Miracle-dz/UniFAR-FTUs huggingface dataset:
Toll-Like Receptor Ligands and CD154 Stimulate Microglia to Produce a Factor(s) That Promotes Excess Cholinergic Differentiation in the Developing Rat Basal Forebrain: Implications for Neurodevelopmental Disorders

Maternal inflammation plays a role in the etiology of certain neurodevelopmental disorders including autism and schizophrenia. Because maternal inflammation can lead to activation of fetal microglia, we have examined effects of inflamed microglia on cultured neural progenitors from rat embryonic septal region and basal forebrain. These cells give rise to cholinergic neurons projecting to cortex and hippocampus. Microglia stimulated with lipopolysaccharide (LPS), peptidoglycan, Poly I:C and CD154 produce conditioned media (CM) that promotes excessive numbers of cholinergic neurons and levels of choline acetyltransferase (ChAT) activity 6–8 times that of untreated cultures. Expression of the neural-specific transcription factor MATH1 increases substantially within 1 h of plating in LPS-CM. Untreated cultures do not attain equivalent levels until 6 h. By contrast, expression of glial-related transcription factors in LPS-CM-treated cultures never attains the elevated levels of untreated cultures. LPS-CM-treated clones derived from individual progenitors labeled with a LacZ-expressing retrovirus showed >2.5-fold increase in the percentage of cholinergic cells compared with untreated clones. Thus, CM from activated microglia prompts excess cholinergic differentiation from undifferentiated progenitors suggesting that microglial inflammation during critical stages can lead to aberrant brain development.
Vagal mechanisms underlying gastric protection induced by chemical activation of raphe pallidus in rats

Kaneko, Hiroshi, Jonathan Kaunitz, and Yvette Taché. Vagal mechanisms underlying gastric protection induced by chemical activation of raphe pallidus in rats. Am. J. Physiol. 275 (Gastrointest. Liver Physiol. 38): G1056–G1062, 1998. —Peripheral mechanisms involved in kainic acid injected into the raphe pallidus (Rpa)-induced gastric protection were investigated in urethan-anesthetized rats. Gastric mucosal blood flow (GMBF), acid secretion, and gastric injury induced by intragastric ethanol (60%) were measured in response to kainic acid (25 pg) injected into the Rpa. Kainic acid reduced ethanol-induced gastric lesions by 57%. The protective effect was blocked by vagotomy, capsaicin deafferentation, and intravenous injection of the calcitonin generelated peptide (CGRP) antagonist CGRP-(8—37) and NGnitro-L-arginine methyl ester (L-NAME). Lbut not D-arginine reversed the L-NAME action. Kainic acid injected into the Rpa, unlike outside sites, increased basal GMBF but not acid secretion. Indomethacin unmasked an acid secretory response to kainic acid. These results show that kainic acid injected into the Rpa at a dose that did not stimulate acid secretion, due to the inhibitory effect of prostaglandins, protects against ethanol-induced gastric injury through vagaldependent activation of CGRP contained in capsaicinsensitive afferents and nitric oxide-mediated gastric vasodilatory mechanisms.
Genome-Wide Innate Immune Responses in HIV-1-Infected Macrophages Are Preserved Despite Attenuation of the NF-κB Activation Pathway1

Macrophages contribute to HIV-1 infection at many levels. They provide permissive cells at the site of inoculation, augment virus transfer to T cells, generate long-lived viral reservoirs, and cause bystander cell apoptosis. A body of evidence suggests that the role of macrophages in cellular host defense is also compromised by HIV-1 infection. In this respect, macrophages are potent cells of the innate immune system that initiate and regulate wide-ranging immunological responses. This study focuses on the effect of HIV-1 infection on innate immune responses by macrophages at the level of signal transduction, whole genome transcriptional profiling, and cytokine secretion. We show that in an ex vivo model, M-CSF-differentiated monocyte-derived macrophages uniformly infected with replicating CCR5-tropic HIV-1, without cytopathic effect, exhibit selective attenuation of the NF-κB activation pathway in response to TLR4 and TLR2 stimulation. However, functional annotation clustering analysis of genome-wide transcriptional responses to LPS stimulation suggests substantial preservation of gene expression changes at the systems level, with modest attenuation of a subset of up-regulated LPS-responsive genes, and no effect on a selection of inflammatory cytokine responses at the protein level. These results extend existing reports of inhibitory interactions between HIV-1 accessory proteins and NF-κB signaling pathways, and whole genome expression profiling provides comprehensive assessment of the consequent effects on immune response gene expression. Unexpectedly, our data suggest innate immune responses are broadly preserved with limited exceptions, and pave the way for further study of the complex relationship between HIV-1 and immunological pathways within macrophages.
Human pathologies associated with defective RNA transport and localization in the nervous system

