Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology.

Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form

Virtual Blocks: a serious game for spatial ability improvement on mobile devices

This paper presents a novel spatial instruction system for improving spatial abilities of engineering students. A 3D mobile game application called Virtual Blocks has been designed to provide a 3D virtual environment to build models with cubes that help students to perform visualization tasks to promote the development of their spatial ability during a short remedial course. A validation study with 26 freshman engineering students at La Laguna University (Spain) has concluded that the training had a measurable and positive impact on students spatial ability. In addition, the results obtained using a satisfaction questionnaire show that Virtual Blocks is considered an easy to use and stimulating application.This work has been partially supported by the (Spanish) National Program for Studies and Analysis project "Evaluation and development of competencies associated to the spatial ability in the new engineering undergraduate courses" (Ref. EA2009-0025) and the (Spanish) National Science Project "Enhancing Spatial REasoning and VIsual Cognition with advanced technological tools (ESREVIC)" (Ref TIN2010-21296-C02-02)Martín Dorta, NN.; Sanchez Berriel, I.; Bravo, M.; Hernández, J.; Saorin, JL.; Contero, M. (2014). Virtual Blocks: a serious game for spatial ability improvement on mobile devices. Multimedia Tools and Applications. 73(3):1575-1595. https://doi.org/10.1007/s11042-013-1652-0S15751595733Baartmans BG, Sorby SA (1996) Introduction to 3-D spatial visualization. Prentice Hall, Englewood CliffsClements D, Battista M (1992) Geometry and spatial reasoning. In: Grouws DA (ed) Handbook of research on mathematics teaching and learning. New York, pp 420–464Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Erlbaum, HillsdaleDe Lisi R, Cammarano DM (1996) Computer experience and gender differences in undergraduate mental rotation performance. Comput Hum Behav 12:351–361Deno JA (1995) The relationship of previous experiences to spatial visualization ability. Eng Des Graph J 59(3):5–17Feng J, Spence I, Pratt J (2007) Playing an action video game reduces gender differences in spatial cognition. Psychol Sci 18(10):850–855French JW (1951) The description of aptitude and achievement tests in terms of rotated factors. Psychometric monograph 5Guilford JP, Lacy JI (1947) Printed classification tests, A.A.F. Aviation Psychological Progress Research Report, 5. US. Government Printing Office, Washington DCHalpern DF (2000) Sex differences and cognitive abilities. Erlbaum, MahwahHöfele C (2007) Mobile 3D graphics: learning 3D graphics with the Java Micro Edition. Editorial ThomsonKajiya JT, Kay TL (1989) Rendering fur with three dimensional textures. In Proceedings of the 16th Annual Conference on Computer Graphics and interactive Techniques SIGGRAPH ’89. ACM Press, New York pp 271–280Linn MC, Petersen AC (1985) Emergence and characterization of gender differences in spatial abilities: a meta-analysis. Child Dev 56:1479–1498Martin-Dorta N, Sanchez-Berriel I, Bravo M, Hernandez J, Saorin JL, Contero M (2010) A 3D educational mobile game to enhance student’s spatial skills, ICALT, pp.6–10, 2010 10th IEEE International Conference on Advanced Learning TechnologiesMartin-Dorta N, Saorin J, Contero M (2008) Development of a fast remedial course to improve the spatial abilities of engineering students. J Eng Educ 27(4):505–514Martin-Dorta N, Saorin JL, Contero M (2011) Web-based spatial training using handheld touch screen devices. Educ Technol Soc 14(3):163–177McGee MG (1979) Human spatial abilities: psychometric studies and environmental, genetic, hormonal, and neurological influences. Psychol Bull 86:889–918Noguera JM, Segura RJ, Ogayar CJ, Joan-Arinyo R (2011) Navigating large terrains using commodity mobile devices. Comput Geosci 37:1218–1233Okagaki L, Frensch PA (1994) Effects of video game playing on measures of spatial performance: gender effects in late adolescence. J Appl Dev Psychol 15(1):33–58Pulli K, Aarnio T, Miettinen V, Roimela K, Vaarala J (2007) Mobile 3D graphics with OpenGL ES and M3G. Editorial Morgan KaufmannQuaiser-Pohl C, Geiser C, Lehmann W (2005) The relationship between computer-game preference, gender, and mental-rotation ability. Personal Individ Differ 40(3):609–619Smith IM (1964) Spatial ability- its educational and social significance. The University of London Press, LondonSorby S (2007) Developing 3D spatial skills for engineering students. Australas Assoc Eng Educ 13(1):1–11Terlecki MS, Newcombe NS (2005) How important is the digital divide? The relation of computer and videogame usage to gender differences in mental rotation ability. Sex Roles 53(5/6):433–441Terlecki MS, Newcombe NS, Little M (2008) Durable and generalized effects of spatial experience on mental rotation: gender differences in growth patterns. Appl Cogn Psychol 22:996–1013Thurstone LL (1950) Some primary abilities in visual thinking (Tech. Rep. No. 59). IL University of Chicago Psychometric Laboratory, ChicagoThurstone LL, Thurstone TG (1941) Factorial studies of intelligence. Psychometric monographs. Chicago Press, ChicagoVanderberg S, Kuse A (1978) Mental Rotation, a group test of three dimensional spatial visualization. Percept Mot Skills 47:599–604Zimmerman WS (1954) Hypotheses concerning the nature of the spatial factors. Educ Psychol Meas 14:396–40

