Fighting HIV Infection by Defining Mechanisms to Remodel Semen-Derived Amyloid Fibrils

Human immunodeficiency virus (HIV) is a major public health threat worldwide, with 80% of infections acquired through sexual transmission. Semen is the principal vector for the transmission of HIV and several endogenous peptides in semen, including fragments of prostatic acid phosphatase (PAP248-286 and PAP85-120) and semenogelins (SEM1 and SEM2), assemble into amyloid fibrils that promote HIV infection. Semen-derived amyloid fibrils enhance infectivity by capturing HIV virions and facilitating their attachment and fusion to target cells. Deciphering methods to dissolve seminal amyloid fibrils would provide a novel preventative strategy for reducing HIV infection via sexual transmission. Three previously described anti-amyloid agents were used to disassemble and/or counteract seminal amyloid fibrils: 1) Hsp104, an amyloid-remodeling factor from yeast, 2) CLR01, a lysine-specific molecular tweezer, and 3) EGCG, a small molecule polyphenol from green tea. Each strategy was found to antagonize seminal amyloid activity through diverse mechanisms. For instance, Hsp104 and a potentiated Hsp104 variant, Hsp104A503V, remodeled seminal amyloid fibrils into non-fibrillar aggregates and catalytically inactive Hsp104 scaffolds clustered fibrils into larger assemblies. Additionally, Hsp104 was modified to interact with the chambered protease ClpP, to enable coupled remodeling and degradation of seminal amyloid. CLR01 remodeled pre-formed amyloid fibrils through disruption of critical lysine residues, neutralized the cationic fibril surface charge, and exhibited a direct anti-viral effect via disruption of the viral membrane. Finally, epigallocatechin gallate (EGCG) is the first small molecule that can eradicate all four classes of seminal amyloid. Thus, all three strategies were highly effective at antagonizing seminal amyloid fibrils and could have therapeutic utility. Altogether, these findings provide insight into developing microbicidal agents that can abolish the infection-enhancing capabilities of seminal amyloid and counter HIV transmission

Novi nalaz velikookog psa lisice, Alopias superciliosus Lowe, 1841, u sjeverozapadnom Sredozemlju s pregledom svih dosadašnjih nalaza u Sredozemlju

On 9th September 2015 the head of a shark belonging to the genus Alopias, was landed at Camogli harbour in the Ligurian Sea (North Western Mediterranean). The specimen has been caught 16 miles far from the coast (44° 06’ N, 008° 57’ E) as by-catch of the mesopelagic swordfish longline, but only the head was recovered, due to the predatory/scavenging activity by other shark specimens. The specimen was a female of big-eye thresher shark Alopias superciliosus a highly migratory species worldwide distributed in tropical and temperate waters but rarely caught in the Mediterranean Sea. The present record is the northenmost reported for this species in the Mediterranean area and the sixth in Italian waters.Dana 9. rujna 2015. godine pronađena je glava morskog psa roda Alopias u luci Camogli na Ligurskom moru (sjeverozapadni Mediteran). Primjerak glave je ulovljen 16 milja daleko od obale (44 ° 06 ‘N, 008 ° 57’ E) tijekom lova na sabljarke mezopelagičnim parangalom, te je zbog grabežljivosti i uklanjanja drugih primjeraka morskih pasa, utvrđena samo glava. Primjerak glave je pripadao ženki morskog psa Alopias superciliosus, koji spada u visoko migratorne vrste rasprostranjene širom svijeta u tropskim i umjerenim vodama, no rijetko su ulovljene u Sredozemnom moru. Ovaj je nalaz najsjeverniji za ovu vrstu u Sredozemlju i ujedno je šesti nalaz za talijanske vode

Análisis estratégico de la industria aérea en España.

