Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of an extracellular 130-kDa protein involved in early cardiac morphogenesis.

Previous studies indicate that the transformation of cardiac endothelium into mesenchyme is dependent upon a developmentally regulated signal expressed by its associated myocardium. This process can be mimicked in culture by substituting a non-cytolytic EDTA extract of embryonic heart tissue for the presence of myocardium. Polyclonal antibodies (ES1) generated against the EDTA-extractable proteins both localized to the cardiac extracellular matrix preceding the transformation of endothelium and blocked this process in culture. Based on these observations, we hypothesized that ES1 antigens participate in the formation of cardiac mesenchyme. The present study was undertaken to prepare cDNA and antibody probes for individual ES1 antigens to better characterize their involvement in this important morphogenetic event. An expression library was constructed in Uni-ZAP using poly(A+) RNA from embryonic cardiocyte cultures that had been shown previously to secrete proteins that engender the formation of cardiac mesenchyme. Screening of this expression library with ES1 antibodies resulted in several clones, one of which ("ES1-2.1a") is described in this report. ES1-2.1a has a 2.6-kilobase pair insert, the sequence of which exhibits no apparent homology to those in data banks. A fragment (852 base pairs) from the 5' region of ES1-2.1a cDNA was subcloned into the expression vector pGEX-2T, and a 20-kDa fragment of the resulting protein used to prepare affinity-purified antibodies. Immunoblotting detected a 130-kDa protein ("ES/130") in two preparations that elicit mesenchyme formation, i.e. EDTA extracts of embryonic hearts and conditioned medium of cardiocyte cultures. Functional studies showed that antibodies to ES/130 inhibited the epithelial-mesenchymal transformation of cardiac endothelium in culture. Immunohistochemistry of cardiocyte cultures localized ES/130 protein to the vacuolar system and secretory granules. By polymerase chain reaction analysis, the message for ES/130 was detected in the developing heart just prior to and during mesenchyme formation. These results are consistent with ES/130 being involved at a critical step in the initiation of the epithelial-mesenchymal transformation of cardiac endothelium.
Human Aflatoxin Albumin Adducts Quantitatively Compared by ELISA, HPLC with Fluorescence Detection, and HPLC with Isotope Dilution Mass Spectrometry

Essential to the conduct of epidemiologic studies examining aflatoxin exposure and the risk of heptocellular carcinoma, impaired growth, and acute toxicity has been the development of quantitative biomarkers of exposure to aflatoxins, particularly aflatoxin B1. In this study, identical serum sample sets were analyzed for aflatoxin-albumin adducts by ELISA, high-performance liquid chromatography (HPLC) with fluorescence detection (HPLC-f), and HPLC with isotope dilution mass spectrometry (IDMS). The human samples analyzed were from an acute aflatoxicosis outbreak in Kenya in 2004 (n = 102) and the measured values ranged from 0.018 to 67.0, nondetectable to 13.6, and 0.002 to 17.7 ng/mg albumin for the respective methods. The Deming regression slopes for the HPLC-f and ELISA concentrations as a function of the IDMS concentrations were 0.71 (r2 = 0.95) and 3.3 (r2 = 0.96), respectively. When the samples were classified as cases or controls, based on clinical diagnosis, all methods were predictive of outcome (P < 0.01). Further, to evaluate assay precision, duplicate samples were prepared at three levels by dilution of an exposed human sample and were analyzed on three separate days. Excluding one assay value by ELISA and one assay by HPLC-f, the overall relative SD were 8.7%, 10.5%, and 9.4% for IDMS, HPLC-f, and ELISA, respectively. IDMS was the most sensitive technique and HPLC-f was the least sensitive method. Overall, this study shows an excellent correlation between three independent methodologies conducted in different laboratories and supports the validation of these technologies for assessment of human exposure to this environmental toxin and carcinogen. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1653–7)
An Initiation Zone of Chromosomal DNA Replication at the Chicken Lysozyme Gene Locus*

