Miracle-dz/UniFAR-FTUs huggingface dataset:
Protection of apigenin against kainate-induced excitotoxicity by anti-oxidative effects.

Apigenin (5,7,4'-trihydroxyflavone) is a principal ingredient of Cirsium japonicum. These experiments were performed to determine whether apigenin has neuroprotective effects against kainic acid (KA)-induced excitotoxicity in vitro and in vivo. Intraperitoneal (i.p.) administration of apigenin (25, 50 mg/kg) decreased the seizure scores induced by KA injection (40 mg/kg, i.p.) in mice. In addition, the convulsion onset time was significantly delayed by apigenin administration. Moreover, we found that apigenin blocked KA-induced seizure-form electroencephalogram (EEG) discharge activity in the brain cortex. In hippocampal cells, apigenin inhibited KA-induced excitotoxicity in a dose-dependent manner as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To study the possible mechanisms underlying the in vitro neuroprotective effects of apigenin against KA-induced cytotoxicity, we also examined the effect of apigenin on intracellular reactive oxygen species (ROS) elevations in cultured hippocampal neurons and found that apigenin treatment dose-dependently inhibited intracellular ROS elevation. The remarkable reduction of glutathione (GSH) levels induced by KA in hippocampal tissues was reversed by apigenin in a dose-dependent manner. In addition, similar results were obtained after pretreatment with free radical scavengers such as trolox and dimethylthiourea (DMTU). Finally, after confirming the protective effect of apigenin in hippocampal CA3 region, we found apigenin is an active compound in KA-induced neuroprotection. These results collectively indicate that apigenin alleviates KA-induced excitotoxicity by quenching ROS as well as inhibiting GSH depletion in hippocampal neurons.
Digestive Physiology of Octopus maya and O. mimus: Temporality of Digestion and Assimilation Processes

Digestive physiology is one of the bottlenecks of octopus aquaculture. Although, there are successful experimentally formulated feeds, knowledge of the digestive physiology of cephalopods is fragmented, and focused mainly on Octopus vulgaris. Considering that the digestive physiology could vary in tropical and sub-tropical species through temperature modulations of the digestive dynamics and nutritional requirements of different organisms, the present review was focused on the digestive physiology timing of Octopus maya and Octopus mimus, two promising aquaculture species living in tropical (22–30°C) and sub-tropical (15–24°C) ecosystems, respectively. We provide a detailed description of how soluble and complex nutrients are digested, absorbed, and assimilated in these species, describing the digestive process and providing insight into how the environment can modulate the digestion and final use of nutrients for these and presumably other octopus species. To date, research on these octopus species has demonstrated that soluble protein and other nutrients flow through the digestive tract to the digestive gland in a similar manner in both species. However, differences in the use of nutrients were noted: in O. mimus, lipids were mobilized faster than protein, while in O. maya, the inverse process was observed, suggesting that lipid mobilization in species that live in relatively colder environments occurs differently to those in tropical ecosystems. Those differences are related to the particular adaptations of animals to their habitat, and indicate that this knowledge is important when formulating feed for octopus species.
Initiation of baculovirus DNA replication: early promoter regions can function as infection-dependent replicating sequences in a plasmid-based replication assay

From the results of transient plasmid-based replication assays, it has been postulated that homologous regions (hrs) of Autographa californica nuclear polyhedrosis virus (AcMNPV) function as origins of viral DNA replication. However, these assays vary in specificity according to the methodology used and may not be dependent solely on the presence of hr sequences. To determine the role that hrs and other sequences might play in the replication process, a series of plasmids containing specific deletions of various hrs was generated and tested in a standardized replication assay. Deletion of the AcMNPV hr2 and hr5 sequences abolished the ability of plasmids to replicate in the standard infection-dependent replication assay, while deletion of hr1, hr3, and hr4a sequences decreased but did not eliminate plasmid replication in this assay. Plasmids carrying the complete ie-2 and pe38 genes, the ie-1 gene upstream region, or a variety of baculovirus genes including 11 early promoter regions were also able to replicate in virus-infected cells, suggesting that early viral promoter sequences could also function as putative origins of replication. These data suggest that the standard infection-dependent replication assay may identify a broad range of infection-dependent replicating sequences, only one or a few of which may represent genuine viral origins used by the virus in vivo. We propose a model suggesting that the selection of replication initiation sites may be imposed directly by chromatin structure and indirectly by primary sequence and that the process of viral DNA replication may be linked with viral transcription.
The Impact of a Loss of Confidence in Emerging Market Economies to the World Economy: A Simulation with the G-Cubed Model