Cytogenetic analysis of Astylus antis (Perty, 1830) (Coleoptera, Melyridae): Karyotype, heterochromatin and location of ribosomal genes

Cytogenetic analysis of Astylus antis using mitotic and meiotic cells was performed to characterize the haploid and diploid numbers, sex determination system, chromosome morphology, constitutive heterochromatin distribution pattern and chromosomes carrying nucleolus organizer regions (NORs). Analysis of spermatogonial metaphase cells revealed the diploid number 2n = 18, with mostly metacentric chromosomes. Metaphase I cells exhibited 2n = 8II+Xyp and a parachute configuration of the sex chromosomes. Spermatogonial metaphase cells submitted to C-banding showed the presence of small dots of constitutive heterochromatin in the centromeric regions of nearly all the autosomes and on the short arm of the X chromosome (Xp), as well as an additional band on one of the arms of pair 1. Mitotic cells submitted to double staining with base-specific fluorochromes (DAPI-CMA3 ) revealed no regions rich in A+T or G+C sequences. Analysis of spermatogonial mitotic cells after sequential Giemsa/AgNO 3 staining did not reveal any specific mark on the chromosomes. Meiotic metaphase I cells stained with silver nitrate revealed a strong impregnation associated to the sex chromosomes, and in situ hybridization with an 18S rDNA probe showed ribosomal cistrons in an autosomal bivalent

Comparison of silicon oil removal with various viscosities after complex retinal detachment surgery

BACKGROUND: Despite the progress in vitreoretinal surgery and the importance of silicone oil as an adjunct for the treatment of complex forms of retinal detachment, controversy still surrounds the issue of selecting the proper oil viscosity for clinical use. Herein, we evaluate the outcomes of retinal detachment (RD) surgery after removing silicone oils of different viscosities. METHODS: In this retropsective cohort study, eighty-two eyes with surgically re-attached retinas, of which 53 were filled with 5000cs silicone oil and 29 with 1000cs silicone oil were enrolled. We evaluated the outcomes and complications following silicone oil removal. Final anatomic success (stable re-attachment), final visual acuity (VA) and intraocular pressure (IOP)were recorded and analysed. RESULTS: Of 82 eyes, 41 had proliferative vitreoretinopathy (PVR), 24 were associated with intraocular foreign bodies, 10 had endophthalmitis and 7 had proliferative diabetic retinopathy with tractional retinal detachment. Prior to silicone oil removal, the retina was attached in all eyes, 29% had VA ≥ 6/120 and 52% had IOP ≥ 21 mmHg. After silicone oil removal, the retina remained attached in 59(72%) of the eyes, 34% had VA ≥ 6/120 and 9% had IOP ≥ 21 mmHg. Comparing 1000cs and 5000cs silicone oil filled eyes, redetachment occurred more frequently in the latter group especially in cases with associated PVR. Final VA worse than 6/120 was associated with initial VA < 6/120 (OR = 32.2 95%CI 7.4–140.2) and use of 5000cs silicone oil (OR = 7.9 95%CI 1.9–32.2). No factor was significantly associated with final IOP ≥ 21 mmHg. CONCLUSION: In complicated retinal detachment surgery, use of 5000cs silicone oil may be associated with a poorer anatomic and visual outcome compared with 1000cs silicone oil. However there was no difference between the two viscosities in IOP elevation. A randomized controlled study is necessary to further evaluate such a possibility

