Miracle-dz/UniFAR-FTUs huggingface dataset:
Protease-Deficient DegP Suppresses Lethal Effects of a Mutant OmpC Protein by Its Capture

ABSTRACT The expression of assembly-defective outer membrane proteins can confer lethality if they are not degraded by envelope proteases. We report here that the expression of a mutant OmpC protein, OmpC2Cys, which forms disulfide bonds in the periplasm due to the presence of two non-native cysteine residues, is lethal in cells lacking the major periplasmic protease, DegP. This lethality is not observed in dsbA strains that have diminished ability to form periplasmic disulfide bonds. Our data show that this OmpC2Cys-mediated lethality in a degP::KmrdsbA+ background can be reversed by a DegP variant, DegPS210A, that is devoid of its proteolytic activity but retains its reported chaperone activity. However, DegPS210A does not reverse the lethal effect of OmpC2Cys by correcting its assembly but rather by capturing misfolded mutant OmpC polypeptides and thus removing them from the assembly pathway. Displacement of OmpC2Cys by DegPS210A also alleviates the negative effect that the mutant OmpC protein has on wild-type OmpF.
Andropause: knowledge and perceptions among the general public and health care professionals.

BACKGROUND Andropause, the natural age-related decline in testosterone in men, has been debated in the literature. The nonsexual benefits of testosterone replacement therapy (TRT) in male hypogonadism are well documented, but whether health care professionals (HCPs) and members of the general public are aware of these benefits is not known. This study assesses the knowledge and perceptions of andropause and TRT among HCPs and members of the general public. METHODS Brief surveys were administered to HCPs and members of the general public who called a medical information telephone line. Trained clinical interviewers surveyed participants for experiences with andropause and TRT and knowledge about nonsexual effects of low testosterone in men. RESULTS Of 443 general public callers, 377 (85%) agreed to participate in the survey. Of these participants, 77% had heard of andropause or male menopause, and 63% had taken TRT. Of 88 HCP callers, 57 (65%) participated. Of these participants, 65% were pharmacists, 80% had encountered patients with symptoms of low testosterone, and 50% reported that patients rarely or never initiated conversations about low testosterone. Among HCPs and the general public, respectively, 98% and 91% knew that low testosterone is treatable with medication, and 60% and 57% knew that it results in osteoporosis. Only 25% of HCPs and 14% of the general public knew that low testosterone does not cause loss of urinary control. CONCLUSIONS HCPs and members of the general public are knowledgeable about some aspects of low testosterone and have misconceptions about others. Educational initiatives are needed.
Exploring the response shift phenomenon in childhood patients with cancer and its effect on health-related quality of life.

PURPOSE/OBJECTIVES To explore the response shift phenomenon in pediatric patients with cancer and to determine its effects on ratings of health-related quality of life (HRQOL). DESIGN Retrospective pre- and post-test design. SETTING Pediatric oncology department in the northern part of the Netherlands. SAMPLE 37 children newly diagnosed with cancer and 80 parents. METHODS The then-test method was used to determine response shift. HRQOL was assessed within two weeks postdiagnosis (pretest) and three months later (post-test) using both child and parent reports of PedsQL and Cantril's ladder. The post-test and then-test were administered concurrently. MAIN RESEARCH VARIABLES Overall and multidimensional HRQOL. FINDINGS Scores on Cantril's then-test were lower than the pretest in both child and parent reports, indicating response shift in the assessment of overall HRQOL. Children experienced a greater response shift than parents. No differences were found between the PedsQL then- and pretests. CONCLUSIONS Both child- and parent-report ratings of overall HRQOL were affected by response shift, resulting in an underestimation of the improvement in overall HRQOL between diagnosis and three months postdiagnosis. No response shift was demonstrated in the more specific domains of HRQOL (PedsQL). IMPLICATIONS FOR NURSING Knowledge of the response shift phenomenon helps nurses to better interpret the outcomes of HRQOL. The use of the PedsQL instrument is recommended in future studies that aim to demonstrate changes in HRQOL.
Long-Term Improvement in Postinfarct Left Ventricular Global and Regional Contractile Function Is Mediated by Embryonic Stem Cell–Derived Cardiomyocytes

