Miracle-dz/UniFAR-FTUs huggingface dataset:
MC1568 Inhibits Thimerosal-Induced Apoptotic Cell Death by Preventing HDAC4 Up-Regulation in Neuronal Cells and in Rat Prefrontal Cortex.

Ethylmercury thiosalicylate (thimerosal) is an organic mercury-based compound commonly used as an antimicrobial preservative that has been found to be neurotoxic. In contrast, histone deacetylases (HDACs) inhibition has been found to be neuroprotective against several environmental contaminants, such as polychlorinated biphenyls, di-2-ethylhexyl phthalate, and methylmercury. The aim of this study was to investigate the effect of HDAC inhibition on thimerosal-induced neurotoxicity in neuroblastoma cells and cortical neurons. Interestingly, we found that thimerosal, at 0.5 μM in SH-SY5Y cells and at 1 μM in neurons, caused cell death by activation of apoptosis, which was prevented by the HDAC class IIA inhibitor MC1568 but not the class I inhibitor MS275. Furthermore, thimerosal specifically increased HDAC4 protein expression but not that of HDACs 5, 6, 7, and 9. Western blot analysis revealed that MC1568 prevented thimerosal-induced HDAC4 increase. In addition, both HDAC4 knocking-down and MC1568 inhibited thimerosal-induced cell death in SH-SY5Y cells and cortical neurons. Importantly, intramuscular injection of 12 μg/kg thimerosal on postnatal days 7, 9, 11, and 15 increased HDAC4 levels in the prefrontal cortex (PFC), which decreased histone H4 acetylation in infant male rats, in parallel increased motor activity changes. In addition, coadministration of 40 mg/kg MC1568 (intraperitoneal injection) moderated the HDAC4 increase which reduced histone H4 deacetylation and caspase-3 cleavage in the PFC. Finally, open-field testing showed that thimerosal-induced motor activity changes are reduced by MC1568. These findings indicate that HDAC4 regulates thimerosal-induced cell death in neurons and that treatment with MC1568 prevents thimerosal-induced activation of caspase-3 in the rat PFC.
DNA barcoding for squids of the family Gonatidae (Cephalopoda: Teuthida) from the boreal North Pacific

Abstract A fragment of cytochrome c oxidase I was used to assess whether species of the squid family Gonatidae from the North Pacific could be identified using DNA barcoding approach. Pairwise intra- and interspecific p-distances were assessed, and systematic relationships among species were estimated by NJ analysis. Examined species formed well-differentiated species-specific clades on the neighbor-joining and Bayesian trees. Multiple taxa formed clades supported by both tree topologies and species hypothesis-free ABGD method. Species morphologically identified as Gonatus tinro and Gonatopsis okutanii demonstrated intraspecific level of molecular genetic divergence (0.2–0.3%) indicating that they are conspecific. Genetic differences between the G. berryi clade and a squid morphologically close to that species may indicate a new cryptic species. High levels (>6.2%) of genetic differentiation within B. borealis suggested the existence of two cryptic species. This study confirms the usefulness of DNA barcoding for identifying species as well as discovering cryptic diversity in the gonatid squids, and indicates the need for further deeper insights into the phylogeny of the Gonatidae.
Purification Toxoplasma gondii Tissue Cysts Using Percoll Gradients

The protozoan parasite Toxoplasma gondii is capable of infecting all warm‐blooded animals and humans. Infectious, transmissible forms of the parasite include oocysts produced by the sexual cycle within the definitive feline host and tissue cysts that form Toxoplasma in the central nervous system and muscle during the asexual cycle within all chronically infected warm‐blooded hosts. These tissue cysts are populated with slow‐growing bradyzoites, which until recently have been thought to be dormant entities in the context of immune sufficiency. Reactivation to active growth during immune suppression is of critical clinical importance. However, little is known about tissue cysts or the bradyzoites they house, as the diversity of tissue cysts cannot be replicated in cell culture systems. This protocol for optimization of tissue cyst purification from the brains of infected mice using Percoll gradients provides an efficient means to recover in vivo–derived tissue cysts that can be applied to imaging, cell biological, biochemical, transcriptomic, and proteomic analyses. © 2017 by John Wiley & Sons, Inc.
Multitarget, quantitative nanoplasmonic electrical field-enhanced resonating device (NE2RD) for diagnostics

