Miracle-dz/UniFAR-FTUs huggingface dataset:
[Role of multiple myeloma cells on normal endothelial cells in co-culture system].

OBJECTIVE To study the influence of multiple myeloma (MM) cells on normal endothelial cells in co-culture system in vitro. METHODS A co-culture system of human MM cell line RPMI8226 with human umbilical vein endothelial cells (HUVECs) was established in vitro. Mono-cultured normal endothelial cells were used as control. Light microscopy and transmission electron microscopy were used to observe the morphology of the endothelial cells. The effects of HUVECs co-cultured with RPMI8226 on HUVECs angiogenesis were studied by modified transwell migration assay and net-like formation assay. The protein expression of brain derived neurotrophic factor (BDNF), TrkB, Endoglin, Tie-2, beta 3 integrin and vascular cell adhesion molecule-1 (VCAM-1) in HUVECs were determined by FACS and Western blot analysis, respectively. RESULTS The morphology of HUVECs co-cultured with RPMI8226 cells became a narrower apart of extended shape as they began to align themselves. The sizes of nucleus and nucleolus were enlarged with an increased ratio of nuclear to nucleoplasm. The endoplasm was lose and distorted and the number of surface microvilli decreased. The RPMI8226 cell stimulated the migration and net-like formation of HUVEC, the number of net-like structure and migration cell being increased by 112% and 136%, respectively, compared with that of mono-cultured HUVECs. The expressions of BDNF, TrkB, Endoglin, Tie-2, beta 3 integrin and VCAM-1 in the ECs co-cultured with RPMI8226 were all up-regulated in comparison with those in the controls. CONCLUSION The MM cells promote formation of new vessels in co-cultured endothelial cells and the endothelial cells in MM are different from the normal ECs in character, and behavior.
Quantitative Assessment of Microstructural Changes of the Retina in Infants With Congenital Zika Syndrome

Importance A better pathophysiologic understanding of the neurodevelopmental abnormalities observed in neonates exposed in utero to Zika virus (ZIKV) is needed to develop treatments. The retina as an extension of the diencephalon accessible to in vivo microcopy with spectral-domain optical coherence tomography (SD-OCT) can provide an insight into the pathophysiology of congenital Zika syndrome (CZS). Objective To quantify the microstructural changes of the retina in CZS and compare these changes with those of cobalamin C (cblC) deficiency, a disease with potential retinal maldevelopment. Design, Setting, and Participants This case series included 8 infants with CZS and 8 individuals with cblC deficiency. All patients underwent ophthalmologic evaluation at 2 university teaching hospitals and SD-OCT imaging in at least 1 eye. Patients with cblC deficiency were homozygous or compound heterozygotes for mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Data were collected from January 1 to March 17, 2016, for patients with CZS and from May 4, 2015, to April 23, 2016, for patients with cblC deficiency. Main Outcomes and Measures The SD-OCT cross-sections were segmented using automatic segmentation algorithms embedded in the SD-OCT systems. Each retinal layer thickness was measured at critical eccentricities using the position of the signal peaks and troughs on longitudinal reflectivity profiles. Results Eight infants with CZS (5 girls and 3 boys; age range, 3-5 months) and 8 patients with cblC deficiency (3 girls and 5 boys; age range, 4 months to 15 years) were included in the analysis. All 8 patients with CZS had foveal abnormalities in the analyzed eyes (8 eyes), including discontinuities of the ellipsoid zone, thinning of the central retina with increased backscatter, and severe structural disorganization, with 3 eyes showing macular pseudocolobomas. Pericentral retina with normal lamination showed a thinned (<30% of normal thickness) ganglion cell layer (GCL) that colocalized in 7 of 8 eyes with a normal photoreceptor layer. The inner nuclear layer was normal or had borderline thinning. The central retinal degeneration was similar to that of cblC deficiency. Conclusions and Relevance Congenital Zika syndrome showed a central retinal degeneration with severe GCL loss, borderline inner nuclear layer thinning, and less prominent photoreceptor loss. The findings provide the first, to date, in vivo evidence in humans for possible retinal maldevelopment with a predilection for retinal GCL loss in CZS, consistent with a murine model of the disease and suggestive of in utero depletion of this neuronal population as a consequence of Zika virus infection.
Inmigración y escuelas taller en Navarra. Procesos de expulsión en la sociedad del riesgo

