Miracle-dz/UniFAR-FTUs huggingface dataset:
GATA‐1 Deficiency Rescues Trabecular but not Cortical Bone in OPG Deficient Mice

GATA‐1low/low mice have an increase in megakaryocytes (MKs) and trabecular bone. The latter is thought to result from MKs directly stimulating osteoblastic bone formation while simultaneously inhibiting osteoclastogenesis. Osteoprotegerin (OPG) is known to inhibit osteoclastogenesis and OPG−/− mice have reduced trabecular and cortical bone due to increased osteoclastogenesis. Interestingly, GATA‐1low/low mice have increased OPG levels. Here, we sought to determine whether GATA‐1 knockdown in OPG−/− mice could rescue the observed osteoporotic bone phenotype. GATA‐1low/low mice were bred with OPG−/− mice and bone phenotype assessed. GATA‐1low/low × OPG−/− mice have increased cortical bone porosity, similar to OPG−/− mice. Both OPG−/− and GATA‐1low/low × OPG−/− mice, were found to have increased osteoclasts localized to cortical bone, possibly producing the observed elevated porosity. Biomechanical assessment indicates that OPG−/− and GATA‐1low/low × OPG−/− femurs are weaker and less stiff than C57BL/6 or GATA‐1low/low femurs. Notably, GATA‐1low/low × OPG−/− mice had trabecular bone parameters that were not different from C57BL/6 values, suggesting that GATA‐1 deficiency can partially rescue the trabecular bone loss observed with OPG deficiency. The fact that GATA‐1 deficiency appears to be able to partially rescue the trabecular, but not the cortical bone phenotype suggests that MKs can locally enhance trabecular bone volume, but that MK secreted factors cannot access cortical bone sufficiently to inhibit osteoclastogenesis or that OPG itself is required to inhibit osteoclastogenesis in cortical bone. J. Cell. Physiol. 230: 783–790, 2015. © 2014 Wiley Periodicals, Inc.
Chemical Offense by Means of Toxicysts in the Freshwater Ciliate, Coleps hirtus

Coleps hirtus is a small common freshwater ciliate belonging to the protostomatid group, its body covered by calcified plates assembled to form an armor. Coleps feeds on bacteria, algae, flagellates, living and dead ciliates, animal and plant tissues. To assist its carnivorous feeding the ciliate is equipped with offensive extrusomes (toxicysts), clustering mainly in and around its oral aperture. In this study, we isolated the discharge of the toxicysts from living cells, evaluating its cytotoxic effects against various ciliate species, and demonstrating that it is essential for the effectiveness of Coleps’ predatory behavior. The analysis of the toxicyst discharge performed by liquid chromatography‐electrospray‐mass spectrometry and gas chromatography‐mass spectrometry, revealed the presence of a mixture of 19 saturated, monounsaturated and polyunsaturated free fatty acids with the addition of a minor amount of a diterpenoid (phytanic acid).
Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis

The endoplasmic reticulum (ER) is a cellular organelle where secretory and membrane proteins, as well as lipids, are synthesized and modified. When cells are subjected to ER stress, an adaptive mechanism referred to as the Unfolded Protein Response (UPR) is triggered to allow the cells to restore homeostasis. Evidence has accumulated that the UPR pathways provide specialized and unique roles in diverse development and metabolic processes. The glucose regulated proteins (GRPs) are traditionally regarded as ER proteins with chaperone and calcium binding properties. The GRPs are constitutively expressed at basal levels in all organs, and as stress‐inducible ER chaperones, they are major players in protein folding, assembly and degradation. This conventional concept is augmented by recent discoveries that GRPs can be actively translocated to other cellular locations such as the cell surface, where they assume novel functions that regulate signaling, proliferation, apoptosis and immunity. Recent construction and characterization of mouse models where the gene encoding for the UPR components and the GRPs is genetically altered provide new insights on the physiological contribution of these proteins in vivo. This review highlights recent progress towards the understanding of the role of the UPR and two major GRPs (GRP78 and GRP94) in regulating homeostasis of organs arising from the endoderm, mesoderm and ectoderm. GRP78 and GRP94 exhibit shared and unique functions, and in specific organs their depletion elicits adaptive responses with physiological consequences. J. Cell. Physiol. 230: 1413–1420, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
Dynamically Regulated CFTR Expression and Its Functional Role in Cutaneous Wound Healing

