Miracle-dz/UniFAR-FTUs huggingface dataset:
PI3P-dependent regulation of cell size and autophagy by phosphatidylinositol 5-phosphate 4-kinase

PIP4K is a lipid kinase implicated in tumour growth, immune function, and metabolic regulation. This study shows that PIP4K regulates PI3P levels and autophagy, thereby controlling cell size in Drosophila salivary glands. Phosphatidylinositol 3-phosphate (PI3P) and phosphatidylinositol 5-phosphate (PI5P) are low-abundance phosphoinositides crucial for key cellular events such as endosomal trafficking and autophagy. Phosphatidylinositol 5-phosphate 4-kinase (PIP4K) is an enzyme that regulates PI5P in vivo but can act on both PI5P and PI3P in vitro. In this study, we report a role for PIP4K in regulating PI3P levels in Drosophila. Loss-of-function mutants of the only Drosophila PIP4K gene show reduced cell size in salivary glands. PI3P levels are elevated in dPIP4K29 and reverting PI3P levels back towards WT, without changes in PI5P levels, can rescue the reduced cell size. dPIP4K29 mutants also show up-regulation in autophagy and the reduced cell size can be reverted by depleting Atg8a that is required for autophagy. Lastly, increasing PI3P levels in WT can phenocopy the reduction in cell size and associated autophagy up-regulation seen in dPIP4K29. Thus, our study reports a role for a PIP4K-regulated PI3P pool in the control of autophagy and cell size.
Systemic silencing and DNA methylation of a host reporter gene induced by a beneficial fungal root endophyte

A growing body of evidence suggests that RNA interference (RNAi) plays a pivotal role in the communication between plants and pathogenic fungi, where a bi-directional cross-kingdom RNAi is established to the advantage of either the host or the pathogen. Similar mechanisms acting during plant association with non-pathogenic symbiotic microorganisms have been elusive to this date. Here, we report on an RNAi-based mechanism of communication between a beneficial fungal endophyte, Fusarium solani strain K (FsK) and its host plants. This soil-borne endophyte that confers resistance and/or tolerance to biotic and abiotic stress in tomato and, as shown in this study, promotes plant growth in Nicotiana benthamiana, is restricted to the root system in both host plants. We first showed that the fungus has a functional core RNAi machinery; double stranded RNAs (dsRNAs) are processed into short interfering RNAs (siRNAs) of predominantly 21-nt in size, which lead to the degradation of homologous mRNAs. Importantly, by using an RNAi sensor system, we demonstrated that root colonization of N. benthamiana by FsK led to the induction of systemic silencing and DNA methylation of a host reporter gene. These data reflect a more general but so far unrecognized mechanism wherein root endophytes systemically translocate RNAi signals to the aboveground tissues of their hosts to modulate gene expression during symbiosis, which may be translated to the beneficial phenotypes. Highlight A root-restricted, beneficial fungal endophyte can induce systemic silencing and epigenetic modifications to its host plant.
Trim69 is a microtubule regulator that acts as a pantropic viral inhibitor

To identify novel cellular modulators of HIV-1 infection in IFN-stimulated myeloid cells, we have carried out a screen that combines functional and evolutionary analyses in THP-1-PMA cells that led us to the Tripartite Motif Protein 69 (Trim69), a poorly studied member of the Trim family of innate immunity regulators. Trim69 inhibits HIV-1, primate lentiviruses and the negative and positive-strand RNA viruses VSV and SARS-CoV2, overall indicating it is a broad-spectrum antiviral factor. Trim69 binds directly to microtubules and its antiviral activity is intimately linked to its ability to promote the accumulation of stable MTs, a specialized subset of microtubules. By analyzing the behavior of primary blood cells, we provide evidence that a program of MT stabilization is commonly observed in response to IFN-I in cells of the myeloid lineage and Trim69 is the key factor behind this program. Overall, our study identifies Trim69 as the first antiviral innate defense factor that regulates the properties of microtubules to limit viral spread, highlighting the possibility that the cytoskeleton may be a novel unappreciated fighting ground in the host-pathogen interactions that underlie viral infections.
Anisotropic dense collagen hydrogels possessing two ranges of porosity to create the adequate microenvironment for muscle bundles: a step towards skeletal muscle modeling

