- Prediction of S-sulfenylation sites using mRMR feature selection and fuzzy support vector machine algorithm. [Journal Article]
- JTJ Theor Biol 2018 Aug 17
- Cysteine S-sulfenylation is an important protein post-translational modification, which plays a crucial role in transcriptional regulation, cell signaling, and protein functions. To better elucidate ...
Cysteine S-sulfenylation is an important protein post-translational modification, which plays a crucial role in transcriptional regulation, cell signaling, and protein functions. To better elucidate the molecular mechanism of S-sulfenylation, it is important to identify S-sulfenylated substrates and their corresponding S-sulfenylation sites accurately. In this study, a novel bioinformatics tool named Sulf_FSVM is proposed to predict S-sulfenylation sites by using multiple feature extraction and fuzzy support vector machine algorithm. On the one hand, amino acid factors, binary encoding, and the composition of k-spaced amino acid pairs features are incorporated to encode S-sulfenylation sites. And the maximum relevance minimum redundancy method are adopted to remove the redundant features. On the other hand, a fuzzy support vector machine algorithm is used to handle the class imbalance and noise problem in S-sulfenylation sites training dataset. As illustrated by 10-fold cross-validation, the performance of Sulf_FSVM achieves a satisfactory performance with a Sensitivity of 73.26%, a Specificity of 70.78%, an Accuracy of 71.07% and a Matthew's correlation coefficient of 0.2971. Independent tests also show that Sulf_FSVM significantly outperforms existing S-sulfenylation sites predictors. Therefore, Sulf_FSVM can be a useful tool for accurate prediction of protein S-sulfenylation sites.
- MicroRNA expression profiling of dibenzalacetone (DBA) treated intracellular amastigotes of Leishmania donovani. [Journal Article]
- EPExp Parasitol 2018 Aug 17
- CONCLUSIONS: We conclude that curcumin analog DBA triggers imbalance between two known phenotypes of cell death viz apoptosis and autophagy.
- Effects of prior cold stimulation on inflammatory and immune regulation in ileum of cold-stressed broilers. [Journal Article]
- PSPoult Sci 2018 Aug 14
- Acclimation can alleviate the negative impacts of adverse environmental factors on an organism. To investigate the effects of prior cold stimulation on inflammatory and immune regulation in ileum of ...
Acclimation can alleviate the negative impacts of adverse environmental factors on an organism. To investigate the effects of prior cold stimulation on inflammatory and immune regulation in ileum of cold-stressed broilers, 360 1-d-old chicks (Arbor Acres) were divided into 3 groups (G1, G2, G3) and raised at normal (thermal comfort) temperatures during 1 to 7 d. From 8 d, G1 (control) continued to be raised at normal temperatures, whereas G2 and G3 (treatments) were cold-stimulated at 3°C and 12°C, respectively, below the temperature of G1, but not below 17°C (reached at 32 d in G2 and 14 d in G3). At 42 d, all the groups were subjected to a 24-h acute cold stress of 7°C, designated as S1, S2, and S3. Ileum tissues and serum of the birds were collected at 42 d and 43 d to detect the levels of pro-inflammatory and immune-related factors as well as morphology changes. At 42 d, ileum of G1 and G2 had intact morphological structure and clear outline, with no differences in levels of iNOS, NF-κB, COX-2, PTGEs, TNF-α, IFN-γ, or IL-4 (P > 0.05). G3 ileum suffered inflammatory injuries, with levels of iNOS, COX-2, PTGEs, TNF-α, and IL-4 being higher than those of G1 (P < 0.05). At 43 d, compared with G1, S1 had severely damaged ileum, increased levels of iNOS, NF-κB, COX-2, PTGEs, TNF-α, and IL-4 (P < 0.05), but decreased level of IFN-γ (P < 0.05). The morphological structure of S2 was intact, and there were no differences between G2 and S2 in levels of NF-κB, PTGEs, TNF-α, IFN-γ, or IL-4 (P > 0.05). Compared with S1, S2 had decreased levels of iNOS, NF-κB, COX-2, PTGEs, TNF-α, and IL-4 (P < 0.05), but increased level of IFN-γ (P < 0.05). There were no differences between G1 and S2 in levels of NF-κB, PTGEs, TNF-α, IFN-γ, or IL-4 (P > 0.05). The results demonstrate that a 3°C-lower-than-normal temperature stimulation of the broilers from 8 to 42 d led to cold acclimation. This prior cold acclimation effectively alleviated elevation of pro-inflammatory cytokines and Th1/Th2 imbalance of the birds induced by subsequent cold stress.
