Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Immunodeficiency Virus Type 1 Gag Polyprotein Multimerization Requires the Nucleocapsid Domain and RNA and Is Promoted by the Capsid-Dimer Interface and the Basic Region of Matrix Protein

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) Gag polyprotein directs the formation of virions from productively infected cells. Manygag mutations disrupt virion assembly, but little is known about the biochemical effects of many of these mutations. Protein-protein interactions among Gag monomers are believed to be necessary for virion assembly, and data suggest that RNA may modify protein-protein interactions or even serve as a bridge linking Gag polyprotein monomers. To evaluate the primary sequence requirements for HIV-1 Gag homomeric interactions, a panel of HIV-1 Gag deletion mutants was expressed in bacteria and evaluated for the ability to associate with full-length Gag in vitro. The nucleocapsid protein, the major RNA-binding domain of Gag, exhibited activity comparable to that of the complete polyprotein. In the absence of the nucleocapsid protein, relatively weak activity was observed that was dependent upon both the capsid-dimer interface and basic residues within the matrix domain. The relevance of the in vitro findings was confirmed with an assay in which nonmyristylated mutant Gags were assessed for the ability to be incorporated into virions produced by wild-type Gag expressed intrans. Evidence of the importance of RNA for Gag-Gag interaction was provided by the demonstration that RNase impairs the Gag-Gag interaction and that HIV-1 Gag interacts efficiently with Gags encoded by distantly related retroviruses and with structurally unrelated RNA-binding proteins. These results are consistent with models in which Gag multimerization involves indirect contacts via an RNA bridge as well as direct protein-protein interactions.
Vital organ blood flow with the impedance threshold device

Objective:The purpose of this study is to review cardiopulmonary resuscitation hemodynamics and vital organ blood flow in animal models with the use of the impedance threshold device (ITD) and to correlate these findings with the results of human clinical trials. Results:Animal studies have demonstrated near normalization of cerebral blood flow and an increase between 50% and 100% in cardiac blood flow with use of the ITD. Coincident coronary perfusion pressure is significantly increased with the ITD. Results of human clinical trials generally reflect the data seen in animal models, with near normal blood pressure during active compression–decompression cardiopulmonary resuscitation and the ITD, near doubling of blood pressure with standard cardiopulmonary resuscitation plus the ITD, and significantly increased short-term survival rates. Conclusions:Improved vital organ perfusion with ITD use during cardiopulmonary resuscitation is an important advance in resuscitation. Incorporation of the ITD into protocols that improve other aspects of the care of patients during cardiac arrest and after successful resuscitation should result in further benefit from the ITD.
Involvement of Nitric Oxide in Biofilm Dispersal of Pseudomonas aeruginosa

ABSTRACT Bacterial biofilms at times undergo regulated and coordinated dispersal events where sessile biofilm cells convert to free-swimming, planktonic bacteria. In the opportunistic pathogen Pseudomonas aeruginosa, we previously observed that dispersal occurs concurrently with three interrelated processes within mature biofilms: (i) production of oxidative or nitrosative stress-inducing molecules inside biofilm structures, (ii) bacteriophage induction, and (iii) cell lysis. Here we examine whether specific reactive oxygen or nitrogen intermediates play a role in cell dispersal from P. aeruginosa biofilms. We demonstrate the involvement of anaerobic respiration processes in P. aeruginosa biofilm dispersal and show that nitric oxide (NO), used widely as a signaling molecule in biological systems, causes dispersal of P. aeruginosa biofilm bacteria. Dispersal was induced with low, sublethal concentrations (25 to 500 nM) of the NO donor sodium nitroprusside (SNP). Moreover, a P. aeruginosa mutant lacking the only enzyme capable of generating metabolic NO through anaerobic respiration (nitrite reductase, ΔnirS) did not disperse, whereas a NO reductase mutant (ΔnorCB) exhibited greatly enhanced dispersal. Strategies to induce biofilm dispersal are of interest due to their potential to prevent biofilms and biofilm-related infections. We observed that exposure to SNP (500 nM) greatly enhanced the efficacy of antimicrobial compounds (tobramycin, hydrogen peroxide, and sodium dodecyl sulfate) in the removal of established P. aeruginosa biofilms from a glass surface. Combined exposure to both NO and antimicrobial agents may therefore offer a novel strategy to control preestablished, persistent P. aeruginosa biofilms and biofilm-related infections.
Comparison of equine endometrial cytology samples collected with uterine swab, uterine brush, and low-volume lavage from healthy mares.

