Miracle-dz/UniFAR-FTUs huggingface dataset:
Selective Targeting of Different Neural Cell Adhesion Molecule Isoforms during Motoneuron–Myotube Synapse Formation in Culture and the Switch from an Immature to Mature Form of Synaptic Vesicle Cycling

Characterization of neuromuscular junction formation and function in mice lacking all neural cell adhesion molecule (NCAM) isoforms or only the 180 isoform demonstrated that the 180 isoform was required at adult synapses to maintain effective transmission with repetitive stimulation whereas the 140 and/or 120 isoform(s) were sufficient to mediate the downregulation of synaptic vesicle cycling along the axon after synapse formation. However, the expression and targeting of each isoform and its relationship to distinct forms of synaptic vesicle cycling before and after synapse formation was previously unknown. By transfecting chick motoneurons with fluorescently tagged mouse 180, 140 and 120 isoforms, we show that before myotube contact the 180 and 140 isoforms are expressed in distinct puncta along the axon which are sites of an immature form (Brefeldin A sensitive, L-type Ca2+ channel mediated) of vesicle cycling. After myotube contact the 140 and 180 isoforms are downregulated from the axon and selectively targeted to the presynaptic terminal. This coincided with the downregulation of vesicle cycling along the axon and the expression of the mature form (BFA insensitive, P/Q type Ca2+ channel mediated) of vesicle cycling at the terminal. The synaptic targeting of exogenously expressed 180 and 140 isoforms also occurred when chick motoneurons contacted +/+ mouse myotubes; however only the 180 but not the 140 isoform was targeted on contact with NCAM−/− myotubes. These observations indicate that postsynaptic NCAM is required for the synaptic targeting of presynaptic 140 NCAM but that the localization of presynaptic 180 NCAM occurs via a different mechanism.
A High Prevalence of Exotropia in Patients With Duane Retraction Syndrome in a Tertiary Eye Care Center in South India.

PURPOSE To determine the prevalence and clinical characteristics of patients with Duane retraction syndrome presenting with exotropia in a tertiary eye care center. METHODS Medical records of 140 patients with Duane retraction syndrome and exotropia (of the total 441 patients with Duane retraction syndrome) seen from 2000 to 2009 were reviewed. Characteristics studied included age at presentation, gender, laterality, manifest primary position, abnormal head posture, ocular motility, and overshoots. Data were collected regarding associated ocular or systemic abnormalities and amblyopia. RESULTS The mean age of the patients at presentation was 16.96 ± 15.09 years (range: 1 to 70 years). Of the 140 patients with Duane retraction syndrome and exotropia, 59 (42%) were male. Unilateral type I Duane retraction syndrome accounted for 118 (84.2%), type II for 7 (5%), and type III for 10 (7.1%) patients, whereas 5 (3.6%) had Duane retraction syndrome and bilateral exotropia. Duane retraction syndrome was seen in the left eye, right eye, and both eyes in 97 (69%), 37 (26%), and 6 (4%) patients, respectively. Exotropia ranged from 10 to 60 prism diopters. An abnormal head posture was noted in 101 (72%) and upshoot in 26 (18.6%) patients. Reported ocular and systemic abnormalities in these patients included cataract (6), aniridia (1), nasolacrimal duct block (1), and retinal breaks (1). CONCLUSIONS This is an exclusive study on a large series of patients with Duane retraction syndrome and exotropia. Almost one-third of patients with Duane retraction syndrome patients might have exotropia. Although patients with Duane retraction syndrome and exotropia had clinical characteristics and associations similar to those with Duane retraction syndrome and esotropia, there was an increased propensity for overshoots and face turn opposite to the affected eye, which the authors hypothesize to be due to a tight or short lateral rectus muscle. [J Pediatr Ophthalmol Strabismus. 2017;54(2):117-122. ].
Evaluation and therapeutic approaches of voiding and erectile dysfunction in neurological Behçet's syndrome.