Las escuelas taller atienden a adolescentes y jóvenes entre 16 y 24 años con trayectorias homogéneas por el desempleo y el fracaso escolar. En ellas una gran proporción de jóvenes inmigrantes han encontrado un espacio de formación y acogida. Sin embargo, poco se conoce acerca del tipo de relación entre inmigración y escuelas-taller y como le afecta un escenario de crisis económica. Para ello se ha investigado el fenómeno de la inmigración en las estructuras de las escuelas taller de la Comunidad Foral de Navarra desde el principio de pluralidad metodológica, por tanto, se exponen hallazgos provenientes de la aplicación de metodologías cuantitativa y cualitativa. Los resultados evidencian que se constituyen como una de las principales opciones de formación laboral para los jóvenes de nacionalidad extranjera, tanto es así que, en el territorio investigado, estos representan a más de la mitad del alumnado total. No obstante, en el escenario actual de crisis económica se aceleran los procesos y mecanismos de expulsión que dificultan la entrada y permanencia de los/las jóvenes de nacionalidad extranjera en las escuelas-taller de Navarra.
Music information retrieval in compressed audio files: a survey

In this paper, we present an organized survey of the existing literature on music information retrieval systems in which descriptor features are extracted directly from the compressed audio files, without prior decompression to pulse-code modulation format. Avoiding the decompression step and utilizing the readily available compressed-domain information can significantly lighten the computational cost of a music information retrieval system, allowing application to large-scale music databases. We identify a number of systems relying on compressed-domain information and form a systematic classification of the features they extract, the retrieval tasks they tackle and the degree in which they achieve an actual increase in the overall speed—as well as any resulting loss in accuracy. Finally, we discuss recent developments in the field, and the potential research directions they open toward ultra-fast, scalable systems.
Analysis of the sequence and structural features of the left‐handed β‐helical fold

The left‐handed parallel β‐helix (LβH) is a structurally repetitive, highly regular, and symmetrical fold formed by coiling of elongated β‐sheets into helical “rungs. ” This canonical fold has recently received interest as a possible solution to the fibril structure of amyloid and as a building block of self‐assembled nanotubular structures. In light of this interest, we aimed to understand the structural requirements of the LβH fold. We first sought to determine the sequence characteristics of the repeats by analyzing known structures to identify positional preferences of specific residues types. We then used molecular dynamics simulations to demonstrate the stabilizing effect of successive rungs and the hydrophobic core of the LβH. We show that a two‐rung structure is the minimally stable LβH structure. In addition, we defined the structure‐based sequence preference of the LβH and undertook a genome‐wide sequence search to determine the prevalence of this unique protein fold. This profile‐based LβH search algorithm predicted a large fraction of LβH proteins from microbial origins. However, the relative number of predicted LβH proteins per specie was approximately equal across the genomes from prokaryotes to eukaryotes. Proteins 2008. © 2008 Wiley‐Liss, Inc.
The Stability of the G Protein-coupled Receptor-β-Arrestin Interaction Determines the Mechanism and Functional Consequence of ERK Activation*

By binding to agonist-activated G protein-coupled receptors (GPCRs), β-arrestins mediate homologous receptor desensitization and endocytosis via clathrin-coated pits. Recent data suggest that β-arrestins also contribute to GPCR signaling by acting as scaffolds for components of the ERK mitogen-activated protein kinase cascade. Because of these dual functions, we hypothesized that the stability of the receptor-β-arrestin interaction might affect the mechanism and functional consequences of GPCR-stimulated ERK activation. In transfected COS-7 cells, we found that angiotensin AT1a and vasopressin V2 receptors, which form stable receptor-β-arrestin complexes, activated a β-arrestin-bound pool of ERK2 more efficiently than α1b and β2 adrenergic receptors, which form transient receptor-β-arrestin complexes. We next studied chimeric receptors in which the pattern of β-arrestin binding was reversed by exchanging the C-terminal tails of the β2 and V2 receptors. The ability of the V2β2 and β2V2 chimeras to activate β-arrestin-bound ERK2 corresponded to the pattern of β-arrestin binding, suggesting that the stability of the receptor-β-arrestin complex determined the mechanism of ERK2 activation. Analysis of covalently cross-linked detergent lysates and cellular fractionation revealed that wild type V2 receptors generated a larger pool of cytosolic phospho-ERK1/2 and less nuclear phospho-ERK1/2 than the chimeric V2β2 receptor, consistent with the cytosolic retention of β-arrestin-bound ERK. In stably transfected HEK-293 cells, the V2β2 receptor increased ERK1/2-mediated, Elk-1-driven transcription of a luciferase reporter to a greater extent than the wild type V2 receptor. Furthermore, the V2β2, but not the V2 receptor, was capable of eliciting a mitogenic response. These data suggest that the C-terminal tail of a GPCR, by determining the stability of the receptor-β-arrestin complex, controls the extent of β-arrestin-bound ERK activation, and influences both the subcellular localization of activated ERK and the physiologic consequences of ERK activation.
Influence of spontaneous fermentation on some quality characteristics of maize-based cowpea-fortified nixtamalized foods

