bluuebunny/crossref_metadata_2025_split huggingface dataset:
NPY controls fear conditioning and fear extinction by combined action on Y1 and Y2 receptors
Authors: Verma D , Tasan RO , Herzog H , Sperk G 
Published: January 2012

BACKGROUND AND PURPOSE Neuropeptide Y (NPY) and its receptors have been implicated in the control of emotional‐affective processing, but the mechanism is unclear. While it is increasingly evident that stimulation of Y1 and inhibition of Y2 receptors produce prominent anxiolytic and antidepressant effects, the contribution of the individual NPY receptor subtypes in the acquisition and extinction of learned fear are unknown.EXPERIMENTAL APPROACH Here we performed Pavlovian fear conditioning and extinction in NPY knockout (KO) and in NPY receptor KO mice.KEY RESULTS NPY KO mice display a dramatically accelerated acquisition of conditioned fear. Deletion of Y1 receptors revealed only a moderately accelerated acquisition of conditioned fear, while lack of Y2 receptors was without any effect on fear learning. However, the strong phenotype seen in NPY KO mice was reproduced in mice lacking both Y1 and Y2 receptors. In addition, NPY KO mice showed excessive recall of conditioned fear and impaired fear extinction. This behaviour was replicated only after deletion of both Y1 and Y2 receptors. In Y1 receptor single KO mice, fear extinction was delayed and was unchanged in Y2 receptor KO mice. Deletion of NPY and particularly Y2 receptors resulted in a generalization of conditioned fear.CONCLUSIONS AND IMPLICATIONS Our data demonstrate that NPY delays the acquisition, reduces the expression of conditioned fear while promoting fear extinction. Although these effects appear to be primarily mediated by Y1 receptors, the pronounced phenotype of Y1Y2 receptor double KO mice suggests a synergistic role of Y2 receptors in fear acquisition and in fear extinction.
Role of mixed ion channel effects in the cardiovascular safety assessment of the novel anti‐MRSA fluoroquinolone JNJ‐Q2
Authors: Eichenbaum G , Pugsley MK , Gallacher DJ , Towart R , McIntyre G , Shukla U , Davenport JM , Lu HR , Rohrbacher J , Hillsamer V 
Published: January 2012

BACKGROUND AND PURPOSEJNJ‐Q2, a novel broad‐spectrum fluoroquinolone with anti‐methicillin‐resistant Staphylococcus aureus activity, was evaluated in a comprehensive set of non‐clinical and clinical cardiovascular safety studies. The effect of JNJ‐Q2 on different cardiovascular parameters was compared with that of moxifloxacin, sparfloxacin and ofloxacin. Through comparisons with these well‐known fluoroquinolones, the importance of effects on compensatory ion channels to the cardiovascular safety of JNJ‐Q2 was investigated.EXPERIMENTAL APPROACHJNJ‐Q2 and comparator fluoroquinolones were evaluated in the following models/test systems: hERG‐transfected HEK293 cells sodium channel‐transfected CHO cells, guinea pig right atria, arterially perfused rabbit left ventricular wedge preparations and in vivo studies in anaesthetized guinea pigs, anaesthetized and conscious telemetered dogs, and a thorough QT study in humans.KEY RESULTSThe trend for effects of JNJ‐Q2 on Tp–Te, QT, QRS and PR intervals in the non‐clinical models and the plateau in QTc with increasing plasma concentration in humans are consistent with offsetting sodium and calcium channel activities that were observed in the non‐clinical studies. These mixed ion channel activities result in the less pronounced or comparable increase in QTc interval for JNJ‐Q2 compared with moxifloxacin and sparfloxacin despite its greater in vitro inhibition of IKr.CONCLUSIONS AND IMPLICATIONSBased on the non‐clinical and clinical cardiovascular safety assessment, JNJ‐Q2 has a safe cardiovascular profile for administration in humans with comparable or reduced potential to prolong QT intervals, compared with moxifloxacin. The results demonstrate the importance of compensatory sodium and calcium channel activity in offsetting potassium channel activity for compounds with a fluoroquinolone core.
Inhibition of Na+‐H+ exchange as a mechanism of rapid cardioprotection by resveratrol
Authors: Thuc Luong Cong , Teshima Yasushi , Takahashi Naohiko , Nishio Satoru , Fukui Akira , Kume Osamu , Saito Shotaro , Nakagawa Mikiko , Saikawa Tetsunori 
Published: January 2012