The physiological role of cystic fibrosis transmembrane conductance regulator (CFTR) in keratinocytes and skin wound healing is completely unknown. The present study shows that CFTR is expressed in the multiple layers of keratinocytes in mouse epidermis and exhibits a dynamic expression pattern in a dorsal skin wound healing model, with diminishing levels observed from day 3 to day 5 and re‐appearing from day 7 to day 10 after wounding. Knockdown of CFTR in cultured human keratinocytes promotes cell migration but inhibits differentiation, while overexpression of CFTR suppresses migration but enhances differentiation, indicating an important role of CFTR in regulating keratinocyte behavior. In addition, we have demonstrated a direct association of CFTR with epithelial junction formation as knockdown of CFTR downregulates the expression of adhesion molecules, such as E‐cadherin, ZO‐1 and β‐catenin, and disrupts the formation of cell junction, while overexpression of CFTR enhances cell junction formation. More importantly, we have shown that ΔF508cftr−/− mice with defective CFTR exhibit delayed wound healing as compared to wild type mice, indicating that normal function of CFTR is critical for wound repair. Taken together, the present study has revealed a previously undefined role of CFTR in regulating skin wound healing processes, which may have implications in injury repair of other epithelial tissues. J. Cell. Physiol. 230: 2049–2058, 2015. © 2015 Wiley Periodicals, Inc.
Morphology and Molecular Phylogeny of Pseudocyrtohymena koreana n. g., n. sp. and Antarctic Neokeronopsis asiatica Foissner et al., 2010 (Ciliophora, Sporadotrichida), with a Brief Discussion of the Cyrtohymena Undulating Membranes Pattern

We discovered a new brackish water oxytrichid Pseudocyrtohymena koreana n. g. , n. sp. in South Korea and investigated the new species on the basis of morphology, ontogenesis, and 18S rRNA gene sequences. The new genus has the 18 frontal‐ventral‐transverse cirri of typical oxytrichids with flexible body, cortical granules, Cyrtohymena undulating membranes (UM), and one left and one right marginal cirral row. Ontogenesis of the new species indicated that dorsal kinety anlage 3 stretches within the parental row without any fragmentations (Urosomoida pattern) and exclusively forms all caudal cirri. The new genus is morphologically similar to Cyrtohymena Foissner, 1989, but has the following distinctive features: (i) caudal cirri absent in dorsal kineties 1 and 2 (vs. present in Cyrtohymena); and (ii) dorsal kinety 3 nonfragmented (vs. fragmented in Cyrtohymena). Further, we collected an additional species Neokeronopsis asiatica Foissner et al. 2010, from King George Island, Antarctica, and the species shares the morphology of UM with Cyrtohymena. Herein, we describe the previously unidentified characteristics of N. asiatica (i.e., cortical granules, body flexibility, contractile vacuole, and 18S rRNA gene sequence). In addition, we obtained two 18S rRNA gene sequences from Cyrtohymena muscorum and Parasterkiella thompsoni to expand samples for phylogenetic analysis. Our 18S rRNA gene tree supports the hypothesis that the Cyrtohymena UM pattern might have evolved several times in hypotrichs (e.g., Neokeronopsidae, Oxytrichinae, and Stylonychinae).
Capacidad predictiva de los criterios diagnósticos del síndrome metabólico sobre la resistencia a la insulina y el riesgo coronario