Despite the crucial role of the extracellular matrix (ECM) in the organotypic organization and function of skeletal muscles, most 3D models do not mimic its specific characteristics, namely its biochemical composition, stiffness, anisotropy, and porosity. Here, a novel 3D in vitro model of muscle extracellular matrix was developed to differentiate myogenic cells (C2C12 line) into myotubes and reproduce their natural cell/cell and cell/matrix interactions. An anisotropic hydrogel mimicking the perimysium was obtained thanks to unidirectional 3D printing of dense collagen with aligned collagen fibrils. The space between the different layers was tuned to generate an intrinsic porosity (100 µm) suitable for nutrient and oxygen diffusion. By modulating the gelling conditions, the mechanical properties of the construct reached those measured in the physiological muscle ECM. The addition of large channels (600 µm) by molding permitted to create a second range of porosity suitable for cell colonization without altering the physical properties of the hydrogel. C2C12 cells embedded in Matrigel®, seeded within the channels, organized in 3D, and differentiated into multinucleated mature myotubes. This organization reproduced the global muscular bundles, i.e., the endomysium encompassing myotubes. These results show that porous and anisotropic dense collagen hydrogels colonized with myoblasts are promising biomaterials to model skeletal muscle. Table of contents Highlights A novel extracellular matrix-like hydrogel increases the physiological relevance of the skeletal muscle model. Porous and anisotropic dense collagen hydrogels mimic the muscle ECM physical properties. Unidirectional printing of dense collagen creates a porous and anisotropic scaffold in a single step. Anisotropic dense collagen hydrogels promote C2C12 differentiation into myotubes and their 3D organization.
Effects of palmitic acid on milk production and insulin sensitivity in mid-lactation dairy cows

EFFECTS OF PALMITIC ACID ON MILK PRODUCTION AND INSULIN SENSITIVITY IN MID-LACTATION DAIRY COWS. Alice Mathews This masters of science research evaluates the effects of palmitic acid (C16:0) supplementation on milk production and insulin sensitivity in mid-lactation dairy cows. The ability of saturated fatty acids (SFA) to enhance milk yield in dairy cows may be due to shifts in glucose utilization caused by reduced insulin sensitivity in adipose tissue. Our objective was to evaluate the effects of palmitic acid (C16:0) on milk production and insulin sensitivity in cows. Twenty multiparous mid-lactation Holstein cows were enrolled in a study consisting of a 5 d covariate, 49 d treatment, and 14 d post-treatment period. All cows received a common sorghum silage-based diet and were randomly assigned to a diet containing no supplemental fat (control; n = 10; 138 ± 45 DIM) or C16:0 at 4% of ration DM (PALM; 98% C16:0; n = 10; 136 ± 44 DIM). Blood and milk were collected at routine intervals. Intravenous glucose tolerance tests (300 mg/kg of body weight (BW); GTT) were performed at d -1, 21, and 49 relative to start of treatment. Data were analyzed as repeated measures using a mixed model with fixed effects of treatment and time, and milk yield served as a covariate. PALM increased milk yield, energycorrected milk (ECM), and milk fat yield at wk 3, responses that were maintained at wk 7. Furthermore, PALM increased protein yield at wk 7. Changes in milk production occurred in parallel with enhanced energy intake and improved feed efficiency (ECM/dry matter intake). Enhanced milk fat yield during PALM treatment was due to increased C16:0 and C16:1 incorporation. Supplementation of PALM had no effect on concentration of milk components, BW, or body condition score. Two weeks post-treatment, ECM and milk fat yield remained elevated in PALM-fed cows while yields of milk were similar between treatments. The concentration of non-esterified fatty acids (NEFA) in plasma increased by d 4, 6, and 8 of PALM treatment, a response not observed thereafter. Although PALM supplementation did not modify insulin, glucose, or triacylglycerol levels in plasma, total cholesterol in plasma was elevated by wk 3. Estimated insulin sensitivity was lower during the first week of PALM treatment; however, glucose disposal following GTT was not modified. In contrast, PALM feeding reduced glucose-stimulated NEFA disappearance by wk 7. Results demonstrate that increasing dietary energy from C16:0 for a 7 wk duration improves milk yield and milk composition without modifying systemic glucose tolerance. Reduced glucose-stimulated NEFA disappearance with PALM supplementation and elevated circulating NEFA may reflect changes in adipose tissue insulin sensitivity.
In silico EsxG EsxH rational epitope selection: Candidate epitopes for vaccine design against pulmonary tuberculosis

