Special Issue on ‘‘Ribogenomics-the study of RNA-centric molecular mechanisms and cellular processes’’

The journal Genomics Proteomics&Bioinformatics(GPB)is now inviting submissions for a special issue(to be published in spring of 2014)on the topic of‘‘The Ribogenomics of Life’’.Life was born of the RNA world.The RNA world was governed by RNA-centric mechanisms and processes in single cells.These operationally defined cells became more complex and heterogeneous:some were robust against changes but lost potential for diversity and others became complex but more opportunistic.Proteins w     

Cellular and molecular mechanisms implicated in pathogenesis of selective neurodegeneration in Huntington’s disease

Huntington??s disease (HD) is one of the most common dominantly-inherited neurodegenerative disorders and is caused by a CAG repeat expansion in the huntingtin gene. HD is characterized by selective degeneration of subpopulations of neurons in the brain, however the precise underlying mechanisms how a ubiquitously expressed disease protein could target specific types of neurons for degeneration remains a critical, yet unanswered question for HD and other major neurodegenerative disorders. In this review, we describe the expanding view of selective neuronal vulnerability in HD, based on recent neuropathological and neuroimaging studies. We will also summarize the systematic effort to define the cell types in which mutant Huntingtin expression is critical for pathogenesis of vulnerable neurons in the striatum and cortex. Finally, we will describe selected, emerging molecular mechanisms that are implicated in selective disease processes in HD. Together, the field has begun to appreciate the distinct molecular pathogenic roles of mutant huntingtin in different cell types that may contribute to the selective neuronal vulnerability, with dissection of such mechanisms likely to yield novel molecular targets for HD therapy.     

Effects of MagPro™ on muscle performance

Athletes are on an endless quest to enhance performance and are frequently barraged by products that purport to contribute to various components of athletic activity. The purpose of this study was to determine if MagPro? influenced muscle flexibility or muscle endurance. This was a double-blind, randomized, controlled study using a repeated-measures design. The Institutional Review Board approved consent was obtained. The participants were healthy, physically active adults (n = 38 for phase 1; n = 18 for phase 2). Two creams were used: MagPro? (Mg cream) and a placebo. In phase 1, each cream was applied to the gastroc-soleus muscles. A stretching protocol was completed, and ankle dorsiflexion was compared. In phase 2, 1 cream was applied to both quadriceps muscles. An endurance protocol using a Life Fitness bicycle was completed. The procedure was repeated with the other cream on the quadriceps muscle 1 week later. For the flexibility phase, an analysis of variance with repeated measures revealed no difference between the 2 creams (p = 0.50), but there was a change in the flexibility over time (p = 0.00). For the endurance phase, paired t-tests revealed that there was no significant difference between the first (p = 0.26) or second (p = 0.35) cycling bouts of either cream. Likewise, there were no differences between the first and second cycling bouts of both the creams (MagPro? p = 0.46; Placebo p = 0.08). Despite previous studies demonstrating improved performance with Mg supplements, MagPro? did not enhance the outcome measures of this study. Examination of alternative application techniques and other outcome measures would be appropriate.     

Integrated insight into the molecular mechanisms of selenium-modulated,MPP+-induced cytotoxicity in a Parkinson’s disease model

ObjectiveParkinson’s disease (PD) is a neurodegenerative disease that is associated with oxidative stress. Due to the anti-inflammatory and antioxidant functions of Selenium (Se), this molecule may have neuroprotective functions in PD; however, the involvement of Se in such a protective function is unclear.Methods1-methyl-4-phenylpyridinium (MPP⁺), which inhibits mitochondrial respiration, is generally used to produce a reliable cellular model of PD. In this study, a MPP⁺-induced PD model was used to test if Se could modulate cytotoxicity, and we further capture gene expression profiles following PC12 cell treatment with MPP⁺ with or without Se by genome wide high-throughput sequencing.ResultsWe identified 351 differentially expressed genes (DEGs) and 14 differentially expressed long non-coding RNAs (DELs) in MPP⁺-treated cells when compared to controls. We further document 244 DEGs and 27 DELs in cells treated with MPP⁺ and Se vs. cells treated with MPP⁺ only. Functional annotation analysis of DEGs and DELs revealed that these groups were enriched in genes that respond to reactive oxygen species (ROS), metabolic processes, and mitochondrial control of apoptosis. Thioredoxin reductase 1 (Txnrd1) was also identified as a biomarker of Se treatment.ConclusionsOur data suggests that the DEGs Txnrd1, Siglec1 and Klf2, and the DEL AABR07044454.1 which we hypothesize to function in cis on the target gene Cdkn1a, may modulate the underlying neurodegenerative process, and act a protective function in the PC12 cell PD model. This study further systematically demonstrated that mRNAs and lncRNAs induced by Se are involved in neuroprotection in PD, and provides novel insight into how Se modulates cytotoxicity in the MPP⁺-induced PD model.     