El presente trabajo se basa en la elaboración de un análisis estratégico de la industria aérea en España. El hecho de ser un país con una gran afluencia de turistas y un alto número de vuelos domésticos hace que la industria cuente con un gran número de empresas, intensificada tras la liberalización del sector en Europa en los años 80 y 90. El objetivo de este trabajo consiste en identificar las estrategias y ventajas competitivas de los distintos grupos estratégicos. Con ese fin, se ha realizado un análisis del entorno de la industria, así como de los principales competidores que amenazan la demanda del sector. Además, la reciente aparición de aerolíneas de bajo coste, así como la integración de nuevas tecnologías en la flota aérea hacen que la estructura de la industria se haya visto modificada en los últimos años. Finalmente podemos hablar de una creciente demanda en el mercado y de una evolución del sector con objetivos que cumplir de cara a la próxima década

Guided reminiscence support tool

Trabajo de Fin de Grado en Ingeniería Informática, Facultad de Informática UCM, Departamento de Ingeniería del Software e Inteligencia Artificial, Curso 2020/2021.Actualmente, unas 50 millones de personas sufren demencia, una cifra que va en aumento. La demencia y otros síndromes similares, que implican el deterioro de la memoria, son considerados una prioridad de salud pública, y afectan sobre todo a la población mayor de 60 años. Aunque el deterioro cognitivo no es algo reversible, sí que existen terapias que lo ralentizan. En este trabajo nos centramos específicamente en la memoria, y estudiamos cómo las terapias adecuadas ayudan a frenar la pérdida de la misma. Basándonos en ellas, construimos una herramienta de ayuda a la reminiscencia que permita la evocación de recuerdos a partir de sugerencias relevantes: conceptos de alto valor emocional extraídos de un análisis de texto previo y archivos multimedia personales. La aplicación pretende ser un apoyo tanto para terapeutas como para familiares. A partir del proceso guiado que presentan ambos estímulos, ellos se encargarán de introducir toda la información que el afectado recuerde, resultando en un almacén de recuerdos y del progreso realizado. La visualización de dicha información se presenta de varias maneras, siendo las más relevantes en grafos y diccionarios.As of today, an estimated 50 million people suffer from dementia, and this number continues to grow. Dementia and other similar syndromes, which involve memory loss, are considered a public health priority, mainly affecting people over the age of 60. Although cognitive impairment is not reversible, therapies that can slow it down exist. In this paper we focus specifically on memory, and study how appropriate therapies help to slow down the process of memory loss. Based on these, we build a reminiscence support tool that allows the evocation of memories based on relevant suggestions: emotionally valuable concepts extracted from a previous text analysis and personal multimedia files. The application is intended to support both therapists and family members. Based on the guided process presented by the two stimuli, they will input all the information that the concerned person remembers, resulting in a warehouse of memories and progress made. The visualisation of this information is presented in various ways, being graphs and dictionaries the most relevant.Depto. de Ingeniería de Software e Inteligencia Artificial (ISIA)Fac. de InformáticaTRUEunpu

La transición de inmigrantes con hijos en edad escolar

La perspectiva intercultural ante la diversidad en España coincide con la presencia cada vez más numerosa de inmigrantes. De esta manera los sistemas educativos tienen que hacer frente a la diversidad cultural y de ofrecer a todos los alumnos una educación capaz de promover la integración y mejorar la convivencia entre los diferentes sectores de la población. De aquí la necesidad de llevar a cabo estudios que sirvan de base para que la educación intercultural sea una realidad mediante actuaciones y diseños de programas que sirvan como guías de orientación para mejorar las prácticas educativas en los centros educativos. Esta investigación analiza las variables sociofamiliares, laborales y educativas de los inmigrantes, poniendo de relieve los puntos fuertes y las necesidades de mejora que se han de tener en cuenta para favorecer la integración de la población inmigrante.The intercultural perspective in the diversity in Spain coincides with the presence of more and more immigrants. Thus, the educative systems have to face the intercultural diversity and they have to offer all the students an education which is able to promote the integration and improve the coexistence of different sections of the society. For these reasons, it is neces- sary to conduct studies which allow the intercultural education to become a reality by means of programme designs. As a result, these programmes may be used as orientation guides to improve the educative practices in the educative institutions. This study analyses the immi- grants’ sociofamiliar, labour and educative variables, focusing on the strong points and weaknesses that have to be taken into account to favour the integration of immigrant

Structural basis for substrate gripping and translocation by the ClpB AAA+ disaggregase.

