Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of long-lived proteins retained in cells undergoing repeated asymmetric divisions

Significance Long-lived proteins in extracellular spaces (joints/tissues) or within specialized nondividing cells (eye-lens) are associated with age-related decline. However, aging also occurs in dividing stem cells. Although several hypotheses have been proposed to explain how stem cells age, none have addressed whether long-lived proteins contribute to aging, partially because of technical challenges in identifying such proteins. We developed a method to overcome these limitations in the model system Saccharomyces cerevisiae. We identified two classes of long-lived asymmetrically retained proteins (LARPs). Full-length LARPs remain intact throughout the mother cell lifespan and accumulate in abundance or become posttranslationally modified. Fragmented LARPs are original proteins that are partially degraded, yet retained by the mother cell during aging. We speculate that LARPs contribute to the aging process. Long-lived proteins have been implicated in age-associated decline in metazoa, but they have only been identified in extracellular matrices or postmitotic cells. However, the aging process also occurs in dividing cells undergoing repeated asymmetric divisions. It was not clear whether long-lived proteins exist in asymmetrically dividing cells or whether they are involved in aging. Here we identify long-lived proteins in dividing cells during aging using the budding yeast, Saccharomyces cerevisiae. Yeast mother cells undergo a limited number of asymmetric divisions that define replicative lifespan. We used stable-isotope pulse-chase and total proteome mass-spectrometry to identify proteins that were both long-lived and retained in aging mother cells after ∼18 cells divisions. We identified ∼135 proteins that we designate as long-lived asymmetrically retained proteins (LARPS). Surprisingly, the majority of LARPs appeared to be stable fragments of their original full-length protein. However, 15% of LARPs were full-length proteins and we confirmed several candidates to be long-lived and retained in mother cells by time-lapse microscopy. Some LARPs localized to the plasma membrane and remained robustly in the mother cell upon cell division. Other full-length LARPs were assembled into large cytoplasmic structures that had a strong bias to remain in mother cells. We identified age-associated changes to LARPs that include an increase in their levels during aging because of their continued synthesis, which is not balanced by turnover. Additionally, several LARPs were posttranslationally modified during aging. We suggest that LARPs contribute to age-associated phenotypes and likely exist in other organisms.
Lung heme oxygenase-1 is elevated in acute respiratory distress syndrome

Objective:We aimed to quantify concentrations of inducible heme oxygenase (HO)-1 in the lungs of patients with acute respiratory distress syndrome (ARDS) and to investigate its role as a source of ferrous iron and as a signaling agent for iron regulation. Control of such processes by heme oxygenase has implications for the onset, progression, and resolution of ARDS. Design:Retrospective analysis of archived samples. Setting:Adult intensive care unit of a postgraduate teaching hospital. Patients:Patients admitted to the adult intensive care unit who fulfilled the American-European Consensus Conference criteria for ARDS. Interventions:Biochemical and immunohistochemical studies using bronchoalveolar lavage fluid or lung tissue were performed in patients with established ARDS and in those undergoing lung resection (controls). Measurements and Main Results:Concentrations of heme oxygenase protein were significantly elevated in lung tissue (193.7 ± 13.27 vs. 81.0 ± 16.0%, p < .01) and in bronchoalveolar lavage fluid (2.4 × 105 vs. 1.4 × 105 densitometric units, p = .047) taken from patients with ARDS compared with controls. Concentrations of heme oxygenase protein in bronchoalveolar lavage fluid from patients with ARDS correlated positively and significantly with changes in the concentrations of ferritin (r = .697, p = .02) and the iron saturation of transferrin (r = .8, p = .014) but correlated negatively and significantly with concentrations of bleomycin-detectable (redoxactive) iron (r = −.73, p = .031). Significantly elevated (p < .05) concentrations of heme oxygenase staining in cell types expressing this protein were detected in patients with ARDS, compared with concentrations in the same cells taken from controls undergoing lung resection. Conclusions:Heme oxygenase protein is elevated in the lungs of patients with ARDS and may contribute to the changes in iron mobilization, signaling, and regulation seen in this condition.
Utility of a Mathematical Nomogram to Predict Delayed Graft Function: A Single-Center Experience

