270 research outputs found
Munc13-4 interacts with syntaxin 7 and regulates late endosomal maturation, endosomal signaling, and TLR9-initiated cellular responses
No full textThe molecular mechanisms that regulate late endosomal maturation and function are not completely elucidated, and direct evidence of a calcium sensor is lacking. Here we identify a novel mechanism of late endosomal maturation that involves a new molecular interaction between the tethering factor Munc13-4, syntaxin 7, and VAMP8. Munc13-4 binding to syntaxin 7 was significantly increased by calcium. Colocalization of Munc13-4 and syntaxin 7 at late endosomes was demonstrated by high-resolution and live-cell microscopy. Munc13-4-deficient cells show increased numbers of significantly enlarged late endosomes, a phenotype that was mimicked by the fusion inhibitor chloroquine in wild-type cells and rescued by expression of Munc13-4 but not by a syntaxin 7-binding-deficient mutant. Late endosomes from Munc13-4-KO neutrophils show decreased degradative capacity. Munc13-4-knockout neutrophils show impaired endosomal-initiated, TLR9-dependent signaling and deficient TLR9-specific CD11b up-regulation. Thus we present a novel mechanism of late endosomal maturation and propose that Munc13-4 regulates the late endocytic machinery and late endosomal-associated innate immune cellular functions
Computational models of dopamine release measured by fast scan cyclic voltammetry in vivo
No full textDopamine neurotransmission in the striatum is central to many normal and disease functions. Ventral midbrain dopamine neurons exhibit ongoing tonic firing that produces low extrasynaptic levels of dopamine below the detection of conventional extrasynaptic cyclic voltammetry (∼10–20 nanomolar), with superimposed bursts that can saturate the dopamine uptake transporter and produce transient micromolar concentrations. The bursts are known to lead to marked presynaptic plasticity via multiple mechanisms, but analysis methods for these kinetic parameters are limited. To provide a deeper understanding of the mechanics of the modulation of dopamine neurotransmission by physiological, genetic, and pharmacological means, we present three computational models of dopamine release with different levels of spatiotemporal complexity to analyze in vivo fast-scan cyclic voltammetry recordings from the dorsal striatum of mice. The models accurately fit to cyclic voltammetry data and provide estimates of presynaptic dopamine facilitation/depression kinetics and dopamine transporter reuptake kinetics, and we used the models to analyze the role of synuclein proteins in neurotransmission. The models’ results support recent findings linking the presynaptic protein α-synuclein to the short-term facilitation and long-term depression of dopamine release, as well as reveal a new role for β-synuclein and/or γ-synuclein in the long-term regulation of dopamine reuptake
Ascertaining the Role of Acetyl-L-Carnitine in Carpal Tunnel Syndrome – A Randomised Controlled Trial
No full textBackground: Carpal tunnel syndrome is the most common entrapment neuropathy with variable responses to conservative therapy, and Acetyl-L-Carnitine’s putative neuroprotective and analgesic actions warrant evaluation as an adjunctive treatment.
Objectives: To determine the efficacy of Acetyl-L-Carnitine on neuroprotection, neuropathic symptoms, and hand function in carpal tunnel syndrome; and to study recurrence of symptoms in CTS patients on standard treatment.
Methods: We conducted a single-centre, prospective, open-label randomized trial at a neurology outpatient clinic, enrolling adults (18–65 years) with idiopathic CTS (N=80) and allocating them to standard care alone or Acetyl-L-Carnitine 500 mg three times daily for 12 weeks plus standard care. Outcomes (BCTQ-SSS/FSS, DN4) were assessed at baseline, 4, 12, and 20 weeks; median-nerve NCS were performed at baseline and 12 weeks.
Results: Both groups were similar at baseline (age 45.5 vs 47.3 years; p=0.210; female-predominant). Over 12 weeks, electrophysiology improved in both arms but more with ALCAR, notably in sensory metrics: sensory nerve conduction velocity rose 41.12→44.49 m/s (Δ+3.37) vs 40.12→41.78 m/s (Δ+1.66), and sensory distal latency fell 3.77→3.26 ms vs 3.68→3.29 ms; distal motor latency decreased more with ALCAR (−5.84% vs −4.04%; p=0.012). The best discriminator was % increase in sensory conduction velocity (AUC 0.775, 95% CI 0.675–0.875). Patient-reported outcomes favored ALCAR from 4 weeks onward: BCTQ-SSS 20.02 vs 26.00 (p<0.001) at 4 weeks and 16.20 vs 23.63 (p<0.001) at 12 weeks; BCTQ-FSS and DN4 showed parallel advantages, persisting to 20 weeks. Adverse events were mostly nausea (40%) and vomiting (40%); weight gain and hair fall occurred in 10% each.