Significance Biosensing technologies have significant impact on medical diagnostics but difficulties in the handling of complex biospecimens, portability, and nonlinearity in dynamic detection range present considerable technical bottlenecks in their translation into clinical settings. Here, we present the nanoplasmonic electrical field-enhanced resonating device (NE2RD) that detects and quantifies multiple biotargets from distinct clinical specimens (i.e., saliva, serum, and whole blood) with a broad linear dynamic range. Unlike conventional platforms, the NE2RD does not require lengthy sample-preparation steps, skilled personnel, or expensive infrastructure. Further, as a model clinical validation study, we monitored chemotherapy effects on viral load for coinfected patients on a single platform. Therefore, the portable NE2RD can be broadly applied to primary care and point-of-care settings with multiple clinical applications. Recent advances in biosensing technologies present great potential for medical diagnostics, thus improving clinical decisions. However, creating a label-free general sensing platform capable of detecting multiple biotargets in various clinical specimens over a wide dynamic range, without lengthy sample-processing steps, remains a considerable challenge. In practice, these barriers prevent broad applications in clinics and at patients’ homes. Here, we demonstrate the nanoplasmonic electrical field-enhanced resonating device (NE2RD), which addresses all these impediments on a single platform. The NE2RD employs an immunodetection assay to capture biotargets, and precisely measures spectral color changes by their wavelength and extinction intensity shifts in nanoparticles without prior sample labeling or preprocessing. We present through multiple examples, a label-free, quantitative, portable, multitarget platform by rapidly detecting various protein biomarkers, drugs, protein allergens, bacteria, eukaryotic cells, and distinct viruses. The linear dynamic range of NE2RD is five orders of magnitude broader than ELISA, with a sensitivity down to 400 fg/mL This range and sensitivity are achieved by self-assembling gold nanoparticles to generate hot spots on a 3D-oriented substrate for ultrasensitive measurements. We demonstrate that this precise platform handles multiple clinical samples such as whole blood, serum, and saliva without sample preprocessing under diverse conditions of temperature, pH, and ionic strength. The NE2RD’s broad dynamic range, detection limit, and portability integrated with a disposable fluidic chip have broad applications, potentially enabling the transition toward precision medicine at the point-of-care or primary care settings and at patients’ homes.
Loss of constitutive functional γ‐aminobutyric acid type A‐B receptor crosstalk in layer 5 pyramidal neurons of human epileptic temporal cortex

γ‐Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in adult central nervous system, and profound alterations of GABA receptor functions are linked to temporal lobe epilepsy (TLE). Here we describe the functional relationships between GABA receptors type B (GABABR) and type A (GABAAR) in human temporal cortex and how TLE affects this aspect of GABAergic signaling.
Exploiting imbalanced textual and acoustic data for training prosodically-enhanced RNNLMs

There have been many attempts in the past to exploit various sources of information in language modelling besides words, for instance prosody or topic information. With neural network based language models, it became easier to make use of this continuous valued information, because the neural network transforms the discrete valued space into a continuous valued space. So far, models incorporating prosodic information were jointly trained on the auxiliary and the textual information from the beginning. However, in practice the auxiliary information is usually only available for a small amount of the training data. In order to fully exploit text and acoustic data, we propose to re-train a recurrent neural network language model, rather than training a language model from scratch. Using this method we achieved perplexity and word error rate reductions for N-best rescoring on the MIT-OCW lecture corpus.
Cloning and Functional Analysis of Phosphoethanolamine Methyltransferase Promoter from Maize (Zea mays L.)

