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1.
EMBO J ; 39(13): e103695, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32400009

RESUMEN

PP2A is an essential protein phosphatase that regulates most cellular processes through the formation of holoenzymes containing distinct regulatory B-subunits. Only a limited number of PP2A-regulated phosphorylation sites are known. This hampers our understanding of the mechanisms of site-specific dephosphorylation and of its tumor suppressor functions. Here, we develop phosphoproteomic strategies for global substrate identification of PP2A-B56 and PP2A-B55 holoenzymes. Strikingly, we find that B-subunits directly affect the dephosphorylation site preference of the PP2A catalytic subunit, resulting in unique patterns of kinase opposition. For PP2A-B56, these patterns are further modulated by affinity and position of B56 binding motifs. Our screens identify phosphorylation sites in the cancer target ADAM17 that are regulated through a conserved B56 binding site. Binding of PP2A-B56 to ADAM17 protease decreases growth factor signaling and tumor development in mice. This work provides a roadmap for the identification of phosphatase substrates and reveals unexpected mechanisms governing PP2A dephosphorylation site specificity and tumor suppressor function.


Asunto(s)
Proteína ADAM17/metabolismo , Proteína Fosfatasa 2/metabolismo , Proteína ADAM17/genética , Secuencias de Aminoácidos , Animales , Sitios de Unión , Células HeLa , Humanos , Ratones , Fosforilación
2.
Int J Cancer ; 152(6): 1210-1225, 2023 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-36408933

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy with minimal treatment options and a global rise in prevalence. PDAC is characterized by frequent driver mutations including KRAS and TP53 (p53), and a dense, acidic tumor microenvironment (TME). The relation between genotype and TME in PDAC development is unknown. Strikingly, when wild type (WT) Panc02 PDAC cells were adapted to growth in an acidic TME and returned to normal pH to mimic invasive cells escaping acidic regions, they displayed a strong increase of aggressive traits such as increased growth in 3-dimensional (3D) culture, adhesion-independent colony formation and invasive outgrowth. This pattern of acidosis-induced aggressiveness was observed in 3D spheroid culture as well as upon organotypic growth in matrigel, collagen-I and combination thereof, mimicking early and later stages of PDAC development. Acid-adaptation-induced gain of cancerous traits was further increased by p53 knockout (KO), but only in specific extracellular matrix (ECM) compositions. Akt- and Transforming growth factor-ß (TGFß) signaling, as well as expression of the Na+ /H+ exchanger NHE1, were increased by acid adaptation. Whereas Akt inhibition decreased spheroid growth regardless of treatment and genotype, stimulation with TGFßI increased growth of WT control spheroids, and inhibition of TGFß signaling tended to limit growth under acidic conditions only. Our results indicate that a complex crosstalk between tumor acidosis, ECM composition and genotype contributes to PDAC development. The findings may guide future strategies for acidosis-targeted therapies.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Matriz Extracelular/metabolismo , Neoplasias Pancreáticas/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Microambiente Tumoral , Proteína p53 Supresora de Tumor/genética , Neoplasias Pancreáticas
3.
Int J Mol Sci ; 21(2)2020 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-31947579

RESUMEN

We identified and analyzed α2,8-sialyltransferases sequences among 71 ray-finned fish species to provide the first comprehensive view of the Teleost ST8Sia repertoire. This repertoire expanded over the course of Vertebrate evolution and was primarily shaped by the whole genome events R1 and R2, but not by the Teleost-specific R3. We showed that duplicated st8sia genes like st8sia7, st8sia8, and st8sia9 have disappeared from Tetrapods, whereas their orthologues were maintained in Teleosts. Furthermore, several fish species specific genome duplications account for the presence of multiple poly-α2,8-sialyltransferases in the Salmonidae (ST8Sia II-r1 and ST8Sia II-r2) and in Cyprinus carpio (ST8Sia IV-r1 and ST8Sia IV-r2). Paralogy and synteny analyses provided more relevant and solid information that enabled us to reconstruct the evolutionary history of st8sia genes in fish genomes. Our data also indicated that, while the mammalian ST8Sia family is comprised of six subfamilies forming di-, oligo-, or polymers of α2,8-linked sialic acids, the fish ST8Sia family, amounting to a total of 10 genes in fish, appears to be much more diverse and shows a patchy distribution among fish species. A focus on Salmonidae showed that (i) the two copies of st8sia2 genes have overall contrasted tissue-specific expressions, with noticeable changes when compared with human co-orthologue, and that (ii) st8sia4 is weakly expressed. Multiple sequence alignments enabled us to detect changes in the conserved polysialyltransferase domain (PSTD) of the fish sequences that could account for variable enzymatic activities. These data provide the bases for further functional studies using recombinant enzymes.