Background—Pluripotent stem cells represent one promising source for cellular cardiomyoplasty. In this study, we used cardiac magnetic resonance to examine the ability of highly enriched cardiomyocytes (CMs) derived from murine embryonic stem cells (ESC) to form grafts and improve contractile function of infarcted rat hearts. Methods and Results—Highly enriched ESC-CMs were obtained by inducing cardiac differentiation of ESCs stably expressing a cardiac-restricted puromycin resistance gene. At the time of transplantation, enriched ESC-CMs expressed cardiac-specific markers and markers of developing CMs, but only 6% of them were proliferating. A growth factor–containing vehicle solution or ESC-CMs (5 to 10 million) suspended in the same solution was injected into athymic rat hearts 1 week after myocardial infarction. Initial infarct size was measured by cardiac magnetic resonance 1 day after myocardial infarction. Compared with vehicle treatment, treatment with ESC-CMs improved global systolic function 1 and 2 months after injection and significantly increased contractile function in initially infarcted areas and border zones. Immunohistochemistry confirmed successful engraftment and the persistence of &agr;-actinin–positive ESC-CMs that also expressed &agr;-smooth muscle actin. Connexin-43–positive sites were observed between grafted ESC-CMs but only rarely between grafted and host CMs. No teratomas were observed in any of the animals. Conclusions—Highly enriched and early-stage ESC-CMs were safe, formed stable grafts, and mediated a long-term recovery of global and regional myocardial contractile function after infarction.
CD13 is essential for inflammatory trafficking and infarct healing following permanent coronary artery occlusion in mice

Abstract Aims To determine the role of CD13 as an adhesion molecule in trafficking of inflammatory cells to the site of injury in vivo and its function in wound healing following myocardial infarction induced by permanent coronary artery occlusion. Methods and results Seven days post-permanent ligation, hearts from CD13 knockout (CD13KO) mice showed significant reductions in cardiac function, suggesting impaired healing in the absence of CD13. Mechanistically, CD13KO infarcts showed an increase in small, endothelial-lined luminal structures, but no increase in perfusion, arguing against an angiogenic defect in the absence of CD13. Cardiac myocytes of CD13KO mice showed normal basal contractile function, eliminating myocyte dysfunction as a mechanism of adverse remodelling. Conversely, immunohistochemical and flow cytometric analysis of CD13KO infarcts demonstrated a dramatic 65% reduction in infiltrating haematopoietic cells, including monocytes, macrophages, dendritic, and T cells, suggesting a critical role for CD13 adhesion in inflammatory trafficking. Accordingly, CD13KO infarcts also contained fewer myofibroblasts, consistent with attenuation of fibroblast differentiation resulting from the reduced inflammation, leading to adverse remodelling. Conclusion In the ischaemic heart, while compensatory mechanisms apparently relieve potential angiogenic defects, CD13 is essential for proper trafficking of the inflammatory cells necessary to prime and sustain the reparative response, thus promoting optimal post-infarction healing.
Role of HbA1c in management of diabetes mellitus.

OBJECTIVE To represent that glycosylated hemoglobin (HbA1c) is not requested by the physicians in spite of its critical importance in the monitoring of glycemic control and prediction of complications due to diabetes. METHODS A cross-sectional study was conducted at the outpatient department of King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia, between October 2002 and July 2003. Out of the 265 known patients with diabetes, 130 patients were included in the study, which had HbA1c levels registered in their medical records. Demographic features, smoking habit, presence of hypertension, hyperlipidemia were recorded. Detailed information on diabetes were recorded, which included duration, type (type I or type II) and pattern of treatment, degree of glycemic control (assessed by two-points blood sugar and HbA1c levels). Screening for microvascular complications was recorded. RESULTS Only 130 (49%) of the patients with diabetes were included in the study. Poor control was detected in the majority of the patients with diabetes. There was a difference in the detection of poor glycemic control by both methods; HbA1c levels showed poor control in 77% of the patients and by the two-point blood sugar (2-PBS) methods in 69% of the patients. Only 70% of the patients with poor glycemic control by HbA1C showed poor control by 2-PBS (p=0.7). Poor control was detected in 45% of the patients using insulin by measuring HbA1c levels, and by measuring 2-PBS in 34% of the patients (p=0.005, p=0.16). A significant relation was found between HbA1c levels, retinopathy and nephropathy (p=0.02, p=0.05). CONCLUSION Guidelines of the American Diabetic Association (ADA) regarding proper management of patients with diabetes should be followed to achieve the recommended outcome. Glycosylated hemoglobin levels should be checked every 3 months. Physicians and patients must be advised not to depend solely on 2-PBS results, especially for insulin dependent diabetics.
A Region of the Integrin VLAα4 Subunit Involved in Homotypic Cell Aggregation and in Fibronectin but Not Vascular Cell Adhesion Molecule-1 Binding (*)

