bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precision of Reinnervation and Synaptic Remodeling Observed in Neuromuscular Junctions of Living Frogs
Authors: Astrow Stephanie H. , Pitaevski Vladimir , Herrera Albert A. 
Published: April 2018

Repeatedin vivoobservations were used to study regenerated nerve terminals in neuromuscular junctions of the adult frogRana pipiens. Sartorius junctions in living animals were stained with the fluorescent vital dye RH414 and viewed with video fluorescence microscopy. Each junction was observed in the intact muscle and then again 7, 10, and 13 weeks after nerve crush. At 13 weeks, junctions were determined to be mono- or polyneuronally innervated using intracellular recording. Between 7 and 13 weeks, most identified junctions were reinnervated less precisely and completely than described previously. Although some of the original synaptic gutters were reoccupied by regenerated terminal branches, other gutters were only partially occupied, and many appeared abandoned. Junctions showing precise recapitulation of original terminal arborizations comprised a small number of the total examined, as did those where reinnervation was very imprecise. Striking differences in the precision of reinnervation were found within the muscle such that distal terminals regenerated more precisely and completely than did proximal terminals. Terminals in reinnervated muscles were more dynamic than terminals in unoperated muscles over equivalent times. In singly innervated junctions, terminal growth was favored over regression. In doubly innervated junctions, regressive events were more common. Imprecise reinnervation is explained in terms of multisite innervation of muscle fibers and the activity dependence of synaptic stability. We hypothesize that when axons reinnervate the second or third junctions on a fiber, they do so less precisely, because the activity restored by reinnervation of the first junction renders later sites less attractive or less stable.
Melanocortin Antagonists Define Two Distinct Pathways of Cardiovascular Control by α- and γ-Melanocyte-Stimulating Hormones
Authors: Li Si-Jia , Varga Károly , Archer Phillip , Hruby Victor J. , Sharma Shubh D. , Kesterson Robert A. , Cone Roger D. , Kunos George 
Published: April 2018

Melanocortin peptides and at least two subtypes of melanocortin receptors (MC3-R and MC4-R) are present in brain regions involved in cardiovascular regulation. In urethane-anesthetized rats, unilateral microinjection of α-melanocyte-stimulating hormone (MSH) into the medullary dorsal–vagal complex (DVC) causes dose-dependent (125–250 pmol) hypotension and bradycardia, whereas γ-MSH is less effective. The effects of α-MSH are inhibited by microinjection to the same site of the novel MC4-R/MC3-R antagonist SHU9119 (2–100 pmol) but not naloxone (270 pmol), whereas the similar effects of intra-DVC injection of β-endorphin (1 pmol) are inhibited by naloxone and not by SHU9119. Hypotensive and bradycardic responses to electrical stimulation of the arcuate nucleus also are inhibited by ipsilateral intra-DVC microinjection of SHU9119. γ-MSH and ACTH(4–10), but not α-MSH, elicit dose-dependent (0.1–12.5 nmol) pressor and tachycardic effects, which are much more pronounced after intracarotid than after intravenous administration. The effects of γ-MSH (1.25 nmol) are not inhibited by the intracarotid injection of SHU9119 (1.25–12.5 nmol) or the novel MC3-R antagonist SHU9005 (1.25–12.5 nmol). We conclude that the hypotension and bradycardia elicited by the release of α-MSH from arcuate neurons is mediated by neural melanocortin receptors (MC4-R/MC3-R) located in the DVC, whereas the similar effects of β-endorphin, a peptide derived from the same precursor, are mediated by opiate receptors at the same site. In contrast, neither MC3-R nor MC4-R is involved in the centrally mediated pressor and tachycardic actions of γ-MSH, which, likely, are mediated by an as yet unidentified receptor.
Behavioral and Neurochemical Recovery from Partial 6-Hydroxydopamine Lesions of the Substantia Nigra Is Blocked by Daily Treatment with Glutamate Receptor Antagonists MK-801 and CPP
Authors: Emmi Adriana , Rajabi Heshmat , Stewart Jane 
Published: April 2018