RNA localization is emerging as an important process to restrict certain proteins to specific subcellular domains and thus spatially control the expression of genes within cells. It is used, for instance, to compartmentalize the developing embryo during early embryogenesis. The localization of RNA also plays important roles later during development, such as in asymmetric cell divisions, cell migration and the outgrowth and pathfinding of axons and dendrites. In differentiated cells, it serves to subdivide the cell into functionally distinct compartments. For example, in mature neurons it is believed to contribute to the plastic changes of individual synapses underlying learning and memory. In this review, we highlight the importance of subcellular RNA localization for the function of the nervous system and neurological diseases associated with defective RNA localization and translation. These diseases include fragile X mental retardation syndrome, spinocerebellar ataxia and spinal muscular atrophy.
Noninvasive quantification of T2 and concentrations of ascorbate and glutathione in the human brain from the same double‐edited spectra

The transverse relaxation times (T2) and concentrations of Ascorbate (Asc) and glutathione (GSH) were measured from a single dataset of double‐edited spectra that were acquired at several TEs at 4 T in the human brain. Six TEs between 102 and 152 ms were utilized to calculate T2 for the group of 12 subjects scanned five times each. Spectra measured at all six TEs were summed to quantify the concentration in each individual scan. LCModel fitting was optimized for the quantification of the Asc and GSH double‐edited spectra. When the fitted baseline was constrained to be flat, T2 was found to be 67 ms (95% confidence interval, 50–83 ms) for GSH and ≤115 ms for Asc using the sum of spectra measured over 60 scans. The Asc and GSH concentrations quantified in each of the 60 scans were 0.62 ± 0.08 and 0.81 ± 0.11 µmol/g [mean ± standard deviation (SD), n = 60], respectively, using 10 µmol/g N‐acetylaspartate as an internal reference and assuming a constant influence of N‐acetylaspartate and antioxidant T2 relaxation in the reference solution and in vivo. The T2 value of GSH was measured for the first time in the human brain. The data are consistent with short T2 for both antioxidants. These T2 values are essential for the absolute quantification of Asc and GSH concentrations measured at long TE, and provide a critical step towards addressing assumptions about T2, and therefore towards the quantification of concentrations without the possibility of systematic bias. Copyright © 2010 John Wiley & Sons, Ltd.
Production of interleukins 10 and 12 by peripheral blood mononuclear cells (PBMC) in chronic hepatitis C virus (HCV) infection

