bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lmx1a is an activator of Rgs4 and Grb10 and is responsible for the correct specification of rostral and medial mdDA neurons
Authors: Hoekstra Elisa J. , von Oerthel Lars , van der Linden Annemarie J. A. , Schellevis Raymond D. , Scheppink Gerard , Holstege Frank C. P. , Groot‐Koerkamp Marian J. , van der Heide Lars P. , Smidt Marten P. 
Published: October 2012

AbstractThe LIM homeodomain transcription factor Lmx1a is a very potent inducer of stem cells towards dopaminergic neurons. Despite several studies on the function of this gene, the exact in vivo role of Lmx1a in mesodiencephalic dopamine (mdDA) neuronal specification is still not understood. To analyse the genes functioning downstream of Lmx1a, we performed expression microarray analysis of LMX1A‐overexpressing MN9D dopaminergic cells. Several interesting regulated genes were identified, based on their regulation in other previously generated expression arrays and on their expression pattern in the developing mdDA neuronal field. Post analysis through in vivo expression analysis in Lmx1a mouse mutant (dr/dr) embryos demonstrated a clear decrease in expression of the genes Grb10 and Rgs4, in and adjacent to the rostral and dorsal mdDA neuronal field and within the Lmx1a expression domain. Interestingly, the DA marker Vmat2 was significantly up‐regulated as a consequence of increased LMX1A dose, and subsequent analysis on Lmx1a‐mutant E14.5 and adult tissue revealed a significant decrease in Vmat2 expression in mdDA neurons. Taken together, microarray analysis of an LMX1A‐overexpression cell system resulted in the identification of novel direct or indirect downstream targets of Lmx1a in mdDA neurons: Grb10, Rgs4 and Vmat2.
rTMS over human motor cortex can modulate tremor during movement
Authors: Rogasch Nigel C. , Todd Gabrielle 
Published: October 2012

AbstractAbnormally large tremor during movement is a symptom of many movement disorders and significantly impairs activities of daily living. The aim of this study was to investigate whether repetitive magnetic brain stimulation (rTMS) can reduce tremor size during human movement. We hypothesised that inhibitory rTMS over motor cortex would reduce tremor size during subsequent movement. The study involved 26 healthy young adults (21 ± 2 years) and began with application of single TMS stimuli to measure baseline corticospinal excitability. The response to stimulation was recorded in hand muscles with electromyography. Subjects then performed a 3‐min task to measure baseline tremor during movement. This involved matching index finger position with a moving target on a computer screen. Tremor was recorded with an accelerometer on the fingernail. Finger acceleration was analysed with fast‐Fourier transform to quantify tremor in the physiological range (7.8–12.2 Hz). Subjects then received 10 min of real (n = 13) or sham (n = 13) inhibitory rTMS. Tremor and corticospinal excitability were then remeasured. Real rTMS significantly decreased corticospinal excitability by ~30% (P = 0.022) and increased tremor size during movement by ~120% (P = 0.047) relative to sham rTMS. However, the direction of tremor change was opposite to that hypothesised for inhibitory rTMS. The results suggest that rTMS over human motor cortex can modulate action tremor and the level of corticospinal excitability may be important for setting the amplitude of action tremor in healthy young adults.
Effects of the α2‐adrenergic receptor agonist dexmedetomidine on neural, vascular and BOLD fMRI responses in the somatosensory cortex
Authors: Fukuda Mitsuhiro , Vazquez Alberto L. , Zong Xiaopeng , Kim Seong‐Gi 
Published: October 2012

AbstractThis article describes the effects of dexmedetomidine (DEX) – the active ingredient of medetomidine, which is the latest popular sedative for functional magnetic resonance imaging (fMRI) in rodents – on multiple unit activity, local field potential (LFP), cerebral blood flow (CBF), pial vessel diameter [indicative of cerebral blood volume (CBV)], and blood oxygenation level‐dependent (BOLD) fMRI. These measurements were obtained from the rat somatosensory cortex during 10 s of forepaw stimulation. We found that the continuous intravascular systemic infusion of DEX (50 μg/kg/h, doses typically used in fMRI studies) caused epileptic activities, and that supplemental isoflurane (ISO) administration of ~0.3% helped to suppress the development of epileptic activities and maintained robust neuronal and hemodynamic responses for up to 3 h. Supplemental administration of N2O in addition to DEX nearly abolished hemodynamic responses even if neuronal activity remained. Under DEX + ISO anesthesia, spike firing rate and the delta power of LFP increased, whereas beta and gamma power decreased, as compared with ISO‐only anesthesia. DEX administration caused pial arteries and veins to constrict nearly equally, resulting in decreases in baseline CBF and CBV. Evoked LFP and CBF responses to forepaw stimulation were largest at a frequency of 8–10 Hz, and a non‐linear relationship was observed. Similarly, BOLD fMRI responses measured at 9.4 T were largest at a frequency of 10 Hz. Both pial arteries and veins dilated rapidly (artery, 32.2%; vein, 5.8%), and venous diameter returned to baseline slower than arterial diameter. These results will be useful for designing, conducting and interpreting fMRI experiments under DEX sedation.
Neural regulation of the time course for cocaine‐cue extinction consolidation in rats
Authors: Szalay, Jonathan J. , Jordan Chloe J. , Kantak Kathleen M. 
Published: October 2012

