Miracle-dz/UniFAR-FTUs huggingface dataset:
Translocation of YopE and YopN into eukaryotic cells by Yersinia pestis yopN, tyeA, sycN, yscB and lcrG deletion mutants measured using a phosphorylatable peptide tag and phosphospecific antibodies

Yersinia pestis , the causative agent of plague, exports a set of virulence proteins called Yops upon contact with eukaryotic cells. A subset of these Yops is translocated directly into the cytosol of host cells. In this study, a novel protein tag‐based reporter system is used to measure the translocation of Yops into cultured eukaryotic cells. The reporter system uses a small bipartite phosphorylatable peptide tag, termed the Elk tag. Translocation of an Elk‐tagged protein into eukaryotic cells results in host cell protein kinase‐dependent phosphorylation of the tag at a specific serine residue, which can subsequently be detected with phosphospecific antibodies. The YopN, TyeA, SycN, YscB and LcrG proteins function to prevent Yop secretion before host cell contact. The role of these proteins was investigated in the translocation of Elk‐tagged YopE (YopE 129 –Elk) and YopN (YopN 293 –Elk) into HeLa cells. Y. pestis yopN , tyeA , sycN and yscB deletion mutants showed reduced levels of YopE 129 –Elk phosphorylation compared with the parent strain, indicating that these mutants translocate reduced amounts of YopE. We also demonstrate that YopN 293 –Elk is translocated into HeLa cells and that this process is more efficient in a Yersinia yop polymutant strain lacking the six translocated effector Yops. Y. pestis sycN and yscB mutants translocated reduced amounts of YopN 293 –Elk; however, tyeA and lcrG mutants translocated higher amounts of YopN 293 –Elk compared with the parent strain. These data suggest that TyeA and LcrG function to suppress the secretion of YopN before host cell contact, whereas SycN and YscB facilitate YopN secretion and subsequent translocation.
Validation of the Alfentanil Canonical Univariate Parameter as a Measure of Opioid Effect on the Electroencephalogram

Background Several parameters derived from the multivariate electroencephalographic (EEG) signal have been used to characterize the effects of opioids on the central nervous system. These parameters were formulated on an empirical basis. A new statistical method, semilinear canonical correlation, has been used to construct a new EEG parameter (a certain combination of the powers in the EEG power spectrum) that correlates maximally with the concentration of alfentanil at the effect site. To date, this new canonical univariate parameter (CUP) has been tested only in a small sample of subjects receiving alfentanil.
Expression of the enhancer of zeste homolog 2 is correlated with poor prognosis in human gastric cancer

Overexpression of the enhancer of zeste homolog 2 (EZH2) protein, a known repressor of gene transcription, has been reported to be associated with biological malignancy of prostate cancer and several other cancers. The purpose of this study was to examine the expression of EZH2 and analyze its relationship with the clinicopathological features of human gastric cancers. Expression levels of EZH2 mRNA and protein were examined in 13 gastric cancer cell lines and in 83 surgically removed human gastric cancer tissues. Immunohistochemical analysis of the 83 tissue samples and corresponding non‐cancerous gastric mucosa showed that EZH2 was more highly expressed in the cancerous than in the non‐cancerous tissues, and the expression levels of EZH2 were highly correlated with tumor size, depth of invasion, vessel invasion, lymph node metastasis and clinical stages. Univariate analysis of survival rate calculated by the Kaplan‐Meier method revealed that gastric cancer patients with high‐level EZH2 expression had poorer prognosis than those expressing no or low levels of EZH2 (P = 0.0271). These findings suggest that overexpression of EZH2 may contribute to the progression and oncogenesis of human gastric cancers, and thus immunohistochemical study of EZH2 expression may serve as a new biomarker for predicting the prognosis of gastric cancers. (Cancer Sci 2006; 97: 484 – 491)
Role of heparan sulfate proteoglycans in optic disc and stalk morphogenesis