Betaine, a non-toxic osmoprotectant, is believed to accumulate considerably in plants under stress conditions to maintain the osmotic pressure and promote a variety of processes involved in growth and development. Phosphoethanolamine N-methyltransferase (PEAMT), a key enzyme for betaine synthesis, is reported to be regulated by its upstream promoter. In the present investigation, by using the transgenic approach, a 1048 bp long promoter region of ZmPEAMT gene from Zea mays was cloned and functionally characterized in tobacco. Computational analysis affirmed the existence of abiotic stress responsive cis-elements like ABRE, MYC, HST, LST etc., as well as pathogen, wound and phytohormone responsive motifs. For transformation in tobacco, four 5′-deletion constructs of 826 bp (P2), 642 bp (P3), 428 bp (P4) and 245 bp (P5) were constructed from the 1048 bp (P1) promoter fragment. The transgenic plants generated through a single event exhibited a promising expression of GUS reporter protein in the leaf tissues of treated with salt, drought, oxidative and cold stress as well as control plants. The GUS expression level progressively reduced from P1 to P5 in the leaf tissues, whereas a maximal expression was observed with the P3 construct in the leaves of control plants. The expression of GUS was noted to be higher in the leaves of osmotically- or salt-treated transgenic plants than that in the untreated (control) plants. An effective expression of GUS in the transgenic plants manifests that this promoter can be employed for both stress-inducible and constitutive expression of gene(s). Due to this characteristic, this potential promoter can be effectively used for genetic engineering of several crops.
Paeonol Attenuates LPS-Induced Endothelial Dysfunction and Apoptosis by Inhibiting BMP4 and TLR4 Signaling Simultaneously but Independently

Inflammatory injury of the endothelium leads to apoptosis and endothelial dysfunction. The current study explored the effect and mechanisms of paeonol in inflammation-induced apoptosis and endothelial dysfunction induced by lipopolysaccharides (LPSs). The effects of paeonol on LPS-induced inflammatory injury were assessed by Western blotting, flow cytometry and reactive oxygen species (ROS) measurement in human umbilical vein endothelial cells (HUVECs) and C57BL/6J mice. Vascular reactivity of isolated mouse aortae was examined using wire myographs. The exposure of HUVECs to LPS increased the protein presence of Toll-like receptor 4 (TLR4), bone morphogenic protein 4 (BMP4), BMP receptor type 1A, nicotinamide adenine dinucleotide phosphate oxidase subunit 2, mitogen-activated protein kinase (MAPK), inducible nitric oxide synthase (iNOS), and cleaved caspase 3, as well as decreased it in phosphorylated endothelial nitric oxide synthase; these effects were prevented by treatment with paeonol. Similarly, cotreatment with paeonol reversed BMP4-induced apoptosis in HUVECs. Relaxation in response to the endothelium-dependent vasodilator acetylcholine were impaired in mouse aortae after exposure to LPSs; this endothelial dysfunction was reversed by cotreatment with paeonol, noggin (a BMP4 inhibitor), TAK242 (TLR4 antagonist), apocynin (an ROS scavenger), MAPK inhibitors, and AG (an iNOS inhibitor). BMP4 small interfering RNAs (siRNAs) abolished LPS-induced upregulation of BMP4 and cleaved caspase 3 protein, but not in cells treated with TLR4 siRNA and vice versa. The silencing of TLR4 and BMP4 abolished the inhibitory effects of paeonol on LPS-induced activation of cleaved caspase 3. The present results demonstrate that paeonol reduces LPS-induced endothelial dysfunction and apoptosis by inhibiting TLR4 and BMP4 signaling independently.
Gas mixture for deep-UV plasma emission in a hollow-core photonic crystal fiber.

We report on the first deep-ultraviolet/ultraviolet (DUV/UV) emission using a highly compact microwave-driven plasma-core photonic crystal fiber. The latter consists of a few centimeter long micro-plasma column of a gas mixture in the core of Kagome hollow-core photonic crystal fiber. The plasma is generated by nonintrusively exciting a ternary gas mixture of argon, nitrogen, and oxygen (Ar/N2/O2) with a microwave resonator. Several spectral lines in the wavelength range of 200-450 nm were produced, guided by an Ar-N2-O2 plasma-filled fiber, and controlled by simply varying the gas ratio of this gas mixture. An optimum gas mixture ratio was experimentally and theoretically identified for the strongest emission in the DUV range of 200-275 nm. The developed DUV emitting plasma-core fiber represents an important milestone towards the development of tunable and miniaturized DUV/UV laser sources.
Exceptional preservation and the fossil record of tetrapod integument