BACKGROUND AND PURPOSE Resveratrol is a polyphenol abundantly found in grape skin and red wine. In the present study, we investigated whether resveratrol exerts protective effects against cardiac ischaemia/reperfusion and also explored its mechanisms.EXPERIMENTAL APPROACH Infarct size and functional recovery in rat isolated perfused hearts subjected to no‐flow global ischaemia followed by reperfusion were measured. Cultured neonatal rat cardiomyocytes were exposed to H2O2 (100 µmol·L−1) to induce cell injury. Intracellular ion concentrations were measured using specific dyes. Western blotting was used to quantify protein expression levels.KEY RESULTS In rat isolated perfused hearts, treatment with resveratrol (20 and 100 µmol·L−1) 15 min before ischaemia considerably improved left ventricular functional recovery and infarct size. In cultured neonatal rat cardiomyocytes, resveratrol significantly attenuated the increase in reactive oxygen species (ROS) and loss of mitochondrial inner membrane potential. Resveratrol also suppressed the increase in intracellular concentrations of Na+ ([Na+]i) and Ca2+ ([Ca2+]i) after H2O2 application; however, it did not suppress the ouabain‐induced [Ca2+]i increase. By measuring changes in intracellular pH recovery after acidification, we also confirmed that acid‐induced activation of the Na+‐H+ exchanger (NHE) was prevented by pretreatment with resveratrol. Furthermore, resveratrol inhibited the H2O2‐induced translocation of PKC‐α from the cytosol to the cell membrane; this translocation is believed to activate NHE.CONCLUSION AND IMPLICATIONS Resveratrol exerts cardioprotection by reducing ROS and preserving mitochondrial function. The PKC‐α‐dependent inhibition of NHE and subsequent attenuation of [Ca2+]i overload may be a cardioprotective mechanism.
Coexistence of schizophrenia and epilepsy: Record‐linkage studies
Authors: Wotton Clare J. , Goldacre Michael J. 
Published: January 2012

SummaryFor many years, there has been interest in a possible link between epilepsy and schizophrenia. A recent study found a strong, bidirectional link between the two conditions: people with one had a higher than average risk of having the other. Using two large data sets of hospital admission data, we investigated whether schizophrenia and epilepsy occur together in individuals more commonly than expected by chance. We undertook a retrospective cohort study using the Oxford Record Linkage Study (ORLS) and English national linked Hospital Episode Statistics to investigate the coexistence of these conditions. There was an elevated risk of epilepsy in people admitted to hospital with schizophrenia (ORLS rate ratio 2.1, 95% confidence interval 1.6–2.6; England 3.0, 2.9–3.1) and an elevated risk of schizophrenia in people admitted to hospital with epilepsy (ORLS 5.1, 4.1–6.2; England 4.5, 4.3–4.6). We found no consistent difference between male and female patients. Schizophrenia and epilepsy occur together in individuals more frequently than expected by chance.
Subtotal Vaginectomy for Management of Extensive Vaginal Disease in 11 Dogs
Authors: Nelissen Pieter , White Richard A S 
Published: January 2012

ObjectiveTo report (1) a surgical technique for subtotal vaginectomy using a combined abdominal and vestibular approach; (2) intra‐ and postoperative complications; and (3) long‐term outcome.Study DesignRetrospective case series.AnimalsFemale dogs (n = 11) with extensive intramural vaginal disease.MethodsThrough a ventral median celiotomy, the cranial aspect of the vagina was freed and ovariohysterectomy (OVH) was performed in intact females. After episiotomy, the vaginal wall was incised at the vestibulovaginal junction cranial to the urethral orifice, and the vagina freed from any remaining pelvic attachments. Dogs were reexamined at 4 weeks and 6 months. Long‐term outcome was evaluated by contacting the primary veterinarian by phone.ResultsFive dogs had benign vaginal disease and 6 had malignant vaginal neoplasia. A combined abdominal and vestibular approach permitted subtotal vaginectomy in all dogs; 6 dogs also had OVH. No major complications occurred and clinical signs had resolved by 4 weeks. One dog with malignant neoplasia was euthanatized 3 months later for metastatic disease and 1 dog developed postoperative urinary incontinence. Local recurrence or metastases were not identified in the other dogs.ConclusionCombined abdominal and vestibular approach for subtotal vaginectomy allowed complete resection of extensive vaginal lesions, was not associated with major complications, and outcome was favorable.
A recurrent D‐strand association interface is observed in β‐2 microglobulin oligomers
Authors: Colombo Matteo , de Rosa Matteo , Bellotti Vittorio , Ricagno Stefano , Bolognesi Martino 
Published: January 2012

