Miracle-dz/UniFAR-FTUs huggingface dataset:
C Terminus of Nce102 Determines the Structure and Function of Microdomains in the Saccharomyces cerevisiae Plasma Membrane

ABSTRACT The plasma membrane of the yeast Saccharomyces cerevisiae contains stably distributed lateral domains of specific composition and structure, termed MCC (membrane compartment of arginine permease Can1). Accumulation of Can1 and other specific proton symporters within MCC is known to regulate the turnover of these transporters and is controlled by the presence of another MCC protein, Nce102. We show that in an NCE102 deletion strain the function of Nce102 in directing the specific permeases into MCC can be complemented by overexpression of the NCE102 close homolog FHN1 (the previously uncharacterized YGR131W) as well as by distant Schizosaccharomyces pombe homolog fhn1 (SPBC1685.13). We conclude that this mechanism of plasma membrane organization is conserved through the phylum Ascomycota. We used a hemagglutinin (HA)/Suc2/His4C reporter to determine the membrane topology of Nce102. In contrast to predictions, its N and C termini are oriented toward the cytosol. Deletion of the C terminus or even of its last 6 amino acids does not disturb protein trafficking, but it seriously affects the formation of MCC. We show that the C-terminal part of the Nce102 protein is necessary for localization of both Nce102 itself and Can1 to MCC and also for the formation of furrow-like membrane invaginations, the characteristic ultrastructural feature of MCC domains.
Risk factors associated with glucocorticoid-induced adverse effects in children with severe asthma.

BACKGROUND Although high-dose inhaled glucocorticoids (GCs) with or without chronically administered oral GCs are often used in children with severe persistent asthma, the adverse effects associated with their use have not been well-described in this patient population. OBJECTIVE We sought to determine the GC-induced adverse effects profile of older children with severe persistent asthma. METHODS A chart review of 163 consecutive children 9 years of age or older admitted to National Jewish for difficult to control asthma was done. RESULTS The population studied consisted mostly of adolescents (mean +/- SD age, 14.4 +/- 2.1 years) with severe asthma receiving high-dose inhaled GC therapy (1675 +/- 94 microg/d) and averaging 6 systemic GC bursts per year. 50% required chronic oral GC therapy. GC-associated adverse effects were common and included hypertension (88%), cushingoid features (66%), adrenal suppression (56%), myopathy (50%), osteopenia (46%), growth suppression (39%), obesity and hypercholesterolemia (30%), and cataracts (14%). Height standard deviation scores of -0.44, -1.22, and -0.93 for those receiving intermittent, alternate day, and daily oral GCs, respectively, were smaller (less suppressed) than published values from the same institution before inhaled GC therapy (standard deviation scores of -1.26, -1.91, and -1.95, respectively). Osteopenia was strongly associated with growth suppression (odds ratio, 5.6; confidence interval, 2.7-11.8; P <.0001) and was found to be more common in female than male subjects, even after correcting for short stature (42% vs 18%, P <.006). CONCLUSIONS GC-associated adverse effects are still unacceptably common among children with severe asthma, even in those not receiving chronically administered oral GC therapy yet receiving high-dose inhaled GCs. Therefore close monitoring and proper intervention are warranted, especially in female subjects, who appear to be at greater risk for osteopenia. There is clearly a need to consider alternative therapy or earlier intervention. The magnitude of growth suppression, while still a problem, appeared to be less severe with the addition of inhaled GC therapy. This observation suggests that high-dose inhaled GC therapy, by affording better asthma control and allowing less use of systemic therapy, has attenuated the growth-suppressive effects of poorly controlled asthma.
Cross-Scan Asymmetry of AMSU-A Window Channels: Characterization, Correction, and Verification