The chicken lysozyme gene domain is distinguished by a broad knowledge of how its expression is regulated. Here, we examined the in vivo replication of the lysozyme gene locus using polymerase chain reaction amplification and competitive polymerase chain reaction of size-fractionated, nascent DNA strands. We found that DNA replication initiates at multiple sites within a broad initiation zone spanning at least 20 kilobases, which includes most of the lysozyme gene domain. The 5′ border of this zone is probably located downstream of the lysozyme 5′ nuclear matrix attachment region. Preferred initiation occurs in a 3′-located subzone. The initiation zone at the lysozyme gene locus is also active in nonexpressing liver DU249 cells. Furthermore, examining the timing of DNA replication at the lysozyme gene locus revealed that the gene locus replicates early during S phase in both HD11 and DU249 cells, irrespective of its transcriptional activity.
Comparative study between synthetic and phospholipids of natural origin: effect of phospholipid selection on the behavior of a topical liposomal dosage form incorporating terbinafine

Abstract Selection of excipients used is a critical step in the design of a pharmaceutical dosage form as it affects its behavior upon application, as during storage. The purpose of the present study is to evaluate and compare the behavior of six liposomal formulations intended for topical application composed of two widely used phospholipids 1,2-diacyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine with and without incorporation of cholesterol. Liposomal hydrogels made of hydroxyethylcellulose 3% and incorporating the anti-fungal agent terbinafine hydrochloride (E)-N-(6,6-dimethyl-2-hepten-4-inyl)-N-methyl-1-naphthalene-methanamine (-hydrochloride) were prepared, their viscosity was measured and in vitro drug release was studied. Moreover, physical stability and drug retention during storage at two different temperatures (2–8 °C and RT) were examined over time. The results showed differences in the behavior between the two phospholipids while incorporation of cholesterol at the studied concentrations was found to be of minor importance. Drug release was found to be favorable from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomal hydrogels and drug retention was found to be higher at lower storage temperature for all batches. Original physicochemical properties of all batches were found to be retained at least for a week.
Tumor-Associated Embryonic Antigen-Expressing Vaccines that Target CCR6 Elicit Potent CD8+ T Cell-Mediated Protective and Therapeutic Antitumor Immunity1

Despite its potency, the wider use of immunotherapy for B cell malignancies is hampered by the lack of well-defined tumor-specific Ags. In this study, we demonstrate that an evolutionarily conserved 37-kDa immature laminin receptor protein (OFA-iLRP), a nonimmunogenic embryonic Ag expressed by a variety of tumors, is rendered immunogenic if targeted to the APCs using the CCR6 ligands MIP3α/CCL20 and mDF2β. The CCR6 targeting facilitated efficient Ag cross-presentation and induction of tumor-neutralizing CTLs. Although the Ag targeting alone, without activation of dendritic cells (DCs), is proposed to induce tolerance, and MIP3α does not directly activate DCs, the MIP3α-based vaccine efficiently induced protective and therapeutic antitumor responses. The responses were as strong as those elicited by the OFA-iLRP fusions with moieties that activated DCs and Th1-type cytokine responses, mDF2β, or mycobacterial Hsp70 Ag. Although the same cDNA encodes the dimerized high-affinity mature 67-kDa mLRP that is expressed in normal tissues to stabilize the binding of laminin to cell surface integrins, the vaccines expressing OFA-iLRP elicited long-term protective CD8+ T cell-mediated memory responses against syngeneic B cell lymphoma, indicating the potential application of these simple vaccines as preventive and therapeutic formulations for human use.
HIV-1 Nef-associated Factor 1 Enhances Viral Production by Interacting with CRM1 to Promote Nuclear Export of Unspliced HIV-1 gag mRNA*

