Miracle-dz/UniFAR-FTUs huggingface dataset:
Eclipsed distribution: A phenomenon of dual targeting of protein and its significance

One of the surprises from genome sequencing projects is the apparently small number of predicted genes in different eukaryotic cells, particularly human. One possible reason for this ‘shortage’ of genes is multiple distribution of proteins; a single protein is targeted to more than one subcellular compartment and consequently participates in different biochemical pathways and might have completely different functions. Indeed, in recent years, there have been reports on proteins that were found to be localized in cellular compartments other than those initially attributed to them. Furthermore, the phenomenon of highly uneven isoprotein distribution was recently observed and termed ‘eclipsed distribution’. In these cases, the amount of one of the isoproteins, in one of the locations, is significantly minute and its detection by standard biochemical and visualization methods is masked by the presence of the dominant isoprotein. In fact, the minute amounts of eclipsed proteins can be essential. Since detecting eclipsed distribution is difficult, we assume that this phenomenon is probably more common than currently recorded. Hence, developing methods for localization and functional detection of eclipsed proteins is a challenge in cell biology research. Finally, eclipsed distribution may lead to cellular pathologies as has been suggested to occur in human disorders such as Prion diseases and Alzheimer. This review provides a short description of the eclipsed distribution phenomenon followed by an overview of protein distribution mechanisms, examples of eclipsed distribution and experimental approaches for revealing these elusive proteins. BioEssays 29:772–782, 2007. © 2007 Wiley Periodicals, Inc.
Baroreflex Control of Sympathetic Nerve Activity in Hypertensive Pregnant Rats with Reduced Uterine Perfusion

Objective: Baroreflex sensitivity is reduced in women with preeclampsia. The aim of this study was to determine whether baroreflex control of renal sympathetic nerve activity (RSNA) is altered in pregnant rats with reduced uterine perfusion (a model of human preeclampsia). Methods: Uterine perfusion was reduced in the third trimester by clipping the distal aorta and uterine branches of the ovarian arteries. RSNA baroreflex parameters were compared at term gestation in rats with reduced uterine perfusion (n = 12), in normal pregnant rats (n = 14) and in nonpregnant rats (n = 14). Results: Reduced perfusion rats were hypertensive (123.6 ± 2.3 mm Hg), and normal pregnant rats were hypotensive (97.7 ± 2.2 mm Hg), compared with controls. In rats with reduced perfusion, the baroreflex was shifted to a higher set-point, and maximum and minimum RSNA were increased compared with normal pregnant rats. Conclusion: The blunted baroreflex gain of normal pregnancy is maintained in rats with reduced uterine perfusion, but a hypertensive shift in baroreflex function exists in this rat model that is associated with a reversal of the reflex maximum and minimum RSNA observed in normal pregnancy.
Increased IL-10 mRNA and IL-23 mRNA expression in multiple sclerosis: interferon-β treatment increases IL-10 mRNA expression while reducing IL-23 mRNA expression

Background Interferon (IFN)-β therapy in multiple sclerosis (MS) has been suggested to promote a deviation from T lymphocyte production of pathogenic Th1 cytokines to less detrimental Th2 cytokines, but this is still controversial. We studied patterns of in vivo blood mononuclear cell (MNC) and whole blood cytokine and transcription factor mRNA expression before and during IFN-β therapy in MS. Methods Twenty patients with relapsing–remitting MS were sampled before and after 3 months of treatment with IFN-β along with 15 healthy volunteers. An additional 39 patients and 50 healthy volunteers served to confirm initial findings. mRNA was analyzed by real-time reverse transcriptase polymerase chain reaction (PCR). Results We found elevated expression of interleukin (IL)-23 and IL-10 in untreated MS patients. IFN-β therapy increased IL-10 and decreased IL-23 expression independently of any Th1 or Th2 cytokines. The largest changes in cytokine mRNA levels occurred early (~9–12 h) after an IFN-β injection. Conclusion We found no evidence of a Th1- or Th2-mRNA-promoting effect of IFN-β therapy. The therapeutic effect of IFN-β is more likely attributable to the induction of the regulatory cytokine IL-10. The elevated IL-23 mRNA levels in MS patients are noteworthy in view of the newly discovered IL-23-driven Th17 T-cell subset, which is crucial in animal models of MS. Since IFN-β therapy resulted in decreased IL-23 mRNA levels, the Th17 axis could be another target of IFN-β therapy.
The Infusion Illusion