Spontaneous fermentation has been identified to improve the quality characteristics of foods derived from them. When combined with cowpea fortification and nixtamalization, it is expected to improve the nutritional, functional, physico-chemical and sensory qualities of maize based foods thereby improving the qualities as well as broadening the food processing techniques in sub-Saharan Africa. This study was therefore aimed at investigating the influence of spontaneous fermentation on the functional, physico-chemical and sensory characteristics of maize-based cowpeafortified nixtamalized foods. A 3x3x2 factorial experiment with fermentation time (0, 24, 48 h), cowpea (0, 10 and 20%) and alkaline treatment (nixtamalized and nonnixtamalized maize) was used. Samples were analyzed for pH, titratable acidity and water absorption capacity (27°C and 70°C). The blends were dried using the cabinet drier, milled into flour and processed into a snack food. The cylinder probe test was used in a TA-TX2 Texture Analyzer to measure the hardness of processed snack foods and sensory analysis was conducted to determine the acceptability of the snack products. The pH of all the nixtamalized samples decreased with fermentation time and cowpea fortification with concomitant increase in titratable acidity. Cowpea addition caused decreases in the pH from 9.68 to 6.12 in the unfermented nixtamalized samples. Contrary to this trend, general increases in titratable acidity were observed with fermentation and cowpea addition of the products. The water absorption capacities at both 27°C and 70°C of all the nixtamalized blends generally decreased with fermentation time and cowpea fortification. The texture (hardness) of the formulated products were acceptable. Sensory evaluation indicated that the techniques of nixtamalization, fermentation and cowpea fortification used for the processing of the products did not influence their acceptability by the panel. Nixtamalized maize can therefore be subjected to spontaneous fermentation with cowpea fortification to enhance the functional, physico-chemical and sensory properties of products derived from them, thereby serving as alternative food technologies to maize processing in sub-Saharan Africa. Keywords : Maize, fermentation, cowpea-fortification, nixtamalization, functional properties.
Epidemiology of Ocular Toxoplasmosis

Retinal infection with Toxoplasma gondii is the most important cause of posterior uveitis, whereby prevalence and incidence of ocular symptoms after infection depend on socio-economic factors and the circulating parasite genotypes. Ocular toxoplasmosis is more common in South America, Central America, and the Caribbean and parts of tropical Africa as compared to Europe and Northern America, and is quite rare in China. Ocular disease in South America is more severe than in other continents due to the presence of extremely virulent genotypes of the parasite. Drinking untreated water is considered the major source of Toxoplasma infection in developing countries, whereas in the Western world the consumption of raw or undercooked meat (products) is the most important cause. Since acquired infection with T. gondii is currently a more important cause of ocular toxoplasmosis compared to congenital infection, prevention should be directed not only toward pregnant women but toward the general population.
Interleukin‐8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models