We previously reported that interferon‐gamma (IFN‐γ) production by PBMC in response to HCV core protein was increased in patients with type C chronic liver disease. To understand better the pathophysiology of this disease, we evaluated production of IL‐10 and IL‐12 by PBMC from 41 patients with chronic HCV infection, including asymptomatic HCV carriers with persistently normal serum ALT values. IL‐10 is known to inhibit many effector functions of the immune system, suppressing Th1‐type cell development, while IL‐12 stimulates differentiation of Th1‐type cells, facilitating cell‐mediated immunity. IL‐10 production was determined by culturing lymphocytes with concanavalin A (Con A), while IL‐12 was produced by monocytes in the presence of Staphylococcus aureus Cowan 1 (SAC) with or without recombinant HCV core protein, respectively. The cytokine levels in culture supernatants were measured by ELISA. Spontaneous IL‐10 production was greater in patients with chronic hepatitis (CH) (229±119 pg/ml, P<0.01) and liver cirrhosis (LC) (185±88 pg/ml, P<0.05) than in controls (119±27 pg/ml), while it was decreased during IFN treatment (70±25 pg/ml). Both HCV core protein and Con A enhanced IL‐10 production by cells from HCV‐infected patients. IL‐12 was not detectable in medium alone cultures, and SAC‐induced IL‐12 production did not differ between various patient groups and controls. Simultaneous addition of HCV protein resulted in an increase of IL‐12 production in chronic liver disease compared with SAC‐alone cultures. Addition of IL‐10 to the cultures equally suppressed IFN‐γ production for both controls and patient groups, but the enhancing effect of IL‐12 on IFN‐γ production was significantly less in LC than in controls and other patient groups. The findings suggest that secretion of IL‐10/IL‐12 by cells from control individuals and various patient groups may be different, and that the cytokines might show different effects on IFN‐γ production by some cells.
Third Generation WCDMA Uplink Capacity Improvements With 3.5G HSUPA for ITU Macro-Cell Channels

In this work the performance of two high speed uplink packet access (HSUPA) techniques for enhance the third generation (3G) WCDMA reverse link was analyzed. The throughput increases were investigated for a combination of interference cancellation (IC) and multi-user detection (MUD) schemes and for node-B controlled hybrid automatic repeat request (HARQ) mechanisms. Simulations were done for ITU vehicular A (VA) channels, with different mobility scenarios, and the results were obtained by comparing the throughput for the all applied techniques
Contextual learning requires synaptic AMPA receptor delivery in the hippocampus

The hippocampus plays a central role in learning and memory. Although synaptic delivery of AMPA-type glutamate receptors (AMPARs) contributes to experience-dependent synaptic strengthening, its role in hippocampus-dependent learning remains elusive. By combining viral-mediated in vivo gene delivery with in vitro patch-clamp recordings, we found that the inhibitory avoidance task, a hippocampus-dependent contextual fear-learning paradigm, delivered GluR1-containing AMPARs into CA3-CA1 synapses of the dorsal hippocampus. To block the synaptic delivery of endogenous AMPARs, we expressed a fragment of the GluR1-cytoplasmic tail (the 14-aa GluR1 membrane-proximal region with two serines mutated to phospho-mimicking aspartates: MPR-DD). MPR-DD prevented learning-driven synaptic AMPAR delivery in CA1 neurons. Bilateral expression of MPR-DD in the CA1 region of the rat impaired inhibitory avoidance learning, indicating that synaptic GluR1 trafficking in the CA1 region of the hippocampus is required for encoding contextual fear memories. The fraction of CA1 neurons that underwent synaptic strengthening positively correlated with the performance in the inhibitory avoidance fear memory task. These data suggest that the robustness of a contextual memory depends on the number of hippocampal neurons that participate in the encoding of a memory trace.
Short- and Mid-Term Forecasting of Baseload Electricity Prices in the U.K.: The Impact of Intra-Day Price Relationships and Market Fundamentals

In this paper we investigate whether considering the fine structure of half-hourly electricity prices, the market closing prices of fundamentals (natural gas, coal and CO2) and the system-wide demand can lead to significantly more accurate short- and mid-term forecasts of APX U.K. baseload prices. We evaluate the predictive accuracy of a number of univariate and multivariate time series models over a three-year out-of-sample forecasting period and compare it against that of a benchmark autoregressive model. We find that in the short-term, up to a few business days ahead, a disaggregated model which independently predicts the intra-day prices and then takes their average to yield baseload price forecasts is the best performer. However, in the mid-term, factor models which explore the correlation structure of intra-day prices lead to significantly (as measured by the Diebold-Mariano test) better baseload price forecasts. At the same time, we observe that the inclusion of fundamental variables-especially natural gas prices (in the short-term) and coal prices (in the mid-term)-provides significant gains. The CO2 prices, on the other hand, generally do not improve the price forecasts at all, at least in the time period considered in this study (April 2009-December 2013).
Therapeutic Potential of Human Induced Pluripotent Stem Cells in Experimental Stroke

