Miracle-dz/UniFAR-FTUs huggingface dataset:
IRAG1 Deficient Mice Develop PKG1β Dependent Pulmonary Hypertension

PKGs are serine/threonine kinases. PKG1 has two isoforms—PKG1α and β. Inositol trisphosphate receptor (IP3R)-associated cGMP-kinase substrate 1 (IRAG1) is a substrate for PKG1β. IRAG1 is also known to further interact with IP3RI, which mediates intracellular Ca2+ release. However, the role of IRAG1 in PH is not known. Herein, WT and IRAG1 KO mice were kept under normoxic or hypoxic (10% O2) conditions for five weeks. Animals were evaluated for echocardiographic variables and went through right heart catheterization. Animals were further sacrificed to prepare lungs and right ventricular (RV) for immunostaining, western blotting, and pulmonary artery smooth muscle cell (PASMC) isolation. IRAG1 is expressed in PASMCs and downregulated under hypoxic conditions. Genetic deletion of IRAG1 leads to RV hypertrophy, increase in RV systolic pressure, and RV dysfunction in mice. Absence of IRAG1 in lung and RV have direct impacts on PKG1β expression. Attenuated PKG1β expression in IRAG1 KO mice further dysregulates other downstream candidates of PKG1β in RV. IRAG1 KO mice develop PH spontaneously. Our results indicate that PKG1β signaling via IRAG1 is essential for the homeostasis of PASMCs and RV. Disturbing this signaling complex by deleting IRAG1 can lead to RV dysfunction and development of PH in mice.
The Effect of Sea Salt, Dry Sourdough and Fermented Sugar as Sodium Chloride Replacers on Rheological Behavior of Wheat Flour Dough

The aim of this study was to investigate the effects of formulation factors, sea salt (SS), dry sourdough (SD) and fermented sugar (FS) as sodium chloride replacers in wheat flour on dough mixing, extension, pasting and fermentation rheological properties, evaluated by Farinograph, Extensograph, Amylograph and Rheofermentometer devices. With regard to mixing and extension properties, SS and FS presented a strengthening effect, whereas SD presented a weakening one. SS and FS presented a positive effect on dough stability, energy and resistance, whereas SD presented a negative one. On the Amylograph, peak viscosity increased by SS and FS addition and decreased when SD was incorporated in the dough recipe. During fermentation, dough development and gas production in the dough system increased after SS and SD addition, whereas they decreased after FS addition. Response surface methodology (RSM) was used to investigate the effect of independent variables on the rheological properties of the dough. Mathematical models between the independent variables, SS, SD and FS, and the dependent variables, represented by the rheological values of the dough, were obtained. The best formulation obtained was of 0.30 g/100 g SS, 0.50 g/100 g SD and 1.02 mL/100 g FS addition with a 0.618 desirability value, following Derringer’s desirability function approach. For this formulation, bread quality characteristics were better appreciated than for those obtained for the control sample, in which 1.5% NaCl was incorporated in wheat flour.
Genome Sequencing of Paecilomyces Penicillatus Provides Insights into Its Phylogenetic Placement and Mycoparasitism Mechanisms on Morel Mushrooms

Morels (Morchella spp.) are popular edible fungi with significant economic and scientific value. However, white mold disease, caused by Paecilomyces penicillatus, can reduce morel yield by up to 80% in the main cultivation area in China. Paecilomyces is a polyphyletic genus and the exact phylogenetic placement of P. penicillatus is currently still unclear. Here, we obtained the first high-quality genome sequence of P. penicillatus generated through the single-molecule real-time (SMRT) sequencing platform. The assembled draft genome of P. penicillatus was 40.2 Mb, had an N50 value of 2.6 Mb and encoded 9454 genes. Phylogenetic analysis of single-copy orthologous genes revealed that P. penicillatus is in Hypocreales and closely related to Hypocreaceae, which includes several genera exhibiting a mycoparasitic lifestyle. CAZymes analysis demonstrated that P. penicillatus encodes a large number of fungal cell wall degradation enzymes. We identified many gene clusters involved in the production of secondary metabolites known to exhibit antifungal, antibacterial, or insecticidal activities. We further demonstrated through dual culture assays that P. penicillatus secretes certain soluble compounds that are inhibitory to the mycelial growth of Morchella sextelata. This study provides insights into the correct phylogenetic placement of P. penicillatus and the molecular mechanisms that underlie P. penicillatus pathogenesis.
Associations of intimate partner violence and reproductive coercion with contraceptive use in Uttar Pradesh, India: How associations differ across contraceptive methods