Fundamento y objetivo Dado que en la actualidad hay varios criterios diagnosticos del sindrome metabolico (SM), el objetivo del presente estudio ha sido comprobar la utilidad de los criterios de la International Diabetes Federation (IDF) para diagnosticar el SM, su concordancia con otras definiciones previas y con la resistencia a la insulina (RI), asi como estudiar su relacion con el riesgo coronario (RC). Sujetos y metodo Hemos realizado un estudio descriptivo y transversal en el ambito de la atencion primaria de Yecla (Murcia). Estudiamos a 317 personas de 424 seleccionadas mediante muestreo aleatorio estratificado (edad y sexo) a partir de 18.059 con tarjeta sanitaria y edad igual o superior a 30 anos. Se registraron variables sociodemograficas, antropometricas y analiticas (lipidos, microalbuminuria, hemoglobina glucosilada e insulinemia). Se utilizaron los criterios de la Organizacion Mundial de la Salud (OMS), del tercer informe del National Cholesterol Education Program (NCEP-III), del Grupo Europeo de Estudio de la Insulinorresistencia (EGIR) y de la IDF para diagnosticar el SM. Definimos RI cuando el indice HOMA era igual o mayor de 3,8. La concordancia entre definiciones del SM se valoro mediante el indice kappa. El RC se cuantifico mediante el metodo de Anderson de 1991. Resultados La prevalencia del SM fue: segun criterios de la OMS, del 35,3% (intervalo de confianza [IC] del 95%, 29,8-40,8); segun NCEP, del 20,2% (IC del 95%, 15,6-24,8); segun EGIR, del 24% (IC del 95%, 19,1-28,9), y segun IDF, del 28,9% (IC del 95% 23,8-34). La prevalencia de la RI fue del 27,7% (IC del 95%, 22,6-32,8). La concordancia entre los criterios mas clinicos (NCEP e IDF) y los mas bioquimicos (OMS, EGIR y HOMA) fue baja (kappa Conclusiones Existe una prevalencia alta de SM en Yecla, con una buena concordancia entre las definiciones mas clinicas del sindrome (NCEP e IDF), que se asocian con mayor RC.
Phosphorylation of Runx2, induced by cyclic mechanical tension via ERK1/2 pathway, contributes to osteodifferentiation of human periodontal ligament fibroblasts

Occlusal force is an important stimulus for maintaining periodontal homeostasis. This is attributed to the quality of human periodontal ligament fibroblasts (hPDLFs) that could transfer occlusal force into biological signals modulating osteoblst differentiation. However, few studies investigated the mechanism of occlusal force‐induced osteodifferentiation of hPDLFs. In our study, we used the cyclic mechanical tension (CMT) at 10% elongation with 0.5 Hz to mimic occlusal force, and explored its effects on osteogenesis of hPDLFs. Firstly, elevated expressions of several osteoblast marker genes (Runx2, ATF4, SP7, OCN, and BSP), as well as activated ERK1/2 pathway were detected during CMT loading for 1, 3, 6, 12, 18, and 24 h. To gain further insight into how CMT contributed to those effects, we focused on the classic ERK1/2‐Runx2 pathway by inhibiting ERK1/2 and overexpressing Runx2. Our results reflected that Runx2 overexpression alone could induce osteodifferentiation of hPDLFs. Meanwhile, CMT loading could intensify while combined ERK1/2 blockage could weaken this process. Furthermore, we found that CMT promoted Runx2 transcription and phosphorylation via ERK1/2; protein level of phospho‐Runx2 (p‐Runx2), rather than Runx2, was in parallel with mRNA expressions of SP7, OCN, and BSP. Taken together, our study proved that p‐Runx2, elevated by CMT via ERK1/2 pathway, is the predominate factor in promoting osteoblast differentiation of hPDLFs. J. Cell. Physiol. 230: 2426–2436, 2015. © 2015 Wiley Periodicals, Inc.
Sterol Composition and Biosynthetic Genes of Vitrella brassicaformis, a Recently Discovered Chromerid: Comparison to Chromera velia and Phylogenetic Relationship with Apicomplexan Parasites

Vitrella brassicaformis is the second discovered species in the Chromerida, and first in the family Vitrellaceae. Chromera velia, the first discovered species, forms an independent photosynthetic lineage with V. brassicaformis, and both are closely related to peridinin‐containing dinoflagellates and nonphotosynthetic apicomplexans; both also show phylogenetic closeness with red algal plastids. We have utilized gas chromatography/mass spectrometry to identify two free sterols, 24‐ethylcholest‐5‐en‐3β‐ol, and a minor unknown sterol which appeared to be a C28:4 compound. We have also used RNA Seq analysis to identify seven genes found in the nonmevalonate/methylerythritol pathway (MEP) for sterol biosynthesis. Subsequent genome analysis of V. brassicaformis showed the presence of two mevalonate (MVA) pathway genes, though the genes were not observed in the transcriptome analysis. Transcripts from four genes (dxr, ispf, ispd, and idi) were selected and translated into proteins to study the phylogenetic relationship of sterol biosynthesis in V. brassicaformis and C. velia to other groups of algae and apicomplexans. On the basis of our genomic and transcriptomic analyses, we hypothesize that the MEP pathway was the primary pathway that apicomplexans used for sterol biosynthesis before they lost their sterol biosynthesis ability, although contribution of the MVA pathway cannot be discounted.
Brg1 Controls the Expression of Pax7 to Promote Viability and Proliferation of Mouse Primary Myoblasts