Interleukin‐8 (IL‐8), a chemokine with a defining CXC amino acid motif, is known to possess tumorigenic and proangiogenic properties. Overexpression of IL‐8 has been detected in many human tumors, including colorectal cancer (CRC), and is associated with poor prognosis. The goal of our study was to determine the role of IL‐8 overexpression in CRC cells in vitro and in vivo. We stably transfected the IL‐8 cDNA into two human colon cancer cell lines, HCT116 and Caco2, and selected IL‐8‐secreting transfectants. Real‐time RT‐PCR confirmed that IL‐8 mRNA was overexpressed in IL‐8 transfectants with 45‐ to 85‐fold higher than parental cells. The IL‐8‐transfected clones secreted 19‐ to 28‐fold more IL‐8 protein than control and parental cells as detected by ELISA. The IL‐8 transfectants demonstrated increased cellular proliferation, cell migration and invasion based on functional assays. Growth inhibition studies showed that IL‐8 overexpression lead to a significant resistance to oxaliplatin (p < 0.0001). Inhibition of IL‐8 overexpression with small interfering RNA reversed the observed increases in tumorigenic functions and oxaliplatin resistance, suggesting that IL‐8 not only provides a proliferative advantage but also promotes the metastatic potential of colon cancer cells. Using a tumor xenograft model, IL‐8‐expressing cells formed significantly larger tumors than the control cells with increased microvessel density. Together, these findings indicate that overexpression of IL‐8 promotes tumor growth, metastasis, chemoresistance and angiogenesis, implying IL‐8 to be an important therapeutic target in CRC.
Transcriptional Profiling of the Arabidopsis Embryo1[W][OA]

We have used laser-capture microdissection to isolate RNA from discrete tissues of globular, heart, and torpedo stage embryos of Arabidopsis (Arabidopsis thaliana). This was amplified and analyzed by DNA microarray using the Affymetrix ATH1 GeneChip, representing approximately 22,800 Arabidopsis genes. Cluster analysis showed that spatial differences in gene expression were less significant than temporal differences. Time course analysis reveals the dynamics and complexity of gene expression in both apical and basal domains of the developing embryo, with several classes of synexpressed genes identifiable. The transition from globular to heart stage is associated in particular with an up-regulation of genes involved in cell cycle control, transcriptional regulation, and energetics and metabolism. The transition from heart to torpedo stage is associated with a repression of cell cycle genes and an up-regulation of genes encoding storage proteins, and pathways of cell growth, energy, and metabolism. The torpedo stage embryo shows strong functional differentiation in the root and cotyledon, as inferred from the classes of genes expressed in these tissues. The time course of expression of the essential EMBRYO-DEFECTIVE genes shows that most are expressed at unchanging levels across all stages of embryogenesis. We show how identified genes can be used to generate cell type-specific markers and promoter activities for future application in cell biology.
Proteins in vacuo: denaturing and folding mechanisms studied with computer-simulated molecular dynamics.

Mounting evidence from experiments suggests that the native fold in solution is metastable in dehydrated proteins. Results from a number of experiments that use mass spectrometry indicate also that folding-unfolding transitions take place in protein ions even in the absence of water. These observations on anhydrous proteins call for a re-evaluation of our understanding of the folding transition. In this context, computer-assisted simulations are an important complementary tool. Here, we provide an overview of recent progress on the simulation of proteins in vacuo. In particular, we discuss the response of proteins and protein ions to perturbations that trigger unfolding and re-folding transitions. By comparing the general patterns emerging from theory and experiment, we propose a series of new measurements that could help to validate, and improve, current simulation models.
HIV‐1 prevalence and subtype/recombinant distribution among travelers entering China from Vietnam at the HeKou port in the Yunnan province, China, between 2003 and 2012

The aim of this study was to assess HIV‐1 prevalence and the distribution of HIV‐1 subtypes among travelers crossing the border at the HeKou land port. Between 2003 and 2012, 22,799 persons were randomly recruited from people entering China from Vietnam. In this crossing border population, a total of 161 (0.71%) travelers were determined as HIV‐1‐positive. From them, 140 HIV‐1‐positive serum samples were collected for RNA extraction and subsequent RT‐nested PCR amplification of the group‐specific antigen (gag)‐RT with a length of 2.6 kb. The DNA sequences were analyzed to determine the HIV‐1 subtypes/recombinants. We found that the circulating recombinant form 01_AE (CRF01_AE) was the most common HIV‐1 subtype, accounting for 49.4% (41/83) of the subtyped 83 samples, followed by CRF08_BC (26.5%, 22/83) and CRF07_BC (7.2%, 6/83). Only 1 sample was classified as subtype C. Thirteen cases could not be clustered into any known subtypes or CRFs and presented as unique recombinant forms (URFs). Of them, 6 recombination patterns were identified. They had distinct structures consisting of fragments of subtypes B, C, CRF01_AE, CRF07_BC and CRF08_BC. Between 2003 and 2012, CRF01_AE and CRE08_BC were shown to be the most prevalent recombinant forms identified each year. But yearly change of each subtype is uncertain regular among in these travelers during the past decade. Understanding the distribution of HIV‐1 subtypes/recombinants and how it changes across time among individuals entering China from Vietnam through this land port is crucial to establish strategies for the prevention of HIV cross‐border transmission. J. Med. Virol. 87:1500–1509, 2015. © 2015 Wiley Periodicals, Inc.
5‐HT1B autoreceptor regulation of serotonin transporter activity in synaptosomes