The effects of acute and prolonged muscle vibration on the function of the muscle spindle’s reflex arc

Abstract

Purpose:?Localized mechanical vibration, applied directly to a muscle, is known to have powerful, duration-dependent effects on the muscle spindle’s reflex arc. Here, the conditioning of the function of the spindle reflex arc via vibration was examined with considerations for use as a non-invasive, sensorimotor research tool.

Methods:?Muscle spindle function was examined with patellar tendon taps prior to and following exposure to muscle vibration applied to the quadriceps femoris for acute (<5?s) and prolonged (20?min) durations. Surface electromyography (sEMG), torque, and accelerometry signals were obtained during the taps to quantify various measures of reflex magnitude and latency.

Results:?Our findings suggest that acute vibration had no effect on normalized reflex torque or sEMG amplitude (p?>?0.05), but increased total reflex latency (p?=?0.022). Alternatively, prolonged vibration reduced normalized reflex torque and sEMG amplitude (p?<?0.001), and increased reflex latency (p?<?0.001).

Conclusions:?Our findings support the use of prolonged vibration as a practical means to decrease the function of the muscle spindle’s reflex arc. Overall, this suppressive effect was evident in the majority of subjects, but the extent was variable. This approach could potentially be used to help delineate the muscle spindle’s role in various sensory or motor tasks in which more direct measures are not feasible. Acute vibration, however, did not potentiate muscle spindle function as hypothesized. Rather, our results suggest that acute vibration increased total reflex latency. Accordingly, potential mechanical and neurophysiological mechanisms are discussed.     

Effects of (−)-epicatechin on molecular modulators of skeletal muscle growth and differentiation

Sarcopenia is a notable and debilitating age-associated condition. Flavonoids are known for their healthy effects and limited toxicity. The flavanol (−)-epicatechin (Epi) enhances exercise capacity in mice, and Epi-rich cocoa improves skeletal muscle structure in heart failure patients. (−)-Epicatechin may thus hold promise as treatment for sarcopenia.We examined changes in protein levels of molecular modulators of growth and differentiation in young vs. old, human and mouse skeletal muscle. We report the effects of Epi in mice and the results of an initial proof-of-concept trial in humans, where muscle strength and levels of modulators of muscle growth were measured. In mice, myostatin and senescence-associated β-galactosidase levels increase with aging, while those of follistatin and Myf5 decrease. (−)-Epicatechin decreases myostatin and β-galactosidase and increases levels of markers of muscle growth. In humans, myostatin and β-galactosidase increase with aging while follistatin, MyoD and myogenin decrease. Treatment for 7 days with (−)-epicatechin increases hand grip strength and the ratio of plasma follistatin/myostatin.In conclusion, aging has deleterious effects on modulators of muscle growth/differentiation, and the consumption of modest amounts of the flavanol (−)-epicatechin can partially reverse these changes. This flavanol warrants its comprehensive evaluation for the treatment of sarcopenia.     

