okazaki Shota , Shishido Tetsuya , Teramura Kentaro , Tanaka Tsunehiro
Published: November 2011

An alumina-supported tantalum(V) oxide (Ta2O5/Al2O3) calcined at 1223 K promoted the Friedel–Crafts alkylation of anisole with benzyl alcohol, and exhibited Brønsted acidity despite the high-temperature calcination. Among the Ta2O5/Al2O3 catalysts tested, 33 wt % Ta2O5/Al2O3 calcined at 1223 K showed the highest activity.
Main bronchial diverticula in the subcarinal region: Their relation to airflow limitations
Authors: Higuchi Takeshi , Takahashi Naoya , Shiotani Motoi , Sato Suguru , Ohta Atsushi , Maeda Haruo , Nakajima Haruhiko , Itoh Kazuhiko , Tsukada Hiroki
Published: November 2011

Background

To date, bronchial diverticula have generally been treated as a pathological condition associated with chronic obstructive pulmonary disease (COPD), although only a limited amount of published information is available on the relationship between bronchial diverticula as depicted by multidetector computed tomography (MDCT) and airflow limitations.

Purpose

To evaluate the relationship between airflow limitations and main bronchial diverticula in the subcarinal region using spirometry and thin-section MDCT.

Material and Methods

A total of 189 consecutive adult patients were retrospectively evaluated based on spirometry and thin-section MDCT of the chest. All examinations were performed at our institution between June and October 2008. The study group included 70 women and 119 men with a mean age of 65 years (range 19–86 years). The relationship between the FEV1% and bronchial diverticula in the subcarinal region was analyzed (Student's t-test).

Results

The indications for conducting the examinations were pulmonary diseases (82 patients), cardiovascular diseases (22), extrapulmonary malignancies (74), and other conditions (11). A total of 84/189 (44.4%) patients showed bronchial diverticula, and the FEV1% of 70/84 (83.3%) patients was above 70. The FEV1% of patients with lesions ranged from 26.0 to 97.8 (mean 76.8), whereas the range was 28.1–94.4 (mean 73.7) in those without lesions. There was no significant association between the FEV1% and the presence of subcarinal bronchial diverticula ( P > 0.05).

Conclusion

Our data demonstrate that thin-section chest CT commonly demonstrates main bronchial diverticula in the subcarinal region in patients without airflow limitations. We propose that the presence of a small number of tiny bronchial diverticula under the carina may not be a criterion for the diagnosis of COPD.
A Study of Mn(II) Ion Capture by Mesoporous Silica
Authors: Yuan Na-Juan , Ren Tie-Zhen , Christensen Jeppe
Published: November 2011

The removal of Mn(II) ions from water using mesoporous silica as the adsorbent material is discussed. The mesoporous silica was prepared in an economic manner through the use of sodium silicate as an inexpensive source of silica and decaoxyethylene cetyl ether [C16(EO)10] as the template agent. The properties of the material were characterized and its adsorption capacity for Mn(II) ions from aqueous solution investigated by varying parameters such as the pH of the initial suspension, the contact time, the initial concentration of Mn(II) ions in the solution and the adsorbent dosage. With no subsequent modification, the prepared materials exhibited a high adsorption capability towards Mn(II) ions with qe = 44 mg/g. The adsorption isotherms could be described by both the Langmuir and Freundlich models, the former model providing a better representation of the adsorption process. Characterization using UV–vis spectroscopy, nitrogen sorption isotherms and thermogravimetric analysis after adsorption indicated that the Mn(II) ions were adsorbed onto the mesoporous silica surface.
Dynamic Data Driven Experiment Control Coordinated with Anisotropic Elastic Material Characterization
Authors: Michopoulos John G. , Furukawa Tomonari , Hermanson John C. , Lambrakos Samuel G.
Published: November 2011

The goal of this paper is to propose and demonstrate a multi level design optimization approach for the coordinated determination of a material constitutive model synchronously to the design of the experimental procedure needed to acquire the necessary data. The methodology achieves both online (real-time) and offline design of optimum experiments required for characterization of the material system under consideration, while it also achieves the constitutive characterization of the system. The approach is based on the availability of mechatronic systems that can expose specimens to multidimensional loading paths and can automate the acquisition of data associated with stimulus and response behavior of the specimen. Material characterization is achieved by minimizing the difference between system responses that are measured experimentally and predicted based on the associated model representation. The performance metrics of the material characterization process are used to construct objective functions for the design of experiments at a higherlevel optimization. Distinguishability and uniqueness of solutions that characterize the system are used as two of many possible measures adopted for construction of objective functions required for design of experiments. Finally, a demonstration of the methodology is presented that considers the best loading path of a two degree-of-freedom loading machine for characterization of the linear elastic constitutive response of anisotropic materials.
Dynamic Decision and Data-Driven Strategies for the Optimal Management of Subsurface Geo-Systems
Authors: Parashar Manish , Klie Hector , Kurc Tahsin , Catalyurek Umit , Saltz Joel , Wheeler Mary F.
Published: November 2011