Asunto(s)
Sialiltransferasas/genética , Vertebrados/genética , Secuencia de Aminoácidos , Animales , Mapeo Cromosómico , Biología Computacional/métodos , Evolución Molecular , Peces/genética , Peces/metabolismo , Expresión Génica , Sitios Genéticos , Modelos Moleculares , Familia de Multigenes , Filogenia , Conformación Proteica , Sialiltransferasas/química , Sialiltransferasas/metabolismo , Relación Estructura-Actividad , Vertebrados/metabolismo
4.
Proc Natl Acad Sci U S A ; 113(34): 9498-503, 2016 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-27444013

RESUMEN

Sialic acids (Sias) are abundant terminal modifications of protein-linked glycans. A unique feature of Sia, compared with other monosaccharides, is the formation of linear homo-polymers, with its most complex form polysialic acid (polySia). Sia and polySia mediate diverse biological functions and have great potential for therapeutic use. However, technological hurdles in producing defined protein sialylation due to the enormous structural diversity render their precise investigation a challenge. Here, we describe a plant-based expression platform that enables the controlled in vivo synthesis of sialylated structures with different interlinkages and degree of polymerization (DP). The approach relies on a combination of stably transformed plants with transient expression modules. By the introduction of multigene vectors carrying the human sialylation pathway into glycosylation-destructed mutants, transgenic plants that sialylate glycoproteins in α2,6- or α2,3-linkage were generated. Moreover, by the transient coexpression of human α2,8-polysialyltransferases, polySia structures with a DP >40 were synthesized in these plants. Importantly, plant-derived polySia are functionally active, as demonstrated by a cell-based cytotoxicity assay and inhibition of microglia activation. This pathway engineering approach enables experimental investigations of defined sialylation and facilitates a rational design of glycan structures with optimized biotechnological functions.

5.
Dis Aquat Organ ; 128(2): 93-103, 2018 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-29733024

RESUMEN

Amphibian populations are in decline worldwide as they face a barrage of challenges, including infectious diseases caused by ranaviruses and the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd). Here we describe seasonal dynamics of Bd and ranavirus detection in free-ranging post-metamorphic wood frogs Lithobates sylvaticus, boreal chorus frogs Pseudacris maculata/triseriata, and gray treefrogs Hyla versicolor/chrysoscelis, sampled over a 3 season gradient in Minnesota (USA) wetlands. We detected Bd in 36% (n = 259) of individuals sampled in 3 wetlands in 2014, and 33% (n = 255) of individuals sampled in 8 wetlands in 2015. We also detected ranavirus in 60% and 18% of individuals sampled in 2014 and 2015, respectively. Ranavirus and Bd were detected concurrently in 26% and 2% of animals sampled in 2014 and 2015, respectively. We report clinical signs and associated infection status of sampled frogs; of the clinical signs observed, skin discoloration was significantly associated with ranavirus infection. Using generalized estimating equations, we found that species, season, wetland, and a species × season interaction term were significant predictors of Bd detection, whereas test year approached significance as a predictor of ranavirus detection. The odds of detecting both pathogens concurrently was significantly influenced by species, season, a species × season interaction term, year, and environmental ammonia. We propose an amphibian health monitoring scheme that couples population size surveys with seasonal molecular surveys of pathogen presence. This information is crucial to monitoring the health of remaining strongholds of healthy amphibian populations, as they face an uncertain future of further anthropogenic change.