Risks in emerging market economies have considerably gone up as capital inflows have soared since the global financial crises in 2008. Once the advanced economies recover, especially in the US where its monetary stimulus ends, market expectations change. It may then potentially lead to sudden capital outflows from emerging economies which could lead to loss of confidence in the emerging market economies. To study the impacts of such event, this paper simulates with the G-Cubed Model. The results show that once financial shocks hit emerging market economies, it can produce critical real effects in the economic downturn which will last for a long period. The simulation also shows the strong interdependence between financial and real economies. In the emerging economies, expected future incomes and wealth fall, while the developed economies gain through the reallocation of investment. Another important channel of the shocks is through trade channel as most emerging market economies rely on imports for their production inputs.
Functional analysis of C‐TAK1 substrate binding and identification of PKP2 as a new C‐TAK1 substrate

Cdc25C‐associated kinase 1 (C‐TAK1) has been implicated in cell cycle regulation and Ras signaling through its interactions with two putative substrates, the Cdc25C phosphatase and the MAPK scaffold KSR1. Here, we identify sequence motifs required for stable C‐TAK1 association and substrate phosphorylation. Using a mutational approach to disrupt binding of C‐TAK1 to KSR1 and Cdc25C, we demonstrate that C‐TAK1 contributes to the regulation of these proteins in vivo through the generation of 14‐3‐3‐binding sites. KSR1 proteins defective in C‐TAK1 binding had severely reduced phosphorylation at the 14‐3‐3‐binding site in vivo, were constitutively localized to the plasma membrane and had increased biological activity. Disruption of the Cdc25C–C‐TAK1 interaction resulted in reduced 14‐3‐3‐binding site phosphorylation and nuclear accumulation of Cdc25C in interphase cells. Finally, utilizing the acquired C‐TAK1 binding and substrate phosphorylation data, we identify plakophilin 2 (PKP2) as a novel C‐TAK1 substrate. Phosphorylation of PKP2 by C‐TAK1 also generates a 14‐3‐3‐binding site that influences PKP2 localization. These findings underscore the importance of C‐TAK1 as a regulator of 14‐3‐3 binding and protein localization.
The role of functional social support in treatment retention and outcomes among outpatient adult substance abusers.

AIMS The goals of this study were: (1) to compare patients with high and low functional social support at intake and 6 months later on various risk factors; (2) to test the stress-buffering role of functional social support on treatment outcomes, and (3) to determine whether levels of functional social support at intake predicted treatment retention. DESIGN Consecutive admissions to an outpatient treatment program were assessed at intake (n = 206) and at 6 month follow-up (n = 172) using the Addition Severity Index (ASI). Patients completed questionnaires pertaining to social support, stress and psychological functioning both at intake and at 6 months. FINDINGS Both high and low social support groups experienced marked declines in negative affect and in the severity of substance abuse over time. There were some group differences: for example, symptoms of depression and psychological distress were higher among patients with low social support at intake and at 6 months. Patients with low social support at intake reported higher severity of alcohol and drug abuse at 6 months. Hierarchical regression analyses showed that functional social support was a modest predictor of reductions in the severity of alcohol abuse at follow-up, after controlling for the number of days in treatment. Higher levels of social support explained a modest (6%) proportion of the variance in alcohol-related outcomes, but did not predict reductions in drug abuse. Survival analysis demonstrated that the rate of dropping out of treatment was significantly higher for patients with low social support. CONCLUSIONS Higher functional social support at intake is a positive predictor of retention in treatment, and a modest predictor of reductions in alcohol intake, but not in drug use. Overall, social support accounts for a small percentage of the variance in drug/alcohol-related outcomes, underscoring the need for further research into variables accounting for treatment success and failure.
TrxR, a New CovR-Repressed Response Regulator That Activates the Mga Virulence Regulon in Group A Streptococcus