To determine whether glutamate plays a role in the recovery from lesions of the substantia nigra, measures of behavioral functioning and extracellular levels of striatal dopamine (DA) were made after partial unilateral 6-OHDA lesions in adult male rats. In experiments 1 and 2, animals were treated on days 1–8 after lesioning with the noncompetitive NMDA receptor antagonist dizocilpine maleate (MK-801; 0.25 mg/kg, i.p.) or saline, and in experiment 3 with the competitive antagonist 3-[(±)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP; 1.0 mg/kg, i.p.) or saline. In experiment 1, behavior was assessed 3 and 8 d after lesioning before daily drug treatment; on days 9 and 10, basal extracellular DA and metabolites were measured in both striata using microdialysis. In experiments 2 and 3, behavior was assessed on days 3 and 15 and microdialysis on days 16 and 17, 8–9 d post-termination of drug treatments. On day 3, all animals turned ipsilateral to the lesion. On days 8 or 15, saline-treated animals showed no behavioral asymmetries, whereas MK-801- and CPP-treated animals turned ipsilaterally. In antagonist-treated animals, basal levels of extracellular DA were lower on the lesioned side whether measured 9–10 or 16–17 d after lesioning, whereas in saline-treated animals DA levels on the two sides did not differ. These results suggest that glutamate plays a role in the development of compensatory changes in the DA neurons that accompany behavioral recovery from partial lesions of nigrostriatal DA system.
BEN/SC1/DM-GRASP Expression during Neuromuscular Development: a Cell Adhesion Molecule Regulated by Innervation
Authors: Fournier-Thibault C. , Pourquié O. , Rouaud T. , Le Douarin N. M. 
Published: April 2018

BEN/SC1/DM-GRASP is a cell adhesion molecule belonging to the Ig superfamily that is transiently expressed during avian embryogenesis in a variety of cell types, including the motoneurons of the spinal cord. We have investigated the pattern of BEN expression during neuromuscular development of the chick. We show that both motoneurons and their target myoblasts express BEN during early embryonic development and that the protein becomes restricted at neuromuscular contacts as soon as postsynaptic acetylcholine receptor clusters are observed in muscle fibers. Muscle cells grownin vitroexpress and maintain BEN expression even when they fuse and give rise to mature myotubes. When embryos are deprived of innervation by neural tube ablation, BEN expression is observed in muscle fibers, whereas, in control, the protein is already restricted at neuromuscular synaptic sites. These results demonstrate that all myogenic cells intrinsically express BEN and maintain the protein in the absence of innervation.Conversely, when neurons are added to myogenic cultures, BEN is rapidly downregulated in muscle cells, demonstrating that innervation controls the restricted pattern of BEN expression seen in innervated muscles. After nerve section in postnatal muscles, BEN protein becomes again widely spread over muscle fibers. When denervated muscles are allowed to be reinnervated, the protein is reexpressed in regenerating motor axons, and reinnervation of synaptic sites leads to the concentration of BEN at neuromuscular junctions.Our results suggest that BEN cell adhesion molecule acts both in the formation of neuromuscular contacts during development and in the events leading to muscle reinnervation.
Optokinetic and Vestibular Stimulation Determines the Spatial Orientation of Negative Optokinetic Afternystagmus in the Rabbit
Authors: Pettorossi Vito E. , Errico Pierangelo , Ferraresi Aldo , Barmack Neal H. 
Published: April 2018

Prolonged binocular optokinetic stimulation (OKS) in the rabbit induces a high-velocity negative optokinetic afternystagmus (OKAN II) that persists for several hours. We have taken advantage of this uniform nystagmus to study how changes in static head orientation in the pitch plane might influence the orientation of the nystagmus. After horizontal OKS, the rotation axis of the OKAN II remained almost constant in space as it was kept aligned with the gravity vector when the head was pitched by as much as 80° up and 35° down. Moreover, during reorientation, slow-phase eye velocity decreased according to the head pitch angle.Thereafter, we analyzed the space orientation of OKAN II after optokinetic stimulation during which the head and/or the OKS were pitched upward and downward. The rotation axis of OKAN II did not remain aligned with an earth vertical axis nor a head vertical axis, but it tended to be aligned with that of the OKS respace. The slow-phase eye velocity of OKAN II was also affected by the head pitch angle during OKS, because maximal OKAN II velocity occurred at the same head pitch angle as that during optokinetic stimulation.We suggest that OKAN II is coded in gravity-centered rather than in head-centered coordinates, but that this coordinate system may be influenced by optokinetic and vestibular stimulation. Moreover, the velocity attenuation of OKAN II seems to depend on the mismatch between the space-centered nystagmus rotation axis orientation and that of the “remembered” head-centered optokinetic pathway activated by OKS.
Reorganization of Cholinergic Terminals in the Cerebral Cortex and Hippocampus in Transgenic Mice Carrying Mutated Presenilin-1 and Amyloid Precursor Protein Transgenes
Authors: Wong Tak Pan , Debeir Thomas , Duff Karen , Cuello A. Claudio 
Published: April 2018