The VLA-4 (α4β1) integrin is involved in the adhesion of cells to fibronectin and vascular cell adhesion molecule-1 (VCAM-1). In order to study α4 structure-function relationships, we have expressed mutated α4 subunit by transfection into VLA-4-negative K562 cells. Substitutions at α4 residues Arg89-Asp90, which show the highest surface probability indexes inside the N-terminal α4/80 fragment, resulted in a reduction in the reactivity of all anti-α4 epitope A monoclonal antibodies (mAbs) tested, compared with the reactivity with anti-α4 epitopes B1, B2, and C mAb, both by transfectant flow cytometry, and by immunoprecipitation and SDS-polyacrylamide gel electrophoresis analysis of transfectant surface-iodinated proteins. In contrast, substitutions at nearby residues, Gln101, Pro102, and Ile108 did not affect the reactivity of any anti-α4 mAb representing the known α4 epitopes. Homotypic cell aggregation triggered by anti-α4 epitope A mAb was prevented in the transfectants expressing mutated α4 Arg89-Asp90Asp residues, while cell aggregation was fully achieved with either anti-α4 epitope B2 or anti-β1 mAb. Mutations at α4 residues Gln101, Pro102, and Ile108 did not affect the homotypic cell aggregation of the transfectants expressing these mutations. In addition, the adhesion of mutant Arg89-Asp90 α4 transfectants to the connecting segment-1-containing fibronectin-40 (FN-40) fragment of fibronectin was diminished compared to wild type α4 transfectants, as well as to other mutant α4 transfectants. This adhesion to FN-40 was restored when the activating anti-β1 TS2/16 mAb was present in the adhesion assays. In contrast, adhesion to VCAM-1 was not affected by mutations at Arg89-Asp90, nor at Gln101, Pro102, and Ile108 α4 residues. Altogether, these results indicate that α4 residues Arg89 and Asp90 are included in a region involved in homotypic cell aggregation, as well as in adhesion to FN-40, but not to VCAM-1.
Heterogeneity of HPA‐3 alloantibodies: consequences for the diagnosis of alloimmune thrombocytopenic syndromes

BACKGROUND: Immunization against the human platelet alloantigen (HPA)‐3a residing on αIIbβ3 integrin accounts for approximately 2 percent of fetal and neonatal alloimmune thrombocytopenia (FNAIT). Anti‐HPA‐3a alloantibodies are sometimes difficult to detect and can be overlooked by standard antigen capture assays.
Accuracy of an oscillometric blood pressure monitor during phenylephrine-induced hypertension in dogs.

OBJECTIVE To examine the agreement between direct arterial blood pressure measurements obtained from 2 arteries and indirect blood pressure measurements obtained with an oscillometric blood pressure monitor (OBPM) during normotension and phenylephrine-induced hypertension in dogs. ANIMALS 16 male Beagles. PROCEDURES In anesthetized dogs, arterial catheters were placed in the lingual and dorsal pedal arteries for measurement of arterial blood pressure. A blood pressure cuff was placed on either the dog's fore- or hind limb and connected to an OBPM. Systolic, diastolic, and mean arterial blood pressures (SAP, DAP, and MAP, respectively) were recorded from both arteries and the OBPM every 5 minutes for 30 minutes (baseline), during a 30-minute period in which dogs received a phenylephrine infusion IV to induce hypertension, and for 30 minutes after discontinuation of the infusion. Mean differences in blood pressure values and confidence intervals were calculated to compare the indirect and direct measurement techniques. RESULTS In dogs, oscillometry underestimated SAP during normotension, and the difference between oscillometric and direct measurements increased during hypertension. Oscillometry underestimated DAP, but the difference between oscillometric and direct measurements decreased during hypertension. There was close agreement among techniques for MAP determinations. Biases between direct measurements and OPBM blood pressure values measured from dogs' forelimbs or hind limbs were not significantly different. CONCLUSIONS AND CLINICAL RELEVANCE In normotensive dogs, oscillometric measurements of MAP and SAP agreed more closely with direct arterial pressure measurements than oscillometric estimates of DAP. Oscillometric measurement of MAP was accurate during both normotension and hypertension in dogs.
Acceptability and Safety of Novel Infant Porridges Containing Lyophilized Meat Powder and Iron-Fortified Wheat Flour

