Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteasome inhibitor model of Parkinson's disease in mice is confounded by neurotoxicity of the ethanol vehicle

Defects in the ubiquitin‐proteasome system have been implicated in Parkinson's Disease (PD). Recently, a rat model of PD was developed using a synthetic proteasome inhibitor (PSI), (Z‐lle‐Glu(OtBu)‐Ala‐Leu‐al). We attempted to transfer this model to mouse studies, where genetics can be more readily investigated due to the availability of genetically modified mice. We treated C57BL/6 (B6) mice with six intraperitoneal injections of 6 mg/kg PSI in 50 μl of 70% ethanol over a 2‐week‐period. We found significant decreases in nigrostriatal dopamine in PSI‐treated mice compared with saline‐treated mice. However, we observed similar decreases in the ethanol‐treated vehicle control group. Administration of ethanol alone led to significant long‐term alterations in dopamine levels. Ethanol significantly eclipses the effects of PSI in the dopamine system, and therefore is a confounding vehicle for this model. © 2006 Movement Disorder Society
Neuroticism scores increase with late‐life cognitive decline

Neuroticism has been reported as both a risk factor for cognitive decline and a characteristic that increases in parallel with the development of mild cognitive impairment (MCI) and dementia. However, the evidence for these associations is inconclusive, and whether effects are stronger for particular cognitive domains is unknown. We investigated these issues and determined if associations differ among different components of neuroticism.
Serotonin receptors are selectively expressed in the avian germ cells and early embryos

Summary The expression of nine serotonin (5-HT) receptor transcripts was studied using reverse transcription polymerase chain reaction (RT-PCR) in germ cells, cleavage and gastrulation stages of Japanese quail, and qPCR for 5-HT3 and 5-HT4 receptors in oocytes and embryos. We show the presence/absence of nine serotonin transcripts known in birds for receptors 5-HT1A, 5-HT1F, 5-HT2B, 5-HT2C, 5-HT3, 5-HT4, 5-HT5A, 5-HT6 and 5-HT7A in avian germ cells and early embryos. The absence of 5-HT3 and 5-HT5A in primordial germ cells and of 5-HT3 and 5-HT7A in sperm is characteristic. All transcripts appeared in oocytes at all stages (except for 5-HT3 and 5-HT5A transcripts) and all were present in cleaving embryos and at gastrulation, except for 5-HT3, which was permanently observed as late as in stage 4. Interestingly, 5-HT3 and 5-HT5A receptors accumulated in 3-mm and F1 oocytes but were degraded at ovulation and started to be re-transcribed in cleavage stage II embryos and beyond. The selective appearance of 5-HT receptors in germ cells and early embryos supports the hypothesis that serotonin may act as a signalling molecule at early stages of germ line and embryo differentiation via individual receptors present during different stages, when specialized communication systems are not yet developed.
Das Kern-Problem der EU

Dieser Beitrag stellt die Frage, inwieweit das Weisbuch der EU-Kommission zur Zukunft der Europaischen Union erfolgversprechende Szenarien fur eine kunftige Ausgestaltung der europaischen Integration skizziert. Es wird gezeigt, dass die EU-Kommission bei dieser Aufgabe an einem Kern-Problem scheitert, namlich der Definition und Begrundung von Kernkompetenzen der EU anhand eines geeigneten Referenzsystems. Um dieses Kern-Problem zu losen, werden auf Grundlage des okonomischen Subsidiaritatsprinzips acht Kernkompetenzen und ein Sonderfall abgeleitet. Die Analyse verdeutlicht, dass die Handels-, Kapital- und Niederlassungsfreiheit, die Fusions- und Beihilfenaufsicht sowie die Asyl-, Sicherheits- und Umweltpolitik den thematischen Kern einer kunftigen Ausgestaltung des europaischen Integrationsprozesses bilden sollten.
Challenges and Motivations behind Sustaining a Volunteer-Based Forest Management Organization: A Case Study of the Southeastern Illinois Prescribed Burn Association

Fire frequency far below historic norms is threatening eastern oak ecosystem integrity. Increasingly, private family forest landowners are interested in using prescribed fire as a tool for maintaining oak dominance and associated wildlife habitat and wildfire protection. The Southeastern Illinois Prescribed Burn Association (SIPBA) empowers landowners to apply prescribed burning as a management tool. Prescribed fire use is consistent with the established land ethic expressed by members and serves as a means of modeling the practice for nonmember neighbors. SIPBA members regard dependence on outside funding as a limit to both the capacity and, potentially, the sustainability of this novel cooperative land management organization.
The proteome and transcriptome of the infectious metacyclic form of Trypanosoma brucei define quiescent cells primed for mammalian invasion

The infectious metacyclic forms of Trypanosoma brucei result from a complex development in the tsetse fly vector. When they infect mammals, they cause African sleeping sickness in humans. Due to scarcity of biological material and difficulties of the tsetse fly as an experimental system, very limited information is available concerning the gene expression profile of metacyclic forms. We used an in vitro system based on expressing the RNA binding protein 6 to obtain infectious metacyclics and determined their protein and mRNA repertoires by mass‐spectrometry (MS) based proteomics and mRNA sequencing (RNA‐Seq) in comparison to non‐infectious procyclic trypanosomes. We showed that metacyclics are quiescent cells, and propose this influences the choice of a monocistronic variant surface glycoprotein expression site. Metacyclics have a largely bloodstream‐form type transcriptome, and thus are programmed to translate a bloodstream‐form type proteome upon entry into the mammalian host and resumption of cell division. Genes encoding cell surface components showed the largest changes between procyclics and metacyclics, observed at both the transcript and protein levels. Genes encoding metabolic enzymes exhibited expression in metacyclics with features of both procyclic and bloodstream forms, suggesting that this intermediate‐type metabolism is dictated by the availability of nutrients in the tsetse fly vector.
The F‐box protein Skp2 is a ubiquitylation target of a Cul1‐based core ubiquitin ligase complex: evidence for a role of Cul1 in the suppression of Skp2 expression in quiescent fibroblasts

The ubiquitin protein ligase SCFSkp2 is composed of Skp1, Cul1, Roc1/Rbx1 and the F‐box protein Skp2, the substrate‐recognition subunit. Levels of Skp2 decrease as cells exit the cell cycle and increase as cells re‐enter the cycle. Ectopic expression of Skp2 in quiescent fibroblasts causes mitogen‐independent S‐phase entry. Hence, mechanisms must exist for limiting Skp2 protein expression during the G0/G1 phases. Here we show that Skp2 is degraded by the proteasome in G0/G1 and is stabilized when cells re‐enter the cell cycle. Rapid degradation of Skp2 in quiescent cells depends on Skp2 sequences that contribute to Cul1 binding and interference with endogenous Cul1 function in serum‐deprived cells induces Skp2 expression. Furthermore, recombinant Cul1–Roc1/Rbx1–Skp1 complexes can catalyse Skp2 ubiquitylation in vitro. These results suggest that degradation of Skp2 in G0/G1 is mediated, at least in part, by an autocatalytic mechanism involving a Skp2‐bound Cul1‐based core ubiquitin ligase and imply a role for this mechanism in the suppression of SCFSkp2 ubiquitin protein ligase function during the G0/G1 phases of the cell cycle.
Rural environments reduce the genetic influence on adolescent substance use and rule-breaking behavior

Background There is increasing evidence that certain environmental factors can modify genetic effects. This is an important area of investigation as such work will help to guide the development of new intervention programs. In this paper, we address whether rural environments moderate the genetic influence on adolescent substance use and rule-breaking behavior (i.e. externalizing psychopathology). Method Over 1200 Minnesotan 17-year-old twins were classified as either urban or rural. Externalizing behavior was operationalized as the use and abuse of alcohol and drugs along with symptoms of conduct, oppositional defiant, and antisocial personality disorders. Biometric factor modeling estimated whether the relative contribution of genetic and shared environmental factors varied from urban to rural settings. Results Residency effects reached statistical significance in the male sample only. In urban environments, externalizing behavior was substantially influenced by genetic factors, but in rural environments, shared environmental factors became more influential. This was apparent at both the individual-variable and factor levels. Conclusions These findings suggest a gene–environment interaction in the development of male adolescents' problem behaviors, including substance use. The results fit within an expanding literature demonstrating both the contextual nature of the heritability statistic and how certain environments may constrain the expression of genetic tendencies.
BMP Signalling at the Crossroad of Liver Fibrosis and Regeneration

Bone Morphogenetic Proteins (BMPs) belong to the Transforming Growth Factor-β (TGF-β) family. Initially identified due to their ability to induce bone formation, they are now known to have multiple functions in a variety of tissues, being critical not only during development for tissue morphogenesis and organogenesis but also during adult tissue homeostasis. This review focus on the liver as a target tissue for BMPs actions, devoting most efforts to summarize our knowledge on their recently recognized and/or emerging roles on regulation of the liver regenerative response to various insults, either acute or chronic and their effects on development and progression of liver fibrosis in different pathological conditions. In an attempt to provide the basis for guiding research efforts in this field both the more solid and more controversial areas of research were highlighted.
Altered control of cellular proliferation in the absence of mammalian brahma (SNF2α)

The mammalian SWI–SNF complex is an evolutionarily conserved, multi‐subunit machine, involved in chromatin remodelling during transcriptional activation. Within this complex, the BRM (SNF2α) and BRG1 (SNF2β) proteins are mutually exclusive subunits that are believed to affect nucleosomal structures using the energy of ATP hydrolysis. In order to characterize possible differences in the function of BRM and BRG1, and to gain further insights into the role of BRM‐containing SWI–SNF complexes, the mouse BRM gene was inactivated by homologous recombination. BRM−/− mice develop normally, suggesting that an observed up‐regulation of the BRG1 protein can functionally replace BRM in the SWI–SNF complexes of mutant cells. Nonetheless, adult mutant mice were ∼15% heavier than control littermates. This may be caused by increased cell proliferation, as demonstrated by a higher mitotic index detected in mutant livers. This is supported further by the observation that mutant embryonic fibroblasts were significantly deficient in their ability to arrest in the G0/G1 phase of the cell cycle in response to cell confluency or DNA damage. These studies suggest that BRM participates in the regulation of cell proliferation in adult mice.
Two-Stage Energy Management for Office Buildings With Workplace EV Charging and Renewable Energy

Workplace electric vehicle (EV) charging is now supported by more and more companies to encourage EV adoption. In the meantime, renewable energies are becoming an important power source. To participate in the day-ahead power market, decisions have to be made before knowing the actual power demand. This paper addresses the challenges of energy scheduling in office buildings integrated with photovoltaic systems and workplace EV charging. It proposes to leverage day-ahead power market and time-of-use electricity, and uses stochastic programming to address the uncertainties in EV charging demand. Two computationally efficient control algorithms, stochastic programming and load forecasting for energy management with two stages (SPLET) and sample average approximation-based SPLET, are proposed. Both algorithms contain two stages: day-ahead scheduling and real-time operation. First, they try to find the amount of power to purchase from the day-ahead power market while leveraging the flexibility of the load. Then, the real-time demand is satisfied while incorporating the uncertainties realization. Case study based on real-world data shows the proposed two algorithms could provide 7.2% and 6.9% average cost reduction, respectively. Vehicle-to-building and stand-alone battery system can serve as countermeasures for the mismatch between the day-ahead scheduling and real-time demand to further reduce the operation cost.
Improving Employees' Compliance Through Information Systems Security Training: An Action Research Study

Employee noncompliance with information systems security policies is a key concern for organizations. If users do not comply with IS security policies, security solutions lose their efficacy. Of the different IS security policy compliance approaches, training is the most commonly suggested in the literature. Yet, few of the existing studies about training to promote IS policy compliance utilize theory to explain what learning principles affect user compliance with IS security policies, or offer empirical evidence of their practical effectiveness. Consequently, there is a need for IS security training approaches that are theory-based and empirically evaluated. Accordingly, we propose a training program based on two theories: the universal constructive instructional theory and the elaboration likelihood model. We then validate the training program for IS security policy compliance training through an action research project. The action research intervention suggests that the theory-based training achieved positive results and was practical to deploy. Moreover, the intervention suggests that information security training should utilize contents and methods that activate and motivate the learners to systematic cognitive processing of information they receive during the training. In addition, the action research study made clear that a continuous communication process was also required to improve user IS security policy compliance. The findings of this study offer new insights for scholars and practitioners involved in IS security policy compliance.
Nucleotide and pentose synthesis after serum‐stimulation of resting 3T6 fibroblasts

We have investigated the de novo synthesis of intermediates of purine nucleotides in 3T6 fibroblasts and determined the manner by which the activity of this pathway is increased in resting cells by the addition of fresh serum. Within 30 minutes after stimulation, 3T6 cells began to synthesize increased amounts of purines by the de novo pathway as measured by increased amounts of formylglycinamide ribonucleotide, a representative intermediate of this pathway. Within 15 minutes after serum‐stimulation 3T6 cells exhibited a substantial increase in their capacity to synthesize ribose compounds, particularly in the form of 5‐phosphoribosylpyrophosphate (PRPP). The availability of PRPP appeared to be limiting for the synthesis of purine nucleotides in resting fibroblasts, but not necessarily in serum‐stimulated cells.
Effect of alfaxalone infusion on the electroencephalogram of dogs anaesthetized with halothane.

OBJECTIVE To describe the effects of alfaxalone on the canine electroencephalogram (EEG). STUDY DESIGN Experimental study. ANIMALS Eight healthy adult Huntaway dogs. METHODS Anaesthesia was induced with propofol and maintained with halothane (0.85-0.95 end-tidal volume %) in oxygen. Animals were ventilated to maintain stable end-tidal CO(2) and halothane concentrations. Following a 30 minute stabilisation period, alfaxalone (0.5 mg kg(-1) ) was infused intravenously over a 5 minute period. The electroencephalogram was recorded from the beginning of the stabilisation period until 60 minutes following the start of alfaxalone treatment. Data were subjected to fast Fourier transformation, and median frequency, 95% spectral edge frequency and total EEG power were calculated. Two-factorial repeated measures anova (time and EEG channels were factors) was used for statistical analysis (p < 0.05). RESULTS A shift in the dominant frequency band from beta to delta after alfaxalone treatment and occasional burst suppression were observed. Median frequency decreased significantly below baseline (9.2 ± 1.4 Hz) (mean ± SD) during alfaxalone infusion. The lowest value (4.8 ± 1.2 Hz) was recorded 5 minutes after the start of infusion. Spectral edge frequency also decreased below baseline (26.2 ± 1.5 Hz) and the lowest value (22.6 ± 1.5 Hz) also was detected at 5 minutes after the start of infusion. Total EEG power did not change significantly. In some frequencies EEG power increased soon after the start of alfaxalone infusion, then decreased below baseline later (biphasic pattern). CONCLUSIONS AND CLINICAL RELEVANCE Alfaxalone induced biphasic changes on EEG and decreased F(50) and F(95) in halothane anaesthetized dogs.
7-Nitroindazole and its rapidly emerging role in opioid pain management and withdrawal

Correspondence: Shailendra Kapoor 2300 E Cary Street, Richmond, VA 23223, USA Email shailendrakapoor@yahoo.com To the editor I read with great interest the paper by Jin et al in a recent issue of your journal. The article is highly thought-provoking. Interestingly, the past few years have also seen the emergence of nitric oxide synthetase inhibitors, especially 7-nitroindazole, as novel new agents with significant benefits in opioid pain management and withdrawal. For instance, 7-nitroindazole attenuates the development of tolerance to the antinociceptive activity of kappa and mu opioid receptors. Similarly, 7-nitroindazole blocks the neurotoxicity secondary to ketamine in animal models. This may very well play a significant role in protecting the human brain from the toxicity of ketamine, especially in the pediatric population. 7-Nitroindazole also has a negative impact on morphine dependency. Tian et al have shown that 7-nitroindazole decreases physical dependence on opioid agonist/antagonist agents such as butorphanol. Medvedev et al have recently shown that administration of 7-nitroindazole also decreases symptoms of opioid withdrawal, such as tremors and diarrhea. The clinical benefit of 7-nitroindazole in individuals with opioid withdrawal is that it does not cause hypertension, unlike other nitric oxide synthase inhibitors, such as L-NG-nitroarginine methyl esters. 7-Nitroindazole may also have other benefits. For instance, 7-nitroindazole injection into the bronchial vasculature decreases pulmonary changes such as edema secondary to hypoxic trauma. The examples cited here clearly illustrate the beneficial effects of 7-nitroindazole and the need for further large-scale studies to elaborate fully its beneficial effects in pain management.
SISUA: Semi-Supervised Generative Autoencoder for Single Cell Data

Single-cell transcriptomics offers a tool to study the diversity of cell phenotypes through snapshots of the abundance of mRNA in individual cells. Often there is additional information available besides the single cell gene expression counts, such as bulk transcriptome data from the same tissue, or quantification of surface protein levels from the same cells. In this study, we propose models based on the Bayesian generative approach, where protein quantification available as CITE-seq counts from the same cells are used to constrain the learning process, thus forming a semi-supervised model. The generative model is based on the deep variational autoencoder (VAE) neural network architecture.
Configuration Generation of Aircraft Swarm Based on Communication Distance Constraint

Aiming at the requirements of the aircraft swarm combat task and information consensus, the control method of swarm configuration generation of aircraft swarm based on communication distance constraint is studied. We build the swarm communication relation model based on graph theory combined with the self-organizing obstacle avoidance control strategy and design the control protocol of aircraft swarm space configuration generation. We prove the stability and convergence of the system based on the Lyapunov stability theory and LaSalle invariable principle. Simulation results show that the proposed control protocol can ensure that the aircrafts can stabilize to the desired configuration under the premise of successfully avoiding environmental obstacles.
Comparative Genomic and Functional Analysis of Lactobacillus casei and Lactobacillus rhamnosus Strains Marketed as Probiotics

ABSTRACT Four Lactobacillus strains were isolated from marketed probiotic products, including L. rhamnosus strains from Vifit (Friesland Campina) and Idoform (Ferrosan) and L. casei strains from Actimel (Danone) and Yakult (Yakult Honsa Co.). Their genomes and phenotypes were characterized and compared in detail with L. casei strain BL23 and L. rhamnosus strain GG. Phenotypic analysis of the new isolates indicated differences in carbohydrate utilization between L. casei and L. rhamnosus strains, which could be linked to their genotypes. The two isolated L. rhamnosus strains had genomes that were virtually identical to that of L. rhamnosus GG, testifying to their genomic stability and integrity in food products. The L. casei strains showed much greater genomic heterogeneity. Remarkably, all strains contained an intact spaCBA pilus gene cluster. However, only the L. rhamnosus strains produced mucus-binding SpaCBA pili under the conditions tested. Transcription initiation mapping demonstrated that the insertion of an iso-IS30 element upstream of the pilus gene cluster in L. rhamnosus strains but absent in L. casei strains had constituted a functional promoter driving pilus gene expression. All L. rhamnosus strains triggered an NF-κB response via Toll-like receptor 2 (TLR2) in a reporter cell line, whereas the L. casei strains did not or did so to a much lesser extent. This study demonstrates that the two L. rhamnosus strains isolated from probiotic products are virtually identical to L. rhamnosus GG and further highlights the differences between these and L. casei strains widely marketed as probiotics, in terms of genome content, mucus-binding and metabolic capacities, and host signaling capabilities.
The immunogenicity of various peptide antigens inducing cross-reacting antibodies to a cell surface protein antigen of Streptococcus mutans.

A cell surface protein antigen (PAc) of Streptococcus mutans may be involved in the binding of bacteria to the tooth surface, and has long been focused upon as a candidate for a preventive vaccine of dental caries. Previously the peptide PAc (365-377) was shown to raise an antibody in B10.D2 mice which inhibited the binding of salivary components to the PAc molecule. Using this peptide as a unit peptide, two constructs based on multiple antigenic peptides, and several types of tandem repeats of two or three copies were synthesized to estimate the immunogenicity of these peptides. Increase in the immunogenicity was observed for all constructs with the use of an adjuvant compared to the unit peptide alone. However, the tandem repeat constructs generally induced antibody production in the absence of adjuvant, while the multiple antigenic peptide constructs did not induce antibody production under the same condition. Although such a phenomenon may be restricted to this particular peptide sequence, these results may influence the strategy for the design of peptide vaccines.