Background. In 2003, Irish and colleagues published a weighted nomogram designed to predict the risk of delayed graft function (DGF) in a given transplant. It was anticipated that the predictive nomogram would permit preemptive therapies or allocation decisions based on the risk of DGF. The potential for reducing unfavorable outcomes and expenses appeared significant. This nomogram, however, was developed using population data found in the United States Renal Data System and has not been prospectively validated. Methods. We evaluated the accuracy and utility of this nomogram in all cadaver renal transplants performed at a single transplant center. In addition, we correlated DGF with a variety of independent donor and recipient variables outside the established nomogram. Results. The average nomogram DGF risk was 0.41 (a 41% chance of DGF) among the 169 cases in our population. The mean was 0.45±0.14 (confidence interval: 0.40–0.49) for the 42 DGF-positive subjects, and 0.40±0.14 (confidence interval: 0.38–0.43) for the 127 DGF-negatives (t=1.80; P=0.07). Conclusions. Although there was a trend showing the predictive value of the nomogram the overlap was tremendous, limiting the accuracy of the calculation for any single recipient. Prospective application of a nomogram on a case-by-case basis did not contribute meaningful information that could guide clinical decision-making regarding use, allocation or immunosuppressive regimen aimed at minimizing DGF.
Aspects of the Macroscopic Testicular and Epididymal Morphology in the Greater Rhea, Rhea Americana (Linneaus – 1758) Birds

The purpose of this research was to study the macroscopic testicular and epididymal morphology of the greater rhea. The testicles of 54 greater rhea bred in captivity were utilized. The samples were collected November 2005 (n = 14), December 2006 (n = 20) and May 2007 (n = 20). During commercial slaughter, the testicles and epididymides were collected and their following morphometric parameters were immediately measured: length, width, thickness, circumference, volume, weight of the parenchyma and the tunica albuginea, also aspects such as shape, cavity implantation, relationship with other organs and vascularization. The testicles presented cylindrical shape, with a thin, dense and transparent tunica albuginea, and the vascularization was accomplished by the testicular artery that ramifies from the cranial rectal artery. In the samples from December 2006 and May 2007, the media from the macroscopic measures of the right testicles were volume 58.7 and 14.7 ml, length 9.87 and 3.5 cm, width 2.4 and 0.6 cm, thickness 2.4 and 0.5 cm, circumference 8.0 and 2.3 cm, parenchyma weight 27.6 and 6.1 g and tunica albuginea weight 1.0 and 0.3 g, P < 0.05, respectively. The epididymides, the media from macroscopic measures December 2006 and May 2007 were volume 7.7 and 3.0 ml, length 5.8 and 1.3 cm, width 0.7 and 0.3 cm, thickness 0.6 and 0.3 cm, circumference 2.5 and 1.2 cm, tissue weight 6.4 and 2.8 g and capsule weight 0.4 and 0.1 g, P < 0.05, respectively. Some measures from the right testicle and epididymis were superior to measures taken from the left ones (P < 0.05), but these were not characterizing asymmetry. The morphometric parameters observed during November 2005 remained on an intermediate situation (P < 0.05); however, they were quantitatively closer to the means of December 2006, which may characterize it as a potential transition period between repose and sexual activity. Morphologically, the testicles and epididymides of greater rhea have common points with other researched birds; however, differences were observed. The testicles and epididymides of the Rhea americana are influenced by the environment, presenting reproductive activity season (November–December) during late spring, early summer and sexual repose season (May) during autumn–winter. The morphometric testicular and epididymal measurements were introduced. The morphometric parameters of testicles and epididymides exhibited differences between winter and spring–summer that could be established like sexual activity season.
Measurement of the mechanical properties of structural adhesives in tension and shear over a wide range of temperatures

