130 research outputs found

    The role of eEF1A2 in the pathogenesis of motor neurone disease in wasted mice

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    Regional differences in fertility in Thailand

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    This thesis is concerned with an analysis of changes in fertility levels and patterns for Thailand and differences in fertility for the four regions, the North, Northeast, Central and South. The data used are the 1960 and 1970 Censuses and the birth registration data for 1975 to 1978. Some data from the Longitudinal Surveys and the Survey of Fertility in Thailand (SOFT) are used to explain these changes and regional differences in fertility. During the intercensal period 1960-70, the decline in fertility occurred in all regions except the South. The age shape of the fertility schedules for all four regions was similar during that period. However, the mean age of the fertility schedules was lower in North and South than in Northeast and Central regions. The adjusted birth registration data suggested that the decline in fertility was accelerating between 1975 and 1978. The decline occurred in all regions, especially the North and South. The regional fertility level during this period indicates that South has the higher fertility followed by Northeast, Central and North in that order. This study suggests that since the mid 1960s the age pattern of fertility for the whole country has shifted towards a younger pattern. The change in pattern is more obvious between 1975 and 1978, especially in both the North and Central Regions and the rural sectors of Thailand. The changes in fertility levels and patterns are due to changes in nuptiality patterns and contraceptive knowledge and practice

    Neuroprotective Effects of Alpha-Mangostin on MPP +

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    In vitro studies have shown that extracts from mangosteen (Garcinia mangostana Linn.) act as antioxidants and cytoprotective agents against oxidative damage. The protective effect of alpha-mangostin, the major xanthone found in the pericarp of the mangosteen, in cellular models of Parkinson’s disease (PD), has not been investigated. This study aims to investigate whether alpha-mangostin could protect SH-SY5Y neuroblastoma cells from MPP+-induced apoptosis. The effects of alpha-mangostin on MPP+-induced cell death were evaluated with a cell viability assay, staining for nuclear DNA morphology, flow cytometry for apoptotic cells and reactive oxygen species (ROS) production, quantitative real-time PCR for the expression of p53, Bax, and Bcl-2, and western blot analysis for cleaved caspase-3. Concomitant treatment with alpha-mangostin attenuated the effect of MPP+ on cell viability and apoptotic cell death. Alpha-mangostin reduced ROS formation induced by MPP+. Bax/Bcl-2 expression ratio and expression of p53 were significantly lower in cells cocultured with alpha-mangostin and MPP+. The cotreated cells showed a significant decrease in activated caspase-3 compared with MPP+ treatment alone. Our data suggest that cytoprotection of alpha-mangostin against MPP+-induced apoptosis may be associated with the reduction of ROS production, modulating the balance of pro- and antiapoptotic genes, and suppression of caspase-3 activation

    Comparative mRNA Expression of eEF1A Isoforms and a PI3K/Akt/mTOR Pathway in a Cellular Model of Parkinson’s Disease

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    The PI3K/Akt/mTOR pathway is one of dysregulated pathways in Parkinson’s disease (PD). Previous studies in nonneuronal cells showed that Akt regulation can be increased by eukaryotic protein elongation factor 1 alpha 2 (eEF1A2). eEF1A2 is proposed to contribute protection against apoptotic death, likely through activation of the PI3K/Akt pathway. Whether eEF1A2 plays a role in the prevention of cell death in PD has not been investigated. Recently, gene profiling on dopaminergic neurons from postmortem PD patients showed both upregulation and downregulation of some PI3K and mTOR genes. In this paper, the expression of all gene members of the PI3K/Akt/mTOR pathway in relation to those of the eEF1A isoforms in a cellular model of PD was investigated at the mRNA level. The results showed a similar trend of upregulation of genes of the eEF1A isoforms (eEF1A1 and eEF1A2) and of the PI3K (classes I–III)/Akt (Akt1, Akt2, and Akt3)/mTOR (mTORC1 and mTORC2) pathway in both nondifferentiated and differentiated SH-SY5Y dopaminergic cells treated with 1-methyl-4-phenylpyridinium (MPP+). Upregulation of eEF1A2, Akt1, and mTORC1 was consistent with the relative increase of eEF1A2, Akt, phospho-Akt, and mTORC1 proteins. The possible role of eEF1A isoforms in the regulation of the PI3K/Akt/mTOR pathway in PD is discussed

    In vivo characterization of the role of tissue-specific translation elongation factor 1A2 in protein synthesis reveals insights into muscle atrophy

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    Translation elongation factor 1A2 (eEF1A2), uniquely among translation factors, is expressed specifically in neurons and muscle. eEF1A2‐null mutant wasted mice develop an aggressive, early‐onset form of neurodegeneration, but it is unknown whether the wasting results from denervation of the muscles, or whether the mice have a primary myopathy resulting from loss of translation activity in muscle. We set out to establish the relative contributions of loss of eEF1A2 in the different tissues to this postnatal lethal phenotype. We used tissue‐specific transgenesis to show that correction of eEF1A2 levels in muscle fails to ameliorate the overt phenotypic abnormalities or time of death of wasted mice. Molecular markers of muscle atrophy such as Fbxo32 were dramatically upregulated at the RNA level in wasted mice, both in the presence and in the absence of muscle‐specific expression of eEF1A2, but the degree of upregulation at the protein level was significantly lower in those wasted mice without transgene‐derived expression of eEF1A2 in muscle. This provides the first in vivo confirmation that eEF1A2 plays an important role in translation. In spite of the inability of the nontransgenic wasted mice to upregulate key atrogenes at the protein level in response to denervation to the same degree as their transgenic counterparts, there were no measurable differences between transgenic and nontransgenic wasted mice in terms of weight loss, grip strength, or muscle pathology. This suggests that a compromised ability fully to execute the atrogene pathway in denervated muscle does not affect the process of muscle atrophy in the short term