AbstractSites within the hippocampus, amygdala and prefrontal cortex may regulate how responses maintained by cues associated with cocaine are extinguished. To test the role of various brain sites in the consolidation of cocaine‐cue extinction learning, the dorsal subiculum (dSUB), rostral basolateral amygdala (rBLA) and infralimbic prefrontal cortex (IL) were manipulated in rats. Following cocaine self‐administration training (cues present, cocaine available), responding was assessed during 1‐h extinction tests (cues present, no cocaine available). To study extinction consolidation specifically, the protein synthesis inhibitor anisomycin or vehicle was infused bilaterally into the dSUB, rBLA or IL either immediately following or 6 h after the first two of three extinction training sessions. With manipulations made immediately after extinction sessions, infusions of anisomycin into the dSUB or the rBLA deterred extinction. Rats maintained elevated levels of cocaine seeking relative to vehicle despite the absence of cocaine delivery. Manipulations of IL had no effect. Control studies showed that bilateral protein synthesis inhibition in dSUB and rBLA 6 h after the extinction sessions ended was unable to deter extinction. Rats reduced cocaine seeking in the usual manner in the absence of cocaine delivery. Collectively, these findings suggest that the dSUB and rBLA are neural substrates important for consolidation of cocaine‐cue extinction learning and have time‐dependent roles. Understanding the contribution of individual neural substrates for cocaine‐cue extinction consolidation may help guide treatment strategies aimed at enhancing cue exposure therapy in cocaine‐dependent people.
Major vault protein promotes locomotor recovery and regeneration after spinal cord injury in adult zebrafish
Authors: Pan Hong‐Chao , Lin Jin‐Fei , Ma Li‐Ping , Shen Yan‐Qin , Schachner Melitta 
Published: October 2012

AbstractIn contrast to mammals, adult zebrafish recover locomotor functions after spinal cord injury (SCI), in part due to axonal regrowth and regeneration permissivity of the central nervous system. Upregulation of major vault protein (MVP) expression after spinal cord injury in the brainstem of the adult zebrafish prompted us to probe for its contribution to recovery after SCI. MVP is a multifunctional protein expressed not only in many types of tumours but also in the nervous system, where its importance for regeneration is, however, unclear. Using an established zebrafish SCI model, we found that MVP mRNA and protein expression levels were increased in ependymal cells in the spinal cord caudal to the lesion site at 6 and 11 days after SCI. Double immunolabelling showed that MVP was co‐localised with Islet‐1 or tyrosine hydroxylase around the central canal of the spinal cord in sham‐injured control fish and injured fish 11 days after surgery. MVP co‐localised with the neural stem cell marker nestin in ependymal cells after injury. By using an in vivo morpholino‐based knock‐down approach, we found that the distance moved by MVP morpholino‐treated fish was reduced at 4, 5 and 6 weeks after SCI when compared to fish treated with standard control morpholino. Knock‐down of MVP resulted in reduced regrowth of axons from brainstem neurons into the spinal cord caudal to the lesion site. These results indicate that MVP supports locomotor recovery and axonal regrowth after SCI in adult zebrafish.
Medical management of sand enteropathy in 62 horses
Authors: Hart K. A. , Linnenkohl W. , Mayer J. R. , House A. M. , Gold J. R. , Giguère S. 
Published: October 2012