Currently, the standard of care for high-risk peptic ulcer bleeding involves the use of a continuous intravenous proton pump inhibitor (PPI) infusion over 72 h. However, the article by Andruilli et al. details the results of a randomized controlled trial indicating that a less intensive regimen consisting of a once-daily bolus of PPI injection may lead to similar outcomes when compared to standard therapy. We will discuss these findings as well as comment on their validity, generalizability, and adaptability to clinical practice.
Failure to complement infectivity of EBV and HSV-1 glycoprotein B (gB) deletion mutants with gBs from different human herpesvirus subfamilies.

Glycoprotein B (gB) is conserved among the herpesvirus family which infects a broad range of species. To investigate the functional homology of human alpha-herpesviruses, beta-herpesviruses, and gamma-herpesviruses gB proteins, complementation studies were performed with gB genes from each subfamily member using EBV gp110 (EBV gB homologue) and HSV-1 gB null mutants. Neither the alpha-herpesvirus HSV-1 gB gene nor the beta-herpesvirus HCMV gB gene were able to complement the gp110 null mutant. Conversely, neither the beta-herpesvirus HCMV gB or the gamma-herpesvirus EBV gp110 gene were able to complement HSV-1 gB null mutants. To further investigate functional domains of EBV gp110 and HSV-1 gB, gB-gp110 chimeric proteins were constructed. Surprisingly, none of the chimeric proteins were able to complement either HSV-1 gB null mutants or EBV gp110 null mutants. These results demonstrate that there is not sufficient functional homology between the different gBs to allow complementation in other subfamily members of the herpesvirus family.
Comparison of pulp response to mineral trioxide aggregate and a bioceramic paste in partial pulpotomy of sound human premolars: a randomized controlled trial.

AIM This randomized clinical trial evaluated clinical sign/symptoms as well as histological pulp reactions in terms of inflammation and mineralized bridge formation after partial pulpotomy of sound human premolars and placement of a bioceramic paste (iRoot BP) or tooth-colored ProRoot MTA as pulp-covering biomaterials. METHODOLOGY Twenty-four human sound premolars were randomly allocated into two experimental groups (n = 12) treated either with iRoot BP or MTA subsequent to partial pulpotomy. Six weeks after treatment, clinical sign/symptoms and radiographic changes were evaluated. The teeth were then extracted and examined histologically for inflammatory status of the pulp, formation of hard tissue bridge and appearance of the bridge. In terms of pulp inflammation and dentinal bridge formation, the Mann-Whitney U, and for clinical signs, the chi-square test was used (α = 0.05). RESULTS In terms of pulp inflammation, formation of hard tissue bridge and its appearance, the differences between the two experimental groups were not significant. However, clinical sensitivity to cold was significantly less for teeth treated with MTA (P < 0.05). All cases had formed a hard tissue bridge, and none of the specimens in either group had pulpal necrosis. CONCLUSION When treating teeth with healthy pulps, the response to partial pulpotomy treatment with both MTA and iRoot BP was favourable. However, pulps covered with iRoot BP were more sensitive to cold stimuli.
Medicines Compliance and Reimbursement Level in Portugal

During a severe financial crisis, it is a priority to use scientific evidence to identify factors that enable therapeutic compliance by patients. This study aimed to evaluate a possible association between the number of patients who attended a medical appointment and had medicine prescribed and the number of these same patients who purchased the prescribed medicine and whether the level of reimbursement was a deciding factor. We perform a correlation analysis at primary care centers in Portugal, between 2010 and 2012 (n = 96). We found a moderate to high positive association, which is statistical significant, between the number of the patients with medicines dispensing and medicines reimbursement levels. The correlation coefficient varies from . 5 to . 63 (P < .01). The compliance increases along with the increase in the reimbursement levels.
Chylomicronemia With a Mutant GPIHBP1 (Q115P) That Cannot Bind Lipoprotein Lipase