Ischemic stroke mainly caused by middle cerebral artery occlusion (MCAo) is a major type of stroke, but there are currently very limited therapeutic options for its cure. Neural stem cells (NSCs) or neural precursor cells (NPCs) derived from various sources are known to survive and improve neurological functions when they are engrafted in animal models of stroke. Induced pluripotent stem cells (iPSCs) generated from somatic cells of patients are novel cells that promise the autologous cell therapy for stroke. In this study, we successfully differentiated iPSCs derived from human fibroblasts into NPCs and found their robust therapeutic potential in a rodent MCAo stroke model. We observed the significant graft-induced behavioral recovery, as well as extensive neural tissue formation. Animal MRI results indicated that the majority of contralaterally transplanted iPSC-derived NPCs migrated to the peri-infarct area, showing a pathotropism critical for tissue recovery. The transplanted animals exhibited the significant reduction of stroke-induced inflammatory response, gliosis and apoptosis, and the contribution to the endogenous neurogenesis. Our results demonstrate that iPSC-derived NPCs are effective cells for the treatment of stroke.
Application of molecular genetics to the diagnosis of lymphoid‐rich effusions: Study of 95 cases with concomitant immunophenotyping

The cytological differentiation between reactive lymphocytosis and malignant lymphoma in serous effusions is often difficult. The present study was designed to evaluate the potential contribution of molecular genetic clonality analysis to a solution to this problem. We examined the cytological specimens of 95 consecutive patients collected during a 4‐yr period, including 74 pleural, 20 peritoneal, and one pericardial fluids. Cytological diagnosis in the 95 lymphocyte‐rich effusions was positive for lymphoma in 20 cases, suspicious for lymphoma in 26 cases, and negative in 49 cases. The analysis by ICC was not carried out, inconclusive, or noninterpretable in 25 cases. In five cases molecular genetic analysis was hampered by technical problems. By immunocytochemistry, eight additional cases of lymphoma were detected and lineage classification was achieved in 15 of the 20 cytologically positive effusions. PCR and Southern blot analysis were used to assess B‐ and T‐cell clonality. Monoclonality was found in 40 (42%) of the 95 effusions analyzed. One‐third of the effusions with a monoclonal B‐cell gene rearrangement were detected by Southern blot analysis but not by the PCR performed in parallel. The results of molecular genetic analysis were corroborated by histological findings and/or clinical evolution in 15 cases. Our results indicate that molecular genetic analysis is a useful tool in the analysis of lymphocyte‐rich serous effusions. Diagn. Cytopathol. 2002;27:90–95. © 2002 Wiley‐Liss, Inc.
Activation of Insect Phenoloxidase after Injury: Endogenous versus Foreign Elicitors

The enzyme phenoloxidase (PO) is one of the first immune molecules that was identified in invertebrates. Recently, the immune function of PO has been challenged. We tested how PO is activated following injury in 2 insects, i.e. the fruit fly Drosophila melanogaster and the wax moth Galleria mellonella. Rapid PO activation in Drosophila was limited to discrete areas of the hemolymph clot which forms after injury. Surprisingly, unlike systemic PO activation during bacterial sepsis, clot melanization was not sensitive to microbial elicitors in our assay. Instead, Drosophila clot melanization was activated by endogenous signals such as apoptotic cells and was superinduced by phosphatidylserine, a negatively charged phospholipid normally found on the inner surface of the plasma membrane and exposed during apoptosis. In contrast, melanization in G. mellonella hemolymph was stronger and more uniform and was sensitive to peptidoglycan. This shows that both exogenous and endogenous signals can trigger the same immune mechanism in species- and context-dependent ways. Our findings have implications for the evolutionary dynamics of immune mechanisms and are in agreement with recent comparisons of insect immune transcriptomes.
Evaluation of turmeric extract on performance indices impressed by induced aflatoxicosis in broiler chickens