BACKGROUND There have been no studies evaluating and comparing the quality of equine endometrial cytology samples obtained via the 3 most common sampling techniques from healthy mares. OBJECTIVES The objective was to compare the quality and contents of equine endometrial samples obtained by 3 different sampling techniques: double-guarded uterine swab, double-guarded uterine brush, and low-volume lavage (LVL), all collected from clinically healthy mares. METHODS Samples were collected from 24 healthy mares in early estrus. In 19 mares, samples were obtained in a sequential manner, first with the swab, then with the brush, followed by LVL. Cytologic evaluation included estimates of quality, cellularity, and presence of inflammatory cells. The clinical pathologist performing the evaluations was blinded to the collection technique. The Friedman test with Dunn's multiple comparisons was used to compare rankings of quality, cellularity, and the presence or absence of inflammatory cells. Observed cytologic differences were described. RESULTS All techniques provided diagnostic samples, but swabs yielded the lowest quality sample. In our hands, the uterine brush provided the highest quality sample. Low-volume lavage samples contained higher numbers of neutrophils, although, in general, < 1 neutrophil/400× field is expected for all endometrial sampling techniques in healthy mares. CONCLUSIONS All sampling techniques can be adequate methods for endometrial cytology, but the brush technique consistently provided the best sample. Sample contamination or poor slide quality can adversely affect interpretation. The most accurate criteria for determining what constitutes mild endometritis in mares have yet to be established.
Number of satellite nevi as a correlate for neurocutaneous melanocytosis in patients with large congenital melanocytic nevi.

BACKGROUND Patients with large congenital melanocytic nevi (LCMN) are at risk for neurocutaneous melanocytosis (NCM). Patients with LCMN on the posterior axis or in conjunction with many satellite melanocytic nevi seem to represent subgroups at greatest risk. OBJECTIVE To determine the relationship between LCMN location, number of satellite nevi, and risk of NCM. DESIGN Descriptive survey study. SETTING An Internet Web-based registry of patients with LCMN, maintained by a nevus support group (Nevus Outreach Inc). PARTICIPANTS Individuals with LCMN or their guardians visiting the Nevus Outreach Web site were provided the opportunity to complete the questionnaire. OUTCOME MEASURES Location of LCMN, number of satellite nevi, and NCM as assessed by patient self-report. RESULTS A total of 379 patients with LCMN were evaluated, 26 of whom had NCM. A significantly higher percentage of patients with NCM had their LCMN on the posterior axis compared with patients without NCM (96% and 70%, respectively). Patients with NCM had significantly more satellite melanocytic nevi compared with non-NCM patients (median, 68.5 and 18, respectively). Furthermore, patients with LCMN and more than 20 satellites had a 5.1-fold (95% confidence interval, 1.9-14.0) increased risk for NCM compared with LCMN patients with 20 or fewer satellites. Logistic regression analysis, controlling for age, sex, number of satellite nevi, and LCMN location, identified number of satellite nevi as the only significant risk factor for NCM. CONCLUSIONS The presence of large numbers of satellite nevi is the most important risk factor for NCM in patients with LCMN. Although location of the LCMN on the posterior axis was a moderate risk factor for NCM in univariate analysis, the strength of the relationship was attenuated in the multivariate analysis.
Synthesis and anticonvulsant activity of enaminones. 2. Further structure-activity correlations.