Objective—GPIHBP1 is an endothelial cell protein that binds lipoprotein lipase (LPL) and chylomicrons. Because GPIHBP1 deficiency causes chylomicronemia in mice, we sought to determine whether some cases of chylomicronemia in humans could be attributable to defective GPIHBP1 proteins. Methods and Results—Patients with severe hypertriglyceridemia (n=60, with plasma triglycerides above the 95th percentile for age and gender) were screened for mutations in GPIHBP1. A homozygous GPIHBP1 mutation (c.344A>C) that changed a highly conserved glutamine at residue 115 to a proline (p.Q115P) was identified in a 33-year-old male with lifelong chylomicronemia. The patient had failure-to-thrive as a child but had no history of pancreatitis. He had no mutations in LPL, APOA5, or APOC2. The Q115P substitution did not affect the ability of GPIHBP1 to reach the cell surface. However, unlike wild-type GPIHBP1, GPIHBP1-Q115P lacked the ability to bind LPL or chylomicrons (d < 1.006 g/mL lipoproteins from Gpihbp1−/− mice). Mouse GPIHBP1 with the corresponding mutation (Q114P) also could not bind LPL. Conclusions—A homozygous missense mutation in GPIHBP1 (Q115P) was identified in a patient with chylomicronemia. The mutation eliminated the ability of GPIHBP1 to bind LPL and chylomicrons, strongly suggesting that it caused the patient’s chylomicronemia.
Molecular Inflammatory Mediators in Peripheral Nerve Degeneration and Regeneration

Wallerian degeneration, the self-destructive set of cellular and molecular processes by which degenerating axons and myelin are cleared after injury, is initiated by macrophages and Schwann cells. Molecular inflammatory mediators such as cytokines (IL-1, IL-6, IL-10, and TNF-α, among others), transcription factors (NF-ĸB, c-Jun), the complement system and arachidonic acid metabolites have been shown to modulate these processes in various studies. However, the exact role that each of these mediators plays during axonal degeneration and regeneration has not been fully established. Understanding the molecular basis of these interactions between the immune system and peripheral nerve injury would open the possibility of targeting these inflammatory mediators as therapeutic interventions. In this review we attempt to integrate the current evidence generated around this issue, and to explore the therapeutic possibilities that arise.
Comparative study of root-canal preparation using Lightspeed and Quantec SC rotary NiTi instruments.

AIM To compare several parameters of root-canal preparation using two different rotary nickel-titanium (NiTi) instruments: Lightspeed (Lightspeed Inc, San Antonio, TX, USA) and Quantec SC (Tycom, Irvine, USA). METHODOLOGY Fifty extracted mandibular molars with root-canal curvatures between 20 degrees and 40 degrees were embedded into a muffle system. All root canals were prepared to size 45 followed by a stepback in 1-mm increments to size 70 (Lightspeed) or 45 (Quantec SC), using a high-torque motor at 1300 or 350 r.p.m. respectively. In both groups, irrigation was performed with 2 mL NaOCl (3%) after each instrument size. RC-Prep (Premier, PA, USA) was used as a chelating agent. The following parameters were evaluated: straightening of curved root canals, postoperative root-canal diameter, working safety (instrument fractures, perforations, apical blockages, loss of working length (WL)), cleaning ability and working time. Cleanliness of the root-canal walls was investigated under SEM using 5-score indices for debris and smear layer. Statistical analysis was performed using the Wilcoxon's test (P < 0.05) for straightening and Fisher's exact test (P < 0.05) for comparison of cross-sections, contact between pre- and postoperative diameter, root-canal cleanliness and working time. RESULTS Both NiTi systems maintained the curvature well: the mean degree of straightening was 1.8 degrees for Lightspeed and 1.7 degrees for Quantec SC; differences were not significant. Procedural incidents occurred with Quantec SC in 12 root canals (three fractures, four apical blockages and five cases of loss of WL), preparation with Lightspeed resulted in five fractures, one apical blockage and five cases of loss of WL (11 incidents). Following preparation with Lightspeed, 55.5% of the root canals had a round diameter, 25% an oval and 19.5% an irregular diameter; Quantec SC preparations resulted in a round diameter in 51.5%, oval shape in 33.3% and irregular cross-sections in 15.2% of the cases. Mean working time was similar for Quantec SC (161 s) and Lightspeed (155 s); the difference was not significant. For debris, Lightspeed and Quantec achieved 64 and 63% for scores 1 and 2, respectively. For smear layer, Lightspeed and Quantec achieved only 13.3 and 27.4% for scores 1 and 2, respectively. Differences were not significant for either debris or smear layer. CONCLUSIONS Both systems respected original root-canal curvature well and prepared acceptable diameter forms. The cleaning ability was judged not satisfactory for both systems. Both systems showed deficiencies in working safety.
Increased sensitization in urban vs. rural environment – Rural protection or an urban living effect?

In a population‐based longitudinal cohort study, we tested the hypothesis that children growing up in a high‐traffic polluted urban area (UA) in the Athens’ basin have higher prevalence of allergies and sensitization when compared with those growing up in a Greek provincial rural area (RA). We recruited 478 and 342 children aged 8–10 living in the UA and the RA, respectively. Respiratory health was assessed by a parent‐completed questionnaire in three phases: 1995–96 (phase 1), 1999–2000 (phase 2), 2003–04 (phase 3) and skin‐prick testing to common indoor and outdoor aeroallergens was performed at phases 1 and 2. Reported asthma and eczema did not differ between the two areas, whereas reported hay fever was persistently more prevalent in the UA than in the RA (16.5%, 17.0%, 18.2% vs. 7.0%, 8.3%, 9.6%, respectively). Sensitization was more prevalent in the UA at both phases (19.0% vs. 12.1% in phase 1, 20.0% vs. 14.1% in phase 2). Residential area contributed independently to sensitization to ≥1 aeroallergens (OR: 0.29; 95% CI: 0.13–0.66; p = 0.003) and to polysensitization (OR: 0.28; 95% CI: 0.10–0.82; p = 0.020) in phase 1. These associations were independent of farming practices. No significant contributions were found in phase 2. Our results suggest that long‐term exposure to urban environment is associated with a higher prevalence of hay fever but not of asthma or eczema. The negative association between rural living and the risk of atopy during childhood, which is independent of farming practices, implies that it is mainly driven by an urban living effect.
A statistical process control approach for automatic anti-islanding detection using synchrophasors

Anti-islanding protection is becoming increasingly important due to the rapid installation of distributed generation from renewable resources like wind, tidal and wave, solar PV, bio-fuels, as well as from other resources like diesel. Unintentional islanding presents a potential risk for damaging utility plants and equipment connected from the demand side, as well as to public and personnel in utility plants. This paper investigates automatic islanding detection. This is achieved by deploying a statistical process control approach for fault detection with the real-time data acquired through a wide area measurement system, which is based on Phasor Measurement Unit (PMU) technology. In particular, the principal component analysis (PCA) is used to project the data into principal component subspace and residual space, and two statistics are used to detect the occurrence of fault. Then a fault reconstruction method is used to identify the fault and its development over time. The proposed scheme has been used in a real system and the results have confirmed that the proposed method can correctly identify the fault and islanding site.
Mapping of the Region of Complement Receptor (CR) 1 Required for Plasmodium falciparum Rosetting and Demonstration of the Importance of CR1 in Rosetting in Field Isolates1

The malaria parasite Plasmodium falciparum induces a number of novel adhesion properties in the erythrocytes that it infects. One of these properties, the ability of infected erythrocytes to bind uninfected erythrocytes to form rosettes, is associated with severe malaria and may play a direct role in the pathogenesis of disease. Previous work has shown that erythrocytes deficient in complement receptor (CR) 1 (CR1, CD35; C3b/C4b receptor) have greatly reduced rosetting capacity, indicating an essential role for CR1 in rosette formation. Using deletion mutants and mAbs, we have localized the region of CR1 required for the formation of P. falciparum rosettes to the area of long homologous repeat regions B and C that also acts as the binding site for the activated complement component C3b. This result raises the possibility that C3b could be an intermediary in rosetting, bridging between the infected erythrocyte and CR1. We were able to exclude this hypothesis, however, as parasites grown in C3-deficient human serum formed rosettes normally. We have also shown in this report that rosettes can be reversed by mAb J3B11 that recognizes the C3b binding site of CR1. This rosette-reversing activity was demonstrated in a range of laboratory-adapted parasite strains and field isolates from Kenya and Malawi. Thus, we have mapped the region of CR1 required for rosetting and demonstrated that the CR1-dependent rosetting mechanism occurs commonly in P. falciparum isolates, and could therefore be a potential target for future therapeutic interventions to treat severe malaria.
Spatiotemporal Characteristics of Acid Refluxate and Relationship to Symptoms in Premature and Term Infants with Chronic Lung Disease