Background: Heparan sulfate proteoglycans (HSPG) are important for embryonic development by means of the regulation of gradient formation and signaling of multiple growth factors and morphogens. Previous studies have shown that Bmp/Shh/Fgf signaling are required for the regionalization of the optic vesicle (OV) and for the closure of the optic fissure (OF), the disturbance of which underlie ocular anomalies such as microphthalmia, coloboma, and optic nerve hypoplasia. Results:To study HSPG‐dependent coordination of these signaling pathways during mammalian visual system development, we have generated a series of OV‐specific mutations in the heparan sulfate (HS) N‐sulfotransferase genes (Ndst1 and Ndst2) and HS O‐sulfotransferase genes (Hs2st, Hs6st1, and Hs6st2) in mice. Of interest, the resulting HS undersulfation still allowed for normal retinal neurogenesis and optic fissure closure, but led to defective optic disc and stalk development. The adult mutant animals further developed optic nerve aplasia/hypoplasia and displayed retinal degeneration. We observed that MAPK/ERK signaling was down‐regulated in Ndst mutants, and consistent with this, HS‐related optic nerve morphogenesis defects in mutant mice could partially be rescued by constitutive Kras activation. Conclusions: These results suggest that HSPGs, depending on their HS sulfation pattern, regulate multiple signaling pathways in optic disc and stalk morphogenesis. Developmental Dynamics 243:1310–1316, 2014. © 2014 Wiley Periodicals, Inc.
Diagnostic and prognostic significance of serum MicroRNAs in colorectal cancer

MicroRNAs are short non‐coding RNA molecules involved in the regulation of gene expression. There are few studies related to the determination of serum microRNAs in colorectal cancer. The identification of microRNAs in peripheral blood as noninvasive markers of tumor disease may lead to potential applications, although further clinical studies focusing on serum microRNAs are required to determine their clinical significance for the diagnosis and prognosis outcome of colorectal cancer. J. Surg. Oncol. 2013;107:217–220. © 2012 Wiley Periodicals, Inc.
Epilepsy-Associated KCNQ2 Channels Regulate Multiple Intrinsic Properties of Layer 2/3 Pyramidal Neurons

KCNQ2 potassium channels are critical for normal brain function, as both loss-of-function and gain-of-function KCNQ2 variants can lead to various forms of neonatal epilepsy. Despite recent progress, the full spectrum of consequences as a result of KCNQ2 dysfunction in neocortical pyramidal neurons is still unknown. Here, we report that conditional ablation of Kcnq2 from mouse neocortex leads to hyperexcitability of layer 2/3 (L2/3) pyramidal neurons, exhibiting an increased input resistance and action potential frequency, as well as a reduced medium afterhyperpolarization (mAHP), a conductance partly mediated by KCNQ2 channels. Importantly, we show that introducing the KCNQ2 loss-of-function variant KCNQ2I205V into L2/3 pyramidal neurons using in utero electroporation also results in a hyperexcitable phenotype similar to the conditional knock-out. KCNQ2I205V has a right-shifted conductance-to-voltage relationship, suggesting loss of KCNQ2 channel activity at subthreshold membrane potentials is sufficient to drive large changes in L2/3 pyramidal neuronal excitability even in the presence of an intact mAHP. We also found that the changes in excitability following Kcnq2 ablation are accompanied by alterations at action potential properties, including action potential amplitude in Kcnq2-null neurons. Importantly, partial inhibition of Nav1.6 channels was sufficient to counteract the hyperexcitability of Kcnq2-null neurons. Therefore, our work shows that loss of KCNQ2 channels alters the intrinsic neuronal excitability and action potential properties of L2/3 pyramidal neurons, and identifies Nav1.6 as a new potential molecular target to reduce excitability in patients with KCNQ2 encephalopathy. SIGNIFICANCE STATEMENT KCNQ2 channels are critical for the development of normal brain function, as KCNQ2 variants could lead to epileptic encephalopathy. However, the role of KCNQ2 channels in regulating the properties of neocortical neurons is largely unexplored. Here, we find that Kcnq2 ablation or loss-of-function at subthreshold membrane potentials leads to increased neuronal excitability of neocortical layer 2/3 (L2/3) pyramidal neurons. We also demonstrate that Kcnq2 ablation unexpectedly leads to a larger action potential amplitude. Importantly, we propose the Nav1.6 channel as a new molecular target for patients with KCNQ2 encephalopathy, as partial inhibition of these channels counteracts the increased L2/3 pyramidal neuron hyperexcitability of Kcnq2-null neurons.
Use of the Dermatology Life Quality Index (DLQI) in a midwestern US urban clinic.

