The role of cyclase-associated protein (CAP) in actin dynamics during cell motility and morphogenesis

The highly dynamic remodeling of the actin cytoskeleton is responsible for most motile and morphogenetic processes in all eukaryotic cells. In order to generate appropriate spatial and temporal movements, the actin dynamics must be under tight control of an array of actin binding proteins (ABPs). Many proteins have been shown to play a specific role in actin filament growth or disassembly of older filaments. Very little is known about the proteins affecting recycling i.e. the step where newly depolymerized actin monomers are funneled into new rounds of filament assembly. A central protein family involved in the regulation of actin turnover is cyclase-associated proteins (CAP, called Srv2 in budding yeast). This 50-60 kDa protein was first identified from yeast as a suppressor of an activated RAS-allele and a factor associated with adenylyl cyclase. The CAP proteins harbor N-terminal coiled-coil (cc) domain, originally identified as a site for adenylyl cyclase binding. In the N-terminal half is also a 14-3-3 like domain, which is followed by central proline-rich domains and the WH2 domain. In the C-terminal end locates the highly conserved ADP-G-actin binding domain. In this study, we identified two previously suggested but poorly characterized interaction partners for Srv2/CAP: profilin and ADF/cofilin. Profilins are small proteins (12-16 kDa) that bind ATP-actin monomers and promote the nucleotide exchange of actin. The profilin-ATP-actin complex can be directly targeted to the growth of the filament barbed ends capped by Ena/VASP or formins. ADF/cofilins are also small (13-19 kDa) and highly conserved actin binding proteins. They depolymerize ADP-actin monomers from filament pointed ends and remain bound to ADP-actin strongly inhibiting nucleotide exchange. We revealed that the ADP-actin-cofilin complex is able to directly interact with the 14-3-3 like domain at the N-terminal region of Srv2/CAP. The C-terminal high affinity ADP-actin binding site of Srv2/CAP competes with cofilin for an actin monomer. Cofilin can thus be released from Srv2/CAP for the subsequent round of depolymerization. We also revealed that profilin interacts with the first proline-rich region of Srv2/CAP and that the binding occurs simultaneously with ADP-actin binding to C-terminal domain of Srv2/CAP. Both profilin and Srv2/CAP can promote nucleotide exchange of actin monomer. Because profilin has much higher affinity to ATP-actin than Srv2/CAP, the ATP-actin-profilin complex is released for filament polymerization. While a disruption of cofilin binding in yeast Srv2/CAP produces a severe phenotype comparable to Srv2/CAP deletion, an impairment of profilin binding from Srv2/CAP results in much milder phenotype. This suggests that the interaction with cofilin is essential for the function of Srv2/CAP, whereas profilin can also promote its function without direct interaction with Srv2/CAP. We also show that two CAP isoforms with specific expression patterns are present in mice. CAP1 is the major isoform in most tissues, while CAP2 is predominantly expressed in muscles. Deletion of CAP1 from non-muscle cells results in severe actin phenotype accompanied with mislocalization of cofilin to cytoplasmic aggregates. Together these studies suggest that Srv2/CAP recycles actin monomers from cofilin to profilin and thus it plays a central role in actin dynamics in both yeast and mammalian cells.

Lesbian, gay, bisexual, trans, and queer visibility through selfies: Comparing platform mediators across Ruby Rose’s Instagram and Vine presence

This article investigates the relationship between social media platforms and the production and dissemination of selfies in light of its implications for the visibility of lesbian, gay, bisexual, trans, and queer (LGBTQ) people. Applying an Actor Network Theory lens, two popular visual media apps, Instagram and Vine, are examined through a comparative walkthrough method. This reveals platform elements, or mediators, that can influence the conversational capacity of selfies in terms of the following: range, the variety of discourses addressed within a selfie; reach, circulation within and across publics; and salience, the strength and clarity of discourses communicated through a selfie. These mediators are illustrated through LGBTQ celebrity Ruby Rose’s Instagram selfies and Vine videos. Instagram’s use expectations encourage selfies focused on mainstream discourses of normative beauty and conspicuous consumption with an emphasis on appearance, extending through features constraining selfies’ reach and salience. In contrast, Vine’s broader use expectations enable a variety of discourses to be communicated across publics with an emphasis on creative, first-person sharing. These findings are reflected in Rose’s Instagram selfies, which mute alternative discourses of gender and sexuality through desexualized and aesthetically appealing self-representations, while Vines display her personal side, enabling both LGBTQ and heterosexual, cisgender people to identify with her without minimizing non-normative aspects of her gender and sexuality. These findings demonstrate the relevance of platforms in shaping selfies’ conversational capacity, as mediators can influence whether selfies feature in conversations reinforcing dominant discourses or in counterpublic conversations, contributing to everyday activism that challenges normative gender and sexual discourses.

Studies in sesquiterpenes-XVIII. The proton magnetic resonance spectra of some sesquiterpenes and the structure of humulene

The nuclear magnetic resonance spectra of longifolene, zerumbone, humulene, and their hydroderivatives have been studied in order to gauge the potentialities of this new tool in the field of sesquiterpenes. On the basis of present study, it has been possible to unequivocally fix the positions of the ethylene linkages in humulene and thus provide a straightforward solution of this hitherto unsolved problem.