Asunto(s)
Anuros/microbiología , Quitridiomicetos , Infecciones por Virus ADN/veterinaria , Micosis/veterinaria , Ranavirus , Animales , Coinfección/microbiología , Coinfección/veterinaria , Coinfección/virología , Infecciones por Virus ADN/epidemiología , Infecciones por Virus ADN/virología , Medio Oeste de Estados Unidos/epidemiología , Micosis/epidemiología , Micosis/microbiología , Humedales
6.
J Biol Chem ; 288(1): 355-67, 2013 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-23148228

RESUMEN

Changes in cytoplasmic Ca(2+) concentration, resulting from activation of intracellular Ca(2+) channels within the endoplasmic reticulum, regulate several aspects of cellular growth and differentiation. Ca(2+) homeostasis endoplasmic reticulum protein (CHERP) is a ubiquitously expressed protein that has been proposed as a regulator of both major families of endoplasmic reticulum Ca(2+) channels, inositol 1,4,5-trisphosphate receptors (IP(3)Rs) and ryanodine receptors (RyRs), with resulting effects on mitotic cycling. However, the manner by which CHERP regulates intracellular Ca(2+) channels to impact cellular growth is unknown. Here, we challenge previous findings that CHERP acts as a direct cytoplasmic regulator of IP(3)Rs and RyRs and propose that CHERP acts in the nucleus to impact cellular proliferation by regulating the function of the U2 snRNA spliceosomal complex. The previously reported effects of CHERP on cellular growth therefore are likely indirect effects of altered spliceosomal function, consistent with prior data showing that loss of function of U2 snRNP components can interfere with cell growth and induce cell cycle arrest.


Asunto(s)
Calcio/metabolismo , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica , Proteínas de la Membrana/metabolismo , Nucleosomas/metabolismo , Proteínas de Unión al ARN/metabolismo , Ribonucleoproteínas/metabolismo , Secuencia de Aminoácidos , Señalización del Calcio , Ciclo Celular , Membrana Celular/metabolismo , Citoplasma/metabolismo , Retículo Endoplásmico/metabolismo , Células HEK293 , Homeostasis , Humanos , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Células Jurkat , Datos de Secuencia Molecular , Mutación , Interferencia de ARN , Ribonucleoproteínas/química , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Empalmosomas/metabolismo , Fracciones Subcelulares/metabolismo
7.
J Chem Ecol ; 40(9): 1025-38, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25236380

RESUMEN

Evidence for the the ability of birds to detect olfactory signals is now well documented, yet it remains unclear whether birds secrete chemicals that can be used as social cues. A potential source of chemical cues in birds is the secretion from the uropygial gland, or preen gland, which is thought to waterproof, maintain, and protect feathers from ectoparasites. However, it is possible that preen oil also may be used for individual recognition, mate choice, and signalling social/sexual status. If preen oil secretions can be used as socio-olfactory signals, we should be able to identify the volatile components that could make the secretions more detectable, determine the seasonality of these secretions, and determine whether olfactory signals differ among relevant social groups. We examined the seasonal differences in volatile compounds of the preen oil of captive white-throated sparrows, Zonotrichia albicollis. This species is polymorphic and has genetically determined morphs that occur in both sexes. Mating is almost exclusively disassortative with respect to morph, suggesting strong mate choice. By sampling the preen oil from captive birds in breeding and non-breeding conditions, we identified candidate chemical signals that varied according to season, sex, morph, and species. Linear alcohols with a 10-18 carbon chains, as well as methyl ketones and carboxylic acids, were the most abundant volatile compounds. Both the variety and abundances of some of these compounds were different between the sexes and morphs, with one morph secreting more volatile compounds in the non-breeding season than the other. In addition, 12 compounds were seasonally elevated in amount, and were secreted in high amounts in males. Finally, we found that preen oil signatures tended to be species-specific, with white-throated sparrows differing from the closely related Junco in the abundances and/or prevalence of at least three compounds. Our data suggest roles for preen oil secretions and avian olfaction in both non-social as well as social interactions.