β‐2 microglobulin (β2m) is an amyloidogenic protein responsible for dialysis‐related amyloidosis in man. In the early stages of amyloid fibril formation, β2m associates into dimers and higher oligomers, although the structural details of such aggregates are poorly understood. To characterize the protein–protein interactions supporting the formation of oligomers, three individual β2m cysteine mutants and their disulfide‐linked homodimers (DIMC20, DIMC50 and DIMC60) were prepared. Amyloid propensity, oligomerization state in solution and crystallogenesis were tested for each β2m homodimer: DIMC20 and DIMC50 display a mixture of tetrameric and dimeric species in solution and also yield protein crystals and amyloid fibrils, whereas DIMC60 is dimeric in solution but does not form protein crystals nor amyloid fibrils. The X‐ray structures of DIMC20 and DIMC50 show that the two engineered dimers form a tetrameric assembly; for both tetrameric species, the noncovalent association interface is based on the interaction of facing β2m D‐strands and is conserved. Notably, DIMC20 and DIMC50 trigger amyloid formation in wild‐type β2m in unseeded reactions. Thus, when the D‐D‐strand interface is impaired by an intermolecular disulfide bond (as in DIMC60), the formation of tetramers is hindered, and the protein is not amyloidogenic and does not promote amyloid aggregation of wild‐type β2m. Implications for β2m oligomerization are discussed.DatabaseAtomic coordinates and structure factors have been deposited in the Protein Data Bank database under the accession codes 3TLR and 3TM6 for the structures of DIMC20 and DIMC50, respectively.Structured digital abstract
Beta‐2‐microglobulin and Beta‐2‐microglobulin bind by transmission electron microscopy (View interaction)
Beta‐2‐microglobulin and Beta‐2‐microglobulin bind by fluorescence technology (View interaction)
Mapping the spatial distribution of botanical composition and herbage mass in pastures using hyperspectral imaging
Authors: Suzuki Yumiko , Okamoto Hiroshi , Takahashi Makoto , Kataoka Takashi , Shibata Youichi 
Published: January 2012

AbstractQuantifying the vegetation heterogeneity in pastures is important to understand the behavior and performance of grazing animals. In this study, we developed a technique for mapping spatial distribution of botanical composition (perennial ryegrass, white clover and other plants) and herbage mass of perennial ryegrass in a grazed pasture using a hyperspectral imaging system, which can glean more detailed spectral information than conventional multispectral imaging that uses standard band frequencies. Plant portions were extracted from hyperspectral image using normalized difference vegetation index threshold and classified into the three plant species or species groups using linear discriminant analysis models. The overall success rate of plant extraction and discrimination between plant species or species groups was 91.6 and 80.3%, respectively. Herbage mass of perennial ryegrass was estimated using partial least squares regression analysis, where the estimated values showed a coefficient of determination of 0.60 against the observed values. In consequence of the models, our results suggested that the difference of leaf cell structure and photosynthesis pigments influenced discrimination between plant species or species group and estimation of the herbage mass. The results demonstrate the potential of the hyperspectral imaging system for creating high spatial resolution maps of vegetation characteristics in pastures.
Energy drinks: What is all the hype? The dangers of energy drink consumption
Authors: Rath Mandy 
Published: January 2012