HIV-1 depends on host-cell-encoded factors to complete its life cycle. A comprehensive understanding of how HIV-1 manipulates host machineries during viral infection can facilitate the identification of host targets for antiviral drugs or gene therapy. The cellular protein Naf1 (HIV-1 Nef-associated factor 1) is a CRM1-dependent nucleo-cytoplasmic shuttling protein, and has been identified to regulate multiple receptor-mediated signal pathways in inflammation. The cytoplasm-located Naf1 can inhibit NF-κB activation through binding to A20, and the loss of Naf1 controlled NF-κB activation is associated with multiple autoimmune diseases. However, the effect of Naf1 on HIV-1 mRNA expression has not been characterized. In this study we found that the nucleus-located Naf1 could promote nuclear export of unspliced HIV-1 gag mRNA. We demonstrated that the association between Naf1 and CRM1 was required for this function as the inhibition or knockdown of CRM1 expression significantly impaired Naf1-promoted HIV-1 production. The mutation of Naf1 nuclear export signals (NESs) that account for CRM1 recruitment for nuclear export decreased Naf1 function. Additionally, the mutation of the nuclear localization signal (NLS) of Naf1 diminished its ability to promote HIV-1 production, demonstrating that the shuttling property of Naf1 is required for this function. Our results reveal a novel role of Naf1 in enhancing HIV-1 production, and provide a potential therapeutic target for controlling HIV-1 infection.
Postconcussional Disorder Following Mild to Moderate Traumatic Brain Injury: Anxiety, Depression, and Social Support as Risk Factors and Comorbidities

Previous studies of postconcussional disorder (PCD) have utilized a dimensional approach (i.e., number and/or severity ratings of symptoms) to study postconcussional symptoms. This study used a syndromal approach (modified form of the DSM-IV criteria) for investigating risk factors for developing PCD, 3-months postinjury. The head trauma requirement was waived in order to determine specificity of symptoms to traumatic brain injury. Preliminary results from this ongoing study indicated significant risk factors including female gender, poor social support, and elevated self-reported depressive symptoms at 1-month postinjury. Comorbidities included concurrent diagnosis of major depressive disorder and/or posttraumatic stress disorder. Hispanics were significantly less likely to develop PCD than other racial/ethnic groups. PCD resulted more frequently from motor vehicle accidents and assaults. Screening tests for PCD risk factors/comorbidities performed shortly after injury (i.e., during routine follow-up clinic appointments) coupled with appropriate referrals for psychoeducational interventions and support groups may avoid prolonged loss of productivity and poor perceived quality of life in these patients.
Lipid‐lowering therapy in patients with type 2 diabetes: the case for early intervention

Chronic complications of type 2 diabetes, in particular, macrovascular complications, confer substantial morbidity and mortality and adversely affect a patient's quality of life. Early intensive intervention to control cardiovascular risk factors is essential in clinical management. Atherogenic dyslipidaemia characterized by elevated triglycerides, a low level of high‐density lipoprotein cholesterol (HDL‐C), and an increase in the preponderance of small, dense low‐density lipoprotein (LDL) particles, is a key modifiable risk factor for macrovascular diabetic complications. Lowering low‐density lipoprotein cholesterol (LDL‐C) with a statin (or the combination of statin and ezetimibe) is the main focus for reducing cardiovascular risk in patients with diabetes. However, statins fail to address the residual cardiovascular risk associated with low HDL‐C. Fibrates are effective against all components of the atherogenic dyslipidaemia associated with type 2 diabetes. Secondary analyses of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study suggest a role for early treatment with fenofibrate in improving cardiovascular risk reduction in type 2 diabetes and provide safety data supporting the use of fenofibrate in combination with a statin. Data from the FIELD study suggest that fenofibrate may also have potential to impact on microvascular diabetic complications associated with type 2 diabetes. Data are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study to evaluate the outcome benefits of combining fenofibrate with a statin in patients with type 2 diabetes. Finally, in view of divergent study results and outstanding data, assessment of the risk of the individual with type 2 diabetes is mandatory to assist clinical decision‐making when initiating lipid therapy. Copyright © 2008 John Wiley & Sons, Ltd.
Neutrophil-Gelatinase-Associated Lipocalin and Renal Function after Percutaneous Coronary Interventions