Brg1 (Brahma‐related gene 1) is a catalytic component of the evolutionarily conserved mammalian SWI/SNF ATP‐dependent chromatin remodeling enzymes that disrupt histone‐DNA contacts on the nucleosome. While the requirement for the SWI/SNF enzymes in cell differentiation has been extensively studied, its role in precursor cell proliferation and survival is not as well defined. Muscle satellite cells constitute the stem cell pool that sustains and regenerates myofibers in adult skeletal muscle. Here, we show that deletion of Brg1 in primary mouse myoblasts derived from muscle satellite cells cultured ex vivo leads to a cell proliferation defect and apoptosis. We determined that Brg1 regulates cell proliferation and survival by controlling chromatin remodeling and activating transcription at the Pax7 promoter, which is expressed during somite development and is required for controlling viability of the satellite cell population. Reintroduction of catalytically active Brg1 or of Pax7 into Brg1‐deficient satellite cells rescued the apoptotic phenotype and restored proliferation. These data demonstrate that Brg1 functions as a positive regulator for cellular proliferation and survival of primary myoblasts. Therefore, the regulation of gene expression through Brg1‐mediated chromatin remodeling is critical not just for skeletal muscle differentiation but for maintaining the myoblast population as well. J. Cell. Physiol. 230: 2990–2997, 2015. © 2015 Wiley Periodicals, Inc.
Control of the Normal and Pathological Development of Neural Stem and Progenitor Cells by the PC3/Tis21/Btg2 and Btg1 Genes

The PC3/Tis21/Btg2 and Btg1 genes are transcriptional cofactors belonging to the Btg/Tob family, which regulate the development of several cell types, including neural precursors. We summarize here the actions of these genes on neural precursors in the adult neurogenic niches and the cognitive defects associated when their expression is altered. We consider also recent findings implicating them in neural and non‐neural tumors, since common developmental mechanisms are involved. PC3/Tis21 is required for the regulation of the maturation of stem and progenitor cells in the adult dentate gyrus and subventricular zone (SVZ), by controlling both their exit from the cell cycle and the ensuing terminal differentiation. Such actions are effected by regulating the expression of several genes, including cyclin D1, BMP4, Id3. In cerebellar precursors, however, PC3/Tis21 regulates chiefly their migration rather than proliferation or differentiation, with important implications for the onset of medulloblastoma, the cerebellar tumor. In fact PC3/Tis21 is a medulloblastoma‐suppressor, as its overexpression in cerebellar precursors inhibits this tumor; PC3/Tis21 shows anti‐tumor activity also in non‐neural tumors. Btg1 presents a different functional profile, as it controls proliferation in adult stem/progenitor cells of dentate gyrus and SVZ, where is required to maintain their self‐renewal and quiescence, but is apparently devoid of a direct control of their terminal differentiation or migration. Notably, physical exercise in Btg1‐null mice rescues the loss of proliferative capability occurring in older stem cells. Both genes could be further investigated as therapeutical targets, namely, Btg1 in the process of aging and PC3/Tis21 as a tumor‐suppressor. J. Cell. Physiol. 230: 2881–2890, 2015. © 2015 Wiley Periodicals, Inc.
Avaliação histológica da neurorrafia término-lateral: estudo experimental em ratos

OBJECTIVE: The aim of this study was to histologically compare the axonal sprouting after end-to-side neurorrhaphy with or without epineurotomy. METHODS: twenty male Wistar rats were used, divided into two groups of 10 rats each. A 1.0cm segment of the tibial nerve E was dried and sutured on the opposite side, where it was sutured into the sciatic nerve D. In Group I, the suture was made directly in the epineurium and in Group II, epineurotomy was performed. After 4 weeks, histological evaluation was carried out of the transposed segment and the sciatic nerve distal to the suture. RESULTS: the results showed a small number of remyelinated fibers, varying from 7 to 51 fibers in Group I and from 10 to 91 fibers in Group II. The Mann-Whitney U test was used, with p=0.311, showing there is no statistically significant difference between the two groups. There was no positive relation between the number of remyelinated fibers in the graft and in the suture site distal to the sciatic lesion. CONCLUSION: lateral-ending neurorrhaphy, with or without epineural window, does not promote efficient remyelinization. Level of Evidence: Level II, prospective comparative study.
The Spectrum of E2F in Liver Disease—Mediated Regulation in Biology and Cancer