Asunto(s)
Glándulas Exocrinas/química , Pájaros Cantores/fisiología , Compuestos Orgánicos Volátiles/metabolismo , Animales , Señales (Psicología) , Femenino , Cromatografía de Gases y Espectrometría de Masas , Genotipo , Aseo Animal , Masculino , Percepción Olfatoria , Estaciones del Año , Caracteres Sexuales , Pájaros Cantores/genética , Pájaros Cantores/metabolismo , Especificidad de la Especie
8.
Biochim Biophys Acta Gen Subj ; 1868(8): 130647, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38801837

RESUMEN

BACKGROUND: Sialic acids are essential monosaccharides influencing several biological processes and disease states. The sialyltransferases catalyze the transfer of Sia residues to glycoconjugates playing critical roles in cellular recognition and signaling. Despite their importance, the molecular mechanisms underlying their substrate specificity, especially between different organisms, remain poorly understood. Recently, the human ST8Sia IV, a key enzyme in the synthesis of polysialic acids, was found to accept only CMP-Neu5Ac as a sugar-donor, whereas the whitefish Coregonus maraena enzyme showed a wider donor substrate specificity, accepting CMP-Neu5Ac, CMP-Neu5Gc, and CMP-Kdn. However, what causes these differences in donor substrate specificity is unknown. METHODS: Computational approaches were used to investigate the structural and biochemical determinants of the donor substrate specificity in ST8Sia IV. Accurate structural models of the human and fish ST8Sia IV catalytic domains and their complexes with three sialic acid donors (CMP-Neu5Ac, CMP-Neu5Gc, and CMP-Kdn) were generated. Subsequently, molecular dynamics simulations were conducted to analyze the stability and interactions within these complexes and identify differences in complex stability and substrate binding sites between the two ST8Sia IV. RESULTS: Our MD simulations revealed that the human enzyme effectively stabilizes CMP-Neu5Ac, whereas CMP-Neu5Gc and CMP-Kdn are unstable and explore different conformations. In contrast, the fish ST8Sia IV stabilizes all three donor substrates. Based on these data, we identified the key interacting residues for the different Sias parts of the substrate donors. GENERAL SIGNIFICANCE: This work advances our knowledge of the enzymatic mechanisms governing sialic acid transfer, shedding light on the evolutionary adaptations of sialyltransferases.


Asunto(s)
Simulación de Dinámica Molecular , Ácidos Siálicos , Sialiltransferasas , Sialiltransferasas/metabolismo , Sialiltransferasas/química , Especificidad por Sustrato , Humanos , Animales , Ácidos Siálicos/metabolismo , Ácidos Siálicos/química , Dominio Catalítico
9.
Front Immunol ; 14: 1147356, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37457740

RESUMEN

Galectins are a family of carbohydrate-binding proteins found in vertebrates in great abundance and diversity in terms of both structure and ligand-binding properties as well as physiological function. Proteins with clear relationships to vertebrate galectins are already found in primitive Bilateria. The increasing amount of accessible well-annotated bilaterian genomes has allowed us to reveal, through synteny analyses, a new hypothesis about the phylogenetic history of the galectin family in this animal group. Thus, we can trace the genomic localization of the putative ancestral Bilateria galectin back to the scallops as a still very primitive slow-evolving bilaterian lineage. Intriguingly, our analyses show that the primordial galectin of the Deuterostomata most likely exhibited galectin-8-like characteristics. This basal standing galectin is characterized by a tandem-repeat type with two carbohydrate recognition domains as well as by a sialic acid binding property of the N-terminal domain, which is typical for galectin-8. With the help of synteny, the amplification of this potential primordial galectin to the broad galectin cosmos of modern jawed vertebrates can be reconstructed. Therefore, it is possible to distinguish between the paralogs resulting from small-scale duplication and the ohnologues generated by whole-genome duplication. Our findings support a substantially new hypothesis about the origin of the various members of the galectin family in vertebrates. This allows us to reveal new theories on the kinship relationships of the galectins of Gnatostomata. In addition, we focus for the first time on the galectines of the Cyclostomata, which as a sister group of jawed vertebrates providing important insights into the evolutionary history of the entire subphylum. Our studies also highlight a previously neglected member of the galectin family, galectin-related protein 2. This protein appears to be a widespread ohnologue of the original tandem-repeat ancestor within Gnathostomata that has not been the focus of galectin research due to its nonclassical galactose binding sequence motif and the fact that it was lost during mammalian evolution.


