197,622 research outputs found
Functional characterization of MuSK, receptor tyrosine kinase required for the formation and the maintenance of nerve-muscle synapses : "in vivo" and "in vitro" approaches
No full textThe developing neuromuscular junction (NMJ) serves as one of the best model systems for studying synapse formation since changes in shape, size, and molecular composition can be followed with high spatial and temporal resolution. Formation of the NMJ depends on coordinated interactions between nerve terminals and muscle fibres [1] and requires reciprocal signals from both cells to efficiently regulate all the events taking place during its development. This includes synapse-specific gene expression, generation of action potentials and stabilization events leading to the formation of a sophisticated apparatus which ensures that the muscle fibre is provided with trophic factors as well as electrical stimuli. The receptor tyrosine kinase MuSK and its natural ligand, a neuron-specific isoform of the extracellular matrix molecule agrin, are considered to play a fundamental role in the formation and maintenance of the NMJ. In cultured myotubes, MuSK is activated by neural agrin, and this causes its phosphorylation and results in the formation of AChRs clusters on the cell surface [2-5]. The present study discusses different approaches to understand better the mechanisms of how the NMJ is formed and maintained. In the first project, we addressed the question of MuSK – neural agrin interaction and the necessity for an additional component of the agrin receptor complex. We generated transgenic mice overexpressing MuSK or neural mini-agrin as well as both proteins throughout the entire muscle fibre. We found evidence that in muscle cells MuSK is sufficient to respond to neural agrin with no necessity of any additional co-receptor protein. We also show that Dok-7, a MuSK adaptor protein, limits the formation of ectopic postsynaptic like structures in innervated muscle. From this, we conclude that it is very likely that in muscle cells MuSK serves as a functional receptor for neural agrin. The second project refers to the regulation of the NMJ formation. We found that signal transduction downstream of agrin involves the mitogen-activated protein kinase (MAPK) pathway, particularly ERK1/2 and JNK. It involves MuSK signaling, requires Dok7 and is ErbB-independent. We also show that MAPK phosphatase-1, MKP-1, plays a crucial regulatory role in formation of the nerve-muscle connection. Results of the third project describe that a miniaturized form of agrin is able to fully rescue perinatal death of agrin-deficient mice, and that this function does not depend on local deposition of agrin at synapses. Moreover, we show that acetylcholine together with neural agrin stabilizes the postsynaptic structures at the NMJ. The function of agrin in CNS was our main interest in the fourth project. Using
agrin-deficient mice with a transgenic reconstitution of the expression of neural agrin by motor neurons, we found that in the brain, agrin is localized to the excitatory synapses. Lack of agrin resulted in a strong reduction of synaptic structures in the cerebral cortex coinciding with the attenuation of the frequency of miniature postsynaptic currents. Additionally we found that muscle specific kinase MuSK is also expressed in the brain, thus possibly involved in the formation of the nerve-nerve connections. Finally, we show that agrin function involves MAP kinase signaling
Identification of Erbin interlinking MuSK and ErbB2 and its impact on acetylcholine receptors aggregation at the neuromuscolar junction
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Why Can't Rodents Vomit? A Comparative Behavioral, Anatomical, and Physiological Study