Background Lyophilized meat powder with iron-fortified wheat flour can be used to produce an infant porridge with bioavailable iron, but its acceptability and safety are unknown. Objective To evaluate the acceptability and safety of porridges containing lyophilized meat powder and iron-fortified wheat flour. Methods Peruvian mothers' input was used to develop porridges without (no meat) and with meat powder (low or high chicken liver, low or high chicken thigh). Acceptability was determined by maternal hedonic scoring, 9-day infant intake, and videotape analysis of how well infants liked each porridge. Dry and cooked porridges and meat ingredients were tested for microorganisms; meats were tested for pesticides. Results Mothers gave higher acceptability scores to the no-meat porridge, followed in order by low and high quantities of meat powder (e. g., mean ± SD “taste” scores were 4.5 ± 0.9 for the no-meat, 3.7 ± 1.1 for the low-liver, and 3.3 ± 1.1 for the high-liver porridges, p = .0001). Infants' porridge intake did not differ: 61.4 ± 47.1 g of no-meat, 62.1 ± 44.9 g of low-thigh, and 67.5 ± 42.0 g of low-liver (p = .7), as supported by the video analysis. Microbiologic safety was acceptable except for marginally acceptable molds and yeasts in dry ingredients. No pesticide residues were detected. Conclusions Despite mothers' clear preference for no-meat porridges, infants consumed equal amounts of porridges with and without meat. Thus, if mothers can be convinced to feed the meat-containing porridges to the infants despite their own preferences, the infants will consume these porridges. The mold and yeast content of the porridge ingredients must be reduced.
Pyridoxal-5′-phosphate as an oxygenase cofactor: Discovery of a carboxamide-forming, α-amino acid monooxygenase-decarboxylase

Significance Enzymes that activate dioxygen typically rely on flavins or transition metals as redox cofactors. We describe the discovery of the enzyme catalyst Cap15 that converts 5′-C-glycyluridine (GlyU), an unusual β–hydroxy-α-amino acid, to the modified nucleoside uridine-5′-carboxamide. In contrast to expectations, pyridoxal-5'-phosphate (PLP) is the sole cofactor that serves as the initiating reducing agent to activate dioxygen for incorporation into GlyU prior to decarboxylation. Thus, Cap15 is now classified as an O2- and PLP-dependent monooxygenase-decarboxylase. Also in contrast to expectations, phosphate and the (5′S,6′R) isomer of GlyU—and not (5′S,6′S)-GlyU, the established pathway intermediate—are essential for Cap15 activity. In total, Cap15 utilizes an enzymatic strategy for oxygen incorporation during conversion of an α-amino acid to a carboxamide. Capuramycins are antimycobacterial antibiotics that consist of a modified nucleoside named uridine-5′-carboxamide (CarU). Previous biochemical studies have revealed that CarU is derived from UMP, which is first converted to uridine-5′-aldehyde in a reaction catalyzed by the dioxygenase CapA and subsequently to 5′-C-glycyluridine (GlyU), an unusual β–hydroxy-α-amino acid, in a reaction catalyzed by the pyridoxal-5′-phosphate (PLP)-dependent transaldolase CapH. The remaining steps that are necessary to furnish CarU include decarboxylation, O atom insertion, and oxidation. We demonstrate that Cap15, which has sequence similarity to proteins annotated as bacterial, PLP-dependent l-seryl-tRNA(Sec) selenium transferases, is the sole catalyst responsible for complete conversion of GlyU to CarU. Using a complementary panel of in vitro assays, Cap15 is shown to be dependent upon substrates O2 and (5′S,6′R)-GlyU, the latter of which was unexpected given that (5′S,6′S)-GlyU is the isomeric product of the transaldolase CapH. The two products of Cap15 are identified as the carboxamide-containing CarU and CO2. While known enzymes that catalyze this type of chemistry, namely α-amino acid 2-monooxygenase, utilize flavin adenine dinucleotide as the redox cofactor, Cap15 remarkably requires only PLP. Furthermore, Cap15 does not produce hydrogen peroxide and is shown to directly incorporate a single O atom from O2 into the product CarU and thus is an authentic PLP-dependent monooxygenase. In addition to these unusual discoveries, Cap15 activity is revealed to be dependent upon the inclusion of phosphate. The biochemical characteristics along with initiatory mechanistic studies of Cap15 are reported, which has allowed us to assign Cap15 as a PLP-dependent (5′S,6′R)-GlyU:O2 monooxygenase-decarboxylase.
Gender Equality Among CSR Managers and its Influence on Sustainable Development: A Comparison Among Italy, Spain and United Kingdom