Asunto(s)
Galectinas , Vertebrados , Animales , Filogenia , Galectinas/metabolismo , Vertebrados/genética , Comunicación Celular , Carbohidratos , Mamíferos/metabolismo
10.
Front Med (Lausanne) ; 10: 1290201, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38152301

RESUMEN

Introduction: The elderly population constitutes one of the fastest-growing demographic groups globally. Within this population, mild to moderate traumatic brain injuries (TBI) resulting from ground level falls (GLFs) are prevalent and pose significant challenges. Between 50 and 80% of TBIs in older individuals are due to GLFs. These incidents result in more severe outcomes and extended recovery periods for the elderly, even when controlling for injury severity. Given the increasing incidence of such injuries it becomes essential to identify the key factors that predict complications and in-hospital mortality. Therefore, the aim of this study was to pinpoint the top predictors of complications and in-hospital mortality in geriatric patients who have experienced a moderate TBI following a GLF. Methods: Data were obtained from the American College of Surgeons' Trauma Quality Improvement Program database. A moderate TBI was defined as a head AIS ≤ 3 with a Glasgow Coma Scale (GCS) 9-13, and an AIS ≤ 2 in all other body regions. Potential predictors of complications and in-hospital mortality were included in a logistic regression model and ranked using the permutation importance method. Results: A total of 7,489 patients with a moderate TBI were included in the final analyses. 6.5% suffered a complication and 6.2% died prior to discharge. The top five predictors of complications were the need for neurosurgical intervention, the Revised Cardiac Risk Index, coagulopathy, the spine abbreviated injury severity scale (AIS), and the injury severity score. The top five predictors of mortality were head AIS, age, GCS on admission, the need for neurosurgical intervention, and chronic obstructive pulmonary disease. Conclusion: When predicting both complications and in-hospital mortality in geriatric patients who have suffered a moderate traumatic brain injury after a ground level fall, the most important factors to consider are the need for neurosurgical intervention, cardiac risk, and measures of injury severity. This may allow for better identification of at-risk patients, and at the same time resulting in a more equitable allocation of resources.

11.
Sci Rep ; 13(1): 15610, 2023 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-37730806

RESUMEN

The human polysialyltransferases ST8Sia II and ST8Sia IV catalyze the transfer of several Neu5Ac residues onto glycoproteins forming homopolymers with essential roles during different physiological processes. In salmonids, heterogeneous set of sialic acids polymers have been described in ovary and on eggs cell surface and three genes st8sia4, st8sia2-r1 and st8sia2-r2 were identified that could be implicated in these heteropolymers. The three polysialyltransferases from the salmonid Coregonus maraena were cloned, recombinantly expressed in HEK293 cells and the ST8Sia IV was biochemically characterized. The MicroPlate Sialyltransferase Assay and the non-natural donor substrate CMP-SiaNAl were used to demonstrate enzyme activity and optimize polysialylation reactions. Polysialylation was also carried out with natural donor substrates CMP-Neu5Ac, CMP-Neu5Gc and CMP-Kdn in cell-free and cell-based assays and structural analyses of polysialylated products using the anti-polySia monoclonal antibody 735 and endoneuraminidase N and HPLC approaches. Our data highlighted distinct specificities of human and salmonid polysialyltransferases with notable differences in donor substrates use and the capacity of fish enzymes to generate heteropolymers. This study further suggested an evolution of the biological functions of polySia. C. maraena ST8Sia IV of particular interest to modify glycoproteins with a variety of polySia chains.