The aim of this study was to select suitable adhesives for use in a mixed adhesive joint and to measure their mechanical properties over a wide range of temperatures. Three adhesives were selected: a bismaleimide adhesive (Redux 326) for high temperatures and two paste-form epoxies (Hysol EA 9359.3 and Supreme 10HT) for low temperatures. The mechanical properties in tension (dogbone specimens) and in shear (thick adherend shear test) are presented from −55 to 200°C for all three adhesives. Dynamic tests were also carried out to confirm the static modulus results. The correlations between the tensile and the shear properties are reasonable in terms of stiffness and strength but are poor in terms of ductility. In a single-lap joint, Redux 326 is stronger at high temperatures as it becomes more ductile. However, it is very stiff and brittle until 100°C. Supreme 10HT has very good performance up to 100°C. The combination of Redux 326 and Supreme 10HT formed a joint that had a good load carrying capacity from −55 to 200°C.
Epidermal overexpression of granulocyte-macrophage colony-stimulating factor induces both keratinocyte proliferation and apoptosis.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is released by keratinocytes in sizeable amounts only under pathological conditions, e.g., after topical application of a tumor promoter, in atopic dermatitis (AD), and after wounding. To study the biological function of this cytokine release, we generated transgenic mice that constitutively overexpress GM-CSF in the epidermis. An increase in the numbers of mast cells and Langerhans cells (LCs) in transgenics versus nontransgenic controls was observed but no severe inflammation. This is consistent with a central role of this cytokine in the development and maturation of LCs. Mitotic activity in the epidemnis of transgenic mice was elevated, but epidermal thickness and differentiation were normal. Homeostasis is maintained by an increase of apoptosis in the epidermis. We describe the differential expression of regulators of apoptosis and discuss a potential mechanism for this novel proapoptotic activity of GM-CSF on keratinocytes. Both stimulation of proliferation and promotion of apoptosis are of great relevance to tumorigenesis. The latter may be a means of removing damaged cells after genotoxic stress or injury.
Experimental geomechanics: a laboratory study on the behaviour of granular material using bender elements

On the basis of three methods of preparing well-differentiated triaxial Hostun HN31 sand specimens, namely moist tamping, dry pluviation and water pluviation, we highlight the influence of the reconstitution mode on the mechanical behaviour of sand. Piezoelectric transducers (bender elements) were installed in a triaxial cell and at the lateral edges of the sample in different directions (HH and HV) to investigate the structural anisotropy caused by each deposition mode and its evolution during undrained shearing tests, by measuring shear wave velocities. The results confirm and enrich the observations made with the scanning electron microscope and triaxial apparatus used by Benahmed, 2001; Benahmed, Canou & Dupla, 2004 on loose sand prepared using two different reconstitution procedures. A partir de trois modes de préparation bien différenciés d’éprouvettes triaxiales du sable d’Hostun HN31, à savoir le damage humide, la pluviation à sec et la pluviation sous eau, on met en évidence l’influence du mode de dépôt sur le comportement mécanique du sable. Des capteurs piézoélectriques (Bender elements) ont été placés sur les embases inférieure et supérieure de la cellule triaxiale et sur le pourtour latéral de l’éprouvette d’essai dans différentes directions (HH et HV) afin d’étudier l’anisotropie induite par chaque mode de déposition et son évolution durant les essais de cisaillement non drainé. Ceci est réalisé à travers des mesures de vitesses d’onde de cisaillement. Les résultats obtenus viennent confirmer et enrichir les observations faites avec le microscope électronique à balayage (MEB) par Benahmed, 2001; Benahmed, Canou & Dupla, 2004 sur le sable lâche préparé par deux méthodes de reconstitution différentes.
Model Fractional Chern Insulators.