This report continues the in-depth evaluation of methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxocyclohex-3-en-1-oate , 1 (ADD 196022), and methyl 4-(benzylamino)-6-methyl-2-oxocyclohex-3-en-1-oate, 2, two potent anticonvulsant enaminones. These compounds were evaluated employing the amygdala kindling model. Neither 1 nor 2 was active against amygdala kindled seizures, further supporting the corneal kindled model as a definitive tool for antielectroshock seizure evaluation as previously reported. Additional intraperitoneal (ip) data on 1 revealed toxicity at 24 h at 100 mg/kg. Several active analogs have been prepared with the view to minimizing toxicity. In a special ip rat screen developed by the Antiepileptic Drug Development (ADD) Program, these newer analogs were evaluated for protection against maximal electroshock seizures (MES) at 10 mg/kg and neurotoxicity at 100 mg/kg. From this screen, several compounds were shown to be safer alternatives, the most notable was methyl 4-[(p-bromophenyl)amino]-6-methyl-2-oxocyclohex-3-en-1-oate, 13. Compound 13 had an ip ED50 of 4 mg/kg in the rat and a TD50 of 269 mg/kg, providing a protective index (TD50/ED50) of > 67. By variation in the ring size, additional aromatic substitutions and the synthesis of acyclic analogs, these newer compounds provide a more definitive insight into the structure-activity correlation. CLOGP evaluation and molecular modeling studies are also provided to further elaborate the molecular characteristics of potential anticonvulsant enaminones.
Incorporation of Asynchronous Generators as PQ model in load flow analysis for power systems with wind generation

Asynchronous Generators are commonly used in wind based generating units as electrical power generated by them will be the same as the frequency of the grid irrespective of their shaft speed. In this paper, a new methodology for carrying out the load flow calculations in a power system having asynchronous generators has been presented. The model, which is proposed in this paper, utilizes the solution of the quadratic equation and hence, it will not deteriorate the convergence characteristics of the base load flow program. The proposed model has been incorporated in Newton's method based load flow technique and tested on 30 bus and 118 bus systems which have wind generation. The simulation results are benchmarked with the exact impedance model of the asynchronous generator available in literature in order to demonstrate the usefulness of the proposed model.
Microbiology of pediatric primary pulmonary tuberculosis.

OBJECTIVE To determine the sensitivity of bacteriologic studies in pediatric pulmonary tuberculosis. PATIENTS AND METHODS Between January 1988 and December 1996, 104 consecutive patients aged 0 to 18 years received a diagnosis of primary pulmonary tuberculosis at our institution. Demographic, clinical, laboratory, and bacteriologic data were collected. Clinical specimens were studied for acid-fast bacilli detection by Ziehl-Neelsen stain and cultured for Mycobacterium recovery by Lowenstein-Jensen culture medium. Statistical analysis was performed utilizing chi(2), t tests, and multivariate logistic regression analysis. RESULTS Bacteriologic results were available for 57 patients (54.8%). A positive smear or culture result for Mycobacterium tuberculosis was obtained in 9 of 54 patients (16.6%) and 25 of 50 patients (50%), respectively. Confirmation of M tuberculosis disease was achieved in 28 patients (49.1%). Ziehl-Neelsen stain and Lowenstein-Jensen culture recovery rates were 10.3% (14 of 135) and 52% (48 of 92) of specimens studied, respectively. Sputum, pleural fluid, and biopsy material cultures yielded M tuberculosis in 55%, 75%, and 63% of patients, respectively. Mean +/- SD age (13.7 +/- 4.5 years vs 9.6 +/- 4.5 years) and number of samples submitted for culture (1.93 +/- 0.94 vs 1.31 +/- 0.97) were significantly higher in the confirmed tuberculosis disease group (p < 0.05). The presence of a pleural effusion was also more commonly found in the confirmed tuberculosis disease group (p < 0.05). CONCLUSION The sensitivity of bacteriologic studies in pediatric pulmonary tuberculosis disease was 49.1%. Age is the main factor associated with the positivity of culture results.
Endoscopic unilateral transethmoid‐paraseptal approach to the central skull base