Cholinergic deficits are one of the most consistent neuropathological landmarks in Alzheimer’s disease (AD). We have examined transgenic mouse models (PS1M146L, APPK670N,M671L) and a doubly transgenic line (APPK670N,M671L+ PS1M146L) that overexpress mutated AD-related genes [presenilin-1 (PS1) and the amyloid precursor protein (APP)] to investigate the effect of AD-related gene overexpression and/or amyloidosis on cholinergic parameters.The size of the basal forebrain cholinergic neurons and the pattern of cholinergic synapses in the hippocampus and cerebral cortex were revealed by immunohistochemical staining for choline acetyltransferase and the vesicular acetylcholine transporter, respectively. At the time point studied (8 months), no apparent changes in either the size or density of cholinergic synapses were found in the PS1M146Lmutant relative to the nontransgenic controls. However, the APPK670N,M671Lmutant showed a significant elevation in the density of cholinergic synapses in the frontal and parietal cortices. Most importantly, the double mutant (APPK670N,M671L+ PS1M146L), which had extensive amyloidosis, demonstrated a prominent diminution in the density of cholinergic synapses in the frontal cortex and a reduction in the size of these synapses in the frontal cortex and hippocampus. Nonetheless, no significant changes in the size of basal forebrain cholinergic neurons were observed in these three mutants. This study shows a novel role of APP and a synergistic effect of APP and PS1 that correlates with amyloid load on the reorganization of the cholinergic network in the cerebral cortex and hippocampus at the time point studied.
Muscarinic Inhibition of Calcium Current and M Current in Gαq-Deficient Mice
Authors: Haley Jane E. , Delmas Patrick , Offermanns Stefan , Abogadie Fe C. , Simon Melvin I. , Buckley Noel J. , Brown David A. 
Published: April 2018

Activation of M1muscarinic acetylcholine receptors (M1mAChR) inhibits M-type potassium currents (IK(M)) and N-type calcium currents (ICa) in mammalian sympathetic ganglia. Previous antisense experiments suggested that, in rat superior cervical ganglion (SCG) neurons, both effects were partly mediated by the G-protein Gαq(Delmas et al., 1998a; Haley et al., 1998a), but did not eliminate a contribution by other pertussis toxin (PTX)-insensitive G-proteins. We have tested this further using mice deficient in the Gαqgene.PTX-insensitive M1mAChR inhibition ofICawas strongly reduced in Gαq−/− mouse SCG neurons and was fully restored by acute overexpression of Gαq. In contrast, M1mAChR inhibition ofIK(M)persisted in Gαq−/− mouse SCG cells. However, unlike rat SCG neurons, muscarinic inhibition ofIK(M)was partly PTX-sensitive. Residual (PTX-insensitive)IK(M)inhibition was slightly reduced in Gαq−/− neurons, and the remaining response was then suppressed by anti-Gαq/11antibodies.Bradykinin (BK) also inhibitsIK(M)in rat SCG neurons via a PTX-insensitive G-protein (Gqand/or G11; Jones et al., 1995). In mouse SCG neurons,IK(M)inhibition by BK was fully PTX-resistant. It was unchanged in Gαq−/− mice but was abolished by anti-Gαq/11antibody.We conclude that, in mouse SCG neurons (1) M1mAChR inhibition ofICais mediated principally by Gq, (2) M1mAChR inhibition ofIK(M)is mediated partly by Gq, more substantially by G11, and partly by a PTX-sensitive G-protein(s), and (3) BK-induced inhibition ofIK(M)is mediated wholly by G11.
Medial Frontal Cortex Mediates Perceptual Attentional Set Shifting in the Rat
Authors: Birrell Jennifer M. , Brown Verity J. 
Published: April 2018