We devise local lattice models whose ground states are model fractional Chern insulators-Abelian and non-Abelian topologically ordered states characterized by exact ground state degeneracies at any finite size and infinite entanglement gaps. Most saliently, we construct exact parent Hamiltonians for two distinct families of bosonic lattice generalizations of the Z_{k} parafermion quantum Hall states: (i) color-entangled fractional Chern insulators at band filling fractions ν=k/(C+1) and (ii) nematic states at ν=k/2, where C is the Chern number of the lowest band. In spite of a fluctuating Berry curvature, our construction is partially frustration free: the ground states reside entirely within the lowest band and exactly minimize a local (k+1) body repulsion term by term. In addition to providing the first known models hosting intriguing states such as higher Chern number generalizations of the Fibonacci anyon quantum Hall states, the remarkable stability and finite-size properties make our models particularly well suited for the study of novel phenomena involving, e.g., twist defects and proximity induced superconductivity, as well as being a guide for designing experiments.
Postdischarge problems identified by telephone calls to an advice line.

BACKGROUND Problems experienced after hospital discharge can result in rehospitalizations and unscheduled urgent and emergent care. OBJECTIVE To identify opportunities for improving discharge processes by examining calls to an advice line (AL). DESIGN Prospective cohort. SETTING A 500-bed, university-affiliated hospital. PATIENTS Patients who called an AL between September 1, 2011 and September 1, 2012 and reported being hospitalized within 30 days. INTERVENTION None MEASUREMENTS Caller characteristics, timing of calls, nature of reported problems. RESULTS Over 1 year the AL received calls from 308 unique patients who were hospitalized or had outpatient surgery within 30 days preceding the call. Thirty-one percent and 47% of calls occurred within 24 or 48 hours of discharge, respectively. Sixty-three percent came from surgery patients despite surgery patients accounting for only 38% of the discharges. The most common issues were uncontrolled pain, questions about medications, and aftercare instructions (eg, the care of surgical wounds). The rates of 30-day readmissions and urgent or emergent care visits were higher for patients who called the AL than for those who did not (15% vs 4% and 30% vs 7%, respectively, both P < 0.0001), but sample sizes were too small to accommodate robust matching or multivariate analysis. CONCLUSIONS Problems described in calls by patients to an AL identified several aspects of our discharge processes that needed improvement. Patients calling an AL following discharge may be at increased risk for 30-day rehospitalization and urgent or emergent care visits.
Excited-State Dynamics of the Thiopurine Prodrug 6-Thioguanine: Can N9-Glycosylation Affect Its Phototoxic Activity?

6-Thioguanine, an immunosuppressant and anticancer prodrug, has been shown to induce DNA damage and cell death following exposure to UVA radiation. Its metabolite, 6-thioguanosine, plays a major role in the prodrug’s overall photoreactivity. However, 6-thioguanine itself has proven to be cytotoxic following UVA irradiation, warranting further investigation into its excited-state dynamics. In this contribution, the excited-state dynamics and photochemical properties of 6-thioguanine are studied in aqueous solution following UVA excitation at 345 nm in order to provide mechanistic insight regarding its photochemical reactivity and to scrutinize whether N9-glycosylation modulates its phototoxicity in solution. The experimental results are complemented with time-dependent density functional calculations that include solvent dielectric effects by means of a reaction-field solvation model. UVA excitation results in the initial population of the S2(ππ*) state, which is followed by ultrafast internal conversion to the S1(nπ*) state and then intersystem crossing to the triplet manifold within 560 ± 60 fs. A small fraction (ca. 25%) of the population that reaches the S1(nπ*) state repopulates the ground state. The T1(ππ*) state decays to the ground state in 1.4 ± 0.2 μs under N2-purged conditions, using a 0.2 mM concentration of 6-thioguanine, or it can sensitize singlet oxygen in 0.21 ± 0.02 and 0.23 ± 0.02 yields in air- and O2-saturated solution, respectively. This demonstrates the efficacy of 6-thioguanine to act as a Type II photosensitizer. N9-glycosylation increases the rate of intersystem crossing from the singlet to triplet manifold, as well as from the T1(ππ*) state to the ground state, which lead to a ca. 40% decrease in the singlet oxygen yield under air-saturated conditions. Enhanced vibronic coupling between the singlet and triplet manifolds due to a higher density of vibrational states is proposed to be responsible for the observed increase in the rates of intersystem crossing in 6-thioguanine upon N9-glycosylation.
Mapping in Structured Populations by Resample Model Averaging