Asunto(s)
Ácido N-Acetilneuramínico , Salmonidae , Animales , Femenino , Humanos , Células HEK293 , Bioensayo
12.
Biology (Basel) ; 12(1)2022 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-36671698

RESUMEN

Sialylated milk oligosaccharides and glycoconjugates have several positive effects on the mucosal barrier, the gut microbiome, and an effective immune system. For this reason, they are important biomolecules for mammary gland health and optimal development of offspring. In milk, the major sialic acid, N-acetylneuraminic acid (Neu5Ac), can be attached as monosialyl-residues or as polymers. To investigate the sialylation processes during lactation of German Holstein cows, we analyzed udder tissue in addition to milk at different time points of lactation. The analysis of the milk samples revealed that both the levels of Neu5Ac and its polymer, polysialic acid (polySia), rapidly decreased during the first three days of lactation, and a high interindividual variance was observed. In mature milk, however, the sialylation status remains relatively constant. The results indicate that mammary gland epithelial cells are one source for milk polySia, since immunohistochemistry of udder tissue exhibited strong polySia staining in these cells. Furthermore, both polysialyltransferases, ST8SiaII and ST8SiaIV, are expressed. Based on known functions of monosialyl residues and polySia, we discuss the potential impact of these biomolecules and the consequences of the heterogeneous sialylation status of milk in relation to udder health and offspring health.

13.
Cells ; 9(11)2020 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-33142835

RESUMEN

In vertebrates, the carbohydrate polymer polysialic acid (polySia) is especially well known for its essential role during neuronal development, regulating the migration and proliferation of neural precursor cells, for instance. Nevertheless, sialic acid polymers seem to be regulatory elements in other physiological systems, such as the reproductive tract. Interestingly, trout fish eggs have polySia, but we know little of its cellular distribution and role during oogenesis. Therefore, we localized α2,8-linked N-acetylneuraminic acid polymers in the ovaries of Coregonus maraena by immunohistochemistry and found that prevalent clusters of oogonia showed polySia signals on their surfaces. Remarkably, the genome of this salmonid fish contains two st8sia2 genes and one st8sia4 gene, that is, three polysialyltransferases. The expression analysis revealed that for st8sia2-r2, 60 times more mRNA was present than st8sia2-r1 and st8sia4. To compare polysialylation status regarding various polySiaT configurations, we performed a comparable analysis in Sander lucioperca. The genome of this perciform fish contains only one st8sia2 and no st8sia4 gene. Here, too, clusters of oogonia showed polysialylated cell surfaces, and we detected high mRNA values for st8sia2. These results suggest that in teleosts, polySia is involved in the cellular processes of oogonia during oogenesis.


Asunto(s)
Ovario , Percas/genética , Salmonidae/genética , Ácidos Siálicos/metabolismo , Sialiltransferasas/genética , Animales , Femenino , Técnicas Histológicas , Ácido N-Acetilneuramínico/metabolismo , Oogénesis , Oogonios/metabolismo
14.
ACS Nano ; 14(5): 5570-5580, 2020 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-32255336

RESUMEN

The assembly of one-dimensional nanomaterials into macroscopic fibers can improve mechanical as well as multifunctional performance. Double-walled aluminogermanate imogolite nanotubes are geo-inspired analogues of carbon nanotubes, synthesized at low temperature, with complementary properties. Here, continuous imogolite-based fibers are wet-spun within a poly(vinyl alcohol) matrix. The lyotropic liquid crystallinity of the system produces highly aligned fibers with tensile stiffness and strength up to 24.1 GPa (14.1 N tex-1) and 0.8 GPa (0.46 N tex-1), respectively. Significant enhancements over the pure polymer control are quantitatively attributed to both matrix refinement and direct nanoscale reinforcement, by fitting an analytical model. Most intriguingly, imogolite-based fibers show a high degree of healability via evaporation-induced self-assembly, recovering up to 44% and 19% of the original fiber tensile stiffness and strength, respectively. This recovery at high absolute strength highlights a general strategy for the development of high-performance healable fibers relevant to composite structures and other applications.