AbstractPurpose: To describe the adverse effects associated with energy drink consumption among adolescents and young adults.Data sources: Review of literature utilizing Medscape, the Internet, MD Consult, and CINAHL. The following search terms were used: Energy drinks, caffeine, guarana, taurine, ginseng, sugar, and caffeine toxicity. Search was limited to English language sources from 2005 to 2010.Conclusions: The popularity of energy drinks and the rapid growth of their excessive consumption among adolescents and young adults have brought about great concern in regards to overall health and well‐being. Caffeine, which is readily available to minors, is the most commonly used psychoactive substance in the world and imposes a potentially harmful influence on health, academic performance, and personal adjustments. Teens and young adults account for nearly $2.3 billion of energy drink sales. Adolescents and young adults are often unaware that various products, such as energy drinks, herbal medications, and various other medications that promote alertness, contain caffeine. When these products are taken together, caffeine toxicity and severe adverse effects can occur.Implications for practice: Practitioners need to be aware of the consequences of energy drink consumption and be prepared to provide appropriate patient education.
Early cardiac dysfunction is rescued by upregulation of SERCA2a pump activity in a rat model of metabolic syndrome
Authors: Miklós Z. , Kemecsei P. , Bíró T. , Marincsák R. , Tóth B. I. , Op den Buijs J. , Benis É. , Drozgyik A. , Ivanics T. 
Published: January 2012

AbstractAimVarious components of metabolic syndrome associate with cardiac intracellular calcium () mishandling, a precipitating factor in the development of heart failure. We aimed to provide a thorough description of early stage ‐cycling alterations in the fructose‐fed rat, an experimental model of the disorder, where insulin resistance, hypertension and dyslipidaemia act cooperatively on the heart.MethodRats were fed with fructose‐rich chow. After 6 weeks, echocardiography was performed, which was followed by measurements of myocardial transients recorded by Indo‐1 surface fluorometry in isolated perfused hearts. Sarcoplasmic reticulum (SR) Ca2+‐ATPase (SERCA2a) activity was assessed by administration of its inhibitor cyclopiazonic acid (CPA). Mathematical model analysis of transients was used to estimate kinetic properties of SR Ca2+ transporters. Protein levels of key Ca2+ handling proteins were also measured.ResultsEchocardiography showed signs of cardiac hypertrophy, but in vivo and ex vivo haemodynamic performance of fructose‐fed rat hearts were unaltered. However, a decline in Ca2+ sequestration capacity ( and decay time of transients) was observed. Model estimation showed decreased affinity for Ca2+ (higher Km) and elevated Vmax for SERCA2a. Diseased hearts were more vulnerable to CPA application. Fructose feeding caused elevation in SERCA2a and phosphorylated phospholamban (PLB) expression, while total PLB level remained unchanged.ConclusionIn early stage, metabolic syndrome primarily disturbs SERCA2a function in the heart, but consequential haemodynamic dysfunction is prevented by upregulation of SERCA2a protein level and phosphorylation pathways regulating PLB. However, this compensated state is very vulnerable to a further decline in SERCA2a function.
MM2‐Thalamic Creutzfeldt–Jakob Disease: Neuropathological, Biochemical and Transmission Studies Identify a Distinctive Prion Strain
Authors: Moda Fabio , Suardi Silvia , Di Fede Giuseppe , Indaco Antonio , Limido Lucia , Vimercati Chiara , Ruggerone Margherita , Campagnani Ilaria , Langeveld Jan , Terruzzi Alessandro , Brambilla Antonio , Zerbi Pietro , Fociani Paolo , Bishop Matthew T. , Will Robert G. , Manson Jean C. , Giaccone Giorgio , Tagliavini Fabrizio 
Published: January 2012

AbstractIn Creutzfeldt–Jakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease‐associated prion protein (PrPSc) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico‐pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrPSc and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrPSc are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia.We observed two young patients with MM2‐thalamic CJD. Main neuropathological features were diffuse, synaptic PrP immunoreactivity in the cerebral cortex and severe neuronal loss and gliosis in the thalamus and olivary nucleus. Western blot analysis showed the presence of type 2A PrPSc. Challenge of transgenic mice expressing 129MM human PrP showed that MM2‐thalamic sporadic CJD (sCJD) was able to transmit the disease, at variance with MM2‐cortical sCJD. The affected mice showed deposition of type 2A PrPSc, a scenario that is unprecedented in this mouse line. These data indicate that MM2‐thalamic sCJD is caused by a prion strain distinct from the other sCJD subtypes including the MM2‐cortical form.
Restoration of lordosis and disk height after single‐level transforaminal lumbar interbody fusion
Authors: Kepler Christopher K , Rihn Jeffrey A , Radcliff Kristen E , Patel Amar A , Anderson D Greg , Vaccaro Alexander R , Hilibrand Alan S , Albert Todd J 
Published: January 2012

