Miracle-dz/UniFAR-FTUs huggingface dataset:
Duplication of U3 Sequences in the Long Terminal Repeat of Mink Cell Focus-Inducing Viruses Generates Redundancies of Transcription Factor Binding Sites Important for the Induction of Thymomas

ABSTRACT The ability of mink cell focus-inducing (MCF) viruses to induce thymomas is determined, in part, by transcriptional enhancers in the U3 region of their long terminal repeats (LTRs). To elucidate sequence motifs important for enhancer function in vivo, we injected newborn mice with MCF 1dr (supF), a weakly pathogenic, molecularly tagged (supF) MCF virus containing only one copy of a sequence that is present as two copies (known as the directly repeated [DR] sequence) in the U3 region of MCF 247 and analyzed LTRs from supF-tagged proviruses in two resulting thymomas. Tagged proviruses integrated upstream and in the reverse transcriptional orientation relative to c-myc provided the focus of our studies. These proviruses are thought to contribute to thymoma induction by enhancer-mediated deregulation of c-myc expression. The U3 region in a tagged LTR in one thymoma was cloned and sequenced. Relative to MCF 1dr (supF), the cloned U3 region contained an insertion of 140 bp derived predominantly from the DR sequence of the injected virus. The inserted sequence contains predicted binding sites for transcription factors known to regulate the U3 regions of various murine leukemia viruses. Similar constellations of binding sites were duplicated in two proviral LTRs integrated upstream from c-myc in a second thymoma. We replaced the U3 sequences in an infectious molecular clone of MCF 247 with the cloned proviral U3 sequences from the first thymoma and generated an infectious chimeric virus, MCF ProEn. When injected into neonatal AKR mice, MCF ProEn was more pathogenic than the parental virus, MCF 1dr (supF), as evidenced by the more rapid onset and higher incidence of thymomas. Molecular analyses of the resultant thymomas indicated that the U3 region of MCF ProEn was genetically stable. These data suggest that the arrangement and/or redundancy of transcription factor binding sites generated by specific U3 sequence duplications are important to the biological events mediated by MCF proviruses integrated near c-myc that contribute to transformation.
Articular gelling in osteoarthrosis--a bioengineering study.

Six patients aged 33 to 66 years with various connective tissue diseases developed trigeminal neuropathy. They were not a homogenous group. Three had progressive -systemic sclerosis (PSS), two had systemic lupus erythematosus (SLE) with features of PSS, and one had -dermatomyositis. All noted numbness over the involved -area of the face, and in some the tongue and buccal mucosa were affected. In some patients this was preceded by pain and in one pain was a feature for a year after the onset of the lesion. The onset was subacute and took up to one month to reach maximum development. Subsequently the signs have remained unchanged for periods of up to 6 years. The involvement varied in distribution but usually followed the divisions of the trigeminal nerve. In one case there was bilateral involvement, but in the remainder the involvement was largely unilateral, affecting one, two, or three divisions. The blink reflex was recorded in three patients: one showed a normal response, one showed an increase in latency, and in one there was virtual absence of the first component. There was a similar delay in response to supraorbital stimulation, suggesting that the delay is in nerve conduction. Evidence from these cases suggests that trigeminal neuropathy is a consequence of the connective tissue diseases but that the association is rare.
Inactivation of the RluD Pseudouridine Synthase Has Minimal Effects on Growth and Ribosome Function in Wild-Type Escherichia coli and Salmonella enterica

ABSTRACT The Escherichia coli rluD gene encodes a pseudouridine synthase responsible for the pseudouridine (Ψ) modifications at positions 1911, 1915, and 1917 in helix 69 of 23S rRNA. It has been reported that deletion of rluD in K-12 strains of E. coli is associated with extremely slow growth, increased readthrough of stop codons, and defects in 50S ribosomal subunit assembly and 30S-50S subunit association. Suppressor mutations in the prfB and prfC genes encoding release factor 2 (RF2) and RF3 that restore the wild type-growth rate and also correct the ribosomal defects have now been isolated. These suppressors link helix 69 Ψ residues with the termination phase of protein synthesis. However, further genetic analysis reported here also reveals that the slow growth and other defects associated with inactivation of rluD in E. coli K-12 strains are due to a defective RF2 protein, with a threonine at position 246, which is present in all K-12 strains. This is in contrast to the more typical alanine found at this position in most bacterial RF2s, including those of other E. coli strains. Inactivation of rluD in E. coli strains containing the prfB allele from E. coli B or in Salmonella enterica, both carrying an RF2 with Ala246, has negligible effects on growth, termination, or ribosome function. The results indicate that, in contrast to those in wild bacteria, termination functions in E. coli K-12 strains carrying a partially defective RF2 protein are especially susceptible to perturbation of ribosome-RF interactions, such as that caused by loss of h69 Ψ modifications.
Staphylococcus aureus proteins SSL6 and SElX interact with neutrophil receptors as identified using secretome phage display