Conclusion: Adjunctive Acetyl-L-Carnitine (500 mg three times daily for 12 weeks) significantly improved neuropathic pain, hand function, and sensory nerve conduction in mild–moderate carpal tunnel syndrome versus standard care, with partial symptom return after discontinuation
Role of Acetyl L-Carnitine in the treatment of Carpal Tunnel Syndrome
No full textBACKGROUND:
A cetyl L-carnitine (ALCAR) exerts an energetic effect on nerves and muscles. Recently, preclinical experiments and clinical trails have demonstrated a central anti-nociceptive action.
AIM & OBJECTIVES:
The aim of the study is to study the efficacy of Acetyl L-Carnitine (ALCAR) in the management of patients with carpal tunnel syndrome. Primary Objective is to assess the efficacy of Acetyl L-Carnitine on neuroprotection, neuropathic symptoms, and hand function in carpal tunnel syndrome (CTS).Secondary objective is to assess the recurrence of symptoms in comparison with standard treatment.
METHODS:
It is a prospective, open label, randomized controlled study, done in the Department of Neurology. We enrolled 80 patients with CTS of mild to moderate severity and randomized into Control group and ALCAR group. All patients received splint and physiotherapy, in addition ALCAR group received ALCAR 500mg thrice a day for 3 month and all underwent a conduction study of the median nerve, the Boston Carpal Tunnel Questionnaire (BCTQ) and Douleur Neuropathic Questionnaire (DN4) at baseline and 4th, 8th, 12th and 20th week.
RESULTS:
There was statistically significant difference in sensory nerve conduction velocity (SNCV) (p < 0.001) and Motor distal latency (p = 0.012) at the end of third month in ALCAR group. Other nerve conduction parameters were not significantly improved. There was a significant improvement stastiscally in the scores of BCTQ (FSS and SSS) and DN4 at the end of 1st, 3rd, 5th month, when compared to baseline. At the end of 5th month there were increased mean values of BCTQ SSS & FSS and DN4 scores which might be due to discontinuation of ALCAR at the end of 3rd month.
CONCLUSIONS:
Our clinical and neurophysiological study indicated that 3 months of treatment with ALCAR exerted a neuroprotective effect. ALCAR reduced pain in patients with Mild and moderate CTS, a result that is possibly due to both its neuroprotective action and its central anti-nociceptive properties
In vitro regeneration from different ages of petioles of physic nut (Jatropha curcas L.)
No full textJatropha curcas L. is an important non-edible oil yielding plant growing in wasteland and dry lands. The experiment was conducted to study the plant regeneration of J. curcas from different ages of petioles. Petioles explant grown on Murashige and Skoog’s (MS) medium supplemented with 1 mg/l α-naphthalene acetic acid and 0.2 mg/l kinetin showed the highest frequency of callus induction and the same medium was found to be best suited for callus growth in 1st petiole. Percent of somatic embryo formation was higher (35.16%) from the 1st petiole explant on 0.5 mg/l thidiazuron with 0.4 mg/l gibberellic acid. MS medium supplemented with 1 mg/l N6-benzylaminopurine, 0.5 mg/l indole-3-acetic acid, 0.25 mg/l kinetin recorded the higher somatic embryo germination percentage (66.85%). MS basal medium supplemented with 0.5 mg/l thidiazuron, 0.1 mg/l N6-benzylaminopurine, 0.4 mg/l gibberellic acid was found to be best medium for shoot elongation. Among the auxins tested, the higher frequency of root formation was observed in MS medium supplemented with 0.3 mg/l α-naphthalene acetic acid compared to indole-3-butyric acid and indole-3-acetic acid. The survival rate of in vitro rooted plantlets was dependent on the type of explant source and it varies from 47 to 60%.Keywords: Euphorbiaceae, petiole, callus, indirect organogenesis, biodiesel, plant growth regulatorAfrican Journal of Biotechnology, Vol. 13(2), pp. 265-273, 8 January, 201
Tiller Development and Contribution to Yield under Different Moisture Regimes in two Triticum Species
No full textThe number of productive tillers is an important yield component in wheat and is affected by water stress and genetic factors. A greenhouse experiment was conducted during spring 1992 at ICARDA, Tel Hadya, Syria, with eight genotypes representing two Triticum species (Triticum turgidum L. ssp. durum and Triticum aestivum L. ssp. aestivum) under four soil-moisture regimes (95 %, 75 %, 55 %, and 35 % field capacity) to study the effect of water deficit on tiller development and tiller contribution to grain yield. In the highest watering regime appearance of Tiller 1 was delayed in both species. Also Tiller 2 was suppressed in this treatment in durum, while its appearance was delayed in aestivum. In the driest treatment, a majority of the