ABSTRACT Coordinate regulation of virulence factors by the group A streptococcus (GAS) Streptococcus pyogenes is important in this pathogen's ability to cause disease. To further elucidate the regulatory network in this human pathogen, the CovR-repressed two-component system (TCS) trxSR was chosen for further analysis based on its homology to a virulence-related TCS in Streptococcus pneumoniae. In a murine skin infection model, an insertion mutation in the response regulator gene, trxR, led to a significant reduction in lesion size, lesion severity, and lethality. Curing the trxR mutation restored virulence comparable to the wild-type strain. The trxSR operon was defined in vivo, and CovR was found to directly repress its promoter in vitro. DNA microarray analysis established that TrxR activates transcription of Mga-regulated virulence genes, which may explain the virulence attenuation of the trxR mutant. This regulation appears to occur by activation of the mga promoter, Pmga, as demonstrated by analysis of a luciferase reporter fusion. Complementation of the trxR mutant with trxR on a plasmid restored expression of Mga regulon genes and restored virulence in the mouse model to wild-type levels. TrxR is the first TCS shown to regulate Mga expression. Because it is CovR repressed, TrxR defines a new pathway by which CovR can influence Mga to affect pathogenesis in the GAS.
Are sound abatement measures necessary in the cytology reading room? A study of auditory distraction

Listening to music and other auditory material during microscopy work is common practice among cytologists. While many cytologists would claim several benefits of such activity, research in other fields suggests that it might adversely affect diagnostic performance. Using a cross‐modal distraction paradigm, the aim of the present study was to investigate the effect of auditory stimulation on the visual interpretation of cell images.
Lumbar Subarachnoid Drainage in Cerebrospinal Fluid Leaks After Lateral Skull Base Surgery

Objective To determine the efficacy of lumbar drainage in managing cerebrospinal fluid (CSF) leak after lateral skull base surgery. Study Design Retrospective case review. Setting Academic tertiary referral center. Patients Patients who had a lumbar subarachnoid drain placed after a lateral skull base procedure between July 1999 and February 2010 were included. Interventions Patients were identified by searching medical records for lateral skull base approach Current Procedural Terminology codes. The following variables were recorded for each subject: diagnosis, type of lateral skull base operation, duration of lumbar drainage, need for revision surgery, and presence of meningitis. Main Outcome Measure Successful cessation of postoperative CSF leakage. Results Five hundred eight charts were reviewed, and 63 patients were identified who received a lumbar drain after a lateral skull base operation. The most common diagnosis was acoustic neuroma in 61.9%. The most common skull base approaches were the translabyrinthine, middle fossa, and transpetrosal approaches. Approximately 60.3% of patients had CSF rhinorrhea, 23.8% had an incisional leak, and 14.3% had otorrhea. The mean duration of lumbar drainage was 4.6 days. Forty eight (76.2%) study subjects had resolution of their CSF leak with lumbar drainage. Fifteen patients (23.8%) required revision surgery to stop the CSF leak. Lumbar drainage was successful in 90% of leaks after the translabyrinthine approach but in only 50% of those undergoing a suboccipital approach, which was a statistically significant difference. Conclusion Postoperative CSF leaks after lateral skull base surgery can be managed with a lumbar subarachnoid drain in a majority of cases but is more successful after the translabyrinthine than the suboccipital approach. Recurrent CSF leaks after lumbar drainage is likely to require a revision operation.
Mechanisms of Human Erythrocytic Bioactivation of Nitrite*