The purpose of this study was evaluation of ethanolic turmeric extract (ETE; Curcuma longa) effect on overall performance including body weight (BW), body weight gain (BWG), feed intake and feed conversion ratio (FCR) weekly and cumulative for a period of 4 weeks with 300 commercial broiler chicks (Ross strain). These chicks were randomly divided into four groups with three replicates of 15 chicks in each replicate. In group A, chickens were fed a basal diet, in group B, chickens were fed a basal diet plus 3 ppm productive aflatoxin. In group C, chickens consumed a basal diet plus 0.05% ETE and in group D, chickens received a basal diet with 0.05% ETE plus 3 ppm productive aflatoxin. Aflatoxin production by Aspergillus parasiticus (PTTC NO:1850) in maize was according to the Shotwell method. The results revealed that there were no significant differences in BW, BWG and FCR between groups fed turmeric at 0.05% and the control group. The supplement of ETE in a diet containing 3 ppm aflatoxin can significantly improve performance indices compared with the group that consumed aflatoxin alone. In conclusion, our results suggest that turmeric extract (Curcuma longa) can provide protection against the negative effects of aflatoxin on performance of broiler chickens.
Kinetics of tracheid development explain conifer tree-ring structure.

Conifer tree rings are generally composed of large, thin-walled cells of light earlywood followed by narrow, thick-walled cells of dense latewood. Yet, how wood formation processes and the associated kinetics create this typical pattern remains poorly understood. We monitored tree-ring formation weekly over 3 yr in 45 trees of three conifer species in France. Data were used to model cell development kinetics, and to attribute the relative importance of the duration and rate of cell enlargement and cell wall deposition on tree-ring structure. Cell enlargement duration contributed to 75% of changes in cell diameter along the tree rings. Remarkably, the amount of wall material per cell was quite constant along the rings. Consequently, and in contrast with widespread belief, changes in cell wall thickness were not principally attributed to the duration and rate of wall deposition (33%), but rather to the changes in cell size (67%). Cell enlargement duration, as the main driver of cell size and wall thickness, contributed to 56% of wood density variation along the rings. This mechanistic framework now forms the basis for unraveling how environmental stresses trigger deviations (e.g. false rings) from the normal tree-ring structure.
Continuous Transdermal Dopaminergic Stimulation in Advanced Parkinson's Disease

The objective of the study was to determine the safety and efficacy of increasing doses of Rotigotine CDS in patients with advanced Parkinson's disease. The development of motor complications in Parkinson's disease has been linked to intermittent stimulation of dopamine receptors. Continuous, noninvasive, dopaminergic stimulation has not been available to date. Rotigotine CDS is a lipid-soluble D2 dopamine agonist in a transdermal delivery system that could fill this void. This inpatient study consisted of a 2-week dose escalation phase followed by a 2-week dose maintenance phase at the highest dose (80 cm2). Each individual's L-Dopa dose was back-titrated as feasible. The primary outcome measure was L-Dopa dose, and secondary outcome measures included early morning “off”–L-Dopa Unified Parkinson's Disease Rating Scale motor scores by a blinded evaluator and motor fluctuation data obtained from patient diaries (“on” without dyskinesia, “on” with dyskinesia, and “off”). Seven of 10 subjects provided data that could be evaluated. There were two administrative dropouts, and one individual was eliminated from the study because of recrudescence of hallucinations. The median daily L-Dopa dose decreased from 1,400 to 400 mg (p = 0.018, Wilcoxon test). Unified Parkinson's Disease Rating Scale motor scores were unchanged. Although diary variables improved in most individuals, only the reduction in “off” time attained statistical significance. Adverse effects were mild and consisted mainly of dopaminergic side effects and local skin reactions. The data suggest that Rotigotine CDS is an effective treatment for advanced Parkinson's disease and permits patients to substantially lower L-Dopa doses without loss of antiparkinsonian efficacy. Full-scale controlled clinical trials are warranted. In addition to potential therapeutic benefits, this drug can be used to test the hypothesis that continuous dopaminergic stimulation from the initiation of Parkinson's disease therapy will limit the development of motor complications.