BACKGROUND The Dermatology Life Quality Index (DLQI), a self-administered general dermatology quality of life instrument, was originally developed and published in a dermatology clinic at University Hospital of Wales. OBJECTIVE Our goal was to test the feasibility of having patients answer the DLQI in a busy dermatology clinic and to find out to what extent results vary from those published in Wales. We also wanted to examine the validity of the index in terms of the correlation between DLQI scores and stage of illness (disease severity). METHODS We administered the DLQI to 200 consecutive patients who were seen in a dermatology clinic at Indiana University Medical Center. Results were examined in light of results found by those who originated the DLQI. A pilot group of patients were given the DLQI and rated for severity of disease by means of the Dermatology Index of Disease Severity (DIDS). RESULTS Overall, the DLQI is easy to administer and can be completed within 3 minutes. The scores in our study were compatible with those previously reported by the DLQI originators. There was a "ceiling" effect in that 11% of the patients indicated no quality of life impairment on the DLQI rating. This index shows stratification with severity of disease. CONCLUSION The DLQI is an easy and efficient instrument for assessing quality of life in dermatology patients. Patients needed minimal assistance with the form. Our results were similar to those of the DLQI originators, and this further shows reliability and validity of the DLQI. In addition, this study further supports the use of DLQI as a quality of life instrument suitable for use in international studies.
Invited commentary: assessing latex sensitization using data from NHANES III.

Received for publication July 3, 2000, and accepted for publication August 15, 2000. Abbreviations: IgE, immunoglobulin E; NHANES III, Third National Health and Nutrition Examination Survey. 1 Environmental and Occupational Health Sciences Institute, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ. 2 Environmental and Occupational Health Sciences Institute, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ. Reprint requests to Dr. Daniel Wartenberg, Environmental and Occupational Health Sciences Institute, 170 Frelinghuysen Road, Piscataway, NJ 08854 (e-mail: dew@eohsi.rutgers.edu). Natural latex rubber is a substance commonly used for making gloves to protect health care workers from infections and other hazards. While gloves mediate one extremely high risk by creating a barrier between health care workers and infectious agents, some argue that the occurrence of sensitization and allergic response from the use of these gloves has created an important occupational health concern (1). Consequences of this sensitization and allergic response, in addition to the direct health risks, include job reassignment and disability and may result in compensation claims. It is from this context that Garabrant et al. (2), in their article in this issue of the Journal, assess whether latex sensitization (or allergic response) is more common among health care workers than among the general population by using the National Health and Nutrition Examination Survey (NHANES III) data (3). Specifically, they question whether or not this sensitization likely comes from latex glove use. In this commentary, we address two issues. First, methodologically, we briefly discuss the usefulness of large, publicly available databases for clarifying known public health concerns. Second, specific to their study, we evaluate whether Garabrant et al. provide useful and convincing evidence on the status of the latex issue.
Oral ingestion of silver nanoparticles induces genomic instability and DNA damage in multiple tissues

Abstract Silver nanoparticles (AgNPs) are widely used in consumer and medical products. However, most AgNP toxicity data are based on in vitro studies. Only a few studies were performed in mammals and no studies systematically assessed cancer risk of AgNPs. In this study, we examined whether oral exposure to polyvinylpyrrolidone (PVP)-coated AgNPs induces DNA damage and permanent genome alterations, and modulates DNA repair gene expression in vivo in mice. We found that AgNPs induced large DNA deletions in developing embryos, irreversible chromosomal damage in bone marrow, and double strand breaks and oxidative DNA damage in peripheral blood and/or bone marrow. DNA Repair RT Profiler PCR Array showed that AgNPs altered expression of 36 of the 84 genes from which 24 genes were downregulated and 12 genes were upregulated. In particular, AgNPs downregulated a significant proportion of base excision repair (BER) genes. We hypothesized that downregulation of BER by AgNPs contributes to oxidative DNA damage and subsequent genomic instability, which predicts that BER defects enhance sensitivity to AgNPs. We tested this hypothesis in mice deficient in MutY homologue (Myh). Myh excises adenine mispaired with 8-oxoguanine to counteract its promutagenic activity and also has a role in cell cycle check points and apoptosis. MYH mutations are common in humans and predispose to colorectal and other types of cancer. Myh deficient mice were hypersensitive to AgNP-induced chromosomal damage. In summary, oral ingestion of AgNPs induces permanent genome alterations and may therefore cause cancer. In addition, BER defects, especially, Myh mutations, enhance sensitivity to AgNPs.
Early endothelial progenitor cells in bone marrow are a biomarker of cell therapy success in patients with critical limb ischemia.