SummaryReasons for performing studyMedical management of sand enteropathy is common in equine practice, but the clinical features and outcomes associated with medically managed sand enteropathy are not well described.ObjectivesTo review clinical features, therapeutic approaches and outcomes associated with primary medical management of sand enteropathy in the mature horse.MethodsMedical record databases at 3 equine referral hospitals fromJanuary 2000 toApril 2010 were reviewed for cases of sand enteropathy diagnosed via abdominal radiographs in mature horses that were initially managed medically. Data were collected and descriptive analyses compiled. Uni‐ and multivariate logistic regression was used to evaluate factors potentially associated with treatment failure.ResultsThe medical records of 62 horses were analysed; 90% of horses survived to discharge and 50% of horses that had repeat abdominal radiographs taken demonstrated improvement in the degree of sand accumulation after treatment. Nine horses underwent exploratory laparotomy during hospitalisation, and colonic sand impaction was found in all 9, with a concurrent gastrointestinal lesion identified in 7. Four horses were subjected to euthanasia during or after surgery because of disease severity or complications. Need for exploratory laparotomy was the factor most strongly associated with nonsurvival.ConclusionsThese data suggest that medical management can result in clinical and radiographic resolution of uncomplicated sand enteropathy in mature horses, and is associated with a good prognosis. Horses with sand enteropathy that exhibit persistent colic signs despite medical management are likely to have a concurrent gastrointestinal lesion, so prompt exploratory laparotomy should be considered in such cases.Potential relevanceUncomplicated sand enteropathy can be managed medically in mature horses, and serial abdominal radiography can be used to monitor sand clearance. Surgery to evaluate for and correct concurrent gastrointestinal lesions should be recommended without delay in horses showing persistent colic signs.
SET overexpression decreases cell detoxification efficiency: ALDH2 and GSTP1 are downregulated, DDR is impaired and DNA damage accumulates
Authors: Almeida Luciana O. , Goto Renata N. , Pestana Cezar R. , Uyemura Sérgio A. , Gutkind Silvio , Curti Carlos , Leopoldino Andréia M. 
Published: October 2012

Alcohol and tobacco consumption are risk factors for head and neck squamous cell carcinoma (HNSCC). Aldehyde dehydrogenase 2 (ALDH2) and glutathione S–transferase pi 1 (GSTP1) are important enzymes for cellular detoxification and low efficiencies are implicated in cancer. We assessed the potential role of SET protein overexpression, a histone acetylation modulator accumulated in HNSCC, in gene regulation and protein activity of ALDH2 and GSTP1. SET was knocked down in HN13, HN12 and Cal27, and overexpressed in HEK293 cells; ethanol and cisplatin were the chemical agents. Cells with SET overexpression (HEK293/SET, HN13 and HN12) showed lower ALDH2 and GSTP1 mRNA levels and trichostatin A increased them (real‐time PCR). Ethanol upregulated GSTP1 and ALDH2 mRNAs, whereas cisplatin upregulated GSTP1 in HEK293 cells. SET‐chromatin binding revealed SET interaction with ALDH2 and GSTP1 promoters, specifically via SET NAP domain; ethanol and cisplatin abolished SET binding. ALDH2 and GSTP1 efficiency was assessed by enzymatic and comet assay. A lower ALDH2 activity was associated with greater DNA damage (tail intensity) in HEK293/SET compared with HEK293 cells, whereas HN13/siSET showed ALDH2 activity higher than HN13 cells. HN13/siSET cells showed increased tail intensity. Cisplatin‐induced DNA damage response showed negative relationship between SET overexpression and BRCA2 recruitment. SET downregulated repair genes ATM, BRCA1 and CHEK2 and upregulated TP53. Cisplatin‐induced cell‐cycle arrest occurred in G0/G1 and S in HEK293 cells, whereas HEK293/SET showed G2/M stalling. Overall, cisplatin was more cytotoxic for HN13 than HN13/siSET cells. Our data suggest a role for SET in cellular detoxification, DNA damage response and genome integrity.
Differences in the profile of neonatal abstinence syndrome signs in methadone‐ versus buprenorphine‐exposed neonates
Authors: Gaalema Diann E. , Scott Teresa Linares , Heil Sarah H. , Coyle Mara G. , Kaltenbach Karol , Badger Gary J. , Arria Amelia M. , Stine Susan M. , Martin Peter R. , Jones Hendrée E. 
Published: October 2012