If rodents do not display the behavioral complexity that is subserved in primates by prefrontal cortex, then evolution of prefrontal cortex in the rat should be doubted. Primate prefrontal cortex has been shown to mediate shifts in attention between perceptual dimensions of complex stimuli. This study examined the possibility that medial frontal cortex of the rat is involved in the shifting of perceptual attentional set. We trained rats to perform an attentional set-shifting task that is formally the same as a task used in monkeys and humans. Rats were trained to dig in bowls for a food reward. The bowls were presented in pairs, only one of which was baited. The rat had to select the bowl in which to dig by its odor, the medium that filled the bowl, or the texture that covered its surface. In a single session, rats performed a series of discriminations, including reversals, an intradimensional shift, and an extradimensional shift.Bilateral lesions by injection of ibotenic acid in medial frontal cortex resulted in impairment in neither initial acquisition nor reversal learning. We report here the same selective impairment in shifting of attentional set in the rat as seen in primates with lesions of prefrontal cortex. We conclude that medial frontal cortex of the rat has functional similarity to primate lateral prefrontal cortex.
Norepinephrine in the Prefrontal Cortex Is Critical for Amphetamine-Induced Reward and Mesoaccumbens Dopamine Release
Authors: Ventura Rossella , Cabib Simona , Alcaro Antonio , Orsini Cristina , Puglisi-Allegra Stefano 
Published: April 2018

Increasing evidence points to a major involvement of cortical areas in addictive mechanisms. Noradrenergic transmission in the medial prefrontal cortex (mpFC) has been shown to affect the motor effects of amphetamine, although there is no evidence of its involvement in the rewarding effects of this psychostimulant.The present experiments were aimed at investigating the possibility of a selective involvement of prefrontal cortical norepinephrine (NE) in the rewarding–reinforcing effects of amphetamine. To do so, we evaluated the effects of mpFC NE selective depletion in mice of C57BL/6J inbred strain, a background commonly used in molecular approaches that is known to be highly susceptible to the rewarding effects of the psychostimulant. In a first set of experiments, we demonstrated the absence of amphetamine-induced conditioned place preference in mice bearing prefrontal NE depletion. In a second series of experiments, we demonstrated that the same lesion dramatically reduced amphetamine-induced mesoaccumbens dopamine release as measured by intracerebral microdialysis.These results indicate that noradrenergic prefrontal transmission, by allowing increased dopamine release in the nucleus accumbens induced by amphetamine, is a critical factor for the rewarding–reinforcing effects of this drug.
Subtle Perturbations of the Maize Methylome Reveal Genes and Transposons Silenced by Chromomethylase or RNA-Directed DNA Methylation Pathways
Authors: Anderson Sarah N , Zynda Gregory J , Song Jawon , Han Zhaoxue , Vaughn Matthew W , Li Qing , Springer Nathan M 
Published: April 2018

Abstract
DNA methylation is a chromatin modification that can provide epigenetic regulation of gene and transposon expression. Plants utilize several pathways to establish and maintain DNA methylation in specific sequence contexts. The chromomethylase (CMT) genes maintain CHG (where H = A, C or T) methylation. The RNA-directed DNA methylation (RdDM) pathway is important for CHH methylation. Transcriptome analysis was performed in a collection of Zea mays lines carrying mutant alleles for CMT or RdDM-associated genes. While the majority of the transcriptome was not affected, we identified sets of genes and transposon families sensitive to context-specific decreases in DNA methylation in mutant lines. Many of the genes that are up-regulated in CMT mutant lines have high levels of CHG methylation, while genes that are differentially expressed in RdDM mutants are enriched for having nearby mCHH islands, implicating context-specific DNA methylation in the regulation of expression for a small number of genes. Many genes regulated by CMTs exhibit natural variation for DNA methylation and transcript abundance in a panel of diverse inbred lines. Transposon families with differential expression in the mutant genotypes show few defining features, though several families up-regulated in RdDM mutants show enriched expression in endosperm tissue, highlighting the potential importance for this pathway during reproduction. Taken together, our findings suggest that while the number of genes and transposon families whose expression is reproducibly affected by mild perturbations in context-specific methylation is small, there are distinct patterns for loci impacted by RdDM and CMT mutants.
Security and development: Shifting the focus to interpersonal violence
Authors: Hoeffler Anke 
Published: April 2018

The focus in the security and development debate is on collective violence and the World Bank’s World Development Report 2017 is typical by mainly considering the effects of organized armed conflict. In this article I argue that interpersonal violence affects many more people globally and should receive more attention as well as aid. The adverse consequences from interpersonal violence on socioeconomic development are likely to be large but much of this violence is hidden in plain sight. Women and children are at particularly high risk of being victims of violence but since most of this violence is perpetrated in the domestic sphere it is less likely to affect the collective conscience.
Ranolazine: A true pluripotent cardiovascular drug or jack of all trades, master of none?
Authors: Mezincescu Alice , Karthikeyan V. J. , Nadar Sunil K. 
Published: April 2018