Bacterial ClpB and yeast Hsp104 are homologous Hsp100 protein disaggregases that serve critical functions in proteostasis by solubilizing protein aggregates. Two AAA+ nucleotide binding domains (NBDs) power polypeptide translocation through a central channel comprised of a hexameric spiral of protomers that contact substrate via conserved pore-loop interactions. Here we report cryo-EM structures of a hyperactive ClpB variant bound to the model substrate, casein in the presence of slowly hydrolysable ATPγS, which reveal the translocation mechanism. Distinct substrate-gripping interactions are identified for NBD1 and NBD2 pore loops. A trimer of N-terminal domains define a channel entrance that binds the polypeptide substrate adjacent to the topmost NBD1 contact. NBD conformations at the seam interface reveal how ATP hydrolysis-driven substrate disengagement and re-binding are precisely tuned to drive a directional, stepwise translocation cycle

Participatory Assessment of a Matched Savings Program for Human Trafficking Survivors and their Family Members in the Philippines

Survivors of human trafficking often experience considerable financial difficulties upon exiting human trafficking, including pressure to provide financially for their families, challenges securing employment, lack of savings, and familial debt. Few evaluations have been conducted of reintegration support interventions addressing financial vulnerability among trafficking survivors. In this article, we present findings from a participatory assessment of the BARUG program, a matched savings and financial capability program for survivors of human trafficking and their family members in the Philippines. Photovoice was used to understand the experiences of two cohorts of BARUG participants. Survivors collaborated with research team members in conducting thematic analysis of transcripts from the photovoice sessions. Themes included: the positive emotional impact of financial wellness, overcoming the challenges of saving, applying financial management skills in daily decision making, developing a habit of savings, building a future-oriented mindset, receiving guidance and enlightenment, the learning process, and the change process. Findings reinforce the importance of interventions to support trafficked persons and their family members in getting out of debt and accumulating emergency savings, while also providing emotional support to survivors in coping with family financial pressures. The study also highlights the value of using participatory research methods to understand the experiences of trafficked persons.Überlebende von Menschenhandel erfahren oftmals massive finanzielle Einbußen, verbunden mit Schwierigkeiten, ihre Familien zu unterhalten, sich wieder Arbeit zu beschaffen und Verschuldung. Unterstützungsprogramme für diese Gruppe, die der Reintegration dienen und die finanzielle Vulnerabilität adressieren, wurden bisher kaum evaluiert. In diesem Beitrag berichten wir Ergebnisse aus einem partizipativen Assessment im Rahmen des BARUG-Programms, eines abgestimmten philippinischen Schutzprogramms für Überlebende von Menschenhandel und deren Familien. Photovoice wurde eingesetzt, um die Erfahrungen zweier Kohorten von BARUG-Teilnehmer/innen nachvollziehen zu können. Die Teilnehmenden erarbeiteten gemeinsam mit Mitgliedern des Forschungsteams thematische Analysen der Transkripte aus diesen Photovoice-Sessions. Die so rekonstruierten Themen umfassten u.a. den positiven emotionalen Impact finanzieller Sicherheit, die Bewältigung der Herausforderungen der Rettung, das Erlernen finanzieller Skills für tägliche Entscheidungsprozesse, den Erwerb einer zukunftsorientierten Haltung, den Wunsch nach Anleitung und Aufklärung sowie Lern- und Veränderungsprozesse. Die Ergebnisse unterstreichen die Wichtigkeit von Interventionen, die Betroffenen und deren Familien helfen, aus der Verschuldung herauszukommen und zugleich emotionale Unterstützung für Überlebende bieten, den familiären finanziellen Druck zu bewältigen. Die Studie veranschaulicht auch den Nutzen partizipativer Forschungsmethoden, um das Erleben dieser spezifischen Gruppe angemessen verstehen zu können

Potential Use of Wild Einkorn Wheat for Wheat Grain Quality Improvement: Evaluation and Characterization of Glu-1, Wx and Ha Loci