Objective:  To study radiographic and clinical outcomes after transforaminal lumbar interbody fusion (TLIF) in order to determine the impact of TLIF on lumbar lordosis, intervertebral height and improvement in clinical outcome measures.Methods:  Forty‐five patients who had undergone a single‐level TLIF procedure for a single‐level degenerative condition were retrospectively reviewed and their clinical histories, degree of pre‐ and post‐operative lumbar lordosis, intervertebral height, and cage position recorded. Clinical assessment included use of modified Odom's criteria and a visual analog scale (VAS) for back and leg pain.Results:  At 21 months, the patients had gained an average of 3.6° of lumbar lordosis and 4.5 mm disc height. Change in disc height was significantly associated with an anterior cage position while lumbar lordosis was unaffected by cage position. A spondylolisthesis subgroup demonstrated 31% reduction in the magnitude of anterior slip. Less lordosis was associated with worse back and leg pain as assessed by VAS and greater disk heights were associated with higher Odom's criteria scores. Patients with persistent leg pain at final follow‐up had less lumbar lordosis and intervertebral height than patients without leg pain.Conclusions:  Intervertebral height and lumbar lordosis reconstruction are important for achieving good surgical results; guidance regarding the likely changes in lumbar lordosis and disk height after TLIF is provided by our findings.
A Systematic Approach to Studying Fisheries Governance
Authors: Basurto Xavier , Nenadovic Mateja 
Published: January 2012

AbstractHow can policies for governing marine fisheries become more effective? How can we engage in developing a new science of fisheries governance that promotes knowledge accumulation and collective learning? We look into these issues by reviewing the current social‐ecological status of marine fisheries, common policy approaches in place to govern them, and key learned lessons and shortcomings. While great efforts have been made towards understanding marine governance in the last 50 years, if we are to meet the current and upcoming challenges facing global fisheries, we need to engage with systematic knowledge accumulation about governance performance. To this end we report on a novel classificatory framework which, while nascent, could offer the potential to help us move in that direction.
Expression of OXA-Type and SFO-1 β-Lactamases Induces Changes in Peptidoglycan Composition and Affects Bacterial Fitness
Authors: Fernández Ana , Pérez Astrid , Ayala Juan A. , Mallo Susana , Rumbo-Feal Soraya , Tomás Maria , Poza Margarita , Bou Germán 
Published: January 2012

ABSTRACT

β-Lactamases and penicillin-binding proteins (PBPs) have evolved from a common ancestor. β-Lactamases are enzymes that degrade β-lactam antibiotics, whereas PBPs are involved in the synthesis and processing of peptidoglycan, which forms an elastic network in the bacterial cell wall. This study analyzed the interaction between β-lactamases and peptidoglycan and the impact on fitness and biofilm production. A representative set of all classes of β-lactamases was cloned in the expression vector pBGS18 under the control of the CTX-M promoter and expressed in
Escherichia coli
MG1655. The peptidoglycan composition of all clones was evaluated, and quantitative changes were found in
E. coli
strains expressing OXA-24, OXA-10-like, and SFO-1 (with its upstream regulator AmpR) β-lactamases; the level of cross-linked muropeptides decreased, and their average length increased. These changes were associated with a statistically significant fitness cost, which was demonstrated in both
in vitro
and
in vivo
experiments. The observed changes in peptidoglycan may be explained by the presence of residual
dd
-endopeptidase activity in these β-lactamases, which may result in hydrolysis of the peptide cross bridge. The biological cost associated with these changes provides important data regarding the interaction between β-lactamases and the metabolism of peptidoglycan and may provide an explanation for the epidemiology of these β-lactamases in
Enterobacteriaceae
.