BACKGROUND AND OBJECTIVES:The prevalence of gastroesophageal reflux (GER) is high among infants with chronic lung disease (CLD), and the associated pathogenic mechanisms are not clear. The relationship of symptoms to the extent or duration of acid reflux events (AREs) is not well known in preterm or term infants. Our aim was to evaluate the relationship between spatial (height) and temporal (duration) characteristics of AREs (pH <4.0) with symptoms in CLD. We tested the hypothesis that in infants with CLD, AREs into the pharynx are associated with increased symptom occurrence and delayed clearance.METHODS:Nine infants born at 29.8 ± 5.5 wk gestation (mean ± SD, range 24.7–39.0 wk) with CLD were evaluated for GER at 49.7 ± 8.0 wk postmenstrual age (mean ± SD, range 39.9–67.4 wk). Esophageal manometry was first performed to determine the nares–lower esophageal sphincter (LES) distance. A pH-impedance probe was placed at 87% of the nares–LES distance, and a recording was performed for about 24 h at cribside. Symptoms (respiratory, sensory, and movement) were documented by nurses that were blinded to the pH-impedance recordings. A symptom was considered associated with an ARE if it occurred 2 min before, during, or 2 min after the ARE. The proximal extent and associated clearance mechanisms were correlated with symptom sensitivity index (SSI = number of AREs with symptoms/total AREs * 100). Multiple logistic regression methods, analysis of variance (ANOVA) models, and χ2 tests were performed. Data are described as median, mean ± SD, or %. RESULTS:A total of 511 AREs, based on pH-Impedance methods, were analyzed from 203 h of recordings in the nine infants. The distal esophagus was the maximal height reached in 80% of AREs (P < 0.001, compared to other esophageal segments). Overall 33% of the AREs were associated with symptoms, and an SSI of 77% was noted with high AREs into the pharynx. The average acid clearance time was prolonged with symptomatic AREs versus nonsymptomatic AREs by 3.5-fold (P < 0.001). CONCLUSIONS:The occurrence and frequency of symptoms with AREs depend on the most proximal extent of the ARE and the acid clearance time.
Population pharmacokinetic and pharmacodynamic analyses of teicoplanin in Japanese patients with systemic MRSA infection.

BACKGROUND Teicoplanin is a glycopeptide antibiotic used for the treatment of MRSA infection. An initial loading dose of 400 mg every 12 hours for three doses is the standard dosing regimen. This study aimed to assess whether this regimen was appropriate based on the pharmacokinetic/pharmacodynamic (PK/PD) analyses in Japanese patients. METHODS We conducted a population pharmacokinetic (PPK) analysis of teicoplanin by NONMEM using serum drug concentrations obtained from 116 patients with MRSA infection. PD of the drug was analyzed by a model assuming that the variability of therapeutic responses (assessed by body temperature, serum C-reactive protein concentrations, and white blood cell counts) on the 3rd, 7th or 14th day of treatment is associated with the logarithm of serum unbound drug concentration (Cmax,unbound) divided by the MIC against MRSA (log[Cmax,unbound/MIC]). RESULTS The final PPK model showed that creatinine clearance and serum albumin concentration were significant (p < 0.01) covariates of systemic clearance and peripheral volume of distribution of teicoplanin, respectively. The PD analyses indicated that log[Cmax,unbound/MIC] of 0.30 on Day 3 of teicoplanin therapy was the threshold for achieving successful clinical responses. Integrating the PK and PD data, we consider that the standard loading dose regimen would attain the threshold serum level within the initial 3 days in only less than 50% of the patients. CONCLUSION We propose that an extended loading regimen (400 mg every 12 hours for the first 5 doses) would be a treatment option to maximize the therapeutic effects of teicoplanin in patients with systemic MRSA infection.