Rational design of new vaccines against pulmonary tuberculosis is imperative. EsxG·EsxH complex is involved in metal uptake, drug resistance, and immune response evasion. These characteristics make it an ideal target for rational vaccine development. The aim of this study is to show the rational design of epitope-based peptide vaccines by using bioinformatics and structural vaccinology tools. A total of 4.15 µs of Molecular Dynamics simulations were carried out to describe the behavior in solution of heterodimer, single epitopes, and epitopes loaded into MHC-II complexes. In order to predict T and B cell epitopes for antigenic activation, bioinformatic tools were used. Hence, we propose three epitopes with the potential to design pulmonary tuberculosis vaccines. The possible use of the proposed epitopes includes subunit vaccines, as a booster in BCG vaccination to improve its immune response, as well as the generation of antibodies that interfere with the mycobacterium tuberculosis homeostasis, affecting its survival.
VOLTAGE-DEPENDENT POTASSIUM CURRENT

Elevated intracellular Ca"+ concentration reduces the amplitude of an early, voltage-dependent K+ current (IA) in the Type B photoreceptor of Hermissenda crassicornis. Internal Ca++ is increased by activating a voltage and light-dependent Ca"+ current present in these cells or by direct iontophoresis of Ca"+ ions. Substitution of Ba"+ for Ca++ or elimination of Ca++ from the sea water bathing the cells abolishes the reduction in IA during paired light and depolarizing voltage steps. The delayed K+ current (IB) in these cells is also reduced during paired light and voltage steps, but this decrease of IB is not affected by removal of extracellular Ca" 'B (but not IA). apparently much less dependent on intracellular Ca"+ levels, is reduced by light alone. Ca"+ iontophoresis also abolishes the light-dependent Na+ current, which recovers with a time course of minutes.
Adaptation of existing cardiovascular simulation model to cardiac pumping physiology

Cardiovascular diseases, affecting the heart and blood vessels, are the most common cause of death globally. However, the risk of suffering from a cardiovascular disease could decrease significantly as research improve treatment and identification of symptoms. One way to increase our knowledge and improve education of the cardiovascular system is to develop mathematical simulation models. This thesis project will attend the subject of cardiovascular modeling by analyzing an already implemented simulation model, the CircAdapt model. The project aim to thoroughly analyze the model from a physiological perspective and to derive the mathematical equations constituting the model. In addition to the analysis, extensions to the model have been developed, with the purpose of improving the model structure of the heart to anatomy and known qualities of cardiac pumping. Conclusions of the thesis are that the CircAdapt model well describes the dynamics of the cardiovascular system and consider both physical and physiological properties in its construction. Model limitations in the aspect of cardiovascular physiology have been identified. However, the highest physiological accuracy is the second priority after numerical stability, which can be hard to achieve when working with biomedical modeling. Several adaptations have been executed to improve heart anatomy and physiology. The adaptations differ in accuracy and are in need of future work to improve model stability. (Less)
Análise acústica das consoantes líquidas do Português Brasileiro em crianças com e sem transtorno fonológico Acoustical analysis of the liquid consonants of Brazilian Portuguese in children with and without phonological disorder