- Audiometric and cVEMP Thresholds Show Little Correlation With Symptoms in Superior Semicircular Canal Dehiscence Syndrome. [Journal Article]
- ONOtol Neurotol 2018 Aug 17
- CONCLUSIONS: While threshold audiometry and cVEMP are important tools to diagnose SCD and monitor surgical outcomes, these measures showed no significant correlation with vestibular and most auditory symptoms or their severity.
- Mitochondrial dysfunction in pathophysiology of heart failure. [Journal Article]
- JCIJ Clin Invest 2018 Aug 20
- Mitochondrial dysfunction has been implicated in the development of heart failure. Oxidative metabolism in mitochondria is the main energy source of the heart, and the inability to generate and trans...
Mitochondrial dysfunction has been implicated in the development of heart failure. Oxidative metabolism in mitochondria is the main energy source of the heart, and the inability to generate and transfer energy has long been considered the primary mechanism linking mitochondrial dysfunction and contractile failure. However, the role of mitochondria in heart failure is now increasingly recognized to be beyond that of a failed power plant. In this Review, we summarize recent evidence demonstrating vicious cycles of pathophysiological mechanisms during the pathological remodeling of the heart that drive mitochondrial contributions from being compensatory to being a suicide mission. These mechanisms include bottlenecks of metabolic flux, redox imbalance, protein modification, ROS-induced ROS generation, impaired mitochondrial Ca2+ homeostasis, and inflammation. The interpretation of these findings will lead us to novel avenues for disease mechanisms and therapy.
- Expression of Mucins and Claudins in the Colon during Acute and Chronic Experimental Colitis. [Journal Article]
- BEBull Exp Biol Med 2018 Aug 20
- We studied changes in the expression of mRNA for mucins and claudins in the medial part of the colon in male C57Bl/6 mice on the model of acute and chronic colitis induced by substitution of drinking...
We studied changes in the expression of mRNA for mucins and claudins in the medial part of the colon in male C57Bl/6 mice on the model of acute and chronic colitis induced by substitution of drinking water with 1% solution of dextran sodium sulphate for 5 days. In acute colitis, the expression of the main structural component of glycocalyx, mucin Muc3, decreased and expression of pore-forming claudin Cldn2 increased, which reflected enhanced permeability of tight junctions. In the chronic colitis group, in comparison with the normal group, we observed an increase in expression of mRNA of main structural mucus component Muc2, enhanced of expression of Muc1 associated with carcinogenesis, and reduced expression of Muc13, which led to a more severe course of colitis; the expression of pore-forming claudin Cldn2 was elevated. These findings indicate that the imbalance in the expression of mucins and claudins plays an important role in the mechanisms of development of acute and chronic colitis.
- Dravet Syndrome: A Sodium Channel Interneuronopathy. [Journal Article]
- COCurr Opin Physiol 2018; 2:42-50
- Dravet Syndrome is a devastating childhood epilepsy disorder with high incidence of premature death plus comorbidities of ataxia, circadian rhythm disorder, impaired sleep quality, autistic-like soci...
Dravet Syndrome is a devastating childhood epilepsy disorder with high incidence of premature death plus comorbidities of ataxia, circadian rhythm disorder, impaired sleep quality, autistic-like social-interaction deficits and severe cognitive impairment. It is primarily caused by heterozygous loss-of-function mutations in the SCN1A gene that encodes brain voltage-gated sodium channel type-1, termed NaV1.1. Here I review experiments on mouse genetic models that implicate specific loss of sodium currents and action potential firing in GABAergic inhibitory interneurons as the fundamental cause of Dravet Syndrome. The resulting imbalance of excitatory to inhibitory neurotransmission in neural circuits causes both epilepsy and co-morbidities. Promising therapeutic approaches involving atypical sodium channel blockers, novel drug combinations, and cannabidiol give hope for improved outcomes for Dravet Syndrome patients.
- Central Compensation in Auditory Brainstem after Damaging Noise Exposure. [Journal Article]
- EeNeuro 2018 Jul-Aug; 5(4)
- Noise exposure is one of the most common causes of hearing loss and peripheral damage to the auditory system. A growing literature suggests that the auditory system can compensate for peripheral loss...