No full textThe vomiting (emetic) reflex is documented in numerous mammalian species, including primates and carnivores, yet laboratory rats and mice appear to lack this response. It is unclear whether these rodents do not vomit because of anatomical constraints (e.g., a relatively long abdominal esophagus) or lack of key neural circuits. Moreover, it is unknown whether laboratory rodents are representative of Rodentia with regards to this reflex. Here we conducted behavioral testing of members of all three major groups of Rodentia; mouse-related (rat, mouse, vole, beaver), Ctenohystrica (guinea pig, nutria), and squirrel-related (mountain beaver) species. Prototypical emetic agents, apomorphine (sc), veratrine (sc), and copper sulfate (ig), failed to produce either retching or vomiting in these species (although other behavioral effects, e.g., locomotion, were noted). These rodents also had anatomical constraints, which could limit the efficiency of vomiting should it be attempted, including reduced muscularity of the diaphragm and stomach geometry that is not well structured for moving contents towards the esophagus compared to species that can vomit (cat, ferret, and musk shrew). Lastly, an in situ brainstem preparation was used to make sensitive measures of mouth, esophagus, and shoulder muscular movements, and phrenic nerve activity-key features of emetic episodes. Laboratory mice and rats failed to display any of the common coordinated actions of these indices after typical emetic stimulation (resiniferatoxin and vagal afferent stimulation) compared to musk shrews. Overall the results suggest that the inability to vomit is a general property of Rodentia and that an absent brainstem neurological component is the most likely cause. The implications of these findings for the utility of rodents as models in the area of emesis research are discussed. © 2013 Horn et al
Familial autoimmune MuSK positive myasthenia gravis
No full textThe familial occurrence of autoimmune myasthenia gravis
(MG) with anti-acetylcholine receptor antibodies (AChR
Ab) has been rarely reported. Different antibody
specificity in family members has also been described. To our knowledge, a familial form of MuSK Ab positive MG has never been reported. We studied the HLA allele profile in a family with two sisters affected by MuSK positive MG
Differential Expression of MRNA in MuSK-Deficient Mice
No full textAudrey J. Caudron1, Agnieszka M. Lichanska2, Helen M. Cooper3 and Peter G. Noakes1. 1School of Biomedical Sciences, University of Queensland, Brisbane, Australia. 2 Institute of Molecular Biosciences, University of Queensland, Brisbane, Australia. 3Queensland Brain Institute, University of Queensland, Brisbane, Australia Differential expression of mRNA in MuSK-deficient mice Agrin, a motor nerve derived signal, binds to its receptor the Muscle Specific Kinase (MuSK) to induce the clustering of acetylcholine receptors (AChRs) and other postsynaptic molecules during the formation of the neuromuscular junction (NMJ). MuSK-/- mutant mice display an absence of AChR clusters and an increase in motoneuron survival and muscle nerve branching. These profound defects in both pre- and post-synaptic specialisations suggest that MuSK is a key molecule involved in the inductive interactions between growing motor axons and differentiating muscle cells, essential for healthy synapse formation. We have generated diaphragm muscle mRNA expression profiles from MuSK-deficient E15 embryos and their respective littermate wild-type controls, using Affymetrix® microarrays. Of 20 candidate genes found to be up or down regulated in MuSK-deficient muscles compared to wild-type muscles, 3 have been confirmed to be differentially expressed in MuSK mutants by real-time PCR (Quantitative PCR). Zyxin, a cell adhesion molecule, Mlf-1, a cell cycle regulator and the alpha-AChR (in diaphragm and limb muscles). Our results suggest that these genes are regulated by the neural Agrin-MuSK pathway and could explain the phenotypic differences seen between the wild-type and the mutant mice
The musk deer and its musk in classical Indian literature
No full textThe musk deer (Moschus chrysogaster Hodgson) is a small hornless animal, only 40–60 cm high. It lives in the Himalayas and Tibet between 2100 and 3300 m. The caudal musk gland of the adult male provides the famous aromatic black substance known as musk which is traditionally much used in perfumery.
After a short introduction about the animal and its habits, its role in Indian classical literature is discussed. It is missing in the Veda and epics (except one short mention in the Mahābhārata), but since the early first millennium it it rather often mentioned. It is variously called karāla, kastūrīmṛga, and mṛganābhi. Part of the accounts are rather fanciful.
The second part of the article concentrates on musk itself, Sankrit kastūrikā, also mṛgamada and kuraṅgamada. It was variously used perfuming the body, clothes, and even as a condiment added to drinks. Physicians mixed it in various medicines.