Effects of training and weight support on muscle activation in Parkinson’s disease

The aim of this study was to investigate the effect of high-intensity locomotor training on knee extensor and flexor muscle activation and adaptability to increased body-weight (BW) support during walking in patients with Parkinson’s disease (PD). Thirteen male patients with idiopathic PD and eight healthy participants were included. The PD patients completed an 8-week training program on a lower-body, positive-pressure treadmill. Knee extensor and flexor muscles activation during steady treadmill walking (3 km/h) were measured before, at the mid-point, and after training. Increasing BW support decreased knee extensor muscle activation (normalization) and increased knee flexor muscle activation (abnormal) in PD patients when compared to healthy participants. Training improved flexor peak muscle activation adaptability to increased (BW) support during walking in PD patients. During walking without BW support shorter knee extensor muscle off-activation time and increased relative peak muscle activation was observed in PD patients and did not improve with 8 weeks of training. In conclusion, patients with PD walked with excessive activation of the knee extensor and flexor muscles when compared to healthy participants. Specialized locomotor training may facilitate adaptive processes related to motor control of walking in PD patients.     

Heterochromatin and the molecular mechanisms of ‘parent-of-origin’ effects in animals

Twenty five years ago it was proposed that conserved components of constitutive heterochromatin assemble heterochromatin-like complexes in euchromatin and this could provide a general mechanism for regulating heritable (cell-to-cell) changes in gene expressibility. As a special case, differences in the assembly of heterochromatin-like complexes on homologous chromosomes might also regulate the parent-of-origin-dependent gene expression observed in placental mammals. Here, the progress made in the intervening period with emphasis on the role of heterochromatin and heterochromatin-like complexes in parent-of-origin effects in animals is reviewed.     

Role of zinc and copper ions in the pathogenetic mechanisms of Alzheimer’s and Parkinson’s diseases

Disbalance of zinc (Zn²⁺) and copper (Cu²⁺) ions in the central nervous system is involved in the pathogenesis of numerous neurodegenerative disorders such as multisystem atrophy, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, Wilson-Konovalov disease, Alzheimer’s disease, and Parkinson’s disease. Among these, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most frequent age-related neurodegenerative pathologies with disorders in Zn²⁺ and Cu²⁺ homeostasis playing a pivotal role in the mechanisms of pathogenesis. In this review we generalized and systematized current literature data concerning this problem. The interactions of Zn²⁺ and Cu²⁺ with amyloid precursor protein (APP), β-amyloid (Abeta), tau-protein, metallothioneins, and GSK3β are considered, as well as the role of these interactions in the generation of free radicals in AD and PD. Analysis of the literature suggests that the main factors of AD and PD pathogenesis (oxidative stress, structural disorders and aggregation of proteins, mitochondrial dysfunction, energy deficiency) that initiate a cascade of events resulting finally in the dysfunction of neuronal networks are mediated by the disbalance of Zn²⁺ and Cu²⁺.     

Update on the role of molecular factors and fibroblasts in the pathogenesis of Dupuytren’s disease

The mechanism by which the fibroblast is able to trigger palmar fibromatosis is still not yet fully understood. It would appear certain that the “abnormal” fibroblasts continuously synthesise profibrotic cytokines which are able to determine the activation to myofibroblasts, to stimulate them to the further proliferation and synthesis of other cytokines, to modify the cells’ differentiation and ultrastructural characteristics, as well as the production of matrix and other proteins. Several fibroblast growth factors have been suggested to be responsible of an abnormal cell activation with an aberrantly elevated collagen synthesis and extracellular deposition in Dupuytren’s disease, as TGF-Beta, TNF-Alfa, PDGF, GM-CSF, free radicals, metalloproteinases, sex hormones, gene modified expression, mechanical stimulation. The Authors review the current state of knowledge in the field, by analyzing the role of these cytokines in the palmar fibromatosis.     

Genetic mouse models of Huntington’s disease: focus on electrophysiological mechanisms

The discovery of the HD (Huntington’s disease) gene in 1993 led to the creation of genetic mouse models of the disease and opened the doors for mechanistic studies. In particular, the early changes and progression of the disease could be followed and examined systematically. The present review focuses on the contribution of these genetic mouse models to the understanding of functional changes in neurons as the HD phenotype progresses, and concentrates on two brain areas: the striatum, the site of most conspicuous pathology in HD, and the cortex, a site that is becoming increasingly important in understanding the widespread behavioural abnormalities. Mounting evidence points to synaptic abnormalities in communication between the cortex and striatum and cell–cell interactions as major determinants of HD symptoms, even in the absence of severe neuronal degeneration and death.     