More than one decade of observations from the Advanced Microwave Sounding Unit-A (AMSU-A) onboard the polar-orbiting satellites NOAA-15 to NOAA-19 and European Meteorological Operational satellite program-A (MetOp-A) provide global information on atmospheric temperature profile, water vapor, cloud, precipitation, etc. However, a pronounced asymmetric cross-scan bias of the AMSU-A window channels was discovered, and it severely impacted water cycle product generation. Several approaches, including vicarious cold and hot reference calibration techniques, are applied to characterize the cross-scan bias. The bias pattern appears to be stable through several years of data examined from the same satellite but is quite different among those onboard the different NOAA (NOAA-15, NOAA-16, NOAA-17, NOAA-18, and NOAA-19) and EUMETSAT (MetOp-A) satellites. The scan bias may be caused by sensor polarization misalignment or cross-polarization, even after the radiance/brightness temperature data have been geocorrected with regard to geolocation and view angles. Based upon the characterization information, two-point and three-point correction approaches are proposed; both approaches provide promising results for AMSU-A window channels at brightness temperature level and product level and outperform the current operational correction approach, which is essentially a one-point correction. This serves as the first step toward a more stable fundamental and thematic climate data record to be used in hydrological and meteorological applications.
The immune response against herpesvirus is more prominent in the early stages of MS

Objective: To assess antibody levels against human herpesvirus type 6 (HHV-6), Epstein-Barr virus (EBV), and Chlamydia pneumoniae (CP) in serum from individuals in the early and late phase of MS. Results: A strong association was found between anti-HHV-6 immunoglobulin M antibodies and early MS (clinically isolated syndromes at high risk for MS, and short duration active relapsing-remitting MS) when compared with healthy controls and secondary progressive MS. Moreover, in this group of patients, titers for anti-EBV immunoglobulin G were also elevated. The authors found no association between the levels of serum antibodies against CP and MS, nor did they detect the presence of DNA for these pathogens in the serum of patients with MS. Finally, serum from two patients with other inflammatory neurologic diseases also had elevated immunoglobulin M antibodies to HHV-6, indicating that the presence of this antibody is not specific to MS. Conclusion: An immune response against herpesviruses such as HHV-6 and EBV is associated with early MS.
The Impact of Item Characteristics on Item and Scale Validity

This study describes the relation between personality items' validities, defined as the items' correlations with acquaintance ratings on the Big 5 personality factors, and other itemmetric properties including ambiguity, syntactic complexity, social desirability, content, and trait indicativity. Five external validity coefficients for each item on the California Psychological Inventory were correlated with a number of itemmetric variables often assumed to affect item validity. Item validity correlated positively with social desirability and trait indicativity and negatively with ambiguity across the five factors. Other characteristics had a more limited influence on item validity. Multiple regression analyses revealed trait indicativity -- how obviously an item response indicates a trait -- to be the most important determinant of item validity. Scales built from itemmetrically sound versus poor items showed differential validity in two additional samples. Implications for the psychological processes underlying responses to personality items are discussed.
On the design of economic NMPC based on approximate turnpike properties

We discuss the design of sampled-data economic nonlinear model predictive control schemes for continuous-time systems based on turnpike properties. In a recent paper we have shown that an exact turnpike property allows establishing finite-time convergence of the NMPC scheme to the optimal steady state, and also recursive feasibility, without using terminal penalties or terminal constraints. Herein, we extend our previous results to the more general case of approximate turnpikes. We establish sufficient conditions, based on a dissipativity assumption, that guarantee (i) convergence to a neighborhood of the optimal steady state, and (ii) recursive feasibility in the presence of state constraints. The proposed conditions do not rely on terminal regions or terminal penalties. A key step in our developments is the use of a storage function as a penalty on the initial condition in the NMPC scheme. We draw upon the example of a chemical reactor to illustrate our findings.
Effect of Omega-3 Fatty Acids in Diet of Type I Diabetic Subjects on Lipid Values and Hemorheological Parameters

Twelve type I (insulin-dependent) diabetic subjects in stable metabolic control for at least 3 mo received a controlled diet containing 50% carbohydrate, 35% fat, and 15% protein. Calorie intake varied from 1800 to 2200 calories, depending on individual needs. Part of the polyunsaturated omega-6 fatty acids (ω6FAs) were isocalorically exchanged with ω3FAs (2.7 g/day provided by fish oil concentrates) for 10 wk. Subject selection was based on the fact that the atherogenic index (total cholesterol/high-density lipoprotein cholesterol [HDL-chol]) remained >5. Total cholesterol did not change, but HDL-chol (P < .05) increased significantly, and the mean ± SD atherogenic index decreased from 5.9 ± 1.1 to 5.1 ± 1.3. Plasma triglyceride levels also decreased (P < .05). There was a small (∼2%) but significant (P < .05) decrease of whole-blood viscosity at low shear rate because of a similarly small (∼2%) decrease (P < .05) of plasma viscosity. Erythrocyte viscosity values and the erythrocyte transit time, measured with the St. George's filtrometer, remained unchanged during fish oil intake. Four weeks after stopping the ω3FA administration, the triglyceride level was again increased (P < .05) and was even higher than the starting value (P < .05). Plasma and whole-blood viscosity also increased to the starting levels, demonstrating that lipid alterations are accompanied with blood viscosity changes in the presence of a stable metabolic control.
A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B.

BACKGROUND Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus (HBV). METHODS In this phase 3, double-blind trial, we randomly assigned 715 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had not previously received a nucleoside analogue to receive either 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks. The primary efficacy end point was histologic improvement (a decrease by at least two points in the Knodell necroinflammatory score, without worsening of fibrosis) at week 48. Secondary end points included a reduction in the serum HBV DNA level, HBeAg loss and seroconversion, and normalization of the alanine aminotransferase level. RESULTS Histologic improvement after 48 weeks occurred in 226 of 314 patients in the entecavir group (72 percent) and 195 of 314 patients in the lamivudine group (62 percent, P=0.009). More patients in the entecavir group than in the lamivudine group had undetectable serum HBV DNA levels according to a polymerase-chain-reaction assay (67 percent vs. 36 percent, P<0.001) and normalization of alanine aminotransferase levels (68 percent vs. 60 percent, P=0.02). The mean reduction in serum HBV DNA from baseline to week 48 was greater with entecavir than with lamivudine (6.9 vs. 5.4 log [on a base-10 scale] copies per milliliter, P<0.001). HBeAg seroconversion occurred in 21 percent of entecavir-treated patients and 18 percent of those treated with lamivudine (P=0.33). No viral resistance to entecavir was detected. Safety was similar in the two groups. CONCLUSIONS Among patients with HBeAg-positive chronic hepatitis B, the rates of histologic, virologic, and biochemical improvement are significantly higher with entecavir than with lamivudine. The safety profile of the two agents is similar, and there is no evidence of viral resistance to entecavir. (ClinicalTrials.gov number, NCT00035633.).
Simultaneous quantification of actin monomer and filament dynamics with modeling-assisted analysis of photoactivation

ABSTRACT Photoactivation allows one to pulse-label molecules and obtain quantitative data about their behavior. We have devised a new modeling-based analysis for photoactivatable actin experiments that simultaneously measures properties of monomeric and filamentous actin in a three-dimensional cellular environment. We use this method to determine differences in the dynamic behavior of β- and γ-actin isoforms, showing that both inhabit filaments that depolymerize at equal rates but that β-actin exists in a higher monomer-to-filament ratio. We also demonstrate that cofilin (cofilin 1) equally accelerates depolymerization of filaments made from both isoforms, but is only required to maintain the β-actin monomer pool. Finally, we used modeling-based analysis to assess actin dynamics in axon-like projections of differentiating neuroblastoma cells, showing that the actin monomer concentration is significantly depleted as the axon develops. Importantly, these results would not have been obtained using traditional half-time analysis. Given that parameters of the publicly available modeling platform can be adjusted to suit the experimental system of the user, this method can easily be used to quantify actin dynamics in many different cell types and subcellular compartments. Summary: We have devised a new modeling-based analysis for photoactivatable actin experiments that accurately measures multiple parameters of actin dynamics, providing more detailed results than those obtained using traditional half-time analysis.
A determinant in the cytoplasmic tail of the cation-dependent mannose 6- phosphate receptor prevents trafficking to lysosomes

The bovine cation-dependent mannose 6-phosphate receptor (CD-MPR) is a type 1 transmembrane protein that cycles between the trans-Golgi network, endosomes, and the plasma membrane. When the terminal 40 residues were deleted from the 67-amino acid cytoplasmic tail of the CD- MPR, the half-life of the receptor was drastically decreased and the mutant receptor was recovered in lysosomes. Analysis of additional cytoplasmic tail truncation mutants and alanine-scanning mutants implicated amino acids 34-39 as being critical for avoidance of lysosomal degradation. The cytoplasmic tail of the CD-MPR was partially effective in preventing the lysosomal membrane protein Lamp1 from entering lysosomes. Complete exclusion required both the CD-MPR cytoplasmic tail and transmembrane domain. The transmembrane domain alone had just a minor effect on the distribution of Lamp1. These findings indicate that the cytoplasmic tail of the CD-MPR contains a signal that prevents the receptor from trafficking to lysosomes. The transmembrane domain of the CD-MPR also contributes to this function.
Blocking NMDA-receptors in the pigeon’s “prefrontal” caudal nidopallium impairs appetitive extinction learning in a sign-tracking paradigm

Extinction learning provides the ability to flexibly adapt to new contingencies by learning to inhibit previously acquired associations in a context-dependent manner. The neural networks underlying extinction learning were mostly studied in rodents using fear extinction paradigms. To uncover invariant properties of the neural basis of extinction learning, we employ pigeons as a model system. Since the prefrontal cortex (PFC) of mammals is a key structure for extinction learning, we assessed the role of N-methyl-D-aspartate receptors (NMDARs) in the nidopallium caudolaterale (NCL), the avian functional equivalent of mammalian PFC. Since NMDARs in PFC have been shown to be relevant for extinction learning, we locally antagonized NMDARs through 2-Amino-5-phosphonovalerianacid (APV) during extinction learning in a within-subject sign-tracking ABA-renewal paradigm. APV-injection slowed down extinction learning and in addition also caused a disinhibition of responding to a continuously reinforced control stimulus. In subsequent retrieval sessions, spontaneous recovery was increased while ABA renewal was unaffected. The effect of APV resembles that observed in studies of fear extinction with rodents, suggesting common neural substrates of extinction under both appetitive and aversive conditions and highlighting the similarity of mammalian PFC and the avian caudal nidopallium despite 300 million years of independent evolution.
The Antimicrobial Peptide Cathelicidin Protects Mice from Escherichia coli O157:H7-Mediated Disease

This study investigated the role of the antimicrobial peptide cathelicidin in Escherichia coli O157:H7 infection and subsequent renal damage. Mouse and human cathelicidin, CRAMP and LL-37, respectively, killed E. coli O157:H7 in vitro. Intestines from healthy wild-type (129/SvJ) and cathelicidin-knock-out (Camp−/−) mice were investigated, showing that cathelicidin-deficient mice had a thinner colonic mucus layer compared with wild-type mice. Wild-type (n = 11) and cathelicidin-knock-out (n = 11) mice were inoculated with E. coli O157:H7. Cathelicidin-deficient animals exhibited higher fecal counts of E. coli O157:H7 and bacteria penetrated the mucus forming attaching-and-effacing lesions to a much higher extent than in wild-type animals. Cathelicidin knock-out mice developed symptoms (9/11) as well as anemia, thrombocytopenia and extensive renal tubular damage while all cathelicidin-producing mice remained asymptomatic with normal laboratory findings. When injected with Shiga toxin intraperitoneally, both murine strains developed the same degree of renal tubular damage and clinical disease indicating that differences in sensitivity to infection between the murine strains were related to the initial intestinal response. In conclusion, cathelicidin substantially influenced the antimicrobial barrier in the mouse colon mucosa. Cathelicidin deficiency lead to increased susceptibility to E. coli O157:H7 infection and subsequent renal damage. Administration of cathelicidin or stimulation of endogenous production may prove to be novel treatments for E. coli O157:H7-induced hemolytic uremic syndrome.
Technique and ground reaction forces in the back handspring