Wild einkorn (Triticum monococcum L. ssp. aegilopoides (Link) Thell.) is a diploid wheat species from the Near East that has been classified as an ancestor of the first cultivated wheat (einkorn; T. monococcum L. ssp. monococcum). Its genome (Am), although it is not the donor of the A genome in polyploid wheat, shows high similarity to the Au genome. An important characteristic for wheat improvement is grain quality, which is associated with three components of the wheat grain: endosperm storage proteins (gluten properties), starch synthases (starch characteristics) and puroindolines (grain hardness). In the current study, these grain quality traits were studied in one collection of wild einkorn with the objective of evaluating its variability with respect to these three traits. The combined use of protein and DNA analyses allows detecting numerous variants for each one of the following genes: six for Ax, seven for Ay, eight for Wx, four for Gsp-1, two for Pina and three for Pinb. The high variability presence in this species suggests its potential as a source of novel alleles that could be used in modern wheat breeding

Unidad didáctica : la familia

La familia es el primer grupo social con el que los niños interactúan desde su nacimiento. Consecuentemente, conocer este grupo y saber desenvolverse en él les ayudará a acercarse a organizaciones sociales más complejas. Concretamente, esta unidad didáctica ha sido diseñada para trabajar la familia, su diversidad y los cambios producidos en su estructura en el primer curso de educación primaria. Estas cuestiones se abordan desde una perspectiva histórica, pero también multicultural. Por tanto, pretendemos que los alumnos aprendan a respetar esta variedad y empiecen a formar su identidad en relación con esta realidad, a través de una serie de actividades que se adecuan al marco legal vigente y trabajan todas las competencias básicas, desde la teoría del socioconstructivismo. La família és el primer grup social amb el qual els xiquets interactuen des del seu naixement. Conseqüentment, conèixer aquest grup i saber desenvolupar-se en ell els ajudarà a acostar-se a organitzacions socials més complexes. Concretament, aquesta unitat didàctica ha estat dissenyada per a treballar la família, la seua diversitat i els canvis produïts en la seua estructura en el primer curs d'educació primària. Aquestes qüestions s'aborden des d'una perspectiva històrica, però també multicultural. Per tant, pretenem que els alumnes aprenguen a respectar aquesta varietat i comencen a formar la seua identitat en relació amb aquesta realitat, a través d'una sèrie d'activitats que s’adeqüen al marc legal vigent i treballen totes les competències bàsiques, des de la teoria del socioconstructivisme.Family is the first social group which children interact with since their birth. Consequently, knowing this group and knowing how to behave in it are learnings will help them to approach to more complex social organizations. In particular, this teaching unit has been designed to treat the family, its diversity and its structural changes in the first year of primary education. These issues are discussed from a historical perspective, but also from a multicultural one. Therefore, we pretend that students learn to respect this variety and begin to form their identity in relation to this reality, with a series of activities that fit the existing law and work all the basic skills, from social constructivism theory

Mechanisms of the sperm guidance, an essential aid for meeting the oocyte

In mammals, ejaculated spermatozoa must migrate into the female reproductive tract in order to reach and fertilize the oocyte (Figure 1). The number of spermatozoa that reach the oviductal isthmus (where they attach to oviductal cells and form the sperm reservoir) is small (1,2) and only ~10% of these spermatozoa in humans become capacitated (3) and acquire a state of readiness for fertilizing the oocyte. In addition, the sperm cells have a torturous and long way between the reservoir and the oocyte at the fertilization site (3–5 cm in humans) (2). These facts, together with the tiny dimensions of the gametes in comparison to the tube length make improbable the sperm arrival to the fertilization site and make evident the need for sperm guidance (4). Different guidance mechanisms appear essential for successful sperm arrival to the fertilization site: the short range mechanism such as chemotaxis (swimming up a chemoattractant gradient) (5) and the long range mechanisms such as rheotaxis (swimming against a fluid flow) and thermotaxis (the temperature-oriented cell motility).Fil: Lottero Leconte, Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Alonso, Carlos Agustín Isidro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Castellano, Luciana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Perez Martinez, Silvina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentin