Miracle-dz/UniFAR-FTUs huggingface dataset:
Translocation of Porphyromonas gingivalis Gingipain Adhesin Peptide A44 to Host Mitochondria Prevents Apoptosis

ABSTRACT Porphyromonas gingivalis, a Gram-negative oral anaerobe, is associated with periodontal diseases that, in some form, affect up to 80% of the U.S. population. The organism is highly proteolytic, and noncatalytic adhesin domains of the major proteases, gingipains, are involved in bacterium-host interactions. Recently, we showed that gingipain adhesin peptide A44 hijacks the host's clathrin-dependent endocytosis system, allowing the peptide and whole bacteria to be internalized by epithelial cells. In the present study, we found by cell fractionation assays and confocal microscopy that peptide A44 translocated to host mitochondria. Cell viability assays and quantitative real-time PCR showed that the peptide interacted with the cell death machinery by triggering upregulation of antiapoptotic factors bcl-2 and bcl-XL and prevented staurosporine-induced apoptosis for up to 12 h. We confirmed these findings with Western blot analyses of caspase-9 activation in time course experiments with staurosporine. Finally, we verified a similar antiapoptotic effect for P. gingivalis, showing for the first time that the organism manipulated mitochondrial functions during the first hours of infection, thus resisting host cell clearance by apoptosis of infected cells. This mechanism may enable the bacteria to persist in the protected cellular environment until the next step in pathogenesis, progression or resolution of infection.
Ribosome Inactivation Leads to Attenuation of Intestinal Polymeric Ig Receptor Expression via Differential Regulation of Human Antigen R

The polymeric IgR (pIgR) is a central component in the transport of IgA across enterocytes and thereby plays a crucial role in the defense against enteropathogens and in the regulation of circulating IgA levels. The present study was performed to address the novel regulation of pIgR expression in intestinal epithelia undergoing ribosome inactivation. Insults to mucosa that led to ribosome inactivation attenuated pIgR expression in enterocytes. However, IFN regulatory factor-1 (IRF-1) as a central transcription factor of pIgR induction was superinduced by ribosome inactivation in the presence of IFN-γ as a result of mRNA stabilization by the RNA-binding protein HuR. Another important transcription factor for pIgR expression, NF-κB, was marginally involved in suppression of pIgR by ribosome inactivation. In contrast to a positive contribution of HuR in early induction of IRF-1 expression, extended exposure to ribosome inactivation caused nuclear entrapment of HuR, resulting in destabilization of late-phase–induced pIgR mRNA. These HuR-linked differential regulations of pIgR and of IRF-1 led to a reduced mucosal secretion of IgA and, paradoxically, an induction of IRF-1–activated target genes, including colitis-associated IL-7. Therefore, these events can account for ribosome inactivation–related mucosal disorders and provide new insight into interventions for HuR-linked pathogenesis in diverse mucosa-associated diseases, including inflammatory bowel disease and IgA nephritis.
Electoral participation and development in the states of Mexico, 2000-2012

La participacion electoral en Mexico ha tenido un comportamiento irregular en el tiempo. Ocasionalmente, como sucedio en las elecciones de 1994, la participacion de los votantes alcanzo el 77%, y en un estado del norte alcanzo el 83.7%, mientras que, en las elecciones de 2003, apenas alcanzo el 41.7%. Algunas hipotesis intentan explicar tal diversidad, pero una coyuntura de factores (zapatistas-1994, la reforma electoral -1996 y 1997-, crisis economica -1998 y 2009-, crimen organizado -2006 hasta 2012-), podria haber tenido influencia en tales participaciones. Este articulo establece una relacion entre el desarrollo de cada entidad y la participacion de los votantes, a fin de identificar si la tendencia electoral en cada estado durante las elecciones de diputados federales, muestra alguna asociacion con la evolucion del desarrollo social. Utilizaremos el Indice de Desarrollo Humano y estudiaremos la participacion de los votantes en cada estado, desde 2000 hasta 2012.
Survival and Differentiation of Human Embryonic Stem Cell-Derived Neural Precursors Grafted Spinally in Spinal Ischemia-Injured Rats or in Naive Immunosuppressed Minipigs: A Qualitative and Quantitative Study