Effective geo-system management involves understanding of the interplay between surface entities (e.g., locations of injection and production wells in an oil reservoir) and appropriately effecting subsurface characteristics. This in turn requires efficient integration of complex numerical models of the environment, optimization procedures, and decision making processes. The dynamic, data-driven application systems (DDDAS) paradigm offers a promising framework to address this requirement. To achieve this goal, we have developed advanced multi-physics, multi-scale, and multi-block numerical models and autonomic systems software for dynamic, data-driven applications systems. This work has enabled a new generation of data-driven, interactive and dynamically adaptive strategies for subsurface characterization and management. These strategies have been applied to different aspects of subsurface management in strategically important application areas, including simulation-based optimization for the optimal oil well placement and the data-driven management of the Ruby Gulch Waste Repository. This paper summarizes the key outcomes and achievements of our work, as well as reports ongoing and future activities focused on uncertainty estimation and characterization.
Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Regimen for Multiple Myeloma
Authors: Erin K. Morrison , Waddell J. Aubrey , Dominic A. Solimando
Published: November 2011

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases.
Fidaxomicin
Authors: Dennis J. Cada , Terri L. Levien , Danial E. Baker
Published: November 2011

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. Subscribers to The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X.

Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800–322–4349. The November 2011 monograph topics are on indacaterol, brentuximub vedotin, icatibant injection, aflibercept, and centruroides (Scorpion) immune F(ab′)2. The DUE/MUE is on indacaterol.
Recent Publications on Medications and Pharmacy
Authors: Flint Russett
Published: November 2011

Hospital Pharmacy presents this feature to keep pharmacists abreast of new publications in the medical/pharmacy literature. Articles of interest regarding a broad scope of topics are abstracted monthly. Suggestions or comments may be addressed to Flint Russett, St. Claire Regional Medical Center, 222 Medical Circle, Morehead, KY 40351, or e-mail: FSRussett@st-claire.org .
The Importance of the Context in Brand Extension: How Pictures and Comparisons Shift Consumers' Focus from Fit to Quality
Authors: Meyvis Tom , Goldsmith Kelly , Dhar Ravi
Published: November 2011

It is well established that consumers' evaluations of brand extensions depend on the quality of the parent brand and the fit between that brand and the extension category. The authors propose that the relative importance of these two factors is influenced by two key features of a typical shopping environment: the presence of visual information and the availability of comparison brands. In particular, the authors demonstrate that adding pictures and enabling brand comparisons shift consumers' preference from extensions of better-fitting brands to extensions of higher-quality brands. The authors propose that this occurs because pictures and brand comparisons create a more concrete representation of the extension, which in turn increases the importance of parent brand quality relative to brand–extension fit. They provide support for this underlying mechanism and discuss the practical implications of their findings.
The Liprin Homology Domain Is Essential for the Homomeric Interaction of SYD-2/Liprin-α Protein in Presynaptic Assembly
Authors: Taru Hidenori , Jin Yishi
Published: November 2011

Synapses are asymmetric structures that are specialized for neuronal signal transduction. A unique set of proteins is present at the presynaptic active zone, which is a core structure essential for neurotransmitter release. InCaenorhabditis elegansHSN neurons, SYD-2, a Liprin-α family protein, acts together with a GAP protein SYD-1 to promote presynaptic assembly. Previous studies have shown that elevating the activity ofsyd-2can bypass the requirement ofsyd-1. Liprin-α proteins are composed of coiled-coil-rich regions in the N-terminal half, which mediate interactions with adapter proteins at the presynaptic active zone, and three SAM domains in the C terminus, which bind proteins such as LAR receptor tyrosine phosphatase. To address the molecular mechanism by which SYD-2 activity is regulated, we performed structure–function studies. By monitoring the ability of SYD-2 transgenes to rescuesyd-2(lf)and to suppresssyd-1(lf)phenotypes in HSN neuron synapses, we identified the N-terminal half of SYD-2 as minimally required for rescuingsyd-2(lf)phenotypes. A highly conserved short coiled-coil segment named Liprin Homology 1 (LH1) domain is both necessary and sufficient to suppresssyd-1(lf)defects. We show that the LH1 domain forms a dimer and promotes further oligomerization and/or complex formation of SYD-2/Liprin-α proteins. The role of the LH1 domain in presynaptic assembly can be partially complemented by artificial dimerization. These findings suggest a model by which the self-assembly of SYD-2/Liprin-α proteins mediated by the coiled-coil LH1 domain is one of the key steps to the accumulation of presynaptic components at nascent synaptic junctions.
Inhibition of the Ca2+-Dependent K+Channel,KCNN4/KCa3.1, Improves Tissue Protection and Locomotor Recovery after Spinal Cord Injury
Authors: Bouhy Delphine , Ghasemlou Nader , Lively Starlee , Redensek Adriana , Rathore Khizr I. , Schlichter Lyanne C. , David Samuel
Published: November 2011