In order to cause colonization and invasive disease, pathogenic bacteria secrete proteins that modulate host immune defences. Identification and characterization of these proteins leads to a better understanding of the pathological processes underlying infectious and inflammatory diseases and is essential in the development of new strategies for their prevention and treatment. Current techniques to functionally characterize these proteins are laborious and inefficient. Here we describe a high‐throughput functional selection strategy using phage display in order to identify immune evasion proteins. Using this technique we identified two previously uncharacterized proteins secreted by Staphylococcus aureus, SElX and SSL6 that bind to neutrophil surface receptors. SElX binds PSGL‐1 on neutrophils and thereby inhibits the interaction between PSGL‐1 and P‐selectin, a crucial step in the recruitment of neutrophils to the site of infection. SSL6 is the first bacterial protein identified that binds CD47, a widely expressed cell surface protein recently described as an interesting target in anti‐cancer therapy. Our findings provide new insights into the pathogenesis of S. aureus infections and support phage display as an efficient method to identify bacterial secretome proteins interacting with humoral or cellular immune components.
Endothelial progenitor cell mobilization and platelet microparticle release are influenced by clopidogrel plasma levels in stable coronary artery disease.

BACKGROUND Increased numbers of endothelial (EMP) and platelet (PMP) microparticles have been related to cardiovascular risk factors and coronary artery disease. Little is known about the early effects of statins and clopidogrel on these new biomarkers of vascular homeostasis. The aim of the present study was to evaluate pharmacokinetic interactions between atorvastatin and clopidogrel and their effects, alone or combined, on EMP, PMP, and endothelial progenitor cells (EPC). METHODS AND RESULTS A prospective open-label study enrolled subjects with stable coronary disease (n=26). Drugs were given daily for 3 weeks (atorvastatin 80 mg, visits 1-3; clopidogrel 75 mg, visits 2-4). Counts of EPC (CD34+/CD133+/KDR+), EMP (CD51+) and PMP (CD42+/CD31+), and pharmacokinetic parameters over 24h were assessed at each visit. Atorvastatin plasma concentrations were increased by concomitant therapy with clopidogrel (maximum serum concentration [C(max)], P=0.002; area under the clopidogrel or atorvastatin plasma concentration vs. time curve from 0 to the last detectable concentration [AUC(last)], P=0.03). After atorvastatin withdrawal there was an increase in clopidogrel plasma concentrations (C(max), P=0.009; AUC(last), P=0.039). PMP were inversely correlated with clopidogrel C(max) on visit 3 (rho=-0.57, P=0.006) and on visit 4 (rho=-0.54, P=0.01), and with clopidogrel AUC(last) on visit 3 (rho=-0.44, P=0.04), and on visit 4 (rho=-0.57, P=0.005). In addition, clopidogrel C(max) was correlated with EPC (CD133+/KDR+) on visit 4 (rho=0.48, P=0.025). No correlations of atorvastatin and MP or EPC were found. CONCLUSIONS The balance between platelet MP release and EPC mobilization seems influenced by clopidogrel plasma levels, suggesting a protective mechanism on coronary artery disease.
Structural evolution of amino acid crystals under stress from a non-empirical density functional