Background: Erythrocytes contribute to nitrite-mediated NO signaling, but the mechanism is unclear. Results: Deoxyhemoglobin accounts for virtually all NO made from nitrite by erythrocytes with no contributions from other proposed pathways. Conclusion: Deoxyhemoglobin is the primary erythrocytic nitrite reductase operating under physiological conditions. Significance: Reduction by deoxyhemoglobin accounts for nitrite-mediated NO signaling in blood mediating vessel tone and platelet function. Nitrite signaling likely occurs through its reduction to nitric oxide (NO). Several reports support a role of erythrocytes and hemoglobin in nitrite reduction, but this remains controversial, and alternative reductive pathways have been proposed. In this work we determined whether the primary human erythrocytic nitrite reductase is hemoglobin as opposed to other erythrocytic proteins that have been suggested to be the major source of nitrite reduction. We employed several different assays to determine NO production from nitrite in erythrocytes including electron paramagnetic resonance detection of nitrosyl hemoglobin, chemiluminescent detection of NO, and inhibition of platelet activation and aggregation. Our studies show that NO is formed by red blood cells and inhibits platelet activation. Nitric oxide formation and signaling can be recapitulated with isolated deoxyhemoglobin. Importantly, there is limited NO production from erythrocytic xanthine oxidoreductase and nitric-oxide synthase. Under certain conditions we find dorzolamide (an inhibitor of carbonic anhydrase) results in diminished nitrite bioactivation, but the role of carbonic anhydrase is abrogated when physiological concentrations of CO2 are present. Importantly, carbon monoxide, which inhibits hemoglobin function as a nitrite reductase, abolishes nitrite bioactivation. Overall our data suggest that deoxyhemoglobin is the primary erythrocytic nitrite reductase operating under physiological conditions and accounts for nitrite-mediated NO signaling in blood.
Differentiated Effective Connectivity Patterns of the Executive Control Network in Progressive MCI: A Potential Biomarker for Predicting AD.

OBJECTIVE Mild cognitive impairment (MCI) is often a transitional state between normal aging and Alzheimer's disease (AD). When observed longitudinally, some MCI patients convert to AD, while a considerable portion either remains MCI or revert to a normal functioning state. This divergence has provided some enlightenment on a potential biomarker to be represented in the resting state brain activities of MCI patients with different post-hoc labels. Recent studies have shown impaired executive functions, other than typically explicated memory impairment with AD/MCI patients. This observation raises the question that whether or not the executive control network (ECN) was impaired, which pivotally supports the central executive functions. Given the fact that effective connectivity is a sufficient index in detecting resting brain abnormalities in AD/MCI, the current study specifically asks a question whether the effective connectivity patterns are differentiated in MCI patients with different post-hoc labels. METHODS We divided the MCI subjects into three groups depending on their progressive state obtained longitudinally: 1) 15 MCI-R subjects: MCI reverted to the normal functioning state and stabilized to the normal state in 24 months; 2) 35 MCI-S subjects: MCI patients maintained this disease in a stable state for 24 months; 3) 22 MCI-P subjects: MCI progressed to AD and stabilized to AD in 24 months, and 4) 39 age-matched normal control subjects (NC). We conducted a Granger causality analysis after identifying the core nodes of ECN in all of the subjects using Independent Component Analysis. Our findings revealed that different MCI groups presented different effective connectivity patterns within the ECN compared to the NC group. Specifically, (1) dorsolateral prefrontal cortex (dLPFC) and medial prefrontal cortex (mPFC) were the core nodes in the ECN network that exhibited different connecting patterns; (2) an effective connection circuit "R.dLPFC→ right caudate→ left thalamus→R.dLPFC" in the ECN showed different levels of damage; and (3) there were four pathways between the R.dLPFC and L.LP, and these four pathways were also different. RESULTS Our results would help to understand the potential central mechanism of MCI patients. The differentiated effective connectivity of ECN may serve as a potential biomarker for early detection of AD, which may also provide a reference for clinical researchers to manipulate active but distinctive interventions for MCI patients who have different risks.
Prevalence of essential tremor in patients with Parkinson's disease vs. Parkinson‐plus syndromes