Background/Aims: The value of neutrophil-gelatinase-associated lipocalin (NGAL), a novel biomarker in the detection of acute renal failure in children after cardiac surgery, has been highlighted in previous studies. The incidence of percutaneous coronary intervention (PCI) increases, which may possibly result in increased incidences of contrast nephropathy, its potentially serious complication. Therefore, the aim of our study was to assess prospectively NGAL in patients undergoing elective PCI in relation to serum creatinine. Methods: NGAL was assessed in the serum and urine using commercially available kits. Results: We measured urinary and serum NGAL before, and 2, 4, 12, 24 and 48 h after PCI. We found a significant rise in serum NGAL 2 and 4 h after PCI, and a rise in urinary NGAL 4 and 12 h after PCI. Before PCI, serum NGAL was significantly associated with serum creatinine, urea, urinary NGAL, hemoglobin, hematocrit, albumin, age and presence of diabetes. In multivariate analysis, serum creatinine was the only predictor of serum NGAL. Serum NGAL 2 h after PCI correlated with serum creatinine, duration of PCI, HbA1c, hematocrit, hemoglobin and urinary NGAL. In multivariate analysis, the only predictors of serum NGAL 2 h after PCI were serum creatinine, time of PCI and HbA1c. Serum NGAL before PCI was significantly higher in diabetics than in non-diabetics. Conclusions: NGAL may represent a sensitive early biomarker of renal impairment after PCI. Serum creatinine, duration of PCI, but not type and amount of contrast agent, and appropriate treatment of diabetes, reflected by HbA1c, predict a rise in serum NGAL and kidney function following PCI.
Runright: real-time visual and audio feedback on running

RunRight is a system that gives two different kinds of feedback for runners. First, it creates a visualization of the running movement based on acceleration in vertical and horizontal direction. Second it gives audio feedback on the rhythm. These two types of feedback are valuable when exploring how to design technology that supports athletes in learning how a desired movement should feel.
Intussusception: Jordan University Hospital experience.

BACKGROUND/AIMS The aim of this study was to retrospectively review all children who presented with intussusception over a 24-year period. METHODOLOGY The medical records of children who presented with intussusception from July 1979 through July 2003 at Jordan University Hospital were reviewed. RESULTS One hundred and nine children (74 male, 35 female) presented with intussusception. Their mean age was 16.3 months (range 2 months-14 years). The presenting symptoms were: vomiting (92%), abdominal colic/pain (80%) rectal bleeding (78%), and abdominal mass (65%). Ninety-six cases were ileocolic intussusception (idiopathic type). Eleven patients had small bowel intussusception. Laparotomy was required in 86 cases, manual reduction being successful in 59 (56%); 20 (18%) had bowel resection; 2 had resection of Meckel's diverticulum; and 5 patients underwent Ladd procedure for associated malrotation. CONCLUSIONS Idiopathic intussusception commonly presenting as an ileocolic type constituted the majority of the cases in the present study, occurring in 96 patients (89.7%). The clinical features were classical, vomiting being the most common. The average interval between the onset of symptoms and presentation to the hospital was 46 hours and barium enema reduction was successful in 20 out of 48 cases in which it was attempted. Surgical intervention was required in 86 cases (81%); of which manual reduction was successful in 59 cases, resection was required in 22 cases and 5 patients required an additional Ladd procedure for associated malrotation.
Diagnosis of myalgic encephalomyelitis: where are we now?

INTRODUCTION The World Health Organization has classified myalgic encephalomyelitis (ME) as a neurological disease since 1969 considering chronic fatigue syndrome (CFS) as a synonym used interchangeably for ME since 1969. ME and CFS are considered to be neuro-immune disorders, characterized by specific symptom profiles and a neuro-immune pathophysiology. However, there is controversy as to which criteria should be used to classify patients with "chronic fatigue syndrome. " AREAS COVERED The Centers for Disease Control and Prevention (CDC) criteria consider chronic fatigue (CF) to be distinctive for CFS, whereas the International Consensus Criteria (ICC) stresses the presence of post-exertion malaise (PEM) as the hallmark feature of ME. These case definitions have not been subjected to rigorous external validation methods, for example, pattern recognition analyses, instead being based on clinical insights and consensus. EXPERT OPINION Pattern recognition methods showed the existence of three qualitatively different categories: (a) CF, where CF evident, but not satisfying full CDC syndrome criteria. (b) CFS, satisfying CDC criteria but without PEM. (c) ME, where PEM is evident in CFS. Future research on this "chronic fatigue spectrum" should, therefore, use the above-mentioned validated categories and novel tailored algorithms to classify patients into ME, CFS, or CF.
Expression of membrane-bound carbonic anhydrase isozyme XII in mouse and rat tissues