BACKGROUND AIMS Endothelial progenitor cells (EPC) have been proposed for autologous angiogenic therapy. The objectives of this study were to quantify EPC in the peripheral blood and bone marrow mononuclear cells (BM-MNC) of patients with critical limb ischemia that had received BM-MNC as a cell therapy product, and to study the putative relationship between the presence of EPC and the process of neovascularization in toe or transmetatarsal amputation specimens. METHODS Early and late endothelial progenitor cells (CFU-EC and ECFC) were cultivated and quantified according to published methods in peripheral blood and BM-MNC from patients with critical limb ischemia (CLI; n = 11) enrolled in the OPTIPEC trial ( http://clinicaltrials.gov/ct2/show/NCT00377897 ) to receive BM-MNC as a cell therapy product. RESULTS Eight out of the 11 patients had undergone amputations. Three of the patients displayed a neoangiogenic process that was associated with a higher number of CFU-EC in BM-MNC, while CD3+ , CFU-GM and CD34+ in BM-MNC, and EPC in peripheral blood, did not correlate with the appearance of newly formed vessels. As expected, circulating CFU-EC and ECFC counts were significantly lower in CLI patients compared with age-matched controls. CONCLUSIONS In patients with critical limb ischemia, EPC in peripheral blood were decreased compared with healthy individuals. However, in BM-MNC we found that relative numbers of CFU-EC could be used as an indicator to discriminate patients with neoangiogenic processes. These results need to be confirmed in a randomized study.
Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon

In HCV‐infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)‐based or IFN‐free regimens on HCC recurrence remain unclear.
EGFR through STAT3 modulates ΔN63α expression to sustain tumor‐initiating cell proliferation in squamous cell carcinomas

Many squamous cell carcinomas (SCCs) are characterized by high levels of EGFR and by overexpression of the ΔNp63α isoform. Here, we investigated the regulation of ΔNp63α expression upon EGFR activation and the role of the EGFR–ΔNp63α axis in proliferation of SCC tumor‐initiating cells (TICs). SCC cell lines A‐431, Cal‐27, and SCC‐25 treated with EGF showed a time‐dependent increase in ΔNp63α expression at the protein and mRNA levels, which was blocked by the tyrosine kinase inhibitor (TKI) Lapatinib. RNA interference experiments suggested the role of STAT3 in regulating ΔNp63α expression downstream of EGFR. Inactivation of EGFR by the monoclonal antibody Cetuximab and RNA interference against STAT3 or ΔNp63α impaired the TICs ability to grow under non‐differentiating conditions. Radiation treatment, which triggers EGFR activation, induced ΔNp63α accumulation without affecting TICs proliferation, whereas the combination Cetuximab plus radiation significantly reduced TICs growth under non‐differentiating conditions. Together, our findings provide evidence that ΔNp63α expression is regulated by EGFR activation through STAT3 and that the EGFR–ΔNp63α axis is crucial for proliferation of TICs present in SCCs. J. Cell. Physiol. 228: 871–878, 2013. © 2012 Wiley Periodicals, Inc.
Broad Learning System: An Effective and Efficient Incremental Learning System Without the Need for Deep Architecture