Intimate partner violence (IPV) and reproductive coercion (RC)–largely in the form of pressuring pregnancy—appear to contribute to low use of contraceptives in India; however, little is known about the extent to which these experiences differentially affect use of specific contraceptive methods. The current study assessed the association of IPV and RC with specific contraceptive methods (Intrauterine Devices [IUDs], pills, condoms) among a large population-based sample of currently married women (15–49 years, n = 1424) living in Uttar Pradesh. Outcomes variables included past year modern contraceptive use and type of contraceptive used. Primary independent variables included lifetime experience of RC by current husband or in-laws, and lifetime experiences of physical IPV and sexual IPV by current husband. Multivariate logistic regression models were developed to determine the effect of each form of abuse on women’s contraceptive use. Approximately 1 in 7 women (15.1%) reported experiencing RC from their current husband or in-laws ever in their lifetime, 37.4% reported experience of physical IPV and 8.3% reported experience of sexual IPV by their current husband ever in their lifetime. Women experiencing RC were less likely to use any modern contraceptive (AOR: 0.18; 95% CI: 0.9–0.36). Such women also less likely to report pill and condom use but were more likely to report IUD use. Neither form of IPV were associated with either overall or method specific contraceptive use. Study findings highlight that RC may influence contraceptive use differently based on type of contraceptive, with less detectable, female-controlled contraceptives such as IUD preferred in the context of women facing RC. Unfortunately, IUD uptake remains low in India. Increased access and support for use, particularly for women contending with RC, may be important for improving women’s control over contraceptive use and reducing unintended pregnancy.
Modeling the Interleukin 2 gene expression in activated T cells

Interleukin 2 (IL-2) is a cytokine expressed in human memory T helper cells and the secretion of IL-2 shapes the magnitude and duration of immune responses. In contrast, human regulatory T-cells commonly do not express IL-2. The diverse effects of IL-2 on protective immune responses as well as peripheral immune tolerance form the basis of the profound role of IL-2 in various diseases. The gene expression of IL-2 is induced by the activation of the T-cell receptor signaling network activating the transcription factors AP-1, NFAT, and NF-κB. These transcription factors are crucial for initiating IL-2 gene expression. Within my thesis I explore the regulation of IL-2 gene expression in a detailed modeling approach combined with experiments. I compare the regulation in memory effector Th cells (Teff cells) and regulatory T-cells (Treg cells). In particular, I demonstrate that the transcription factor concentrations correlate with number of IL-2 producers but do not affect IL-2 concentration per cell. Thus, I investigate how the transcription factor concentration of c-fos, NFATc2, p65, and p-c-jun affects the frequency of IL-2 producing cells as a proxy for the probability of a cell to produce IL-2. Using the endogenous heterogeneity of transcription factor concentrations, I predict that the number of IL-2 producers is critically dependent on the amount of c-fos in Teff cells. I use my established model to predict how perturbations of c-fos by the specific inhibitor U0126 decrease the frequency of IL-2 producers in Teff cells. This prediction was than validated by experiments. My models furthermore indicate the cooperative behavior of c-fos and NFATc2 on the level of frequency of IL-2 producers in Teff cells. In Treg cells, my analysis shows that all transcription factors exert a similar sigmoidal effect on the frequency of IL-2 producers. In contrast to the effects seen in Teff cells, all transcription factor have a similar maximal effect on the IL-2 gene expression. I employed an inhibitory model to explore the relation between the Treg cell-specific transcription factor FoxP3 the transcription factors c-fos, NFATc2, p65, and p-c-jun on the frequency of IL-2 producers. This model indicates that FoxP3 counteracts the activating function of NFATc2, AP-1, and also NF-κB. My results are discussed in the context of kinetic proofreading in an immune response and with respect to their implications for autoimmune diseases, such as systemic lupus erythematosus (SLE). Parts of this thesis have been published in “Stable IL-2 decision making by endogenous c-fos amounts in peripheral memory Th cells. ” (Bendfeldt et al., 2012a) and in “IL-2 Expression in Activated Human Memory FOXP3(+) Cells Critically Depends on the Cellular Levels of FOXP3 as Well as of Four Transcription Factors of T Cell Activation. ” (Bendfeldt et al., 2012b).
Editorial [Hot Topic: Non-Reproductive Effects of Sex Steroids: Their Immunoregulatory Role (Guest Editor: Jorge Morales-Monto)]