PURPOSE Behçet's syndrome is a progressive inflammatory disease which involves multiple systems. It is characterized by 3 main symptoms of iridocyclitis, and oral and genital ulcerations. Nervous system involvement is seen rarely in this clinical entity and is known as neurological Behçet's syndrome. Inflammation usually occurs in the brain stem, cerebellum and medulla spinalis. Voiding and erectile dysfunction can be due to progressive inflammatory reactions in the nervous and vascular systems. We prospectively evaluated the dysfunctional bladder and penis, and therapeutic options were evaluated prospectively. MATERIALS AND METHODS A total of 24 consecutive patients diagnosed with neurological Behçet's syndrome after neurological evaluation were enrolled in this study. Neurological involvement and localization of the nervous system were proved on evaluation. Voiding and erectile dysfunction was evaluated regardless of the presence of related symptoms, and the results were compared with those of controls. Patients with voiding dysfunction on urodynamic study were treated and reevaluated symptomatically after 3 and urodynamically after 6 months. RESULTS The rate of erectile dysfunction in neurological Behçet's syndrome was 63%. Mixed type vasculogenic impotence, arterial insufficiency, veno-occlusive dysfunction and neurogenic impotence were identified in 7, 2, 2 and 1 patient, respectively. Detrusor instability was demonstrated in 12 patients with urgency incontinence, including 3 with detrusor-sphincter dyssynergia. Brain stem localization was determined in these patients on neurogenic evaluation. Significant improvement was observed with anticholinergic treatment and clean intermittent catheterization in 3 patients with detrusor-sphincter dyssynergia. Hypersensitive and hypocompliant detrusor was noted in patients with neurological Behçet's syndrome who had normal voiding habits. CONCLUSIONS Incontinence or irritable bladder symptoms should not be considered innocuous clinical findings in neurological Behçet's syndrome. Lower urinary tract function should be evaluated in all patients with this neurological syndrome. The incidence of erectile dysfunction is approximately 65% and the therapeutic approach should be determined according to lower urinary tract function.
Insulin, but Not Contraction, Activates Akt/PKB in Isolated Rat Skeletal Muscle*

Insulin and muscle contraction potently stimulate glucose uptake in mammalian skeletal muscle. Studies in muscle and adipose tissue have shown that insulin induces its receptor-dependent phosphorylation of insulin receptor substrates 1 and 2, which leads to activation of polyphosphatidylinositol (PI) 3′-kinase. In contrast, muscle contraction stimulates glucose transport via a mechanism that is independent of insulin, but the two pathways may converge downstream at the level of stimulation of GLUT4 translocation. In the present study, we have examined the role of Akt, an insulin-activated serine threonine kinase that has previously been shown to increase glucose transport in adipocytes. Either insulin or in vitro muscle contraction significantly elevated glucose transport in isolated rat epitrochlearis and soleus muscles. However, Akt kinase activity was significantly stimulated by insulin and not contraction. Moreover, wortmannin, an inhibitor of PI 3′-kinase, completely blocked the insulin-stimulated increase in Akt activity and glucose transport but did not alter either of these parameters in contracting muscles. The increases in Akt activity were paralleled by a decrease in the electrophoretic mobility of Akt, indicative of phosphorylation of Akt by an upstream kinase. These changes in Akt mobility appeared to be at least partially because of phosphorylation of Akt on serine 473. A putative downstream target of Akt, p70 S6 kinase, showed similar changes in mobility in response to insulin but not contraction. These data support the view that Akt is a downstream target of PI 3′-kinase and is involved in the signaling pathways involved in insulin but not contraction stimulation of glucose transport in skeletal muscle. These data provide further evidence that two distinct pathways exist for the stimulation of glucose transport in mammalian skeletal muscle.
Association of lead exposure, serum uric acid and parameters of renal function in Nigerian lead-exposed workers.