AbstractAimsTo compare the profile of signs of neonatal abstinence syndrome (NAS) in methadone‐ versus buprenorphine‐exposed infants.Design, setting and participantsSecondary analysis of NAS data from a multi‐site, double‐blind, double‐dummy, flexible‐dosing, randomized clinical trial. Data from a total of 129 neonates born to opioid‐dependent women who had been assigned to receive methadone or buprenorphine treatment during pregnancy were examined.MeasurementsFor 10 days after delivery, neonates (methadone = 72, buprenorphine = 57) were assessed regularly using a 19‐item modified Finnegan scale. Data from neonates who required pharmacological treatment (methadone = 41, buprenorphine = 27) were included up to the time treatment was initiated. The incidence and mean severity of the total NAS score and each individual sign of NAS were calculated and compared between medication conditions, as was the median time until morphine treatment initiation among treated infants in each condition.FindingsTwo NAS signs (undisturbed tremors and hyperactive Moro reflex) were observed significantly more frequently in methadone‐exposed neonates and three (nasal stuffiness, sneezing, loose stools) were observed more frequently in buprenorphine‐exposed neonates. Mean severity scores on the total NAS score and five individual signs (disturbed and undisturbed tremors, hyperactive Moro reflex, excessive irritability, failure to thrive) were significantly higher among methadone‐exposed neonates, while sneezing was higher among buprenorphine‐exposed neonates. Among treated neonates, methadone‐exposed infants required treatment significantly earlier than buprenorphine‐exposed infants (36 versus 59 hours postnatal, respectively).ConclusionsThe profile of neonatal abstinence syndrome differs in methadone‐ versus buprenorphine‐exposed neonates, with significant differences in incidence, severity and treatment initiation time. Overall, methadone‐exposed neonates have a more severe neonatal abstinence syndrome.
Neonatal neurobehavior effects following buprenorphine versus methadone exposure
Authors: Coyle Mara G. , Salisbury Amy L. , Lester Barry M. , Jones Hendrée E. , Lin Hai , Graf‐Rohrmeister Klaudia , Fischer Gabriele 
Published: October 2012

AbstractAimTo determine the effects of in utero exposure to methadone or buprenorphine on infant neurobehavior.DesignThree sites from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a double‐blind, double‐dummy, randomized clinical trial participated in this substudy.SettingMedical Centers that provided comprehensive maternal care to opioid‐dependent pregnant women in Baltimore, MD, Providence, RI and Vienna, Austria.ParticipantsThirty‐nine full‐term infants.MeasurementsThe Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS) was administered to a subgroup of infants on postpartum days 3, 5, 7, 10, 14–15 and 28–30.FindingsWhile neurobehavior improved for both medication conditions over time, infants exposed in utero to buprenorphine exhibited fewer stress‐abstinence signs (P < 0.001), were less excitable (P < 0.001) and less over‐aroused (P < 0.01), exhibited less hypertonia (P < 0.007), had better self‐regulation (P < 0.04) and required less handling (P < 0.001) to maintain a quiet alert state relative to in utero methadone‐exposed infants. Infants who were older when they began morphine treatment for withdrawal had higher self‐regulation scores (P < 0.01), and demonstrated the least amount of excitability (P < 0.02) and hypertonia (P < 0.02) on average. Quality of movement was correlated negatively with peak NAS score (P < 0.01), number of days treated with morphine for NAS (P < 0.01) and total amount of morphine received (P < 0.03). Excitability scores were related positively to total morphine dose (P < 0.03).ConclusionWhile neurobehavior improves during the first month of postnatal life for in utero agonist medication‐exposed neonates, buprenorphine exposure results in superior neurobehavioral scores and less severe withdrawal than does methadone exposure.
Opioid dependence during pregnancy: relationships of anxiety and depression symptoms to treatment outcomes
Authors: Benningfield Margaret M. , Dietrich Mary S. , Jones Hendrée E. , Kaltenbach Karol , Heil Sarah H. , Stine Susan M. , Coyle Mara G. , Arria Amelia M. , O'Grady Kevin E. , Fischer Gabriele , Martin Peter R. 
Published: October 2012

AbstractAimsTo examine the relationship of anxiety and depression symptoms with treatment outcomes (treatment discontinuation, rates of ongoing use of illicit drugs and likelihood of preterm delivery) in opioid‐dependent pregnant women and describe their use of psychotropic medications.Design and settingSecondary data analysis from a randomized clinical trial of treatment for opioid dependence during pregnancy.ParticipantsA total of 175 opioid‐dependent pregnant women, of whom 131 completed treatment.MeasurementsSymptoms of anxiety and depression were captured with the 15‐item Mini International Neuropsychiatric Interview (MINI) screen. Use of illicit drugs was measured by urine drug screening. Preterm delivery was defined as delivery prior to 37 weeks' gestation. Self‐reported use of concomitant psychotropic medication at any point during the study was recorded.FindingsWomen reporting only anxiety symptoms at study entry were more likely to discontinue treatment [adjusted odds ratio (OR) = 4.56, 95% confidence interval (CI): 1.91–13.26, P = 0.012], while those reporting only depression symptoms were less likely to discontinue treatment (adjusted OR = 0.14, 95% CI: 0.20–0.88, P = 0.036) compared to women who reported neither depression nor anxiety symptoms. No statistically significant between‐group differences were observed for ongoing illicit drug use or preterm delivery. A majority (61.4%) of women reported use of concomitant psychotropic medication at some point during study participation.ConclusionsOpioid agonist‐treated pregnant patients with co‐occurring symptoms of anxiety require additional clinical resources to prevent premature discontinuation.
Comparison between 8‐prenylnarigenin and narigenin concerning their activities on promotion of rat bone marrow stromal cells’ osteogenic differentiation in vitro
Authors: Ming L. G. , Ge B. F. , Wang M. G. , Chen K. M. 
Published: October 2012