ABSTRACT Purpose: To describe and compare the F1, F2 and F3 formants of the liquids /l, , / produced by children with and withoutphonological impairment. Methods: Fifty nine children were separated into three groups: Control Group (CG), with absence ofdisorders in speech and language development; Experimental Group 1 (EG1), with presence of the process of liquids simplificationand/or cluster simplification; and Experimental Group 2 (EG2), with liquid simplification and any other processes. Children wererequested to repeat the syllables la, li, lu; a, i, u and a, i, u and the words /se’bola/, /’lama/, /’miu/, /aka’E/, /i’afa/,/pa’asu/. Data were stored and analyzed in the Computerized Speech Laboratory. Statistical analyses were provided. Results: Regarding the formants, the CG showed great differences between the three studied sounds. Between-groups analysis showed thatF3 presented the greatest modifications. Distorted sounds did not present significant differences between EG1 and EG2 and thesubstituted ones showed differences in F3 only for the consonant //.
Disaster Warnings and Compliance: The Impact of Social Process Factors over Time

Disaster warnings have proved to be only partially effective in bringing about behaviors that enhance survival. For disasters that are ongoing and associated with repeated warnings, determinants of compliance may change over time. To test this argument, a theoretical working model is developed and tested on the basis of data collected from a field survey of a national representative sample of Israeli households (814). Respondents were asked if they complied with the warning to enter a sealed room (i.e., shelter in place) at the initial and toward the end of a three month long ballistic missile attack on Israeli civilians during the First Gulf War. Compliance decreased with time. We then sought to generate a parsimonious model to explain the drop in compliance by focusing on a variety of factors that included “message” oriented and social process variables. Results of the logistic regression models demonstrated that compliance initially was determined by prior levels of preparedness whereas determinants of behavioral compliance three months later broadened to include gender, risk perceptions, and the source of knowledge for actions to the threat. These results strongly suggest that initial compliance with warnings depend on having available fundamental survival assets. With repeated warnings over time, social process variables significantly affected compliance decisions. Efforts to increase disaster survival should therefore consider the time continuum in terms of the impact of social process variables on complying with warnings.
The Prevalence of Depression among Untreated Obstructive Sleep Apnea

Journal of Clinical Sleep Medicine, Vol. 12, No. 1, 2016 Study Objectives: The aims of this study were: (1) to use a standardized psychiatric interview, conducted by a trained psychologist to assess the prevalence of depression among patients with untreated OSA, and (2) to identify if OSA severity or other comorbid disorders (insomnia, hypertension, and diabetes) are related to depression among patients with untreated OSA. Methods: Participants were newly diagnosed patients with OSA (n = 284) waiting to start positive airway pressure (PAP) treatment. The Mini International Neuropsychiatric Interview (MINI) was used to assess depression. Results: Overall, 15.5% of the sample met the diagnosis for dysthymia. Women had a significantly higher prevalence (29.5% versus 11.7% among men, p < 0.001). The prevalence of major depression was 6% in the overall sample and there was no difference in the prevalence among sexes (5.8% among men versus 6.6 % among women). Obesity, daytime sleepiness, low physical activity, initial and late insomnia, low quality of life, and sleep medication and antidepressant use were all related to depression, whereas OSA severity, as measured by apnea-hypopnea index or oxygen desaturation index, was not. Daytime sleepiness, initial insomnia, and sleep medication use were the strongest predictors of depression in multivariable analyses. Conclusions: Sleep medication use, daytime sleepiness, and symptoms of initial insomnia were independently related to depression but OSA severity was not. Increased awareness of the relationship between depression and OSA and the appropriate use of assessment tools might substantially improve diagnostic accuracy as well as treatment outcome for both disorders.
Persistent Vegetative State and Minimally Conscious State

Background: Acute brain damage can cause major disturbances of consciousness, ranging all the way to the persistent vegetative state (PVS), which is also known as ”unresponsive wakefulness syndrome”. PVS can be hard to distinguish from a state of minimal preserved consciousness (“minimally conscious state,” MCS); the rate of misdiagnosis is high and has been estimated at 37–43%. In contrast, PVS is easily distinguished from brain death. We discuss the various diagnostic techniques that can be used to determine whether a patient is minimally conscious or in a persistent vegetative state.
Long-chain fatty acids regulate liver carnitine palmitoyltransferase I gene (L-CPT I ) expression through a peroxisome-proliferator-activated receptor α (PPARα)-independent pathway