The Sustainable Development Goals (SDGs) of the United Nations’ 2030 Agenda for Sustainable Development are intended to orientate efforts of governments and companies to deal with environmental and social problems affecting contemporary societies. Gender Equality is one of these SDGs, and the women’s participation in leadership at all levels of decision making in political, economic and public life, is one of its crucial targets. The paper analyses the progress in meeting this target with a focus on the European Union (EU) context. Particularly, a qualitative trend analysis is employed on the data from “World Bank Group” database, and the “Global 100: Most Sustainable Corporations in the World” for performing a comparison of the temporal evolution of Gender Equality in Italy, Spain and United Kingdom as countries registered in the “European Organizations of Sustainability Professions” portal. The results show that the mean female share of employment in senior and middle management is growing, and that managerial roles in CSR are a gender-virtuous field of management. Nevertheless, a question arises: is the gender equality among CSR managers an indicator of a sustainability-oriented approach to management? An analysis of Corporate Knights’s ranking of the world’s most sustainable corporations reveals that the female share of CSR managers is not directly linked to the presence of sustainable corporations. These empirical evidences arise some questions as well as some policy suggestions that will be discussed. Keywords: Gender equality; Female leadership; Sustainable Development Goals (SDGs); Sustainable Development; Corporate Social Responsibility (CSR) Manager; Sustainability
Risk factors and comorbid conditions associated with lower urinary tract symptoms: EpiLUTS

To explore the risk factors and comorbid conditions associated with subgroups of lower urinary tract symptoms (LUTS) in men and women aged ≥40 years in three countries, using data from the EpiLUTS study, as LUTS are common amongst men and women and increase in prevalence with age.
Looking for the Tangent Portfolio: Risk Optimization Techniques on Equity Style Buckets

The inflation of multifactor models has questioned the existence of a mean-variance e cient portfolio. We examine the risk-return properties of low-risk portfolios obtained by the risk optimization of characteristic-sorted equity portfolios. We group stocks based on size, value and momentum characteristics through several sorting procedures. We claim that low-risk portfolios constructed using long-only positions on basis portfolios formed using a dependent sorting scale with whole-sample breakpoints deliver superior Sharpe ratio to an optimal portfolio spanning the single or the 3-factor models. Besides, while the three-factor empirical model spans an opportunity set augmented with low-risk portfolios formed on other sorting procedures, the pricing performance of low-risk investment strategies based on these dependent basis portfolios is shown to be superior to that of the single-index factor model, the three-factor model and its competing low-risk benchmarks. Our testing framework is based on bootstrapped mean-variance spanning tests and shows valid conclusions out-of-sample and net of transaction costs. The results still hold when controlling for data snooping biases through multiple testing and luck. Economically, our results are supported by diversification-based properties. *Boris Fays is a PhD candidate at HEC Liège, ULiège. Rue Louvrex 14, Bldg. N1, 4000 Liège, Belgium. E-mail: boris.fays@uliege.be. Phone number: +32 4 232 73 47. Marie Lambert is a Professor of Finance at HEC Liège, ULiège. She is also a Research Associate at EDHEC Risk Institute. Address: HEC Liège, Rue Louvrex 14, Bldg. N1, 4000 Liège, Belgium. E-mail: marie.lambert@uliege.be. Phone number: +32 4 232 74 32. Nicolas Papageorgiou is a Full Professor of Finance at HEC Montreal, and Vice-President and Head of R&D, Fiera Capital Corporation. Mailing address: 3000 Cote Ste Catherine, Montreal, Quebec. E-mail: Nicolas.Papageorgiou@hec.ca Phone number: +1 514 340 7309.