Finally, the role of musk in ancient international trade is discussed. In the Graeco-Roman world it became known in the fourth and fifth century and later on it was also much appreciated in the Islamic world. Its name, Greek μόσχος, Latin muscus, is probably borrowed from Persian (Middle and New Persian mušk ‘musk’) as muṣka in Sanskrit means ‘testicle.’ However, it seems that also in India the musk gland was occasionally confused with testicles
Clinical Features and Prognostic Analysis of MuSK-Antibody-Positive Myasthenia Gravis versus Double-Seropositive Myasthenia Gravis: A Single-Center Study from Central South China
No full textTing He,1,* Kangzhi Chen,1,* Yi Li,1 Zhaohui Luo,1 Mengchuan Luo,2 Huan Yang1 1Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 2Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huan Yang, Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, People’s Republic of China, Email [email protected]: To decipher the discrepancies between muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG) and double-seropositive myasthenia gravis (DSP-MG), and to determine prognostic factors for minimal manifestation status (MMS) achievement in MG patients with MuSK autoantibodies (MuSK-Ab).Patients and Methods: A total of 34 MG patients seropositive for MuSK-Ab were enrolled in this study. The demographic and clinical features were compared between MuSK-MG (n = 28) and DSP-MG (n = 6) patients, and factors affecting MMS induction in all patients with MuSK-Ab were identified using Cox regression analysis.Results: Compared to MuSK-MG patients, those with DSP-MG had similar clinical characteristics, except that they had a lower frequency of bulbar muscle involvement at nadir (50% vs 92.9%; P = 0.029) and higher proportions of comorbidities with diabetes mellitus (33.3% vs 0%; P = 0.027) and thymic abnormalities (33.3% vs 0%; P = 0.027). Higher MG Activities of Daily Living (MG-ADL) scores (HR = 0.16, 95% CI: 0.037– 0.7, P = 0.015) and axial muscle involvement at nadir (HR = 0.39, 95% CI: 0.16– 0.94, P = 0.035) were negative prognostic factors for MMS achievement in patients with MuSK-Ab regardless of acetylcholine receptor antibody (AChR-Ab) positivity. Multivariable Cox regression analysis further established higher MG-ADL scores at the nadir (HR = 0.19, 95% CI: 0.04– 0.94; P = 0.042) as an independent risk factor for MMS achievement.Conclusion: DSP-MG was comparable to MuSK-MG and could be considered a single entity in our cohort. In all MG patients with MuSK-Ab, a higher MG-ADL score at nadir may herald a lower chance of MMS achievement, with no observed potential effect of AChR-Ab presence.Keywords: double-seropositive myasthenia gravis, muscle-specific kinase antibody, acetylcholine receptor antibody, minimal manifestation status, myasthenia gravis activities of daily livin
ANTAGONISTIC EFFECT OF MUSK ON ORGANISMS DIFFERENT TYPES
No full textObjective: This study aims to The research aimed at a comparative study the effect of natural and synthetic musk compared to creams that have an anti-fungal and anti-bacterial effect on the growth of Candida albicans that causes vaginal diseases in women, as well as the growth of the bacteria strains include Staphylococcus aureus, Bacillus subtilis, which would be more effective in inhibiting the growth of these microbes and Achieve the recommendation of the Prophet Muhammad for women to treat the vagina with natural musk, find alternatives to synthetic antibiotics, and reduce their negative effects on human health.
Methods: This study investigates the antagonistic effect of Anti fungal and bacterial Cream and different natural type {Musk (N. M), Black Musk (B. M)} and chemical Musk {white Musk (W. M), cream Musk (M. C) } on some microorganisms. The types of yeast Candida albicans HVS and the bacteria strains include Staphylococcus aureus, Bacillus subtilis, were tested by means of disk diffusion,
Results: Results indicated that Musk has inhibitory effects on the growth of study microorganisms Musk contains active substances similar to antibiotic, alkaloids and volatile oils present in them as they have the ability to stop the growth of many microorganisms. The effect of natural musk was higher than the effect synthetic musk, And the microbes were the most sensitive to musk is Bacillus subtilis. As for anti-microbial creams, the effect of the anti-bacterial cream was more effective in their suppression compared to all kinds of musk unlike the anti-fungal cream which gave a negative result.
Conclusion: This study showed that the different concentrations of natural musk have an effective role in inhibiting some of the microbes of this vaginal pathogen, and it has given a positive opposite result to these microbes, and therefore it can be used as a natural antibiotic that reduces side effects on females and the environment
Life Cycle Studies with Musk Thistle
No full textMusk thistle (Carduus nutans L.) was added to the Nebraska noxious weed list in 1959. The objectives of this study were: (a) to determine the normal life cycle of musk thistle in Nebraska; (b) to determine the variations from the normal life cycle of musk thistle; and (c) to furnish a summary of the phenology for musk thistle in southeastern Nebraska. Observations are used freely throughout the text to describe morphological variations occurring within musk thistle that are not easily quantified
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