The fossil record of exceptionally preserved soft tissues in Konservat-Lagerstätten provides rare yet significant insight into past behaviours and ecologies. Such deposits are known to occur in bursts rather than evenly through time, but reasons for this pattern and implications for the origins of novel structures remain unclear. Previous assessments of these records focused on marine environments preserving chemically heterogeneous tissues from across animals. Here, we investigate the preservation of skin and keratinous integumentary structures in land-dwelling vertebrates (tetrapods) through time, and in distinct terrestrial and marine depositional environments. We also evaluate previously proposed biotic and abiotic controls on the distribution of 143 tetrapod Konservat-Lagerstätten from the Permian to the Pleistocene in a multivariate framework. Gap analyses taking into account sampling intensity and distribution indicate that feathers probably evolved close to their first appearance in the fossil record. By contrast, hair and archosaur filaments are weakly sampled (five times less common than feathers), and their origins may significantly pre-date earliest known occurrences in the fossil record. This work suggests that among-integument variation in preservation can bias the reconstructed first origins of integumentary novelties and has implications for predicting where, and in what depositional environments, to expect further discoveries of exquisitely preserved tetrapod integument.
Vascular Inner Ear Partition:A Concept for Some Forms of Sensorineural Hearing Loss and Vertigo

The results of a series of scanning electron microscopical studies were used to construct a model for the vascular pathways in the inner ear. Corrosion cast preparations of the vessels of the inner ear of the adult rat were used in this study. The inner ear is, like a hand, an end organ containing four sense organs (cochlea, saccule, utricle and the cristae ampullaris). All these specific inner ear structures have their own vascular supply. We have developed a blood flow diagram of the inner ear. This model was used for a classification of different types of ischemia in the inner ear and forms a concept for some forms of sensorineural hearing loss and vertigo. Four types of inner ear ischemia are proposed. In type I (a or b) of inner ear ischemia only the vessels of the cochlea are involved resulting in two types of hearing loss without vertigo. Type II is characterized by ischemia of a part of the cochlea and a part of the vestibular system. In type III (a or b) only the vestibular system is involved, while in type IV no blood circulation will be present in the inner ear resulting in total deafness and severe vertigo. Inner ear partition at ultramicroscopical level of these structures may be possible in the future and new imaging techniques will probably support the vascular schematic model presented in this study.
Response to Tyrosine Kinase Inhibitors in Myeloproliferative Neoplasia with 8p11 Translocation and CEP110-FGFR1 Rearrangement.

This brief communication reports on a patient with an exceedingly rare "8p11 (eight-p-eleven) myeloproliferative syndrome" (EMS) with CEP110-FGFR1 rearrangement who responded to treatment with the multi-tyrosine kinase inhibitor (TKI) dasatinib. Dasatinib improved quality of life substantially by increasing blood counts and reducing the need for transfusions. This report demonstrates that the second-generation TKI may provide a therapeutic option for elderly and frail EMS patients who cannot be offered aggressive therapy, including allogeneic hematopoietic cell transplantation. The Oncologist 2017;22:480-483.
Fractionation enhances acute oligodendrocyte progenitor cell radiation sensitivity and leads to long term depletion

Ionizing radiation (IR) is commonly used to treat central nervous system (CNS) cancers and metastases. While IR promotes remission, frequent side effects including impaired cognition and white matter loss occur following treatment. Fractionation is used to minimize these CNS late side effects, as it reduces IR effects in differentiated normal tissue, but not rapidly proliferating normal or tumor tissue. However, side effects occur even with the use of fractionated paradigms. Oligodendrocyte progenitor cells (OPCs) are a proliferative population within the CNS affected by radiation. We hypothesized that fractionated radiation would lead to OPC loss, which could contribute to the delayed white matter loss seen after radiation exposure. We found that fractionated IR induced a greater early loss of OPCs than an equivalent single dose exposure. Furthermore, OPC recovery was impaired following fractionated IR. Finally, reduced OPC differentiation and mature oligodendrocyte numbers occurred in single dose and fractionated IR paradigms. This work demonstrates that fractionation does not spare normal brain tissue and, importantly, highlights the sensitivity of OPCs to fractionated IR, suggesting that fractionated schedules may promote white matter dysfunction, a point that should be considered in radiotherapy.
Organic Anion Transporter 2 Mediates Hepatic Uptake of Tolbutamide, a CYP2C9 Probe Drug