In previous studies, we have demonstrated that spinal grafting of human or rat fetal spinal neural precursors leads to amelioration of spasticity and improvement in ambulatory function in rats with spinal ischemic injury. In the current study, we characterize the survival and maturation of three different human embryonic stem (ES) cell line-derived neural precursors (hNPCs) once grafted into ischemia-injured lumbar spinal cord in rats or in naive immunosuppressed minipigs. Proliferating HUES-2, HUES-7, or HUES-9 colonies were induced to form embryoid bodies. During the nestin-positive stage, the rosettes were removed and CD184+/CD271-/CD44-/CD24+ population of ES-hNPCs FAC-sorted and expanded. Male Sprague–Dawley rats with spinal ischemic injury or naive immunosuppressed Gottingen–Minnesota minipigs received 10 bilateral injections of ES-NPCs into the L2–L5 gray matter. After cell grafting, animals survived for 2 weeks to 4.5 months, and the presence of grafted cells was confirmed after staining spinal cord sections with a combination of human-specific (hNUMA, HO14, hNSE, hSYN) or nonspecific (DCX, MAP2, CHAT, GFAP, APC) antibodies. In the majority of grafted animals, hNUMA-positive grafted cells were identified. At 2–4 weeks after grafting, double-labeled hNUMA/ DCX-immunoreactive neurons were seen with extensive DCX+ processes. At survival intervals of 4–8 weeks, hNSE+ neurons and expression of hSYN was identified. Some hSYN-positive terminals formed putative synapses with the host neurons. Quantitative analysis of hNUMA+ cells at 2 months after grafting showed comparable cell survival for all three cell lines. In the presence of low-level immunosuppression, no grafted cell survival was seen at 4.5 months after grafting. Spinal grafting of proliferating pluripotent HUES-7 cells led to consistent teratoma formation at 2–6 weeks after cell transplantation. These data show that ES-derived, FAC-sorted NPCs can represent an effective source of human NPCs to be used in CNS cell replacement therapies.
Design and Fabrication of a High-Power Eyeball-Like Microactuator Using a Symmetric Piezoelectric Pusher Element

A novel multidegree-of-freedom (MDOF) eyeball-like microactuator was developed using a symmetric piezoelectric plate and an Ni-Co alloy micropusher element. A LIGA-like technique was employed to manufacture an Ni-Co alloy micropusher with a Vickers hardness value of 550, which was then attached at the midpoint of the long side of a piezoelectric plate with dual electrodes to construct a symmetric piezoelectric pusher element (SPPE). The research integrated the concept of LEGO bricks, and three different vibration modes of the SPPE were designed to develop a high-power MDOF motion platform, which was able to rotate a spherical charge-coupled device (CCD) along three perpendicular axes. This MDOF eyeball-like microactuator consisted of a stator and a rotor: The stator was created from two mutually orthogonal sets of parallel SPPEs to form an MDOF motion platform, and the rotor was a spherical CCD. The experiment demonstrated high-power MDOF eyeball-like microactuator working frequencies along the X-, Y-, and . Z-axes to be 223.4, 223.2, and 225 kHz and the rotation speeds to reach 50, 52, and 180 r/min, respectively, at a driving voltage of 30 Vpp. The volume ratio of rotor to stator was 20.32, and this design can therefore drive a rotor of a volume greater than ten times that of the stator. In addition, the driving voltage was proportional to the rotation speed; hence, when the rotor diameter was increased or the spherical rotor weight reduced, the rotation speed increased. In the future, this MODF eyeball-like microactuator may be used for a number of applications, such as sun-tracking systems for green-energy harvesters and eyeball-like devices for use in the biomedical field.
cDNA Library Enrichment of Full Length Transcripts for SMRT Long Read Sequencing

The utility of genome assemblies does not only rely on the quality of the assembled genome sequence, but also on the quality of the gene annotations. The Pacific Biosciences Iso-Seq technology is a powerful support for accurate eukaryotic gene model annotation as it allows for direct readout of full-length cDNA sequences without the need for noisy short read-based transcript assembly. We propose the implementation of the TeloPrime Full Length cDNA Amplification kit to the Pacific Biosciences Iso-Seq technology in order to enrich for genuine full-length transcripts in the cDNA libraries. We provide evidence that TeloPrime outperforms the commonly used SMARTer PCR cDNA Synthesis Kit in identifying transcription start and end sites in Arabidopsis thaliana. Furthermore, we show that TeloPrime-based Pacific Biosciences Iso-Seq can be successfully applied to the polyploid genome of bread wheat (Triticum aestivum) not only to efficiently annotate gene models, but also to identify novel transcription sites, gene homeologs, splicing isoforms and previously unidentified gene loci.
Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy.