15.
Dtsch Med Wochenschr ; 141(9): 634, 2016 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-27123729

RESUMEN

HISTORY AND ADMISSION FINDINGS: We report the case of a 59-year-old male who was admitted to hospital with acute chest pain. Coronary heart disease was known from the medical history. The patient reported recurrent ostealgia and susceptibility for infection during the last months before admission. INVESTIGATIONS: A 75% stenosis of the circumflex branch was treated with a drug eluting stent. Platelet aggregation was inhibited with acetylsalicylic acid and clopidogrel. Due to persisting ostealgia and inflammatory state, spondylodiscitis was excluded in MRI. However, platelets remained low after successful treatment of the infection. DIAGNOSIS, TREATMENT AND COURSE: Bone marrow biopsy revealed an acute lymphoblastic leukemia with positive detection of the Philadelphia chromosome. After chemotherapy and allogenic hematopoietic cell transplantation the patient remains in remission of his acute lymphoblastic leukemia. CONCLUSIONS: Especially in patients with documented history of coronary heart disease, the differential diagnosis of chest pain can be challenging. In this case, the chest pain was based on a subacute coronary ischemia as well as on proliferation of the acute lymphoblastic leukemia. The management of dual oral anticoagulation was performed with higher transfusion limits for thrombocytes and continuous application of thrombocyte aggregation inhibitors.


Asunto(s)
Dolor en el Pecho/etiología , Enfermedad Coronaria/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Aloinjertos , Examen de la Médula Ósea , Quimioterapia Adyuvante , Diagnóstico Diferencial , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria , Inhibidores de Agregación Plaquetaria/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
16.
PLoS One ; 9(7): e103139, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25078405

RESUMEN

Higher N170 amplitudes to words and to faces were recently reported for faster readers of German. Since the shallow German orthography allows phonological recoding of single letters, the reported speed advantages might have their origin in especially well-developed visual processing skills of faster readers. In contrast to German, adult readers of Hebrew are forced to process letter chunks up to whole words. This dependence on more complex visual processing might have created ceiling effects for this skill. Therefore, the current study examined whether also in the deep Hebrew orthography visual processing skills as reflected by N170 amplitudes explain reading speed differences. Forty university students, native speakers of Hebrew without reading impairments, accomplished a lexical decision task (i.e., deciding whether a visually presented stimulus represents a real or a pseudo word) and a face decision task (i.e., deciding whether a face was presented complete or with missing facial features) while their electroencephalogram was recorded from 64 scalp positions. In both tasks stronger event related potentials (ERPs) were observed for faster readers in time windows at about 200 ms. Unlike in previous studies, ERP waveforms in relevant time windows did not correspond to N170 scalp topographies. The results support the notion of visual processing ability as an orthography independent marker of reading proficiency, which advances our understanding about regular and impaired reading development.


Asunto(s)
Encéfalo/fisiología , Potenciales Evocados , Lenguaje , Lectura , Adulto , Femenino , Humanos , Israel , Masculino , Adulto Joven
17.
Brain Res ; 1528: 42-8, 2013 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-23867864

RESUMEN

When do adults gain in learning an oculomotor sequence? Here we show that oculomotor training can result not only in performance gains within the training session, but also induce robust offline gains in both speed and accuracy. Participants were trained and tested over two consecutive days to perform a sequence of successive saccades. Saccades were directed to four target letters, presented simultaneously at fixed positions. A two alternative-forced choice question, after each trial, ensured that all targets were perceived. Eye tracking measures were tested at the beginning and end of the training session as well as at 24 h post-training. Practice resulted in within-session gains in accuracy and a reduction of target fixation duration (although total trial duration remained unchanged). In addition, the total average path length traveled by the eye increased, reflecting a decrease in undershoot saccades. At 24 h post-training, however, additional gains were expressed in both speed and accuracy of performance; the total trial duration as well as the fixation-position-offsets and the number of corrective saccades decreased. The expression of delayed gains indicates offline skill consolidation processes in the eye-movement control system. Our results show that the optimization of some aspect, specifically saccade speed parameters, of oculomotor sequence performance evolves mainly offline, during the post-training consolidation phase, a pattern suggestive of learning in an expert system.