Serotonin‐1B (5‐HT1B) autoreceptors are located in serotonin (5‐HT) terminals, along with serotonin transporters (SERT), and play a critical role in autoregulation of serotonergic neurotransmission and are implicated in disorders of serotonergic function, particularly emotional regulation. SERT modulates serotonergic neurotransmission by high‐affinity reuptake of 5‐HT. Alterations in SERT activity are associated with increased risk for depression and anxiety. Several neurotransmitter receptors are known to regulate SERT Km and Vmax, and previous work suggests that 5‐HT1B autoreceptors may regulate 5‐HT reuptake, in addition to modulating 5‐HT release and synthesis. We used rotating disk electrode voltammetry to investigate 5‐HT1B autoreceptor regulation of SERT‐mediated 5‐HT uptake into synaptosomes. The selective 5‐HT1B antagonist SB224289 decreased SERT activity in synaptosomes prepared from wild‐type but not 5‐HT1B knockout mice, whereas SERT uptake was enhanced after pretreatment with the selective 5‐HT1B agonist CP94253. Furthermore, SERT activity varies as a function of 5‐HT1B receptor expression—specifically, genetic deletion of 5‐HT1B decreased SERT function, while viral‐mediated overexpression of 5‐HT1B autoreceptors in rat raphe neurons increased SERT activity in rat hippocampal synaptosomes. Considered collectively, these results provide evidence that 5‐HT1B autoreceptors regulate SERT activity. Because SERT clearance rate varies as a function of 5‐HT1B autoreceptor expression levels and is modulated by both activation and inhibition of 5‐HT1B autoreceptors, this dynamic interaction may be an important mechanism of serotonin autoregulation with therapeutic implications. Synapse, 2012. © 2012 Wiley Periodicals, Inc.
In vitro and in vivo effects of an immunomodulator composed of Escherichia coli lipopolysaccharide and Propionibacterium granulosum-inactivated cells in pigs.

The in vitro cytokine profiles of porcine alveolar macrophages and peripheral blood mononuclear cells (PBMC) were examined by reverse transcription-polymerase chain reaction or enzyme-linked immunosorbent assay after stimulation with the immunomodulatory compound INMD [lipopolysaccharide (LPS) and Propionibacterium granulosum]. Expression of interleukin-1 (IL-1), IL-6, IL-12 and tumour necrosis factor-alpha (TNF-alpha), but not of IL-10, was detected in INMD-stimulated alveolar macrophages. Stimulated PBMC expressed IL-1, IL-2, IL-4, IL-6, IL-10 and IL-12 and secreted interferon-gamma (IFN-gamma). In all cases, the level of response was lower with INMD than with E. coli LPS alone, except for IFN-gamma, which was secreted in higher levels in INMD-stimulated cells. In a second experiment, the ex vivo effect of the administration of INMD was evaluated using the product as a coadjuvant of a live attenuated Aujeszky's disease virus (ADV) vaccine. For this purpose, 85 8-10-week-old crossbred pigs were assigned to two groups (group A = 43 and group B = 42) and vaccinated with ADV. Group B received, simultaneously with the first dose of vaccine, an intramuscular dose of INMD equivalent to 20 micrograms/ml LPS and 250 micrograms/ml P. granulosum, while group A was given sterile saline solution as a placebo. At the time of vaccination, 97.6% (42 of 43) and 95.2% (40 of 42) of animals of groups A and B, respectively, had anti-gB maternal antibodies. Of those animals, anti-gE ADV antibodies were detected in 11.6% of animals of group A (five of 43) and 19% of group B (eight of 42). All animals were boosted with ADV vaccine alone 4 weeks later. Pigs to which INMD was administered together with the vaccine showed higher primary humoral responses than the vaccine-alone animals (P < 0.005). However, after boosting significant differences disappeared (P > 0.05).