Uncoordinated cell growth is one of the fundamental concepts in carcinogenesis and occurs secondary to dysregulation of the cell cycle. The E2Fs are a large family of transcription factors and are key regulators of the cell cycle. The activation of E2Fs is intimately regulated by retinoblastoma 1 (RB1). The RB pathway has been implicated in almost every human malignancy. Recently there have been exciting developments in the E2F field using animal models to better understand the role of E2Fs in vivo. Genetic mouse models have proven essential in implicating E2Fs in hepatocellular carcinoma (HCC) and liver disease. In this review, the general structure and function of E2Fs as well as the role for E2Fs in the development of HCC and liver disease is evaluated. Specifically, what is known about E2Fs in human disease is explored in depth, and future directions are discussed. J. Cell. Physiol. 231: 1438–1449, 2016. © 2015 Wiley Periodicals, Inc.
The Involvement of Parasympathetic and Sympathetic Nerve in the Inflammatory Reflex

Production of inflammatory cytokines plays important roles in the response against tissue injury and in host defense. Alterations in the production of inflammatory cytokines may cause local or systemic inflammatory imbalance, culminating in organ failure or lethal systemic inflammation. The cholinergic anti‐inflammatory pathway has been implicated as an important mechanism to regulate inflammation of targeted tissue. In this review, we discuss important advances, conflicting and controversial findings regarding the involvement of parasympathetic vagus and sympathetic splenic nerve through acetylcholine (ACh) release and α7 nicotinic acetylcholine receptor (nAChRα7) activation in the spleen. In addition, we address the involvement of cholinergic control of inflammation in other organs innerved by the vagus nerve such as gut, liver, kidney and lung, and independent of parasympathetic innervations such as skin and skeletal muscle. Then, other structures and mechanisms independent of vagus or splenic nerve may be involved in this process, such as local cells and motor neurons producing ACh. Altogether, the convergence of these findings may contribute to current anti‐inflammatory strategies involving selective drug‐targeting and electrical nerve stimulation. J. Cell. Physiol. 231: 1862–1869, 2016. © 2016 Wiley Periodicals, Inc.
Functionalization of carbon nanotubes with a pH-responsive molecule to produce a pH sensor

Carbon nanotubes were functionalized with the ratiometric pH-responsive dye molecule 6,8-dihydroxy-1,3-pyrenedisulfonic acid disodium salt, which enabled them to indicate pH values over the range of pH 5.6–8.3. The nanotubes were coated with a layer of electron-donating ZnPc, which strengthened the CNT–dye interaction. The range of pH response is relevant for biological systems, which makes the nanotubes suitable for a wide range of applications within nanobiotechnology.
Flavopiridol: An Old Drug With New Perspectives? Implication for Development of New Drugs

Glioblastoma, the most common brain tumor, is characterized by high proliferation rate, invasion, angiogenesis, and chemo‐ and radio‐resistance. One of most remarkable feature of glioblastoma is the switch toward a glycolytic energetic metabolism that leads to high glucose uptake and consumption and a strong production of lactate. Activation of several oncogene pathways like Akt, c‐myc, and ras induces glycolysis and angiogenesis and acts to assure glycolysis prosecution, tumor proliferation, and resistance to therapy. Therefore, the high glycolytic flux depends on the overexpression of glycolysis‐related genes resulting in an overproduction of pyruvate and lactate. Metabolism of glioblastoma thus represents a key issue for cancer research. Flavopiridol is a synthetic flavonoid that inhibits a wide range of Cyclin‐dependent kinase, that has been demonstrate to inactivate glycogen phosphorylase, decreasing glucose availability for glycolysis. In this work the study of glucose metabolism upon flavopiridol treatment in the two different glioblastoma cell lines. The results obtained point towards an effect of flavopiridol in glycolytic cells, thus suggesting a possible new use of this compound or flavopiridol‐derived formulations in combination with anti‐proliferative agents in glioblastoma patients. J. Cell. Physiol. 232: 312–322, 2017. © 2016 Wiley Periodicals, Inc.