Use of the non-local correlation functional vdW-DF (from ‘van der Waals density functional’; Dion M et al 2004 Phys. Rev. Lett. 92 246401) has become a popular approach for including van der Waals interactions within density functional theory. In this work, we extend the vdW-DF theory and derive the corresponding stress tensor in a fashion similar to the LDA and GGA approach, which allows for a straightforward implementation in any electronic structure code. We then apply our methodology to investigate the structural evolution of amino acid crystals of glycine and l-alanine under pressure up to 10 GPa—with and without van der Waals interactions—and find that for an accurate description of intermolecular interactions and phase transitions in these systems, the inclusion of van der Waals interactions is crucial. For glycine, calculations including the vdW-DF (vdW-DF-c09x) functional are found to systematically overestimate (underestimate) the crystal lattice parameters, yet the stability ordering of the different polymorphs is determined accurately, at variance with the GGA case. In the case of l-alanine, our vdW-DF results agree with recent experiments that question the phase transition reported for this crystal at 2.3 GPa, as the a and c cell parameters happen to become equal but no phase transition is observed.
Topical Delivery of Lidocaine in Healthy Volunteers by Electroporation, Electroincorporation, or Iontophoresis: An Evaluation of Skin Anesthesia

Background and Objectives This study was designed to compare the onset, duration, and depth of local anesthesia after the topical delivery of lidocaine using electroporation (EP), electroincorporation (EI), and iontophoresis (IP) in healthy volunteers. EP and EI were performed with prototype devices and IP with a commercial drug/device product. Methods A double-blind, crossover study design was used for 10 randomized volunteers selected for EP treatment with either 4%, 10%, or 20% lidocaine or placebo normal saline. Because it was impossible to blind between IP, EP, and EI, an open label study with randomized volunteers was selected for IP and EP treatments. Onset and duration of anesthesia was determined by measuring warm sensation, cool sensation, and hot pain; depth of anesthesia was determined by measurement of pain sensation to a 27-gauge needle passed through the skin. Results For EP, all concentrations of lidocaine produced significant changes from baseline on 2 or 3 efficacy measures, however, the 4% concentration appeared to be the most efficacious when delivered by the EP method. The EP and EI methods produced a significant elevation in all 3 thermal thresholds, whereas IP produced significant elevations in cool and warm thresholds only. However, IP resulted in a greater depth of anesthesia. Plasma lidocaine levels were undetectable. Conclusions The transdermal delivery of lidocaine by IP, EP, and EI results in similar surface skin anesthesia; however, IP results in a greater depth of anesthesia.
Percutaneous-endoscopic rendezvous procedure for the management of bile duct injuries after cholecystectomy: short- and long-term outcomes

Abstract Background Bile duct injury (BDI) remains a daunting complication of laparoscopic cholecystectomy. In patients with complex BDI, a percutaneous-endoscopic rendezvous procedure may be required to establish bile duct continuity. The aim of this study was to assess short- and long-term outcomes of the rendezvous procedure. Methods All consecutive patients with BDI referred to our tertiary referral center between 1995 and 2016 were analyzed. A rendezvous procedure was performed when endoscopic or radiologic intervention failed, and when deemed feasible by a dedicated multidisciplinary team including hepatopancreaticobiliary surgeons, gastrointestinal endoscopists, and interventional radiologists. Classification of BDI, technical success of the rendezvous procedure, procedure-related adverse events, and outcomes were assessed. Results Among a total of 812 patients, rendezvous was performed in 47 (6 %), 31 (66 %) of whom were diagnosed with complete transection of the bile duct (Amsterdam type D/Strasberg type E injury). The primary success rate of rendezvous was 94 % (44 /47 patients). Overall morbidity was 18 % (10 /55 procedures). No life-threatening adverse events or 90-day mortality occurred. After a median follow-up of 40 months (interquartile range 23 – 54 months), rendezvous was the final successful treatment in 26 /47 patients (55 %). In 14 /47 patients (30 %), rendezvous acted as a bridge to surgery, with hepaticojejunostomy being chosen either primarily or secondarily to treat refractory or relapsing stenosis. Conclusions In experienced hands, rendezvous was a safe procedure, with a long-term success rate of 55 %. When endoscopic or transhepatic interventions fail to restore bile duct continuity in patients with BDI, rendezvous should be considered, either as definitive treatment or as a bridge to elective surgery.
Real-time face location on grayscale static images

This work presents a new approach to automatic face location on gray-scale static images with complex backgrounds. In a "rst stage our technique approximately detects the image positions where the probability of "nding a face is high; during the second stage the location accuracy of the candidate faces is improved and their existence is veri"ed. The experimentation shows that the algorithm performs very well both in terms of detection rate (just one missed detection on 70 images) and of e$ciency (about 13 images/s can be processed on Hardware Intel Pentium II 266 MHz). ( 2000 Pattern Recognition Society. Published by Elsevier Science Ltd. All rights reserved.
Awareness of investigations and treatment of faecal incontinence among the general practitioners: a postal questionnaire survey