Broad Learning System (BLS) that aims to offer an alternative way of learning in deep structure is proposed in this paper. Deep structure and learning suffer from a time-consuming training process because of a large number of connecting parameters in filters and layers. Moreover, it encounters a complete retraining process if the structure is not sufficient to model the system. The BLS is established in the form of a flat network, where the original inputs are transferred and placed as “mapped features” in feature nodes and the structure is expanded in wide sense in the “enhancement nodes. ” The incremental learning algorithms are developed for fast remodeling in broad expansion without a retraining process if the network deems to be expanded. Two incremental learning algorithms are given for both the increment of the feature nodes (or filters in deep structure) and the increment of the enhancement nodes. The designed model and algorithms are very versatile for selecting a model rapidly. In addition, another incremental learning is developed for a system that has been modeled encounters a new incoming input. Specifically, the system can be remodeled in an incremental way without the entire retraining from the beginning. Satisfactory result for model reduction using singular value decomposition is conducted to simplify the final structure. Compared with existing deep neural networks, experimental results on the Modified National Institute of Standards and Technology database and NYU NORB object recognition dataset benchmark data demonstrate the effectiveness of the proposed BLS.
The role of lipolysis in human orosensory fat perception

Taste perception elicited by food constituents and facilitated by sensory cells in the oral cavity is important for the survival of organisms. In addition to the five basic taste modalities, sweet, umami, bitter, sour, and salty, orosensory perception of stimuli such as fat constituents is intensely investigated. Experiments in rodents and humans suggest that free fatty acids represent a major stimulus for the perception of fat-containing food. However, the lipid fraction of foods mainly consists of triglycerides in which fatty acids are esterified with glycerol. Whereas effective lipolysis by secreted lipases (LIPs) liberating fatty acids from triglycerides in the rodent oral cavity is well established, a similar mechanism in humans is disputed. By psychophysical analyses of humans, we demonstrate responses upon stimulation with triglycerides which are attenuated by concomitant LIP inhibitor administration. Moreover, lipolytic activities detected in minor salivary gland secretions directly supplying gustatory papillae were correlated to individual sensitivities for triglycerides, suggesting that differential LIP levels may contribute to variant fat perception. Intriguingly, we found that the LIPF gene coding for lingual/gastric LIP is not expressed in human lingual tissue. Instead, we identified the expression of other LIPs, which may compensate for the absence of LIPF.
The use of molecular assays to establish definitively the clonality of ipsilateral breast tumor recurrences and patterns of in‐breast failure in patients with early‐stage breast cancer treated with breast‐conserving therapy

Results from numerous trials have indicated that breast‐conserving therapy (BCT) produces outcomes equivalent to those produced by mastectomy in terms of both locoregional control and survival. However, conservative treatment has resulted in the dilemma of how best to address recurrences when they appear in a breast treated previously with radiation therapy. Attempts have been made to characterize ipsilateral breast tumor recurrences (IBTRs) as either true recurrences of the treated malignancy or new primary carcinomas, because cancers that represent new primary tumors may be associated with a more favorable prognosis compared with cancers that represent true recurrences.
Nurr1 in Parkinson's disease and related disorders

In mammals, the transcription factor Nurr1 is expressed early in development and continues to be detectable throughout the organism's lifetime. Nurr1 is involved in the establishment and maintenance of the dopaminergic phenotype within specific central nervous system neuronal subpopulations including the nigrostriatal dopamine system. This protein is reduced over the course of normal aging, which is a major risk factor for Parkinson's disease (PD). However, whether Nurr1 expression is affected by PD has not been documented. The present study examined the role of Nurr1 in the maintenance of the dopaminergic phenotype within neurons in substantia nigra in PD compared with patients with diagnoses of progressive supranuclear palsy (PSP) or Alzheimer's disease (AD) or age‐matched‐matched controls. In PD, the optical density (OD) of Nurr1 immunofluorescence was significantly decreased in nigral neurons containing α‐synuclein‐immunoreactive inclusions. Similarly, the OD of Nurr1 immunofluorescence intensity in the nigra of AD cases was decreased in neurons with neurofibrillary tangles (NFTs). In contrast to PD and AD, the OD of Nurr1 immunofluorescence intensity was severely decreased in the neurons with or without NFTs in PSP cases. Decline of Nurr1‐ir neuronal number and OD was observed within substantia nigra (SN) neurons in PD but not within hippocampal neurons. The decline in Nurr1‐ir expression was correlated with loss of tyrosine hydroxylase immunofluorescence across the four groups. These data demonstrate that Nurr1 deficiency in dopaminergic neurons is associated with the intracellular pathology in both synucleinopathies and tauopathies. J. Comp. Neurol. 494:495–514, 2006. © 2005 Wiley‐Liss, Inc.