The ground reaction forces at the hand that produced compression forces and varus/valgus moments at the elbow joint during the double-arm support phase of the back handspring were studied. The relationship of tech nique, namely elbow joint flexion, to these forces were also studied. Compression forces and forces producing valgus moments have been implicated in overuse inju ries to the elbow joint. Video and force plate analysis of six young female gymnasts showed that 1) the elbow joint flexed during the double-arm support phase, and 2) the reaction forces at the hand produced large compression forces (an average of 2.37 times body weight) and sizable valgus moments at the elbow (an average of 0.03 times body weight times body height). The combination of these forces may contribute to the occurrence of lateral compression injuries of the elbow joint (e.g., osteochondritis dissecans of the capitellum). Correlations of measures of elbow angle and measures of reaction force showed that large elbow flexions may protect the elbow from large valgus moments.
Lenalidomide Enhances Antigen-Specific Activity and Decreases CD45RA Expression of T Cells from Patients with Multiple Myeloma

The aim of this study was to investigate whether the specific T cell response against the multiple myeloma Ag HM1.24 is enhanced by the immunomodulatory drug lenalidomide (Revlimid). Ag-specific CD3+CD8+ T cells against the HM1.24 Ag were expanded in vitro by dendritic cells in 29 healthy donors and 26 patients with plasma cell dyscrasias. Ag-specific activation was analyzed by IFN-γ, granzyme B, and perforin secretion using ELISA, ELISPOT assay, and intracellular staining, and generation of Ag-specific T cells was analyzed by tetramer staining. Expression of T cell maturation markers (CD45RA, CD45R0, CCR7, and CD28) was investigated by flow cytometry. We found that activation of HM1.24-specific T cells from healthy donors and patients with plasma cell dyscrasias was enhanced significantly by lenalidomide and furthermore that the impact of lenalidomide on T cells depends on the duration of the exposure. Notably, lenalidomide supports the downregulation of CD45RA on T cells upon activation, observed in healthy donors and in patients in vitro and also in patients during lenalidomide therapy in vivo. We showed for the first time, to our knowledge, that lenalidomide enhances the Ag-specific activation of T cells and the subsequent downregulation of CD45RA expression of T cells in vitro and in vivo.
Early Weight Gain, Linear Growth, and Mid‐childhood Blood Pressure

To investigate relations of change in body mass index (BMI) and length/height during 4 early life age intervals (birth to 6mo, 6mo to 1y, 1 to 2y, and 2 to 3y) with mid‐childhood systolic blood pressure (SBP), and to evaluate for effect modification by birth size (birthweight‐for‐gestational age z‐score).
Increased risk of antibody-mediated rejection of reduced-size liver allografts.

Because of the shortage of liver allografts in children, transplantation of reduced-size liver allografts from adult cadaveric donors or living, related donors is being done more frequently. Reduced-size liver allografts may be used in cases of ABO incompatibility and T-cell warm cross-match positivity. This experimental study in inbred rats was undertaken to determine if reduced-size liver allografts are more sensitive to antibody-mediated rejection than full-size liver allografts. Brown-Norway (BN) (RT1(n)) rats were sensitized by three successive skin grafts at 10-day intervals. Then orthotopic Lewis (LEW) (RT1(1)) liver grafts were transplanted into these BN rats. Full-size liver allografts were compared with reduced-size liver allografts (70% of donor liver). Control groups were composed of full-size and/or reduced-size isografts. Titers of specific antibodies were assayed using a complement-dependent assay before and after orthotopic liver transplantation. Histological and immunofluorescence studies (IgG, IgM, C(3), and fibrinogen deposits) were assessed. Recipients of reduced-size liver allografts died of hyperacute rejection at 36.6 +/- 4.1 h, significantly earlier than recipients receiving full-size liver allografts, which died of accelerated acute rejection at 259.2 +/- 25.2 h (P < 0.001). Either full-size or reduced-size isograft recipients survived indefinitely. A decrease in the titers of donor-specific antibodies was observed in both groups of animals. Slight deposits of IgG, IgM, C(3), and fibrinogen were observed in recipients of reduced-size liver allografts, whereas larger deposits were observed in recipients of full-size liver allografts. Our data demonstrate that there is an increased risk of antibody-mediated rejection of reduced-size liver allografts in sensitized recipients. This may have important clinical implications for partial liver grafting in cases of ABO incompatibility and T-cell warm cross-match positivity.