58,866 research outputs found

    tRNA Profiling of Mesenchymal Stem Cell Exosome

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    Background: Exosomes have great potential in regenerative medicine through the transfer of their bioactive cargos, such as RNA. tRF RNA and tiRNA are tRNAderived non-coding RNA. Here, we sought to identify the tRF/tiRNA profile in human mesenchymal stem cell (hMSC) exosomes. Methods: Bone marrow hMSCs were cultured with/without osteogenic differentiation medium and exosomes were harvested. RNA was extracted from: 1) control cells (Cell-NT); 2) control exosomes (EXO-NT); 3) differentiated cells (Cell-OM); 4) exosomes produced by differentiated cells (EXO-OM). RNA was sequenced to profile the small RNA with a focus on tRF/tiRNA. Results: tRF/tiRNA was highly enriched in hMSC exosomes. Less diversity was seen in the tRF/tiRNA profile in exosomes than that in parent cells. Selective tRF/tiRNA were packed into MSC exosomes and their profile is dependent on the cell maturation status. Conclusions: Our results suggest that tRF/tiRNA may play a role in mediating the function of exosomes in tissue regeneration

    Learning neural trans-dimensional random field language models with noise-contrastive estimation

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    Trans-dimensional random field language models (TRF LMs) where sentences are modeled as a collection of random fields, have shown close performance with LSTM LMs in speech recognition and are computationally more efficient in inference. However, the training efficiency of neural TRF LMs is not satisfactory, which limits the scalability of TRF LMs on large training corpus. In this paper, several techniques on both model formulation and parameter estimation are proposed to improve the training efficiency and the performance of neural TRF LMs. First, TRFs are reformulated in the form of exponential tilting of a reference distribution. Second, noise-contrastive estimation (NCE) is introduced to jointly estimate the model parameters and normalization constants. Third, we extend the neural TRF LMs by marrying the deep convolutional neural network (CNN) and the bidirectional LSTM into the potential function to extract the deep hierarchical features and bidirectionally sequential features. Utilizing all the above techniques enables the successful and efficient training of neural TRF LMs on a 40x larger training set with only 1/3 training time and further reduces the WER with relative reduction of 4.7% on top of a strong LSTM LM baseline.Comment: 5 pages and 2 figure

    Geographical distribution of typhoid risk factors in low and middle income countries

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    Overdispersion. Appendix 2. Full specification of regression outputs. Appendix 3. TRF index (type 5) by sub-national boundary. Appendix 4. Final TRF index values by sub-national boundary. Appendix 5. TRF index in Bangladesh. (ZIP 1995 kb

    Tocotrienol-Rich Fraction Of Palm Oil Attenuates Type II Collagen-Induced Temporomandibular Joint Rheumatoid Arthritis In Rats For Future Clinical Application

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    Temporomandibular joint involvement in rheumatoid arthritis (RA) is not uncommon. Nonsteroidal anti-inflammatory drugs (NSAIDs), are considered main line of RA treatment but they can cause side effects. Tocotrienol rich fraction (TRF) extracted from palm oil was reported to possess potent antioxidant and anti-inflammatory activities. This research was designed to study the therapeutic potential of TRF against TMJ arthritis. 30 Albino Wistar rats were divided into: Control (C), Arthritis (A) and Arthritis + TRF (A-TRF) groups. A-TRF group received TRF daily from day 30 up to day 45 after TMJ arthritis induction was accomplished. Serum inflammatory cytokines were assessed and TMJ histopathological examinations were done. Plasma levels of inflammatory cytokines increased in A-group and they were comparable in both C and A-TRF groups. A-TRF group showed that, the inflammatory changes were mild on examination of stained sections of TMJ. A-TRF-group bone mineral density was notably increased after TRF administration. In conclusion, the decreased plasma levels of inflammatory cytokines and the increased bone mineral density associated with tocotrienolsrich-fraction supplements administration could be provide an evidence that TRF could be used as an effective therapy of TMJ rheumatoid arthritis

    The comparative effects between tocotrieonol-rich fraction (TRF) and α-tocopherol on glutamate toxicity in neuron-astrocyte mono- and co-culture systems