Highly recombinant populations derived from inbred lines, such as advanced intercross lines and heterogeneous stocks, can be used to map loci far more accurately than is possible with standard intercrosses. However, the varying degrees of relatedness that exist between individuals complicate analysis, potentially leading to many false positive signals. We describe a method to deal with these problems that does not require pedigree information and accounts for model uncertainty through model averaging. In our method, we select multiple quantitative trait loci (QTL) models using forward selection applied to resampled data sets obtained by nonparametric bootstrapping and subsampling. We provide model-averaged statistics about the probability of loci or of multilocus regions being included in model selection, and this leads to more accurate identification of QTL than by single-locus mapping. The generality of our approach means it can potentially be applied to any population of unknown structure.
Thrombocytosis and anaemia in women with recurrent ovarian cancer prior to a second-line chemotherapy.

BACKGROUND To investigate the incidence and the prognostic value of platelet count and serum haemoglobin (Hb) in patients with recurrent ovarian cancer prior to second-line chemotherapy. MATERIALS AND METHODS Clinical records were reviewed for 31 patients with recurrent ovarian cancer. Survival analysis was evaluated by univariate (Kaplan-Meier product limit method and log-rank test) analysis. We analysed the results for the overall survival. Anaemia and thrombocytosis were defined as a serum Hb level < 12 g/dl and as platelet count > 300,000/microL, respectively. RESULTS Thrombocytosis and tumour anaemia were present in 55% and 42% of the patients, respectively. Tumour anaemia was of no prognostic value with respect to overall survival in our series. In patients with thrombocytosis, the median survival rate was reduced (p = 0.05). CONCLUSION Our data suggest that a platelet count > 300,000/microL appears to be an adverse prognostic parameter in patients with recurrent ovarian cancer prior to a second-line chemotherapy.
Atherosclerotic plaque in carotid arteries in systemic lupus erythematosus: frequency and associated risk factors.

CONTEXT AND OBJECTIVE Atherosclerotic disease is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. No previous study has estimated carotid disease prevalence in such patients in Brazil. The aim was to evaluate the prevalence of atherosclerotic plaque in carotid arteries, in SLE patients and controls, and to verify possible associations between risk factors and carotid plaque. DESIGN AND SETTING Cross-sectional study, at Universidade Federal de São Paulo--Escola Paulista de Medicina. METHODS Carotid plaque prevalence was assessed by B-mode ultrasound in 82 female SLE patients of mean age 34.0 years and 62 controls of mean age 35.7 years. Plaque was defined as a distinct area of hyperechogenicity and/or focal protrusion of the vessel wall into the lumen. Risk factors for coronary disease and SLE-related variables were determined. RESULTS 50% of patients and 29% of controls presented carotid plaque. Older age, longer disease duration, higher Systemic Lupus International Collaborating Clinics (SLICC) score, higher levels of low-density lipoprotein and greater diabetes, obesity, premature ovarian failure and family history of coronary artery disease were found in patients with carotid plaque than in those without plaque. Patients with plaque were younger than controls with plaque. SLE diagnosis, obesity, older age, higher SLICC score and longer disease duration were independent risk factors for carotid plaque. CONCLUSION Young patients with SLE present higher prevalence of carotid plaque than controls. SLE diagnosis was a significant risk factor for carotid atherosclerosis.