Background and aims: Carbonic anhydrase XII (CA XII) is a membrane-bound isozyme expressed in some normal human tissues, upregulated in some cancers, and is showed to be a hypoxia-inducible gene product. The expression of CA XII mRNA has been demonstrated in mouse kidney. This study concentrated on the research of the expression of CA XII in all mouse tissues, and later on in rat brain tissues. Methods: mRNA transcription was studied by PCR in mouse tissues and by reverse transcriptase-PCR (RT-PCR) in rat tissues. CA XII protein in mouse tissues was studied by Immunohistochemistry (biotin streptavidin complex method). The studies on rat brain tissues were made by in situ hybridization and northern blot methods after kainic acidinduced status epilepticus. In situ hybridization showed the location of the expression where as northern blot served as a measure of quantity of the expression. Results: CA XII mRNA is expressed in mouse kidney, brain, lung, testis and embryos. In embryos the expression became stronger with increasing age indicating developmental regulation. CA XII protein has a very limited expression distribution (mouse kidney and colon). In rat brain tissues CA XII mRNA is expressed mainly in dentate ganule cells, cortex and choroid plexus. Kainic acid stimulated the expression throughout the cortical layer. Conclusions: The high expression of CA XII in mouse kidney and colon suggests a role for CA XII in the maintenance of body ion and pH homeostasis in the mouse. Kainic acid stimulates CA XII expression throughout the cortical layer. The physiological significance of the observed cortical induction of CA XII remains obscure, but the high expression of CA XII in the choroid plexus suggests an analogous role for this membrane-bound isozyme. CA II is known to participate in CSF secretion.
Hot-spot mutations in p110α of phosphatidylinositol 3-kinase (PI3K): Differential interactions with the regulatory subunit p85 and with RAS

The phosphatidylinositol 3-kinase (PI3K) signaling pathway is frequently upregulated in cancer. PIK3CA, the gene coding for the catalytic subunit p110α of PI3K, is mutated in about 12% of all human cancers. Most of these mutants are single amino acid substitutions that map to three positions (hot spots) in the helical or kinase domains of the enzyme. The mutant proteins show gain of enzymatic function, constitutively activate AKT signaling and induce oncogenic transformation in vitro and in animal model systems. We have shown previously that hot-spot mutations in the helical domain and kinase domain of the avian p110α have different requirements for interaction with the regulatory subunit p85 and with RAS-GTP. Here, we have carried out a genetic and biochemical analysis of these "hot-spot" mutations in human p110α. The present studies add support to the proposal that helical and kinase domain mutations in p110α trigger a gain of function by different molecular mechanisms. The gain of function induced by helical domain mutations requires interaction with RAS-GTP. In contrast, the kinase domain mutation is active in the absence of RAS-GTP binding, but depends on the interaction with p85.
Effective Constitutive Parameters Retrieval Method for Bianisotropic Metamaterials Using Waveguide Measurements

An effective method for extraction of electromagnetic properties of bianisotropic biaxial omega-type metamaterial (MM) slabs from waveguide measurements is presented. The method relies on measurements of S-parameters of two MM slab configurations (transverse and longitudinal) to extract electromagnetic properties endowed with strong bianisotropic coupling. An uncertainty analysis is performed for examining the effect of geometrical parameters of the longitudinal configuration on its resonance characteristic. For verification of the proposed method, constitutive parameters of a polyethylene sample are extracted at the <inline-formula> <tex-math notation="LaTeX">$X$ </tex-math></inline-formula>-band (8.2–12.4 GHz). Then, the method is applied for extraction of electromagnetic properties of an MM slab (square split-ring resonators over FR4 substrate) using simulated and measured S-parameters for the two configurations at the <inline-formula> <tex-math notation="LaTeX">$X$ </tex-math></inline-formula>-band. It is noted that extracted electromagnetic properties obtained from measured S-parameters are in good agreement with those obtained from simulated S-parameters except for a small frequency shift and magnitude change, which could arise from fabrication tolerances, air gaps present between MM cells, and local irregular surface of the longitudinal configuration. For completeness, it is analyzed whether extracted properties satisfy the locality conditions.