Noise exposure is one of the most common causes of hearing loss and peripheral damage to the auditory system. A growing literature suggests that the auditory system can compensate for peripheral loss through increased central neural activity. The current study sought to investigate the link between noise exposure, increases in central gain, synaptic reorganization, and auditory function. All axons of the auditory nerve project to the cochlear nucleus, making it a requisite nucleus for sound detection. As the first synapse in the central auditory system, the cochlear nucleus is well positioned to respond plastically to loss of peripheral input. To investigate noise-induced compensation in the central auditory system, we measured auditory brainstem responses (ABRs) and auditory perception and collected tissue from mice exposed to broadband noise. Noise-exposed mice showed elevated ABR thresholds, reduced ABR wave 1 amplitudes, and spiral ganglion neuron loss. Despite peripheral damage, noise-exposed mice were hyperreactive to loud sounds and showed nearly normal behavioral sound detection thresholds. Ratios of late ABR peaks (2-4) relative to the first ABR peak indicated that brainstem pathways were hyperactive in noise-exposed mice, while anatomical analysis indicated there was an imbalance between expression of excitatory and inhibitory proteins in the ventral cochlear nucleus. The results of the current study suggest that a reorganization of excitation and inhibition in the ventral cochlear nucleus may drive hyperactivity in the central auditory system. This increase in central gain can compensate for peripheral loss to restore some aspects of auditory function.
- Relative telomere length and oxidative DNA damage in hypertrophic ligamentum flavum of lumbar spinal stenosis. [Journal Article]
- PPeerJ 2018; 6:e5381
- Lumbar spinal stenosis (LSS) is a common cause of low back pain with degenerative spinal change in older adults. Telomeres are repetitive nucleoprotein DNA sequences of TTAGGG at the ends of chromoso...
Lumbar spinal stenosis (LSS) is a common cause of low back pain with degenerative spinal change in older adults. Telomeres are repetitive nucleoprotein DNA sequences of TTAGGG at the ends of chromosomes. Oxidative stress originates from an imbalance in pro-oxidant and antioxidant homeostasis that results in the production of reactive oxygen species (ROS). The purpose of this study was to investigate relative telomere length (RTL) and oxidative DNA damage in ligamentum flavum (LF) tissue from LSS patients.
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- Impact of Experimentally Induced Cognitive Dietary Restraint on Eating Behavior Traits, Appetite Sensations, and Markers of Stress during Energy Restriction in Overweight/Obese Women. [Journal Article]
- JOJ Obes 2018; 2018:4259389
- Weight loss has been associated with changes in eating behaviors and appetite sensations that favor a regain in body weight. Since traditional weight loss approaches emphasize the importance of incre...
Weight loss has been associated with changes in eating behaviors and appetite sensations that favor a regain in body weight. Since traditional weight loss approaches emphasize the importance of increasing cognitive dietary restraint (CDR) to achieve negative energy imbalance, it is difficult to untangle the respective contributions of energy restriction and increases in CDR on factors that can eventually lead to body weight regain. The present study aimed at comparing the effects of energy restriction alone or in combination with experimentally induced CDR on eating behavior traits, appetite sensations, and markers of stress in overweight and obese women. We hypothesized that the combination of energy restriction and induced CDR would lead to more prevalent food cravings, increased appetite sensations, and higher cortisol concentrations than when energy restriction is not coupled with induced CDR. A total of 60 premenopausal women (mean BMI: 32.0 kg/m2; mean age: 39.4 y) were provided with a low energy density diet corresponding to 85% of their energy needs during a 4-week fully controlled period. At the same time, women were randomized to either a condition inducing an increase in CDR (CDR+ group) or a condition in which CDR was not induced (CRD- group). Eating behavior traits (Three-Factor Eating Questionnaire and Food Craving Questionnaire), appetite sensations (after standardized breakfast), and markers of stress (Perceived Stress Scale; postawakening salivary cortisol) were measured before (T = 0 week) and after (T = 4 weeks) the 4-week energy restriction, as well as 3 months later. There was an increase in CDR in the CDR+ group while no such change was observed in the CDR- group (p=0.0037). No between-group differences were observed for disinhibition, hunger, cravings, appetite sensations, perceived stress, and cortisol concentrations. These results suggest that a slight increase in CDR has no negative impact on factors regulating energy balance in the context of energy restriction.