Tolbutamide is primarily metabolized by CYP2C9, and, thus, is frequently applied as a clinical probe substrate for CYP2C9 activity. However, there is a marked discrepancy in the in vitro-in vivo extrapolation of its metabolic clearance, implying a potential for additional clearance mechanisms. The goal of this study was to evaluate the role of hepatic uptake transport in the pharmacokinetics of tolbutamide and to identify the molecular mechanism thereof. Transport studies using singly transfected cells expressing six major hepatic uptake transporters showed that tolbutamide is a substrate to organic anion transporter 2 (OAT2) alone with transporter affinity [Michaelis-Menten constant (Km)] of 19.5 ± 4.3 µM. Additionally, OAT2-specific transport was inhibited by ketoprofen (an OAT2 inhibitor) and 1 mM rifamycin SV (pan inhibitor), but not by cyclosporine and rifampicin (OAT polypeptides/Na+-taurocholate cotransporting polypeptide inhibitors). Uptake studies in primary human hepatocytes confirmed the predominant role of OAT2 in the active uptake with significant inhibition by rifamycin SV and ketoprofen, but not by the other inhibitors. Concentration-dependent uptake was noted in human hepatocytes with active transport characterized by Km and Vmax values of 39.3 ± 6.6 µM and 426 ± 30 pmol/min per milligram protein, respectively. Bottom-up physiologically based pharmacokinetic modeling was employed to verify the proposed role of OAT2-mediated hepatic uptake. In contrast to the rapid equilibrium (CYP2C9-only) model, the permeability-limited (OAT2-CYP2C9 interplay) model better described the plasma concentration-time profiles of tolbutamide. Additionally, the latter well described tolbutamide pharmacokinetics in carriers of CYP2C9 genetic variants and quantitatively rationalized its known drug-drug interactions. Our results provide first-line evidence for the role of OAT2-mediated hepatic uptake in the pharmacokinetics of tolbutamide, and imply the need for additional clinical studies in this direction.
Forecasting uncertainty of Thailand's electricity consumption compare with using artificial neural network and multiple linear regression methods

In this paper, the accurate electricity consumption forecasting has become important decisions in the energy planning of the developing countries. Last decade has several new techniques are used for electricity consumption forecasting to accurately predict the future demand. The considerable amount of electricity consumption modeling was efforts. This research approach to develop electricity models, statistical approach is a good to engineering approaches when observed and measured data is available. The statistical models, linear regression analysis has shown promising results because of the reasonable accuracy and relatively simple implementation which compared to other methods. In this study, artificial neural network and multiple linear regression analysis were performed data from Electricity Generating Authority of Thailand. In the models, gross electricity generation, installed capacity, gross domestic products (GDP) and population are used as independent variables using historical data from 1993 to 2015. Forecasting results are compared using MAPE and RMSE for the test period data. The results indicate electricity consumption model are accurate and minimum cost for electricity generation in Thailand.
Automated Immunofluorometric Assay for MUC1

The aim of the present study was to establish a robust, reliable and fully automated immunofluorometric assay for the breast cancer serum marker MUC1. This would further serve as a prototype assay for evaluation of other MUC1 assays based on new antibody combinations. Using time-resolved fluorescence as tracer signal we developed an automated immunofluorometric assay for MUC1 (MUC1 IFMA). This assay was compared with two commercial assays. The CA15-3 EIA (CanAg) which use the same antibodies as the MUC1 IFMA, and the ETI-CA-15-3 K (Sorin) which use the original antibodies defining the CA 15-3 assay. The three assays showed comparable results. The coefficient of variation was below 10% from 9 to 2,400 kU/l for the MUC1 IFMA, from 15 to 250 kU/l for the CA15-3 EIA, and from 25 to 200 kU/l for the ETI-CA-15-3 K assay. At a specificity of 0.94 the overall diagnostic sensitivities for the MUC1-IFMA, CA15-3 EIA and ETI-CA-15-3 K assays were 0.40, 0.37, and 0.38, respectively. When applied to metastatic breast cancer, all assays had sensitivities close to 0.80. There was a close correlation (Spearman rank = 0.99) between results from the new assay and the CA15-3EIA. The new automated assay was not strictly immunometric as we could not achieve conditions where solid phase or tracer antibodies were in apparent excess. However, the assay performed well at a wide range of assay conditions. The automation, which minimizes imprecision in pipetting and handling of samples, and the high capacity of the AutoDELFIA instrument enabling measurement of all samples in a single run, were important aspects for establishing a reliable assay. The principle of the new automated immunofluorometric assay will be used as a rapid and reliable evaluation of a wide range of monoclonal antibody combinations in our search for the optimal MUC1 assay. This new automated immunofluorometric assay will be useful in the rapid and reliable evaluation of a wide range of monoclonal antibody combinations in our search for the optimal MUC1 assay.