tillers were suppressed and the ones which emerged were delayed. In durum, the heat units required to produce successive leaves on the tillers were higher than that for the main stem and increased with increasing water stress, causing high rate of tiller abortion. In aestivum, each tiller, once produced, developed leaves at the same rate as on the main stem. Phyllochron of tillers as well as main stem was not affected by water stress in aestivum. In aestivum, contribution by tillers to yield was higher than that of durum in all treatments. Results indicate that early appearance of tillers and faster rate of leaf appearance under water stress result in higher tiller survival and greater tiller contribution to final yield. Hence, tiller dynamics under water stress can be used as a selection criterion for breeding for drought tolerance
A systems approach for monitoring anesthesia
No full textGeneral anesthesia (GA) is an important medical procedure that induces unconsciousness to patients during surgery. Consciousness is a salient feature of the brain, whose neurophysiological features are difficult to be distinguished from unconsciousness. Though it can be defined as an event arising due to interactions in the nervous system, it entirely is not a reliable mechanism. Thus, tracking changes in the brain waves caused by GA is a challenging problem in neuroscience. The exact mechanism to quantify the state of the brain and to distinguish between conscious and unconscious brain is still difficult. Specific features to characterize the state of the brain from the patterns of the brain signal is challenging. Present-day depth of anesthesia monitors index values does not quantify the state of the brain.An alternative approach is to use dynamical systems theory to assess the underlying dynamics of the brain with imaging technology (e.g., electroencephalographic and electrocorticographic data). Previous results from the literature suggest that stability can play a role in the characterization of unconsciousness. This thesis proposes a detailed study that focus on dynamical systems properties that go beyond stability. In particular, the proposed methodology aims to assess which regions of the brain intervene in the process of consciousness and unconsciousness, as well as quantify how often they interact with each other. Specifically, the approach seeks to leverage the eigenstructure of the underlying approximation of the neural activity captured from intracranial electrocorticographic data.Our results show that it is possible to differentiate between anesthetic stages of the brain using eigendecomposition. This was possible through a framework that provides a regularised way to sparsify the state estimates of electrocorticographic (ECoG) signal to get a model for analysis of changes in the brain waves affected by GA. Later to look at the eigenvalues and eigenvectors, which gives the frequency of oscillation and direction between different regions of the brain, respectively. It was also observed that the pattern in the evolution of eigenvalues during different anesthetic stages could be able to interpret if the subject was under anesthesia or not.Mechanical Engineering | Systems and Contro
POST-MODERNISM IN CORMAC MCCARTHY'S OUTER DARK
No full textOuter dark (1968), McCarthy's second novel is brutal and violence which makes every reader wonder about the description of evil that is exposed in the extreme level. Postmodernism has a major knock on traditional ideas about literature art and culture with its playful approach and rebelliousness when it comes to the line between high or low cultures. McCarthy as a post-modern writer exposes his literary talent in the extreme of human sufferings which everyone experiences in the world. Rinthy travels to find her baby and herself to wash out her sin, Culla moves in search of his sister and want to find the menial job for his basic amenities. In the meantime, Culla meets the evil creatures and escapes from the evil cleverly. Thus in Outer Dark McCarthy deals with the dark side of the characters as the representation of nihilism and realism which extends in the world and consequently the author pushes the story into reality to the extreme to reveal the nature of instinct and luck. The author of this paper tries to expose the innocent evils and human experience in the darker side of the world
Characterization of Polyhydroxyalkanoates Produced by Bacillus spp. from Starch Containing Medium
No full textThis Dissertation / Report is the outcome of investigation carried out by the creator(s) / author(s) at the department/division of Central Food Technological Research Institute (CFTRI), Mysore mentioned below in this page
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