Clinical literature suggests an association between essential tremor (ET) and Parkinson's disease (PD), and recent pathological studies describe Lewy bodies in some ET patients. If some ET were an expression of Lewy body disease, one could hypothesize that ET patients who develop parkinsonism would more likely develop PD (a Lewy body disease) than non‐Lewy body forms of parkinsonism. The objective was to compare the proportions of patients with PD vs. Parkinson‐plus syndromes who had diagnoses of ET. Retrospective chart review at the Neurological Institute (NI) of New York. A larger proportion of the 210 PD than 210 Parkinson‐plus syndrome patients had kinetic tremor on examination (119 [56.7%] vs. 70 [33.3%], P < 0.001). Patients with PD were more likely to have a prior diagnosis of ET than were patients with Parkinson‐plus syndromes (7.1% vs. 2.4%, OR 3.16, 95% CI 1.13–8.85, P = 0.02) and more likely to have a diagnosis of ET assigned by an NI neurologist (5.3% vs. 0.0%, OR 12.85, 95% CI 1.66–99.8, P = 0.001). Patients with PD were three to thirteen times more likely to have diagnoses of ET than were patients with Parkinson‐plus syndromes. These data further confirm the link between ET and PD, and possibly, between ET and Lewy body disease. © 2007 Movement Disorder Society
The Irish Newspapers and the Residential Property Price Boom

ABSTRACT There has already been some academic discussion of the role of the Irish newspapers in fuelling the country's residential property boom that crashed in 2008. Several academic commentators have argued that the newspapers intentionally talked up the Irish market because of the conflicts of interest that they faced, particularly arising from advertising and their organisational linkages. This paper argues that these factors have only limited explanatory value, and that the key determinant in the economics sections of the newspapers was their reliance on external expertise to augment their analyses. The article presents quantitative data demonstrating the enormous prevalence of articles written by and citing private-sector economists from organisations with direct stakes in the property market. These commentators were very unlikely to issue unreserved warnings about a crash, and in many cases made unduly positive forecasts with little empirical justification. The article argues that the key fault of the newspapers therefore lay in the failure of management to prevent the tone and coverage of the market from being skewed by external interests. The article contributes to the broader international literature on media bias and the role of external experts.
Nosocomial Spread of ArmA-Mediated High-Level Aminoglycoside Resistance in Enterobacteriaceae Isolates Producing CTX-M-3 β-Lactamase in a Cancer Hospital in Bulgaria

Abstract 1,310 Enterobacteriaceae 242 Pseudomonas aeruginosa and 97 Acinetobacter baumannii clinical isolates collected at a cancer hospital in Bulgaria were screened for the presence of 16S rRNA methylases. The armA methylase gene was identified in 20 (1.5%) Enterobacteriaceae (7 Klebsiella pneumoniae, 3 Escherichia coli, 3 Serratia marcescens, 3 Citrobacter freundii, 3 Enterobacter cloacae and 1 Klebsiella oxytoca). ArmA-mediated aminoglycoside resistance was transferable by conjugation and carried by closely related IncL/M plasmids which also carried ant3”9, dfrXII, sul1, bla TEM-1, and bla CTX-M-3 genes encoding resistance to streptomycin-spectinomycin, trimethoprim, sulfonamides, and β-lactams, respectively. Most of the isolates were genetically different according to PFGE but shared similar restriction patterns of the armA-encoding plasmids. Our findings highlight the strong association of armA and bla CTX-M-3 extended-spectrum β-lactamase genes across various species in the family Enterobacteriaceae. The spread of multiresistant isolates expressing 16S rRNA methylases and ESBLs is a worrisome development requiring continuous monitoring.
Determinants of mortgage arrears in Europe: evidence from household microdata

In purely economic terms, mortgage arrears can pose a risk to the stability of banks and limit households’ future access to credit. Moreover, arrears have social ramifications: they reduce aspects of households’ well-being and health, and addressing such negative effects can lead to a requirement for higher social spending by governments. It is therefore important to identify the drivers of arrears and design policies to reduce them. We use a European household data-set to analyse what drives arrears. Controlling for household characteristics such as age and education, we find that affordability problems, such as unemployment, low income and high mortgage payments, matter. Households facing the dual trigger of affordability problems and negative equity are more likely to go into longer- term arrears. We also find that households in Cyprus and Greece are particularly prone to miss mortgage payments, while those in the United Kingdom and Belgium are very unlikely to do so. Generally, arrears tend to be higher in poor countries and where investors’ rights are poorly protected.