BACKGROUND The presence of hyperuricemia and renal function impairment, especially in the absence of urate stone formation is strongly suggestive of lead nephropathy. The evaluation of this association is essential in areas where lead exposure is still prevalent and uncontrolled. OBJECTIVE To determine the relationship between serum uric acid and renal function indices in lead-exposed workers. METHODS A cross-sectional study of 190 adults with occupational lead exposure and 80 adults (comparison group), matched for age and sex was performed in Port Harcourt, South-south Nigeria. Blood lead was used as the biomarker of lead exposure while serum urea, serum creatinine, urine albumin (using urine albumin:creatinine ratio), estimated glomerular filtration rate (GFR) and serum uric acid were the renal function indices measured. RESULTS Occupationally lead-exposed subjects had a significantly (p = 0.008) higher mean±SD blood lead levels (50.37±24.58 μg/dL) than the comparison group (41.40±26.85). The mean±SD serum urea (8.6±2.3 mg/dL), creatinine (1.0±0.2 mg/dL) and serum uric acid (4.6±1.2 mg/dL) were significantly (p < 0.01) higher in the study subjects than the comparison group (7.6±2.4, 0.9±0.2, and 3.9±1.1 mg/dL, respectively). The mean±SD creatinine clearance was significantly (p = 0.002) lower in the study subjects than the comparison group (98.9±21.3 vs. 108.2±25.2 mL/min/1.72 m2). Serum uric acid level correlated positively with serum creatinine (r = 0.134) and negatively with GFR (r = -0.151). CONCLUSION People with occupational lead exposure are at risk of developing hyperuricemia and renal impairment.
Influence of rotational energy barriers to the conformational search of protein loops in molecular dynamics and ranking the conformations

An adjustable‐barrier dihedral angle potential was added as an extension to a novel, previously presented soft‐core potential to study its contribution to the effectivity of the search of the conformational space in molecular dynamics. As opposed to the conventional soft‐core potential functions, the leading principle in the design of the new soft‐core potential, as well as of its extension, the soft‐core and adjustable‐barrier dihedral angle (SCADA) potential (referred as the SCADA potential), was to maintain the main equilibrium properties of the original force field. This qualifies the methods for a variety of a priori modeling problems without need for additional restraints typically required with the conventional soft‐core potentials. In the present study, the different potential energy functions are applied to the problem of predicting loop conformations in proteins. Comparison of the performance of the soft‐core and SCADA potential showed that the main hurdles for the efficient sampling of the conformational space of (loops in) proteins are related to the high‐energy barriers caused by the Lennard–Jones and Coulombic energy terms, and not to the rotational barriers, although the conformational search can be further enhanced by lowering the rotational barriers of the dihedral angles. Finally, different evaluation methods were studied and a few promising criteria found to distinguish the near‐native loop conformations from the wrong ones. Proteins 2001;44:167–179. © 2001 Wiley‐Liss, Inc.
The Paramidline Forehead Flap: A Clinical and Microanatomic Study

BACKGROUND The traditional paramedian forehead flap (FHF) is an axial flap based on the supratrochlear artery (STA). Doppler examination is often used to ensure inclusion of the STA within the flap. The authors hypothesized that a FHF pedicle design could be simplified to extend from the midline of the glabella to 1.2 cm lateral to the midline without compromising outcomes. OBJECTIVE To compare clinical outcomes and vessel densities of 2 FHF designs. METHODS Two FHF designs were used to repair fifty nasal defects. One was based on Doppler identification of the STA; the other on clinical measurements from the glabellar midline (with no effort to identify the STA). Clinical outcomes, complication rates, and pedicle vasculature of both groups were compared. RESULTS There was no significant difference in flap survival or complication rate. Forehead flaps designed on the paramidline glabella had more arteries within their pedicles than Doppler-based FHFs (p < .05). Small arteries predominated, whereas larger arteries were infrequent in both groups. Size and number of arteries were not related to flap survival. CONCLUSION A paramidline FHF has equivalent clinical outcomes as a flap based on the STA. A simple and reproducible design of the FHF using only surface landmarks is described.
High-dose therapy plus autologous hematopoietic stem cell transplantation for human immunodeficiency virus (HIV)-related lymphoma: results and impact on HIV disease.

BACKGROUND AND OBJECTIVES The aim of this study was to assess the feasibility of high-dose chemotherapy plus autologous hematopoietic stem cell transplantation (HDC/AHSCT) in AIDS-related lymphoma (ARL), and its long-term impact in patients with human immunodeficiency virus (HIV) treated with highly active antiretroviral therapy (HAART). DESIGN AND METHODS Fourteen patients with relapsed or resistant ARL (8 with nonHodgkin's lymphoma and 6 with Hodgkin's disease) were treated with HDC/AHSCT while on HAART. HIV-1 proviral DNA load was quantified in 11 grafts. RESULTS Hematologic reconstitution was good. No toxic deaths occurred. Despite the large number of cells harboring HIV-1 proviral DNA (105 to 109) re-infused with the graft, HAART controlled HIV replication and led to CD4 cell reconstitution in 7 of the 8 patients who were still alive six months after AHSCT. Only two patients had opportunistic infections after AHSCT. There were no significant changes in viral load (VL) or CD4+ cell counts in most patients. One month after AHSCT, 10 patients were in complete remission (CR). Seven patients died from lymphoma between 1 and 10 months after AHSCT, and a further two patients died in CR (one from AIDS at 16 months, one from another tumor at 28 months). Five patients are alive: four are in CR, 14, 19, 32 and 49 months after AHSCT (median CD4+ cell count= 445/mL; undetectable VL in 3 patients), and one is being treated for relapsed lymphoma 36 months after AHSCT. INTERPRETATION AND CONCLUSIONS HDC/AHSCT is feasible in AIDS-related lymphoma, in terms of harvesting, engraftment, adverse events and HIV control. It should be proposed to patients with poor-prognosis chemosensitive lymphoma.
Differential Expression of Virulence-Related Genes in Enterococcus faecalis in Response to Biological Cues in Serum and Urine

ABSTRACT Enterococci rank among leading causes of nosocomial bacteremia and urinary tract infection and are also a leading cause of community acquired subacute endocarditis. Limited evidence suggests that biological cues in serum and urine may play an important role in modulating enterococcal virulence at sites of infection. To determine the extent to which biological cues affect enterococcal virulence-associated gene expression, we used quantitative real-time PCR to compare mRNA levels in Enterococcus faecalis cultures grown in serum or urine to that achieved in laboratory medium. Both environment- and growth phase-specific variations were observed, demonstrating the occurrence of as-yet-uncharacterized mechanisms for control of gene expression in E. faecalis that may play an important role in vivo.
Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis

Significance TNF receptor-associated protein (TRAP1) is found predominantly in mitochondria. A possible direct impact of TRAP1 on mitochondrial metabolism remains unexplored. We used TRAP1-null cells and transient TRAP1 silencing/overexpression to show that TRAP1 regulates a metabolic switch between oxidative phosphorylation and aerobic glycolysis in immortalized mouse fibroblasts and in human tumor cells. TRAP1 deficiency promotes increased mitochondrial respiration, fatty acid oxidation, tricarboxylic acid cycle intermediates, ATP and reactive oxygen species, while concomitantly suppressing glucose metabolism. TRAP1 deficiency also results in strikingly enhanced cell motility and invasiveness. TRAP1 interaction with and regulation of mitochondrial c-Src provide a mechanistic basis for these phenotypes. TRAP1 (TNF receptor-associated protein), a member of the HSP90 chaperone family, is found predominantly in mitochondria. TRAP1 is broadly considered to be an anticancer molecular target. However, current inhibitors cannot distinguish between HSP90 and TRAP1, making their utility as probes of TRAP1-specific function questionable. Some cancers express less TRAP1 than do their normal tissue counterparts, suggesting that TRAP1 function in mitochondria of normal and transformed cells is more complex than previously appreciated. We have used TRAP1-null cells and transient TRAP1 silencing/overexpression to show that TRAP1 regulates a metabolic switch between oxidative phosphorylation and aerobic glycolysis in immortalized mouse fibroblasts and in human tumor cells. TRAP1-deficiency promotes an increase in mitochondrial respiration and fatty acid oxidation, and in cellular accumulation of tricarboxylic acid cycle intermediates, ATP and reactive oxygen species. At the same time, glucose metabolism is suppressed. TRAP1-deficient cells also display strikingly enhanced invasiveness. TRAP1 interaction with and regulation of mitochondrial c-Src provide a mechanistic basis for these phenotypes. Taken together with the observation that TRAP1 expression is inversely correlated with tumor grade in several cancers, these data suggest that, in some settings, this mitochondrial molecular chaperone may act as a tumor suppressor.
Transcripts of the adeno-associated virus genome: mapping of the major RNAs

The four major adeno-associated virus type 2 (AAV2)-specific RNAs were mapped on the linear viral genome by a variety of biochemical techniques, including S1 nuclease and exonuclease VII mapping, RNA gel-transfer hybridization, and analysis of reverse transcriptase extension products. All the major AAV2 RNAs were derived from the minus DNA strand and had 3' termini at position 96. The nucleus-specific 4.3- and 3.6-kilobase (kb) RNAs had 5' termini at positions 6 and 19, respectively. The 5' terminus of the 2.6-kb RNA mapped to position 38.5. The predominant 2.3-kb AAV2 mRNA was spliced and contained a short leader sequence (approximately 50 nucleotides) which mapped to position 38.5, coincident with the 5' terminus of the 2.6-kb RNA. The 5' end of the body of the 2.3-kb RNA mapped to position 46.5. These results are discussed in terms of the involvement of single versus multiple promoters (for transcription) and RNA splicing mechanisms in the generation of the AAV2 RNAs.
Inter‐observer and intra‐observer variability in the diagnosis of dysplasia in patients with inflammatory bowel disease: correlation of pathological and endoscopic findings

Colonic epithelial dysplasia is deemed the precursor lesion of cancer arising in inflammatory bowel disease (IBD). It has been suggested that many dysplastic lesions could be endoscopically detected to obtain target biopsies, leading to better yield. However, the clinical impact of a diagnosis of dysplasia may be hampered by a significant degree of histological and endoscopic intra‐observer and inter‐observer variability. This study aimed to evaluate intra‐observer and inter‐observer variability in the microscopic diagnosis of dysplasia in IBD and correlate endoscopic and histological findings.
Regional brain enlargement in autism: a magnetic resonance imaging study.

OBJECTIVE To determine whether increased brain volume in autism, suggested in previous studies, is the result of general or regional brain size differences and to study the effect of gender on brain size and pattern of enlargement. METHOD Total brain volume and cerebral cortical lobe volumes were examined in 35 autistic and 36 comparison subjects using magnetic resonance imaging and an automated method of brain volume measurement. RESULTS After controlling for height and nonverbal IQ, the authors detected a significant diagnosis x gender effect (F = 7.4; p = .009) for total brain volume. A repeated-measures analysis of variance indicated that the pattern of enlargement (brain region x diagnosis) in autistic subjects differed from that in controls (F = 4.88; p = .0004). Subsequent sex-specific analysis revealed significantly increased total brain volume in autistic males but not females. Analysis of lobe sizes showed significant enlargement in autistic subjects in temporal, parietal, and occipital, but not frontal lobes. CONCLUSIONS These results suggest that brain size is increased in autism and that differences are not generalized but appear to be the result of a pattern of enlargement with increases in the size of specific cortical lobes.
Metabolic syndrome and obesity in an insect

APPLIED PHYSICAL SCIENCES. For the article ‘‘Ionic contrast terahertz near-field imaging of axonal water fluxes,’’ by JeanBaptiste Masson, Martin-Pierre Sauviat, Jean-Louis Martin, and Guilhem Gallot, which appeared in issue 13, March 28, 2006, of Proc Natl Acad Sci USA (103:4808–4812; first published March 17, 2006; 10.1073 pnas.0510945103), the authors note that in Fig. 1 the y scale is incorrect because of a unit conversion error. The corrected figure and its legend appear below. This error does not affect the conclusions of the article. NEUROSCIENCE. For the article ‘‘PSD-95 and PKC converge in regulating NMDA receptor trafficking and gating,’’ by Ying Lin, Teresa Jover-Mengual, Judy Wong, Michael V. L. Bennett, and R. Suzanne Zukin, which appeared in issue 52, December 26, 2006, of Proc Natl Acad Sci USA (103:19902–19907; first published December 18, 2006; 10.1073 pnas.0609924104), the authors note that in Fig. 1 A and B, the same trace was inadvertently used for the after-TPA (Right) records. The corrected figure and its legend appear below. This error does not affect the conclusions of the article.