    Support Vector Machine based method to distinguish proteobacterial proteins from eukaryotic plant proteins

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    Background: Members of the phylum Proteobacteria are most prominent among bacteria causing plant diseases that result in a diminution of the quantity and quality of food produced by agriculture. To ameliorate these losses, there is a need to identify infections in early stages. Recent developments in next generation nucleic acid sequencing and mass spectrometry open the door to screening plants by the sequences of their macromolecules. Such an approach requires the ability to recognize the organismal origin of unknown DNA or peptide fragments. There are many ways to approach this problem but none have emerged as the best protocol. Here we attempt a systematic way to determine organismal origins of peptides by using a machine learning algorithm. The algorithm that we implement is a Support Vector Machine (SVM).Result: The amino acid compositions of proteobacterial proteins were found to be different from those of plant proteins. We developed an SVM model based on amino acid and dipeptide compositions to distinguish between a proteobacterial protein and a plant protein. The amino acid composition (AAC) based SVM model had an accuracy of 92.44% with 0.85 Matthews correlation coefficient (MCC) while the dipeptide composition (DC) based SVM model had a maximum accuracy of 94.67% and 0.89 MCC. We also developed SVM models based on a hybrid approach (AAC and DC), which gave a maximum accuracy 94.86% and a 0.90 MCC. The models were tested on unseen or untrained datasets to assess their validity.Conclusion: The results indicate that the SVM based on the AAC and DC hybrid approach can be used to distinguish proteobacterial from plant protein sequences.Peer reviewedBiochemistry and Molecular Biolog

    Neuroproteomic profiling of human body fluids

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    Early outcome after intravenous thrombolysis in patients with acute ischemic stroke

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    Background : Patients with acute ischemic stroke who had early neurological improvement had better functional outcome. The purpose of this study was to determine factors associated with early clinical improvement and early worsening in patients with acute ischemic stroke treated with intravenous thrombolysis. Patients and Methods : Patients treated with intravenous recombinant tissue plasminogen activator (rtPA) between August 2008 and November 2010 were the subjects of this study. Early improvement was defined by marked, clinical improvement or complete recovery at 24 h (National Institutes of Health Stroke Scale (NIHSS) 0-4 at 24 h). Early worsening was defined by an increase in NIHSS ≄1 from baseline. The baseline characteristics were compared between patients with and without outcome of interest. Results : Of the 203 patients studied, 19 (9.4%) patients had complete recovery and 68 (33.5%) patients had marked clinical improvement (NIHSS 1-4) at 24 h. Most patients with early clinical improvement (86%) had favorable outcome at three months. Of the 22 (10.8%) patients who had early clinical worsening, only three (14%) patients achieved favorable outcome at three months and six (29%) patients died. Multivariate analysis revealed that older age (≄70 years old) (odd ratio (OR) 0.498, P = 0.049), severe stroke (NIHSS ≄15) (OR 0.154, P < 0.0001) and having intracerebral hemorrhage (ICH) (OR 0.364, P = 0.032) were inversely associated with early improvement. History of transient ischemic attack (TIA) (OR 7.724, P = 0.043) and ICH (OR 4.477, P = 0.008) were related to early worsening. Conclusions : The presence of early clinical improvement or worsening within 24 h after treatment with rtPA had major impact on the outcome at three months

    Stroke Outcomes in Thai Elderly Patients Treated with and without Intravenous Thrombolysis

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    Higher mortality was found in very old patients with acute ischemic stroke treated with intravenous recombinant tissue-plasminogen activator (rtPA) as compared to younger patients. The benefit of thrombolytic treatment in this particular subgroup is still a subject of debate. The purpose of this study was to compare stroke outcomes in Thai patients aged over 70 years treated with and without intravenous rtPA. This was a retrospective review of sequential cases and was not a randomized controlled study. One-hundred and five patients with acute ischemic stroke aged over 70 years who were treated with intravenous rtPA and 105 patients without rtPA treatment (control group) were included in the study. Patients’ base-line characteristics and study outcomes of interest were compared. There were significant differences in the base-line characteristics of the two groups. However, for the subgroup of patients aged over 80 years, these characteristics were similar. Those who were treated with intravenous rtPA had a higher rate of favorable outcomes (40% vs 16%; P=0.137) and a lower rate of mortality (22% vs 44%; P=0.128) than patients who did not receive rtPA treatment. In well-matched subgroups of patients aged over 80 years, our retrospective review revealed there was a trend of a higher rate of favorable outcome and lower mortality in patients receiving rtPA treatment. More study is needed to further confirm the suggested benefit of thrombolysis in Asian octogenarian acute stroke patients
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