Objective Faecal incontinence is a distressing condition that can result in significant embarrassment and limitation of routine activities. General practitioners (GP) are the primary carers of such patients. There are recent developments in the surgical treatment options for this under‐reported condition. Awareness of these changes is required to make the best use of them. To the best knowledge of the authors, no studies have examined the awareness of investigations and treatment options for faecal incontinence amongst GPs. This is the focus of our study.
Effect of norepinephrine, isoproterenol, and adrenergic blockers upon the intrarenal distribution of blood flow.

The effect of intrarenal administration of norepinephrine, isoproterenol, and adrenergic blockers upon the intrarenal distribution of blood flow has been studied with the 85Kr method. Norepinephrine produces marked vasoconstriction of the outer cortex while it increases the medullary blood flow rate. Isoproterenol had no effect of its own and antagonized the norepinephrine effect. Phenoxybenzamine produced no particular effect and prevented the hemodynamic modifications produced by norepinephrine. Phenoxybenzamine also unmasked the cortical vasodilating effect of isoproterenol. Propranolol was found to have an adrenergic-like effect on the cortical and medullary circulations which was inhibited by phenoxybenzamine. It is concluded that the cortical circulation is very reactive to vasoactive stimuli whereas the outer medulla seems to present a rather passive vascular bed.
Non-canonical Interaction of Phosphoinositides with Pleckstrin Homology Domains of Tiam1 and ArhGAP9*

Pleckstrin homology (PH) domains are phosphoinositide (PI)-binding modules that target proteins to membrane surfaces. Here we define a family of PH domain proteins, including Tiam1 and ArhGAP9, that demonstrates specificity for PI(4,5)P2, as well as for PI(3,4,5)P3 and PI(3,4)P2, the products of PI 3-kinase. These PH domain family members utilize a non-canonical phosphoinositide binding pocket related to that employed by β-spectrin. Crystal structures of the PH domain of ArhGAP9 in complex with the headgroups of Ins(1,3,4)P3, Ins(1,4,5)P3, and Ins(1,3,5)P3 reveal how two adjacent phosphate positions in PI(3,4)P2, PI(4,5)P2, and PI(3,4,5)P3 are accommodated through flipped conformations of the bound phospholipid. We validate the non-canonical site of phosphoinositide interaction by showing that binding pocket mutations, which disrupt phosphoinositide binding in vitro, also disrupt membrane localization of Tiam1 in cells. We posit that the diversity in PI interaction modes displayed by PH domains contributes to their versatility of use in biological systems.
Comparison of Screening for Gestational Diabetes Mellitusby IADPSG andDIPSI Guidelines: Importance of Fasting Blood Glucose Value in Its Diagnosis and Management

Introduction: Gestational Diabetes Mellitus (GDM) is a common medical disorder complicating pregnancy. Two popular recommendations for screening for GDM in India are The Diabetes in Pregnancy Study Group of India (DIPSI) guidelines and the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. This study aims to compare the diagnostic rates of GDM by both these criteria and assess the severity of GDM in patients diagnosed by fasting value vs. non-fasting value. Methods: A total of 1,470 pregnant women attending antenatal clinic at a tertiary care Armed Forces Hospital underwent a 75-g OGTT in fasting state. Venous plasma glucose was measured, and GDM was diagnosed using both DIPSI and IADPSG criteria. Severity of GDM in these patients was assessed by whether patients were treated with medical nutrition therapy (MNT) alone or required pharmacotherapy. Results: Of the 1470 women screened, IADPSG criteria identified 176 (11.97%) to have GDM vs.58 (3.94%) by DIPSI criteria. 124 (8.43%) patients were diagnosed by fasting values of which 27.4% needed pharmacotherapy vs.58 (3.54%) diagnosed by non-fasting values of which 57.69% needed pharmacotherapy. Conclusions: The DIPSI criteria has low diagnostic rate as compared to IADPSG criteria because it ignores the Fasting Blood Glucose (FBG) levels. Patients diagnosed as GDM by fasting value have similar severity of GDM as those diagnosed by non-fasting values.
Hemangioendothelioma of the parotid gland in infants: sonography and correlative MR imaging.

BACKGROUND AND PURPOSE Hemangioendothelioma is the most common parotid gland tumor of childhood, and is diagnosed on clinical grounds, supported by imaging findings. Previous work has suggested that MR is the best imaging technique for assessment of parotid hemangioendothelioma. Demonstration of a reliable sonographic appearance would reduce the need for MR imaging in infants with this lesion. METHODS We performed high-frequency sonography (including color Doppler and power Doppler imaging) in three patients, each with a diagnosis of parotid hemangioendothelioma confirmed by clinical follow-up. Two patients were also examined with MR imaging and labeled red cell scintigraphy. RESULTS All sonographic studies showed a homogeneous mass enlarging and replacing most or all of the visualized parotid gland, with a lobular internal structure, fine echogenic internal septations, and a mildly lobulated contour. Color Doppler and power Doppler imaging showed extremely high vascularity within the mass. Correlative MR images in two infants showed a well-defined lesion with uniform intense contrast enhancement. Labeled red cell scintigraphy showed a well-defined area of intense activity. CONCLUSION In the presence of a typical clinical history, sonography and clinical follow-up alone may prove to be sufficient for safe management of parotid hemangioendothelioma. MR imaging or labeled red cell scintigraphy may only be required if the sonographic features are atypical. These findings require confirmation in a larger series of patients.
Cell Cycle Redistribution of Cultured Cells After Treatment With Chemical Radiation Protectors

The effect of two radioprotective agents (WR‐1065 and WR‐151326) was tested for their ability to modify cell cycle progression. Each protector was administered at a concentration of 4 mmol to exponentially growing cultures of V79 cells for periods of time up to 3 h. Under these conditions no cell toxicity was observed. At selected times up to and after removal of the protector, aliquots of cells were removed, counted and fixed in cold 70% ethanol. the cells were stained with DAPI in a 0.1% citrate solution and DNA histograms were obtained using a PARTEC PAS‐II flow cytometer. the coefficient of variation of the G1 peaks obtained for unperturbed cell samples routinely ranged from 1.5 to 2.5%. During exposure, both radioprotectors effectively perturbed cell cycle progression, as characterized by a build‐up of cells in S and G2 phases. After the protectors were removed, cells began to redistribute throughout the cell cycle. Twelve hours were required before cells exposed to WR‐1065 approached levels commensurable with controls. In contrast, cells treated with WR‐151236 required about 24 h to redistribute to control levels. These data demonstrate that different thiol‐containing radioprotective compounds can differentially affect the progression and redistribution of exposed cells.
Innervation of the digit on the forepaw of the raccoon

The innervation of the digits on the raccoon forepaw was examined by using immunochemistry for protein gene product 9.5, calcitonin‐gene related peptide, substance P, neuropeptide‐Y, tyrosine hydroxylase, and neurofilament protein. The larger‐caliber axons in the ventral glabrous skin terminate as Pacinian corpuscles deep in the dermis, small corpuscles and Merkel endings around the base of dermal papillae, and Merkel endings on rete pegs in dermal papillae. Extensive fine‐caliber innervation terminates in the epidermis and on the microvasculature. The innervation is more dense in the distal than in the proximal volar pads. Pacinian endings are also concentrated in the transverse crease separating the distal and proximal pads. In the dorsal hairy skin, hair follicles are well innervated with piloneural complexes. Merkel innervation is located under slight epidermal elevations and in some large Merkel rete pegs located at the apex of transverse skin folds just proximal to the claw. No cutaneous Ruffini corpuscles were found anywhere on the digit. The claw is affiliated with dense medial and lateral beds of Pacinian endings, bouquets of highly branched Ruffini‐like endings at the transition from the distal phalanx and unmyelinated innervation in the skin around the perimeter. Encapsulated endings are located at the lateral edge of the articular surface of the distal phalanx. Extensive fine‐caliber innervation is affiliated with sweat glands and with the vasculature and is especially dense at presumptive arteriovenous sphincters. Virtually all of the sweat gland and vascular innervation is peptidergic, whereas most of the unmyelinated epidermal innervation is nonpeptidergic. J. Comp. Neurol. 417:467–490, 2000. © 2000 Wiley‐Liss, Inc.