BACKGROUND Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy and a proposed substrate for arrhythmias and heart failure. In animal models, profibrotic genetic pathways are activated early, before hypertrophic remodeling. Data showing early profibrotic responses to sarcomere-gene mutations in patients with hypertrophic cardiomyopathy are lacking. METHODS We used echocardiography, cardiac magnetic resonance imaging (MRI), and serum biomarkers of collagen metabolism, hemodynamic stress, and myocardial injury to evaluate subjects with hypertrophic cardiomyopathy and a confirmed genotype. RESULTS The study involved 38 subjects with pathogenic sarcomere mutations and overt hypertrophic cardiomyopathy, 39 subjects with mutations but no left ventricular hypertrophy, and 30 controls who did not have mutations. Levels of serum C-terminal propeptide of type I procollagen (PICP) were significantly higher in mutation carriers without left ventricular hypertrophy and in subjects with overt hypertrophic cardiomyopathy than in controls (31% and 69% higher, respectively; P<0.001). The ratio of PICP to C-terminal telopeptide of type I collagen was increased only in subjects with overt hypertrophic cardiomyopathy, suggesting that collagen synthesis exceeds degradation. Cardiac MRI studies showed late gadolinium enhancement, indicating myocardial fibrosis, in 71% of subjects with overt hypertrophic cardiomyopathy but in none of the mutation carriers without left ventricular hypertrophy. CONCLUSIONS Elevated levels of serum PICP indicated increased myocardial collagen synthesis in sarcomere-mutation carriers without overt disease. This profibrotic state preceded the development of left ventricular hypertrophy or fibrosis visible on MRI. (Funded by the National Institutes of Health and others.)
PD‐1 negatively regulates interleukin‐12 expression by limiting STAT‐1 phosphorylation in monocytes/macrophages duringchronic hepatitis C virus infection

Hepatitis C virus (HCV) is remarkably efficient at evading host immunity to establish chronic infection. During chronic HCV infection, interleukin‐12 (IL‐12) produced by monocytes/macrophages (M/Mφ) is significantly suppressed. Programmed death‐1 (PD‐1), an inhibitory receptor on immune cells, plays a pivotal role in suppressing T‐cell responses during chronic viral infection. To determine whether PD‐1 regulates IL‐12 production by M/Mφ during chronic HCV infection, we examined the expressions of PD‐1, its ligand PDL‐1, and their relationship with IL‐12 production in M/Mφ from HCV‐infected, HCV‐resolved, and healthy subjects by flow cytometry. Toll‐like receptor (TLR) ‐mediated IL‐12 production by M/Mφ was selectively suppressed, while PD‐1/PDL‐1 expressions were up‐regulated, in HCV‐infected subjects compared with HCV‐resolved or healthy subjects. Up‐regulation of PD‐1 was inversely associated with the degree of IL‐12 inhibition in HCV infection. Interestingly, the reduced response of M/Mφ from HCV‐infected individuals to TLR ligands appeared not to be the result of a lack of the ability to sense pathogen, but to an impaired activation of intracellular janus kinase/signal transducer and activator of transfection (STAT) pathway as represented by inhibited STAT‐1 phosphorylation in M/Mφ from HCV‐infected individuals compared with HCV‐negative subjects. Successful HCV treatment with pegylated interferon/ribavirin or blocking PD‐1/PDL‐1 engagement ex vivo led to reduced PD‐1 expression and improved IL‐12 production as well as STAT‐1 activation in M/Mφ from HCV‐infected individuals. These results suggest that the PD‐1 inhibitory pathway may negatively regulate IL‐12 expression by limiting STAT‐1 phosphorylation in M/Mφ during chronic HCV infection.
Differential susceptibility of bone marrow‐derived dendritic cells and macrophages to productive infection with Listeria monocytogenes