Spinal cord injury (SCI) triggers inflammatory responses that involve neutrophils, macrophages/microglia and astrocytes and molecules that potentially cause secondary tissue damage and functional impairment. Here, we assessed the contribution of the calcium-dependent K+channelKCNN4(KCa3.1, IK1, SK4) to secondary damage after moderate contusion lesions in the lower thoracic spinal cord of adult mice. Changes inKCNN4mRNA levels (RT-PCR), KCa3.1 protein expression (Western blots), and cellular expression (immunofluorescence) in the mouse spinal cord were monitored between 1 and 28 d after SCI.KCNN4mRNA and KCa3.1 protein rapidly increased after SCI; double labeling identified astrocytes as the main cellular source accounting for this upregulation. Locomotor function after SCI, evaluated for 28 d in an open-field test using the Basso Mouse Scale, was improved in a dose-dependent manner by treating mice with a selective inhibitor of KCa3.1 channels, TRAM-34 (triarylmethane-34). Improved locomotor function was accompanied by reduced tissue loss at 28 d and increased neuron and axon sparing. The rescue of tissue by TRAM-34 treatment was preceded by reduced expression of the proinflammatory mediators, tumor necrosis factor-α and interleukin-1β in spinal cord tissue at 12 h after injury, and reduced expression of inducible nitric oxide synthase at 7 d after SCI. In astrocytesin vitro, TRAM-34 inhibited Ca2+signaling in response to metabotropic purinergic receptor stimulation. These results suggest that blocking the KCa3.1 channel could be a potential therapeutic approach for treating secondary damage after spinal cord injury.
Perirhinal Cortex Removal Dissociates Two Memory Systems in Matching-to-Sample Performance in Rhesus Monkeys
Authors: Tu Hsiao-Wei , Hampton Robert R. , Murray Elisabeth A.
Published: November 2011

Dissociations of memory systems are typically made using independent cognitive tests. For example, in monkeys habits have been inferred from performance in object discrimination tests, while non-matching-to-sample tests are thought to measure familiarity resulting from single exposures. Such tests cannot measure individual memory processes accurately when more than one memory process contributes to performance. In process dissociation procedures (PDPs), two memory processes cooperate and compete in the performance of a single cognitive task, allowing quantitative estimates of the contributions of each process. We used PDP to measure the contributions of habits and one-trial memory to visual matching-to-sample performance. Sets of test images were shown only once in each daily testing session but were repeated day after day. To produce habits, high-frequency images were correct more frequently than other images across days. Habits were manifest in the extent to which choices in the test phase of matching-to-sample trials were made to the high-frequency images, regardless of which image had been presented as the sample. One-trial memory was measured by the extent to which choices at test were made to the image that had appeared as the sample on that trial, regardless of habit. Perirhinal cortex removal reduced the contribution of one-trial memory to matching performance, but left both habits and the ability to discriminate images intact. PDP can be applied in monkeys in a way that parallels its use in humans, providing a new tool for investigating the neurobiology of memory in nonhuman animals and for comparing memory across species.
Adaptation to Conflict via Context-Driven Anticipatory Signals in the Dorsomedial Prefrontal Cortex
Authors: Horga Guillermo , Maia Tiago V. , Wang Pengwei , Wang Zhishun , Marsh Rachel , Peterson Bradley S.
Published: November 2011

Behavioral interference elicited by competing response tendencies adapts to contextual changes. Recent nonhuman primate research suggests a key mnemonic role of distinct prefrontal cells in supporting such context-driven behavioral adjustments by maintaining conflict information across trials, but corresponding prefrontal functions have yet to be probed in humans. Using event-related functional magnetic resonance imaging, we investigated the human neural substrates of contextual adaptations to conflict. We found that a neural system comprising the rostral dorsomedial prefrontal cortex and portions of the dorsolateral prefrontal cortex specifically encodes the history of previously experienced conflict and influences subsequent adaptation to conflict on a trial-by-trial basis. This neural system became active in anticipation of stimulus onsets during preparatory periods and interacted with a second neural system engaged during the processing of conflict. Our findings suggest that a dynamic interaction between a system that represents conflict history and a system that resolves conflict underlies the contextual adaptation to conflict.