: In this special issue of Current Topics in Medicinal Chemistry, the reader will find reviewed some of the hottest topics in the field of the non-reproductive effects of sex steroids. Cabrera-Munoz et al., show that progesterone participates in the regulation of human brain tumors growth. The contribution of Martocchia suggests that sex steroid receptor modulating drugs provide new therapeutic approaches to autoimmune diseases. The role of sex steroid participation in the differentiation of stem cells to neurones is discussed by I. Velasco. Perez-Torres and collaborators demonstrate that sex steroids play an important role in the appearance and development of renal diseases and the metabolic syndrome, the new epidemics of our century. Paris and Frye hypthetize that gestational stress, have effects on cognitive performance and/or neuronal integrity in the fetus, and that exposure to variable stress during gestation can perturb cognitive performance, concomitant with dendrite development in hippocampus and diencephalon. Munoz-Cruz et al. thoroughly review the growing body of evidence that shows reciprocal relationship between sex steroids and the immune system, and conclude that understanding the mechanisms of action of sex steroids on immune cells is important for further progress in the development of novel therapies for chronic diseases associated to immune dysregulation. Besides, the effects of sexual steroids on pancreatic function and diabetes are reviewed by Morimoto et al. Yanes et al. review some of the contradictions raised in the context of the recently proposed critical period hypothesis, which takes into account the frame-time after cessation of ovarian function. Finally, another vey intetresting aspect of the non-reproductive effects of sex-steroids, is the related to some cognition-related aspects, which is reviewed by Picazo et al.
Biology and use for periodontal tissue engineering

Inflammatory periodontal disease is a major cause of loss of tooth-supporting structures. Novel approaches for regeneration of periodontal apparatus is an area of intensive research. Periodontal tissue engineering implies the use of appropriate regenerative cells, delivered through a suitable scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from their relative accessibility and pleasant handling properties. The purpose of this article is to review the biological principles of periodontal tissue engineering, along with the challenges facing the development of a consistent and clinically relevant tissue regeneration platform. This article includes an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors.
Predator-prey interactions : effects of the substances released by the prey Euplotes crassus (Protozoa, Ciliata) on the predator Litonotus lamella (Protozoa, Ciliata)

The stages in the Litonotus-Euplotes (predator-prey) interaction were investigated. These involved detection of prey from a distance; the search for stricken prey; and ingestion. It appears that the factor preceived by the predator is proteinaceous and lies in a molecular weight range between 10 and 30 kD. Moreover, Euplotes crassus releases a molecule which rejects predators, and has a molecular weight of >5 kD. The latter is probably not proteinaceous and in the search for the stricken prey the adenylate cyclase-cAMP system is involved. In addition the cytopharyngeal microtubular basket (tubulin structure), the lamina corticalis (actin structure) participates in the ingestion of prey.
Exploring Sentence Diversity at the Boundary of Typical and Impaired Language Abilities

Purpose This review article summarizes programmatic research on sentence diversity in toddlers developing language typically and explores developmental patterns of sentence diversity in toddlers at risk for specific language impairment. Method The first half of this review article presents a sentence-focused approach to language assessment and intervention and reviews findings from empirical studies of sentence diversity. In the second half, subject and verb diversity in three simple sentence types are explored in an archival database of toddlers with varying levels of grammatical outcomes at 36 months of age: low average, mild/moderate delay, and severe delay. Results Descriptive findings from the archival database replicated previous developmental patterns. All toddlers with low-average language abilities produced diverse simple sentences by 30 months of age and exhibited greater sentence diversity with first-person I-subjects before third-person subjects. Third-person subject diversity emerged in a developmental sequence, increasing in one-argument copula contexts and one-argument subject–verb sentences before two-argument subject–verb–object sentences. This developmental pattern held across all three outcome groups. Third-person subjects were least diverse for children with severe grammatical delays and were absent in all sentence contexts for two children with severe delays at 36 months. Conclusions Sentence diversity increases gradually and expands in predictable patterns. Understanding these developmental patterns may help identify and treat children who display unexpected difficulty combining different subjects and verbs in flexible ways. Supplemental Material and Presentation Video https://doi.org/10.23641/asha.12915320
Lack of phosphatidate phosphatase causes reduced chronological life span through increased energy expenditure and oxidative stress

OF THE DISSERTATION Lack of Phosphatidate Phosphatase Causes Reduced Chronological Life Span through Increased Energy Expenditure and Oxidative Stress By YEONHEE PARK Dissertation Director: Dr. George M. Carman In Saccharomyces cerevisiae, Pah1 phosphatidate phosphatase, which catalyzes the dephosphorylation of phosphatidic acid (PA) to yield diacylglycerol (DAG), plays a major role in the synthesis of the storage lipid triacylglycerol. The evolutionarily conserved enzyme also regulates de novo phospholipid synthesis by controlling the level of PA, a precursor of membrane phospholipids. In this work, we showed that the pah1Δ mutant is defective in growth on non-fermentable carbon sources. Despite its apparent phenotype for respiratory deficiency, the pah1Δ mutant exhibited typical mitochondrial attributes, and even had an elevated mitochondrial membrane potential at the post-diauxic shift. Although oxidative phosphorylation was not compromised, the cellular levels of ATP in quiescent pah1Δ mutant cells were reduced by two-fold, which correlated with a four-fold increase in membrane phospholipids. Furthermore, the quiescent mutant cells exhibited three-fold elevations in mitochondrial superoxide and cellular lipid
Depression, physical function, and disease activity associated with frailty in patients with rheumatoid arthritis