Asunto(s)
Adaptación Fisiológica , Memoria , Práctica Psicológica , Movimientos Sacádicos , Adulto , Femenino , Humanos , Masculino , Adulto Joven
18.
PLoS One ; 7(11): e49223, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23145130

RESUMEN

While foraging theory predicts that predatory responses should be determined by the energy content and size of prey, it is becoming increasingly clear that carnivores regulate their intake of specific nutrients. We tested the hypothesis that prey nutrient composition and predator nutritional history affects foraging intensity, consumption, and prey selection by the wolf spider, Pardosa milvina. By altering the rearing environment for fruit flies, Drosophila melanogaster, we produced high quality flies containing more nitrogen and protein and less lipid than low quality fruit flies. In one experiment, we quantified the proportion of flies taken and consumption across a range of densities of either high or low quality flies and, in a second experiment, we determined the prey capture and consumption of spiders that had been maintained on contrasting diets prior to testing. In both cases, the proportion of prey captured declined with increasing prey density, which characterizes the Type II functional response that is typical of wolf spiders. Spiders with similar nutritional histories killed similar numbers of each prey type but consumed more of the low quality prey. Spiders provided high quality prey in the weeks prior to testing killed more prey than those on the low quality diet but there was no effect of prior diet on consumption. In the third experiment, spiders were maintained on contrasting diets for three weeks and then allowed to select from a mixture of high and low quality prey. Interestingly, feeding history affected prey preferences: spiders that had been on a low quality diet showed no preference but those on the high quality diet selected high quality flies from the mixture. Our results suggest that, even when prey size and species identity are controlled, the nutritional experience of the predator as well as the specific content of the prey shapes predator-prey interactions.


Asunto(s)
Valor Nutritivo , Conducta Predatoria , Arañas/fisiología , Animales , Drosophila melanogaster/metabolismo , Conducta Alimentaria , Metabolismo de los Lípidos , Nitrógeno/metabolismo
19.
Brain Lang ; 120(1): 15-26, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21903250

RESUMEN

Little is known about the relationship of reading speed and early visual processes in normal readers. Here we examined the association of the early P1, N170 and late N1 component in visual event-related potentials (ERPs) with silent reading speed and a number of additional cognitive skills in a sample of 52 adult German readers utilizing a Lexical Decision Task (LDT) and a Face Decision Task (FDT). Amplitudes of the N170 component in the LDT but, interestingly, also in the FDT correlated with behavioral tests measuring silent reading speed. We suggest that reading speed performance can be at least partially accounted for by the extraction of essential structural information from visual stimuli, consisting of a domain-general and a domain-specific expertise-based portion.


Asunto(s)
Encéfalo/fisiología , Potenciales Evocados/fisiología , Lectura , Percepción Visual/fisiología , Electroencefalografía , Femenino , Humanos , Masculino , Tiempo de Reacción/fisiología , Procesamiento de Señales Asistido por Computador , Adulto Joven
20.
Dev Neuropsychol ; 36(7): 944-8, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21978015

RESUMEN

This preliminary study attempted to use Event Related Brain Potentials (ERPs) to identify different causes for slow reading performance. At least two unique brain activity patterns were found for below average readers. Based on visual inspection of the N170 ERP component elicited by words in a lexical decision task, participants were either classified as N170-normal or N170-absent. Although both groups showed very dissimilar brain activity patterns, they did not differ in any reading or cognitive measures. Differences in brain activity were discussed as indicators for disturbances at specific stages of word processing, which should lead to individually adjusted intervention approaches.


Asunto(s)
Dislexia/diagnóstico , Potenciales Relacionados con Evento P300/fisiología , Lectura , Análisis de Varianza , Mapeo Encefálico , Electroencefalografía , Humanos , Lingüística , Estimulación Luminosa , Tiempo de Reacción/fisiología
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