Liver carnitine palmitoyltransferase I (L-CPT I) catalyses the transfer of long-chain fatty acid (LCFA) for translocation across the mitochondrial membrane. Expression of the L-CPT I gene is induced by LCFAs as well as by lipid-lowering compounds such as clofibrate. Previous studies have suggested that the peroxisome-proliferator-activated receptor α (PPARα) is a common mediator of the transcriptional effects of LCFA and clofibrate. We found that free LCFAs rather than acyl-CoA esters are the signal metabolites responsible for the stimulation ofL-CPT I gene expression. Using primary culture of hepatocytes we found that LCFAs failed to stimulate L-CPT I gene expression both in wild-type and PPARα-null mice. These results suggest that the PPARα-knockout mouse does not represent a suitable
Phosphorylation of GMFg by c-Abl Coordinates Lamellipodial and Focal Adhesion Dynamics to Regulate Airway Smooth Muscle Cell Migration

Airway smooth muscle cells require coordinated protrusion and focal adhesion dynamics to migrate properly. However, the signaling cascades that connect these two processes remain incompletely understood. Glia maturation factor (GMF)-g has been implicated in inducing actin debranching and inhibiting nucleation. In this study, we discovered that GMFg phosphorylation at Y104 regulates human airway smooth muscle cell migration. Using high-resolution microscopy coupled with three-dimensional object–based quantitative image analysis software, Imaris 9.2. 0, phosphomimetic mutant, Y104D-GMFg, was enriched at nascent adhesions along the leading edge where it recruited activated neural Wiskott-Aldrich syndrome protein (N-WASP; pY256) to promote actin-branch formation, which enhanced lamellipodial dynamics and limited the growth of focal adhesions. Unexpectedly, we found that nonphosphorylated mutant, Y104F-GMFg, was enriched in growing adhesions where it promoted a linear branch organization and focal adhesion clustering, and recruited zyxin to increase maturation, thus inhibiting lamellipodial dynamics and cellmigration. The localization of GMFg between the leading edge and focal adhesions was dependent upon myosin activity. Furthermore, c-Abl tyrosine kinase regulated theGMFgphosphorylation–dependentprocesses.Together, these results unveil the importance of GMFg phosphorylation in coordinating lamellipodial and focal adhesion dynamics to regulate cell migration.
Divided Loyalties? Some Notes on Translating University Websites into English

The translation of university texts into English, especially web-based texts, can be seen as a very particular case of ‘localization’. In established models of “web localization”, mostly based on translation from English, localization is defined as the adaptation of the linguistic aspects of a product or service to a specific market characterized by a distinct social and cultural profile. However, when addressing an international audience through a lingua franca, as is often the case with institutional websites, there may be no proper target “locale” to speak of and identifying a “target” audience may turn out to be difficult. The paper gives a brief overview of what and how universities translate into English, with special reference to what happens in Italy, and then discusses the implications of translation into lingua-franca English for some fundamental notions employed by scholars and practitioners of translation and cross-cultural communication.
Expression of a2-Macroglobulin Receptor/Low Density Lipoprotein Receptor- related Protein and Scavenger Receptor in Human Atherosclerotic Lesions

Macrophageand smooth muscle cell (SMC)-derived foam cells are typical constituents of human atherosclerotic lesions. At least three receptor systems have been characterized that could be involved in the development of foam cells: a2-macroglobulin receptor/LDL receptor-related protein (a2MR/LRP), scavenger receptor, and LDL receptor. We studied the expression of these receptors in human atherosclerotic lesions with in situ hybridization and immunocytochemistry. An abundant expression ofa2MR/LRP mRNA and protein was found in SMC and macrophages in both early and advanced lesions in human aortas. a2MR/LRP was also present in SMC in normal aortas. Scavenger receptor mRNA and protein were expressed in lesion macrophages but no expression was found in lesion SMC. LDL receptor was absent from the lesion area but was expressed in some aortas in medial SMC located near the adventitial border. The results demonstrate that (a) a2MR/LRP is, so far, the only lipoprotein receptor expressed in lesion SMC in vivo; (b) scavenger receptors are expressed only in lesion macrophages; and (c) both receptors may play important roles in the development of human atherosclerotic lesions. (J. Clin. Invest. 1994. 93:2014-2021.)