Dendritic cells (DC) are required for the immune response against Listeria monocytogenes and are permissive for infection in vivo and in vitro. However, it is unclear if DC provide a desirable intracellular niche for bacterial growth. To address this issue, we have compared the behaviour of L. monocytogenes in murine bone marrow‐derived DC and macrophages (BMM). Similar to BMM, bacteria escaped to the cytosol in DC, replicated, and spread to adjacent cells. However, DC infection was less robust in terms of intracellular doubling time and total increase in bacterial numbers. Immunofluorescence analysis using a strain of L. monocytogenes that expresses green fluorescent protein upon bacterial entry into the cytosol suggested that a subpopulation of DC restricted bacteria to vacuoles, a finding that was confirmed by electron microscopy. In unstimulated DC cultures, L. monocytogenes replicated preferentially in phenotypically immature cells. Furthermore, DC that were induced to mature prior to infection were poor hosts for bacterial growth. We conclude that DC provide a suboptimal niche for L. monocytogenes growth, and this is at least in part a function of the DC maturation state. Therefore, the generation of an effective T cell response may be a net effect of both productive and non‐productive infection of DC.
The reasons for Chinese nursing staff to report adverse events: a questionnaire survey

AIMS To investigate the impact of nurses' perception of patient safety culture and adverse event reporting, and demographic factors on adverse event reporting in Chinese hospitals. BACKGROUND Accurate and timely adverse event reporting is integral in promoting patient safety and professional learning around the incident. METHODS In a cross-sectional survey, a sample of 919 nurses completed a structured questionnaire composed of two validated instruments measuring nurses' perception of patient safety culture and adverse event reporting. Associations between the variables were examined using multiple linear regression analysis. RESULTS The positive response rates of five dimensions of the Patient Safety Culture Assessment Scale varied from 47.55% to 80.62%. The accuracy rate of Adverse Event Reporting Perception Scale was 63.16%. Five hundred and thirty-one (58.03%) nurses did not report adverse event in past 12 months. Six variables were found to be associated with nurses' adverse event reporting: total work experience (P = 0.003), overall patient safety culture score (P < 0.001), safety climate (P < 0.001), teamwork climate (P < 0.001), overall the adverse event reporting perception scale score (P = 0.003) and importance or reporting (P = 0.002). CONCLUSIONS The results confirmed that improvements in the patient safety culture and nurses' perception of adverse event reporting were related to an increase in voluntary adverse event reporting. IMPLICATIONS FOR NURSING MANAGEMENT The knowledge of adverse event reporting should be integrated into the patient safety curriculum. Interventions that target a specific domain are necessary to improve the safety culture.
The EU and the Migration Crisis: reinforcing a security based approach to Migration?

This chapter makes this argument that the EU's narrow, security-based, approach does not succeed in developing a comprehensive migration policy, and neither has it addressed the human issues arising from a crisis such as that currently being seen in the Mediterranean, It does so in three parts. It, first of all, considers the longstanding security focus of the EU in relation to migration and the more recent attempt at moving towards a ‘comprehensive’ approach. It then, secondly, critiques this approach through an examination of the EU’s response through utilising crisis management operations under the EU’s Common Security and Defence Policy (CSDP), in particular the EUNAVFOR Med operation. This contribution argues that utilising military means in order to address a humanitarian question is problematic and the expansion of the EUNAVFOR Med operation in terms of its cooperation with the Libyan authorities shows a further focus on security in place of the apparent ‘comprehensive’ approach here. The existing approach shows little prospect of success and is also now giving rise to increased risk to individuals caught up in this crisis; rather than finding their way to safety, these people are finding themselves in equally dangerous situations. The chapter finally considers the continuing problems and the overall prospects for addressing these issues and developing a renewed, truly comprehensive approach.
Assessment of sleep disturbance in lung cancer patients: Relationship between sleep disturbance and pain, fatigue, quality of life, and psychological distress