Challenges for adaptation in agent societies

The final publication is available at Springer via http://dx.doi.org/[insert DOIAdaptation in multiagent systems societies provides a paradigm for allowing these societies to change dynamically in order to satisfy the current requirements of the system. This support is especially required for the next generation of systems that focus on open, dynamic, and adaptive applications. In this paper, we analyze the current state of the art regarding approaches that tackle the adaptation issue in these agent societies. We survey the most relevant works up to now in order to highlight the most remarkable features according to what they support and how this support is provided. In order to compare these approaches, we also identify different characteristics of the adaptation process that are grouped in different phases. Finally, we discuss some of the most important considerations about the analyzed approaches, and we provide some interesting guidelines as open issues that should be required in future developments.This work has been partially supported by CONSOLIDER-INGENIO 2010 under grant CSD2007-00022, the European Cooperation in the field of Scientific and Technical Research IC0801 AT, and projects TIN2009-13839-C03-01 and TIN2011-27652-C03-01.Alberola Oltra, JM.; Julian Inglada, VJ.; García-Fornes, A. (2014). Challenges for adaptation in agent societies. Knowledge and Information Systems. 38(1):1-34. https://doi.org/10.1007/s10115-012-0565-yS134381Aamodt A, Plaza E (1994) Case-based reasoning; foundational issues, methodological variations, and system approaches. AI Commun 7(1):39–59Abdallah S, Lesser V (2007) Multiagent reinforcement learning and self-organization in a network of agents. 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Upregulation of Circulating PD-L1/PD-1 Is Associated with Poor Post-Cryoablation Prognosis in Patients with HBV-Related Hepatocellular Carcinoma

BACKGROUND: The programmed cell death-1 receptor/programmed cell death-1 ligand (PD-1/PD-L1) pathway plays a crucial role in tumor evasion from host immunity. This study was designed to evaluate the association between circulating PD-L1/PD-1 and prognosis after cryoablation in patients with HBV-related hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS: In the present study, 141 HBV-related HCC patients were enrolled and of those 109 patients received cryoablation. Circulating PD-L1/PD-1 expression was tested by flow cytometry, and 23 patients were simultaneously evaluated for intratumoral PD-L1 expression by immunohistochemical staining. Circulating PD-1/PD-L1 expression was associated with severity of diseases in patients with HCC, and the circulating PD-L1 expression was closely correlated with intratumoral PD-L1 expression. Of the clinical parameters, PD-1/PD-L1 expression was associated with tumor size, blood vessel invasion and BCLC staging. Moreover, PD-1/PD-L1 expression dropped after cryoablation while being elevated at the time of tumor recurrence. Patients with higher expression of circulating PD-L1, as well as circulating PD-1, had a significantly shorter overall survival and tumor-free survival than those with lower expression. Multivariate analysis confirmed that circulating PD-L1 could serve as an independent predictor of overall survival and tumor-recurrence survival in HCC patients after cryoablation. CONCLUSIONS/SIGNIFICANCE: Upregulation of circulating PD-L1/PD-1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma

Genomic Data Reveal Toxoplasma gondii Differentiation Mutants Are Also Impaired with Respect to Switching into a Novel Extracellular Tachyzoite State

Toxoplasma gondii pathogenesis includes the invasion of host cells by extracellular parasites, replication of intracellular tachyzoites, and differentiation to a latent bradyzoite stage. We present the analysis of seven novel T. gondii insertional mutants that do not undergo normal differentiation to bradyzoites. Microarray quantification of the variation in genome-wide RNA levels for each parasite line and times after induction allowed us to describe states in the normal differentiation process, to analyze mutant lines in the context of these states, and to identify genes that may have roles in initiating the transition from tachyzoite to bradyzoite. Gene expression patterns in wild-type parasites undergoing differentiation suggest a novel extracellular state within the tachyzoite stage. All mutant lines exhibit aberrant regulation of bradyzoite gene expression and notably some of the mutant lines appear to exhibit high proportions of the intracellular tachyzoite state regardless of whether they are intracellular or extracellular. In addition to the genes identified by the insertional mutagenesis screen, mixture model analysis allowed us to identify a small number of genes, in mutants, for which expression patterns could not be accounted for using the three parasite states – genes that may play a mechanistic role in switching from the tachyzoite to bradyzoite stage

The impact of rheumatoid foot on disability in Colombian patients with rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>Alterations in the feet of patients with rheumatoid arthritis (RA) are a cause of disability in this population. The purpose of this research was to evaluate the impact that foot impairment has on the patients' global quality of life (QOL) based on validated scales and its relationship to disease activity.</p> <p>Methods</p> <p>This was a cross-sectional study in which 95 patients with RA were enrolled. A complete physical examination, including a full foot assessment, was done. The Spanish versions of the Health Assessment Questionnaire (HAQ) Disability Index and of the Disease Activity Score (DAS 28) were administered. A logistic regression model was used to analyze data and obtain adjusted odds ratios (AORs).</p> <p>Results</p> <p>Foot deformities were observed in 78 (82%) of the patients; hallux valgus (65%), medial longitudinal arch flattening (42%), claw toe (lesser toes) (39%), dorsiflexion restriction (tibiotalar) (34%), cock-up toe (lesser toes) (25%), and transverse arch flattening (25%) were the most frequent. In the logistic regression analysis (adjusted for age, gender and duration of disease), forefoot movement pain, subtalar movement pain, tibiotalar movement pain and plantarflexion restriction (tibiotalar) were strongly associated with disease activity and disability. The positive squeeze test was significantly associated with disability risk (AOR = 6,3; 95% CI, 1.28–30.96; P = 0,02); hallux valgus, and dorsiflexion restriction (tibiotalar) were associated with disease activity.</p> <p>Conclusion</p> <p>Foot abnormalities are associated with active joint disease and disability in RA. Foot examinations provide complementary information related to the disability as an indirect measurement of quality of life and activity of disease in daily practice.</p

Machupo Virus Glycoprotein Determinants for Human Transferrin Receptor 1 Binding and Cell Entry

Machupo virus (MACV) is a highly pathogenic New World arenavirus that causes hemorrhagic fever in humans. MACV, as well as other pathogenic New World arenaviruses, enter cells after their GP1 attachment glycoprotein binds to their cellular receptor, transferrin receptor 1 (TfR1). TfR1 residues essential for this interaction have been described, and a co-crystal of MACV GP1 bound to TfR1 suggests GP1 residues important for this association. We created MACV GP1 variants and tested their effect on TfR1 binding and virus entry to evaluate the functional significance of some of these and additional residues in human and simian cells. We found residues R111, D123, Y122, and F226 to be essential, D155, and P160 important, and D114, S116, D140, and K169 expendable for the GP1-TfR1 interaction and MACV entry. Several MACV GP1 residues that are critical for the interaction with TfR1 are conserved among other New World arenaviruses, indicating a common basis of receptor interaction. Our findings also open avenues for the rational development of viral entry inhibitors