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    Background: Vitamin E, which can be categorized into tocotrienols and tocopherols, is known to protect cells from glutamate neurotoxicity. Studies have shown that tocotrienol-rich fraction (TRF) protecting the brain against oxidative damage more efficient than α-tocopherol. The role of astrocyte in promoting neuronal survival and recovery after glutamate neurotoxicity is also increasingly appreciated. Aims: To elucidate the effects of TRF and α-tocopherol and the synergism between astrocyte and neuron against glutamate neurotoxicity. Methods: Astrocyte and neuron were subjected to glutamate injury followed by TRF and α-tocopherol treatments (100 – 300 ng/ml). Effects of TRF and α-tocopherol on nerve cell viability and glutathione contents against glutamate toxicity were examined. The synergism between astrocyte and neuron was elucidated through co-culture model. Statistical analysis was performed using one way ANOVA. Results: Both TRF and α-tocopherol improved approximately 10% of glutamate-injured astrocyte and neuronal cell viability. In co-culture model, TRF and α-tocopherol provided nearly complete protection from glutamate toxicity. Besides, TRF and α-tocopherol treatments significantly restored at least 20% of glutathione contents in glutamate-injured neurons. In the presence of astrocyte, 300 ng/ml TRF and α-tocopherol completely restored glutathione contents in glutamate-injured neuron. Conclusions: TRF and α-tocopherol had shown promising neuroprotective effects in astrocyte and neuron from glutamate toxicity. Great scavenging effect of both TRF and α-tocopherol against glutamate toxicity was observed in neuron. Similar protective effects between TRF and α-tocopherol were observed. Co-culture model demonstrated the synergistic properties between neuron and astrocyte. Supplementation of TRF and α-tocopherol in co-culture further improved the recovery process

    TRF1 and TRF2 binding to telomeres is modulated by nucleosomal organization

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    The ends of eukaryotic chromosomes need to be protected from the activation of a DNA damage response that leads the cell to replicative senescence or apoptosis. In mammals, protection is accomplished by a six-factor complex named shelterin, which organizes the terminal TTAGGG repeats in a still ill-defined structure, the telomere. The stable interaction of shelterin with telomeres mainly depends on the binding of two of its components, TRF1 and TRF2, to double-stranded telomeric repeats. Tethering of TRF proteins to telomeres occurs in a chromatin environment characterized by a very compact nucleosomal organization. In this work we show that binding of TRF1 and TRF2 to telomeric sequences is modulated by the histone octamer. By means of in vitro models, we found that TRF2 binding is strongly hampered by the presence of telomeric nucleosomes, whereas TRF1 binds efficiently to telomeric DNA in a nucleosomal context and is able to remodel telomeric nucleosomal arrays. Our results indicate that the different behavior of TRF proteins partly depends on the interaction with histone tails of their divergent N-terminal domains. We propose that the interplay between the histone octamer and TRF proteins plays a role in the steps leading to telomere deprotection

    Clinical Significance of Telomere Length and Associated Proteins in Oral Cancer

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    Purpose: Telomere shortening is an important event during carcinogenesis. Although studies suggest role of multiple proteins in telomere length regulation, there is dearth of reports in oral cancer which is a leading malignancy in Asian countries especially in India. Thus the present study was carried out to study these mechanisms and explore the pathways involved in telomere—telomerase regulation and identify possible prognostic markers to understand the biology of oral tumors for better treatment approaches. Methods: Telomere length was determined by Southern Hybridisation method, telomeric repeat binding factor (TRF) 1 and 2 expression was detected by Western blot method and telomerase activation by telomeric repeat amplifi cation protocol. Statistical analysis was done using SPSS (Version 10) software. Results: Significant shortening of telomeres was seen in the tumor tissues as compared to normal tissues. Poor prognosis was observed in the patients with higher telomere length in malignant tissue, higher tumor to normal telomere length ratio (T/N TRF LR). Expression of TRF-2 but not TRF-1 protein was signifi cantly higher in the malignant tissues. We also observed telomerase activation in 75 malignant tissues.Conclusions: Our results reveal signifi cant clinical usefulness of telomere length, T/N TRF LR and telomerase activation in the prognosis of oral cancer patients. TRF-2 overexpression in malignant tissues appears to play an important role in telomere length shortening in oral cancer. Abbreviations: TRF—Terminal restriction fragment; TRF-1—telomeric repeat binding factor-1; TRF-2—telomeric repeat binding factor-2; T/N TRF LR—Tumor/ Normal TRF length ratio
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