The endoscopic technique in transnasal skull base surgery offers optimal visualization and free manipulation in the surgical field. However, it may cause approach‐related sinonasal injury, influencing patients' quality of life (QOL). To minimize rhinological morbidity without restrictions in surgical manipulation and tumor resection, we introduced the unilateral transethmoidal‐paraseptal approach. In this article, we analyzed the long‐term results and sinonasal outcome of this technique.
Meningitis caused by Neisseria Meningitidis, Hemophilus Influenzae Type B and Streptococcus Pneumoniae during 2005–2012 in Turkey

Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ≤ 18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey.
Prognostic significance of microvessel density and vascular endothelial growth factor expression in advanced ovarian serous carcinoma

The aim of the study was to test the prognostic value of the microvessel density (MVD) within the tumor and the vascular endothelial growth factor (VEGF) expression on clinical response to chemotherapy, on brief disease-free interval, and on cause-specific survival in advanced ovarian serous carcinoma. We evaluated 83 ovarian carcinomas homogeneous for stage, type and grade histologic, surgical, and chemotherapeutic treatment. Brief disease-free interval and cause-specific survival rates (Kaplan–Meier method) were compared using the log-rank test. A multivariate analysis (Cox-proportional hazards model) was used to determine the independent effect of each variable on prognosis. Overall 60 and 120 months cause-specific survival rates were 27.7% and 2.4%, respectively. The brief disease-free interval rate was 66.2%. In univariate analysis, VEGF (P = 0.0001 and P = 0.016), MVD (P < 0.0005), and the FIGO stage IIIC even more than FIGO stage IIIA (P = 0.01 and P < 0.0005, respectively) were associated with survival and brief disease-free interval, and the residual tumor was associated with survival (P = 0.021). In multivariate analysis, the factors that were independent predictors of survival were MVD (P < 0.0005), VEGF (P = 0.027), and the FIGO stage IIIC even more than FIGO stage IIIA (P = 0.013). Moreover, MVD was an independent predictor also of brief disease relapse (P = 0.001). Both MVD and VEGF were correlated with clinical response to chemotherapy (P = 0.01 and P = 0.037). Our data suggest that MVD and VEGF may have prognostic significance in advanced ovarian serous carcinoma.
Eccentric loading compared with shock wave treatment for chronic insertional achilles tendinopathy. A randomized, controlled trial.

BACKGROUND Nonoperative management of chronic tendinopathy of the Achilles tendon insertion has been poorly studied. With the recently demonstrated effectiveness of eccentric loading and of repetitive low-energy shock wave therapy in patients with midsubstance Achilles tendinopathy, the aim of the present randomized, controlled trial was to verify the effectiveness of both procedures exclusively in patients with insertional Achilles tendinopathy. METHODS Fifty patients with chronic (six months or more) recalcitrant insertional Achilles tendinopathy were enrolled in a randomized, controlled study. All patients had received treatment, including local injections of an anesthetic and/or corticosteroids, a prescription of nonsteroidal anti-inflammatory drugs, and physiotherapy, without success for at least three months. A computerized random-number generator was used to draw up an allocation schedule. Twenty-five patients were allocated to receive eccentric loading (Group 1), and twenty-five patients were allocated to treatment with repetitive low-energy shock wave therapy (Group 2). Analysis was on an intention-to-treat basis. Primary follow-up was at four months, and afterward patients were allowed to cross over. The last follow-up evaluation was at one year after completion of the initial treatment. The patients were assessed for pain, function, and activity with use of a validated questionnaire (the Victorian Institute of Sport Assessment-Achilles [VISA-A] questionnaire). RESULTS At four months from baseline, the mean VISA-A score had increased in both groups, from 53 to 63 points in Group 1 and from 53 to 80 points in Group 2. The mean pain rating decreased from 7 to 5 points in Group 1 and from 7 to 3 points in Group 2. Seven patients (28%) in Group 1 and sixteen patients (64%) in Group 2 reported that they were completely recovered or much improved. For all outcome measures, the group that received shock wave therapy showed significantly more favorable results than the group treated with eccentric loading (p = 0.002 through p = 0.04). At four months, eighteen of the twenty-five patients from Group I had opted to cross over, as did eight of the twenty-five patients from Group 2. The favorable results after shock wave therapy at four months were stable at the one-year follow-up evaluation. CONCLUSIONS Eccentric loading as applied in the present study showed inferior results to low-energy shock wave therapy as applied in patients with chronic recalcitrant tendinopathy of the insertion of the Achilles tendon at four months of follow-up. Further research is warranted to better define the indications for this treatment modality.
Homeostatic Plasticity Mediated by Rod-Cone Gap Junction Coupling in Retinal Degenerative Dystrophic RCS Rats