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. Although the majority of patients with CVD are treated with interventional procedures, a substantial number require medical therapy in terms of both prognosis and symptomatic relief. However, commonly used agents such as β-blockers and calcium channel blockers reduce blood pressure in patients whose resting pressures are often already low. Ranolazine is a promising agent that does not have significant effects on blood pressure or heart rate. Use of this drug has been documented in various cardiovascular conditions, including ischaemic heart disease, heart failure and arrhythmias. This review article aimed to examine current evidence on the use of ranolazine in various cardiovascular conditions in order to determine whether it is a true pluripotent cardiovascular agent or, on the other hand, a “jack of all trades, master of none.”
Effects of Peer-Facilitated, Video-Based and Combined Peer-and-Video Education on Anxiety Among Patients Undergoing Coronary Angiography: Randomised controlled trial
Authors: Habibzadeh Hosein , Milan Zahra D. , Radfar Moloud , Cund Audrey 
Published: April 2018

Objectives: Coronary angiography can be stressful for patients and anxiety-caused physiological responses during the procedure increase the risk of dysrhythmia, coronary artery spasms and rupture. This study therefore aimed to investigate the effects of peer, video and combined peer-and-video training on anxiety among patients undergoing coronary angiography. Methods: This single-blinded randomised controlled clinical trial was conducted at two large educational hospitals in Iran between April and July 2016. A total of 120 adult patients undergoing coronary angiography were recruited. Using a block randomisation method, participants were assigned to one of four groups, with those in the control group receiving no training and those in the three intervention groups receiving either peer-facilitated training, video-based training or a combination of both. A Persian-language validated version of the State-Trait Anxiety Inventory was used to measure pre- and post-intervention anxiety. Results: There were no statistically significant differences in mean pre-intervention anxiety scores between the four groups (F = 0.31; P = 0.81). In contrast, there was a significant reduction in post-intervention anxiety among all three intervention groups compared to the control group (F = 27.71; P <0.01); however, there was no significant difference in anxiety level in terms of the type of intervention used. Conclusion: Peer, video and combined peer-and-video education were equally effective in reducing angiography-related patient anxiety. Such techniques are recommended to reduce anxiety amongst patients undergoing coronary angiography in hospitals in Iran.
Efficacy of OK-432 Therapy for the Incisionless Treatment of Head and Neck Cystic Masses: Case series
Authors: Hasan Hesham Y. A. , Rizwan Muhammad A. 
Published: April 2018

Head and neck masses can present in different pathologies that usually vary according to the age of the patient. We report five cases of benign head or neck masses occurring among patients of different ages who were managed at the Bahrain Defence Force Royal Medical Services Hospital, Ar-Rifaa, Bahrain, between 2005–2014. All of the patients were treated using the sclerotherapeutic agent OK-432. Although surgical removal is usually considered optimal treatment in the management of such cases, OK-432 appears to be a promising alternative.
Painful Pes Anserine Bursitis Following Total Knee Replacement Surgery: Two cases
Authors: Ariff Mohamed A. M. , Ros Mohd I. A. C. , Yahaya Nor H. M. 
Published: April 2018

Pes anserine bursitis (PAB) is an inflammation of the bursa located between the medial aspect of the tibia and the hamstring muscles. It is common in patients with degenerative or inflammatory knee arthritis, usually has a self-limiting course and tends to respond well to conservative treatment. However, painful PAB directly following total knee replacement surgery is rare. We report two such cases who were diagnosed via ultrasonography at the Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia, in 2015. Both patients were treated locally with triamcinolone acetonide under ultrasound guidance and responded well to treatment.
A Rare Case of Rectovaginal Fistula Due to Consensual Sexual Intercourse
Authors: Al-Asali Fida , Kilani Rami , Rshoud Firas , Mahfouz Ismaiel A. 
Published: April 2018

Rectovaginal fistulae after sexual intercourse are rare. We report a healthy recently married 21-year-old woman who presented to the Jordan Healthcare Centre, Amman, Jordan in 2014 with a five-week history of passing flatus and stool from the vagina. Six weeks prior, she had sustained a rectovaginal injury during initial consensual sexual intercourse, leading to the development of a distal rectovaginal fistula. A successful transvaginal repair was performed nine weeks after presentation which resulted in the complete resolution of her symptoms.