AbstractA number of recent studies have suggested that flavonols (a class of phytochemical with many biological activities), might exert protective effects against post‐menopausal bone loss. In the present study, we compared naringenin (NG) and 8‐prenylnaringenin (PNG), two major naturally occurring flavonols, on in vitro differentiation of osteoblasts and bone resorbing activity, of rat bone marrow stromal cells (BMSCs). Our results indicated that both compounds, at 10−6 m, enhanced BMSCs’ differentiation. Then effects of the two compounds at 10−6 m on ALP activity, osteocalcin secretion and calcium deposition, were compared over a time course. Numbers and areas of colonies stained for ALP (CFU‐FALP) expression, and mineralized bone nodules, were histochemically analysed after 12 days and 16 days osteogenic induction, respectively. Expression of BMP‐2, OPG, OSX, RUNX‐2 genes and p38MAPK protein were examined using real‐time PCR and western blotting, respectively. The data presented indicate that PNG, significantly enhanced the rat BMSCs’ differentiation and mineralization through the BMP‐2/p38MAPK/Runx2/Osterix signal pathway, greater than did NG. In conclusion, PNG has a more pronounced ability to enhance osteoblast differentiation and mineralization, than NG.
Oridonin: targeting programmed cell death pathways as an anti‐tumour agent
Authors: Liu Z. , Ouyang L. , Peng H. , Zhang W.‐Z. 
Published: October 2012

AbstractOridonin, an active diterpenoid isolated from traditional Chinese herbal medicine, has drawn rising attention for its remarkable apoptosis‐ and autophagy‐inducing activity and relevant molecular mechanisms in cancer therapy. Apoptosis is a well known type of cell death, whereas autophagy can play either pro‐survival or pro‐death roles in cancer cells. Accumulating evidence has recently revealed relationships between apoptosis and autophagy induced by oridonin; however, molecular mechanisms behind them remain to be discovered. In this review, we focus on highlighting updated research on oridonin‐induced cell death signalling pathways implicated in apoptosis and autophagy, in many types of cancer. In addition, we further discuss cross‐talk between apoptosis and autophagy induced by oridonin, in cancer. Taken together, these findings open new perspectives for further exploring oridonin as a potential anti‐tumour agent targeting apoptosis and autophagy, in future anti‐cancer therapeutics.
Exposure of immunologically naive laboratory rodents to antigen via the airways. Where does tolerance stop and sensitization begin?
Authors: Guibas G. V. , Makris M. , Spandou E. , Priftis K. N. 
Published: October 2012

SummaryConventional rodent models of respiratory allergy that employ intraperitoneal sensitization to aeroallergen plus adjuvant, have offered greatly to our current knowledge of the pathophysiology of allergic airway diseases. Notwithstanding this significant contribution, non‐adjuvant aided sensitization via respiratory presentation of the allergen, is more naturally relevant and more closely mimics the human exposure. Nevertheless, in the experimental setting, primary respiratory exposure to inert antigen is likely to lead to inhalation tolerance. Inasmuch as divergent and discrepant results are often reported in experimental models employing this method of sensitization, we set out to review the relative literature and identify and discuss factors that are liable to interfere in such protocols and modify the immune response, hence leading to variable outcomes. Protocol design features (including the use of anaesthesia, the nature and dosage of the antigen and the strain/age/sex and handling of the animals) as well as environmental factors (including airborne substances, viruses and lipopolysaccharide) have been identified as key modulators of the immune response that evolves, following primary airway exposure of laboratory rodents to aeroallergen. Delineation of the effect of those factors to induction or abrogation of inhalation tolerance can have important implications in the design of both improved experimental protocols of respiratory allergy and methods to intercept sensitization to inert aeroallergens in the clinical field.