A molecular dynamics study on Young’s modulus and tribology of carbon nanotube reinforced styrene-butadiene rubber

Styrene-butadiene rubber is a copolymer widely used in making car tires and has excellent abrasion resistance. The Young’s modulus and tribology of pure styrene butadiene rubber (SBR) polymer and carbon nanotube reinforced polymer composites have been investigated using molecular dynamics simulations. The mechanism of enhanced tribology properties using carbon nanotube has been studied and discussed. The obtained Young’s modulus shows the enhancement in mechanical properties of SBR polymer when carbon nanotubes are used as reinforcement. The concentration, temperature and velocity profiles, radial distribution function, frictional stresses, and cohesive energy density are calculated and analyzed in detail. The Young’s modulus of SBR matrix increases about 29.16% in the presence of the 5% CNT. The atom movement velocity and average cohesive energy density in the friction area of pure SBR matrix was found to be more than that of the CNT/SBR composite.

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Graphical abstract Initial and final conditions of (a) pure SBR matrix and (b) CNT/SBR matrix subjected toshear loading and frictional stresses of top Fe layers of both pure SBR and CNT/SBR composite

     

The effect estimation and channel testing of the technological progress on China’s regional environmental performance

To study the effects of and approaches to technological progress on China’s regional environmental performance, this study first estimates China’s regional environmental performance and its variation indexes by applying a slack-based model (SBM) and an entropy-based model (EBM). The results indicate that the environmental performance in different regions of China has improved, but the rate of improvement differs greatly. This may be attributed to heterogeneous characteristics and changes in the green technology innovation level in different regions. Considering the overflow effect of environmental pollution among different regions, we study the impact of various technological progress patterns on China’s regional environmental performance using spatial econometrics, and we find that there are significant spatial effects of technology innovation, technology transfer, and imitative innovation on China’s regional environmental performance. Also, different technological progress patterns have different effects. Specifically, independent innovation has failed to effectively improve regional environmental performance, whereas the introduction of technology and imitative innovation have significantly improved this performance. Moreover, after the cross-items of independent innovation and human capital are introduced, the effects of technology introduction and imitative innovation on China’s regional environmental performance through the absorptive capacity of human capital remain significant, whereas the effect of independent innovation on regional environmental performance via the absorptive capacity of human capital becomes more obvious. Based on this and from the perspective of environmental enhancement, we believe that China should strengthen human capital accumulation and give consideration to imitative innovation and technology introduction while emphasizing independent innovation.     

Variation in breeding parameters of Eleonora’s falcon (Falco eleonorae) and factors affecting its reproductive performance

We gathered data for a four-year period (2004?C2007) on the nesting ecology and reproductive performance of Eleonora??s falcon in the Aegean Sea. We investigated in an indirect way the relation between clutch size and pre-laying food availability, the significance of site and pair quality on productivity, and the effects of habitat and intraspecific competition on breeding success. Overall, the species selected nest sites sheltered from sun exposure but not from the prevailing wind. Hatching, fledging, and breeding success rates were estimated at 64, 72%, and 60%, respectively. Fledglings per breeding pair ranged from 1.19 to 1.75, and fledglings per successful pair from 1.84 to 2.0, between the years. Productivity depended on parental care rather than nest-site quality. Breeding parameters varied significantly between the years, exhibiting a strong spatial yet local effect. Low success rates were recorded in specific colonies, which were attributed to adverse weather conditions and habitat degradation. Insect food availability prior to egg-laying, estimated via plant biomass, was positively correlated to clutch size. Meanwhile, low wind strengths in August, large distances from the mainland, and population size in the vicinity of the colonies had negative effects on breeding success. Considering data at the Mediterranean scale, a longitudinal trend is observed across the breeding range of this species, with breeding parameters slightly decreasing from west to east.     