Abstract Objective: We investigated the prevalence of sleep disturbance and psychological distress in lung cancer patients. We also examined the association between sleep disturbance and psychological distress, pain, fatigue, and quality of life in the same population. Method: Fifty lung cancer patients were evaluated. Sleep disturbance was assessed using the Athens Sleep Insomnia Scale (AIS) and psychological distress using the Hospital Anxiety and Depression Scale (HADS). Quality of life (QOL), pain, and fatigue were assessed employing the European Organization of Research and Treatment Quality of Life Questionnaire–Cancer 30 (EORTC QLQ–C30). Results: We observed that 56% of lung cancer patients had sleep disturbance (AIS score ≥6) and 60% had psychological distress (total HADS score ≥11). Patients with sleep disturbance had a HADS score of 14.6 ± 5.8, a fatigue score of 45.3 ± 22.0, and a pain score of 27.2 ± 26.2. In contrast, patients without sleep disturbance had a lower HADS score of 9.9 ± 8.1 (p < 0.05) and a higher fatigue score of 28.5 ± 18.0 (p < 0.01) and a pain score of 8.7 ± 15.8 (p < 0.01). In addition, we found a lower QOL in patients with sleep disturbance (46.3 ± 20.2) than in those without (65.2 ± 20.7) (p < 0.05). We also observed a significant correlation between the AIS, HADS, fatigue, QOL, and pain scores. Significance of Results: Lung cancer patients suffered from combined symptoms related to sleep. Sleeping pills improved sleep induction but were not sufficient to provide sleep quality and prevent daytime dysfunction. Daytime dysfunction was specifically associated with psychological distress. Additionally, the type of sleep disturbance was related to other patient factors, including whether or not they received chemotherapy.
Comparative studies on the genotoxicity and cytotoxicity of polymeric gene carriers polyethylenimine (PEI) and polyamidoamine (PAMAM) dendrimer in Jurkat T-cells

A safe alternative to the viral system used in gene therapy is a nonviral gene delivery system. Although polyethylenimine (PEI) and polyamidoamine (PAMAM) dendrimer are among the most promising gene-carrier candidates for efficient nonviral gene delivery, safety concerns regarding their toxicity remain. The aim of this study was to scrutinize the underlying mechanism of the cytotoxicity and genotoxicity of PEI (25 kDa) and PAMAM (G4). To our knowledge, this is the first study to explore the genotoxic effect of polymeric gene carriers. To evaluate cell death by PEI and PAMAM, we performed propidium-iodide staining and lactate-dehydrogenase release assays. The genotoxicity of the polymers was measured by comet assay and cytokinesis-block micronucleus assay. PEI- and PAMAM-treated groups induced both necrotic and apoptotic cell death. In the comet assay and micronuclei formation, significant increases in DNA damage were observed in both treatments. We conclude that PEI and PAMAM dendrimer can induce not only a relatively weak apoptotic and a strong necrotic effect, but also a moderate genotoxic effect.
Consumer Confidence and Sectoral Stock Returns in China: Evidence from Multi-Resolutions Wavelet and Granger Coherence Analyses

We empirically examine the dynamic relationship between consumer confidence and sectoral returns at diverse time periods in China using monthly data over the period of 1992-2016. Using Wavelet coherence, we find evidence of sectoral returns leading consumer confidence and the interconnection is robust across medium and long run horizons. However, there is no consistent stability in direction of this linkage. Further, the study investigates the causal connection among variables at various time spans using granger coherence. Empirical findings confirm that sectoral returns as a predictor of consumer confidence thus signaling the projective contents of changes in the consumer confidence. The causal relation is significantly stronger in the long term and is notably dominated by deviating causality sways. The results have useful implications for institutional investors, speculators and portfolio managers.
Calibration function estimation using 3D interpolation for indoor EM (electromagnetic) location finding system

Indoor location finding using electromagnetic field strength measurement is one of the methods being used in different applications in recent years. There are two main problems/ challenges in the direct current electromagnetic (EM) accurate location devices which are used for indoor location. First, the changing of positioning data received is not linear when sensors are moving linearly. Second, the distribution of accuracy varies in different places which leads to large positioning error in some areas. In this paper a 3D surface fitting is explored and a location calibration function is estimated, which built the bridge between EM coordinates and the geometric coordinates for received location data and accuracy is comparable to 1 cm. Experiments and simulation showed that accuracy.
Marshall-Lerner Condition and the Balance of Payments Constrained Growth: The Spanish Case

This paper develops an analytical reformulation of the Marshall-Lerner condition. This reformation of the Marshall-Lerner condition leads us to reformulate both the Thirwalias model and the Krugmanias rule in open economies, under the following terms: in the long run, if the MarshallLerner condition is maintained, the balance of payments constrained growth income not only depends on export and import income elasticities, but also on the cross-elasticity values between exports and imports. The analytical development has a series of implications for empirical studies about the Foreign Sector: export and import functions must be estimated considering the possibility of high cross correlations between them in the modelled countries. In the case of Spain, the longterm estimations of the price elasticities of exports and imports, and the respective cross elasticities, lead us to conclude that currency devaluation would, in the long term, improve the balance of trade and increase the constrained growth income in relation with the strong version of Thirwallias law.