Rod-cone gap junctions open at night to allow rod signals to pass to cones and activate the cone-bipolar pathway. This enhances the ability to detect large, dim objects at night. This electrical synaptic switch is governed by the circadian clock and represents a novel form of homeostatic plasticity that regulates retinal excitability according to network activity. We used tracer labeling and ERG recording in the retinae of control and retinal degenerative dystrophic RCS rats. We found that in the control animals, rod-cone gap junction coupling was regulated by the circadian clock via the modulation of the phosphorylation of the melatonin synthetic enzyme arylalkylamine N-acetyltransferase (AANAT). However, in dystrophic RCS rats, AANAT was constitutively phosphorylated, causing rod-cone gap junctions to remain open. A further b/a-wave ratio analysis revealed that dystrophic RCS rats had stronger synaptic strength between photoreceptors and bipolar cells, possibly because rod-cone gap junctions remained open. This was despite the fact that a decrease was observed in the amplitude of both a- and b-waves as a result of the progressive loss of rods during early degenerative stages. These results suggest that electric synaptic strength is increased during the day to allow cone signals to pass to the remaining rods and to be propagated to rod bipolar cells, thereby partially compensating for the weak visual input caused by the loss of rods.
DNA Synthesis and Mitotic Clonal Expansion Is Not a Required Step for 3T3-L1 Preadipocyte Differentiation into Adipocytes*

Upon differentiation induction of 3T3-L1 preadipocytes by a hormone mixture containing 1-isobutyl-3-methylxanthine, dexamethasone, and insulin, the preadipocytes undergo ∼2 rounds of mitotic clonal expansion, which just precedes the adipogenic gene expression program and has been thought to be an essential early step for differentiation initiation. By inducing 3T3-L1 preadipocytes with each individual hormone, it was determined that the mitotic clonal expansion was induced only by insulin and not by 1-isobutyl-3-methylxanthine or dexamethasone. Cell number counting and fluorescence-activated cell-sorting analysis indicated that a significant fraction of 3T3-L1 preadipocytes differentiated into adipocytes without mitotic clonal expansion when induced with the combination of 1-isobutyl-3-methylxanthine and dexamethasone. Furthermore, when normally induced 3T3-L1 preadipocytes were treated with PD98059 (an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1) to block the activation of extracellular signal-regulated kinase (Erk) 1 and Erk2, the mitotic clonal expansion was blocked, but adipocyte differentiation was not affected. These observations were confirmed by bromodeoxyuridine labeling. The differentiated adipocytes induced with 1-isobutyl-3-methylxanthine and dexamethasone or standard hormone mixture plus PD98059 were not labeled by bromodeoxyuridine. Thus, it is evident that 3T3-L1 preadipocytes could differentiate into adipocytes without DNA synthesis and mitotic clonal expansion. Our results also suggested that activation of Erk1 and Erk2 is essential to but not sufficient for induction of mitotic clonal expansion.