Abstract Objectives To investigate the clinical and psychosocial backgrounds of frailty in rheumatoid arthritis (RA) patients. Methods Patients with RA between 40 and 79 years of age who visited university hospitals in an urban area were recruited. Well-validated self-reported questionnaires were used to evaluate patient physical function (Health Assessment Questionnaire, HAQ), depressive symptoms (Beck Depression Inventory-II, BDI-II), and frailty (Kihon Checklist). A 28-point Disease Activity Score (DAS-28) was calculated to evaluate RA disease activity. Results A total of 375 RA patients, 323 of whom were women, were enrolled (average age: 65.2 ± 9.7 years; average disease duration: 16.6 ± 11.9 years). The prevalence rates of frailty, working-age (40–64 years), young-old (65–74 years), and old-old (≥75 years) patients were 18.5, 28.8, and 36.6%, respectively. Higher age and longer disease duration were associated with frailty. Multivariable logistic regression analysis revealed that HAQ, DAS-28, and BDI-II scores were independently associated with frailty in RA patients. Conclusion Frailty is common, even among working-age RA patients. Physical function, disease activity, and depressive symptoms were independently associated with frailty. A multidisciplinary intervention approach, along with adequate pharmacological therapy, may promote successful aging in patients with RA.
COPD at the end of life: Predictors of the emotional distress of patients and their family caregivers

Background Few studies have focused on patients' emotional distress with end-stage chronic obstructive pulmonary disease (COPD) and their main family caregivers. Methods Cross-sectional data about emotional, functional, and burden-related variables were collected from 85 patients with end-stage COPD and their 85 respective main family caregivers to determine the variables that could predict their emotional well-being. Descriptive analyses, comparison of means, hierarchical regression models, and comparative quali-quantitative analyses were carried out. Results Data show that the great majority of patients with COPD spend years with this diagnosis, and have been admitted to the hospital several times in advance stage of illness the previous year of the moment of end-of-life stage. Furthermore, only a tiny percentage of the patients were functionally independent in the advanced stage of illness. Conclusions The emotional distress and the burden of the family caregiver play an essential role in the distress of the patient, in conjunction with the patient's own functional independence and the time living with the disease, and comorbidity. On the other hand, variables of the patient, such as time since diagnosis, number of hospital admissions, comorbidity, functional dependence, and emotional distress, play an important role in the family caregiver's emotional distress and burden. Understanding how these variables are related is key to designing appropriate programs to reduce the emotional distress the patients with COPD at the end of life and their family caregivers.
SPEG: a key regulator of cardiac calcium homeostasis.

Proper cardiac Ca2+ homeostasis is essential for normal excitation-contraction coupling. Perturbations in cardiac Ca2+ handling through altered kinase activity has been implicated in altered cardiac contractility and arrhythmogenesis. Thus, a better understanding of cardiac Ca2+ handling regulation is vital for a better understanding of various human disease processes. 'Striated muscle preferentially expressed protein kinase' (SPEG) is a member of the myosin light chain kinase family that is key for normal cardiac function. Work within the last five years has revealed that SPEG has a crucial role in maintaining normal cardiac Ca2+ handling through maintenance of transverse tubule formation and phosphorylation of junctional membrane complex proteins. Additionally, SPEG has been causally impacted in human genetic diseases such as centronuclear myopathy and dilated cardiomyopathy as well as in common acquired cardiovascular disease such as heart failure and atrial fibrillation. Given the rapidly emerging role of SPEG as a key cardiac Ca2+ regulator, we here present this review in order to summarize recent findings regarding the mechanisms of SPEG regulation of cardiac excitation-contraction coupling in both physiology and human disease. A better understanding of the roles of SPEG will be important for a more complete comprehension of cardiac Ca2+ regulation in physiology and disease.
Variability of beech provenances in spring and autumn phenology

Time of flushing and growth cessation of beech (Fagus sylvatica L.) provenances is important on sites with frequently occuring late or early frosts. The 35 beech provenances growing in a trial in Choczewo in northern Poland were examined as regards flushing (FLUSH) and growth cessation (CESS) in two growing seasons (1997 and 2001). We conclude that in these traits an ecotypical variation pattern exists between provenances. Longitude had the most important influence on FLUSH and CESS - more eastern provenances tending to flush and cease growth earlier. Latitude and altitude also significantly affected phenology - northern populations flushed and ended growing season later as well as those from lower altitudes. In the environmental conditions of the experiment selection for late flushing has little importance.