Effect of Filgrastim on adult male rats’ fertility and reproductive performance

Filgrastim is a recombinant protein used in treatment neutropenia caused by myelosuppressive medications for patients with non-myeloid cancer. However, its effect in male fertility is not clear. So, the current work aims to clarify the effect of Filgrastim on the reproductive state in Wistar rats. Eighteen (18) male Wistar rats were divided into three groups (6/each). Group (I) where the rats were injected with 0.5 ml/kg/day of distilled water and served as Control Group. The Group (II) animals received intraperitoneal injection of therapeutic dose of 30.83 mcg/kg/day of Filgrastim for one week. The Group (III) rats received the same dose by the same route of Filgrastim for two weeks. Sera of blood samples were processed for serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (TS). Semen analysis and resazurine reduction test (RRT) were performed. Assaying for malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) was done. The testes were retrieved for histopathological and immunohistochemical studies for caspase-3 detection. Our results revealed that filgrastim affects sperm morphology, significantly decreased the RRT and the reproductive hormones level, elevated the oxidative stress status and induced several histopathological changes in testes with an increased in immunoexpression of caspase-3 in testes tissues. The results of this work demonstrated that Filgrastim may had a deleterious effect on male fertility.     

Impact of road construction on giant panda’s habitat and its carrying capacity in Qinling Mountains

The Qinling giant panda (Ailuropoda melanoleuca) is an endangered endemic species to China. Despite ongoing efforts to ensure its conservation, concerns about maintaining its populations persist. We used GIS fed with data on land use including road network of 2001, third national giant panda survey, and a digital elevation model (DEM) to assess the impact of road construction on giant panda habitat, and estimate the carrying capacity of the Qinling Mountain area. We assessed habitat suitability with a mechanistic model, and conducted correlation analysis to evaluate relationship between the extent of giant panda habitat and amount of sites occupied by pandas within of 5 km × 5 km grid. We also estimated the carrying capacity of the Qinling Mountainous Area.
Our results revealed a significant correlation (R² = 0.447, P < 0.01) between the number of sites with signs left by giant panda and the extent of habitat within of 5 km × 5 km grid. The minimum habitat area that can support one panda was 10 km². Before the road network construction, the area of habitat suitable for the panda amounted about 1561 km² and that of marginally suitable habitat about 1499 km². The corresponding carrying capacity represented about 240 individuals. After the road network construction, the suitable habitat area was reduced by nearly 30% to 1093 km². Marginally suitable habitat and unsuitable habitat have both increased by 17% and 1%, respectively. As a result, the potential population size which the habitat could support was reduced to 217 individuals. The study results also suggested that most impacts on habitat from road construction took place in the high elevation areas above 1500 m. However, regarding the impact on the giant panda habitat, road networks developed much more inside the current nature reserves than outside of them.     

Impact of road construction on giant panda’s habitat and its carrying capacity in Qinling Mountains

The Qinling giant panda (Ailuropoda melanoleuca) is an endangered endemic species to China. Despite ongoing efforts to ensure its conservation, concerns about maintaining its populations persist. We used GIS fed with data on land use including road network of 2001, third national giant panda survey, and a digital elevation model (DEM) to assess the impact of road construction on giant panda habitat, and estimate the carrying capacity of the Qinling Mountain area. We assessed habitat suitability with a mechanistic model, and conducted correlation analysis to evaluate relationship between the extent of giant panda habitat and amount of sites occupied by pandas within of 5 km × 5 km grid. We also estimated the carrying capacity of the Qinling Mountainous Area.
Our results revealed a significant correlation (R² = 0.447, P < 0.01) between the number of sites with signs left by giant panda and the extent of habitat within of 5 km × 5 km grid. The minimum habitat area that can support one panda was 10 km². Before the road network construction, the area of habitat suitable for the panda amounted about 1561 km² and that of marginally suitable habitat about 1499 km². The corresponding carrying capacity represented about 240 individuals. After the road network construction, the suitable habitat area was reduced by nearly 30% to 1093 km². Marginally suitable habitat and unsuitable habitat have both increased by 17% and 1%, respectively. As a result, the potential population size which the habitat could support was reduced to 217 individuals. The study results also suggested that most impacts on habitat from road construction took place in the high elevation areas above 1500 m. However, regarding the impact on the giant panda habitat, road networks developed much more inside the current nature reserves than outside of them.