The Non-catalytic ``Cap Domain'' of a Mycobacterial Metallophosphoesterase Regulates Its Expression and Localization in the Cell

Despite highly conserved core catalytic domains, members of the metallophosphoesterase (MPE) superfamily perform diverse and crucial functions ranging from nucleotide and nucleic acid metabolism to phospholipid hydrolysis. Unique structural elements outside of the catalytic core called ``cap domains'' are thought to provide specialization to these enzymes; however, no directed study has been performed to substantiate this. The cap domain of Rv0805, an MPE from Mycobacterium tuberculosis, is located C-terminal to its catalytic domain and is dispensable for the catalytic activity of this enzyme in vitro. We show here that this C-terminal extension (CTE) mediates in vivo localization of the protein to the cell membrane and cell wall as well as modulates expression levels of Rv0805 in mycobacteria. We also demonstrate that Rv0805 interacts with the cell wall of mycobacteria, possibly with the mycolyl-arabinogalactan-peptidoglycan complex, by virtue of its C terminus, a hitherto unknown property of this MPE. Using a panel of mutant proteins, we identify interactions between active site residues of Rv0805 and the CTE that determine its association with the cell wall. Finally, we show that Rv0805 and a truncated mutant devoid of the CTE produce different phenotypic effects when expressed in mycobacteria. Our study thus provides a detailed dissection of the functions of the cap domain of an MPE and suggests that the repertoire of cellular functions of MPEs cannot be understood without exploring the modulatory effects of these subdomains.

Stable isotope evidence for ca. 2.7-Ga-old Archean cap carbonates from the Dharwar Supergroup, southern India

Carbon isotope compositions of carbonate rocks from similar to 2.7-Ga-old Neoarchean Vanivilas Formation of the Dharwar Supergroup presented earlier by us are re-evaluated in this study, besides oxygen isotope compositions of a few silica dolomite pairs. The purpose of such a revisit assumes significance in view of recent field evidences that suggest a glaciomarine origin for the matrix-supported conglomerate member, the Talya conglomerate, which underlies the carbonate rocks of the Vanivilas Formation. An in-depth analysis of carbon isotope data reveals preservation of their pristine character despite the rocks having been subjected to metamorphism to different degrees (from lower greenschist to lower amphibolite facies). The dolomitic member of Vanivilas Formation of Marikanive area is characterized by highly depleted delta C-13 value (up to -5 parts per thousand VPDB) and merits as the Indian example of ca. 2.7-Ga-old cap carbonate. This inference is further supported by estimated low temperature of equilibration documented by a few silica dolomite pairs from the Vanivilas Formation collected near Kalche area. These pairs show evidence for oxygen isotopic equilibrium at low temperatures (similar to 0-20 degrees C) with depleted water (delta O-18 = -21 parts per thousand to -15 parts per thousand VSMOW) of glacial origin. We propose that the mineral pairs were deposited during the deglaciation period when the ocean temperature was in its gradual restoration phase. The dolomite of Marikanive area is the first record of cap carbonates from the Indian subcontinent with Neoarchean antiquity.

Teología, 1981, Tomo XVIII nº 037 (número completo)

La Virgen María en el Nuevo Testamento. Aspectos del Evangelio de san Lucas / Luis Heriberto Rivas -- El lugar de María en el discurso cristológico de san Anselmo de Canterbury / Eduardo Briancesco -- Notas sobre el II Concilio Provincial de Lima (1582-1583). Segunda parte: El laicado español / Armando Pedro Ferreccio -- Resonancias marianas en los catecismos hispanoamericanos del siglo XVI / Juan Guillermo Durán -- Culto divino y normas litúrgicas en el III Concilio Provincial de Lima (1582-1583) / Fernando María Bargalló -- El fresco de Daniel en la fosa de los leones en la “capella greca” / Eugenio Guasta -- San Benito y la teología de la vida religiosa / Eduardo Ghiotto -- Encuentro de teología mariana: Documento final -- Notas bibliográficas -- Libros recibidos

Defensa de la vida física del paciente en estado terminal : entre la dignidad y la autonomía

Resumen: Proponemos un análisis crítico de los fundamentos que sustentan la llamada “Ley de Muerte Digna” incorporada en la Ley que consagra la regulación de los derechos del paciente, historia clínica, consentimiento informado, (Art. 2º, inc. “e” párr. 2º de la Ley 26.529 modificada por la Ley 26.742), que introduce en nuestro país la existencia real de un sistema eutanásico formal sin fundamentos de orden científico, éticos e incluso jurídicos. ¿Es moralmente lícito suprimir la vida del enfermo terminal?, ¿la legalización de esta práctica eutanásica es la primera piedra de una nueva “cultura” de la vida? Entendemos que la llamada “tesis de la autonomía”, fundante de la reforma legislativa en cuestión, desde una óptica Bioética personalista, merece serias objeciones bioéticas ya que puede distorsionar gravemente el ejercicio de la medicina y la relación médico paciente.

¿Dónde iniciar el diálogo con el mundo en defensa de la vida?

Resumen: El tema del diálogo interdisciplinar constituye el alma misma de la bioética y su método propio. Este artículo pretende ser un aporte a ese diálogo. Con ese fin, asume los temas controversiales del pasado (la relación ciencia y ética), al mismo tiempo que señala la oportunidad actual de búsqueda y encuentro entre ambas ramas del saber. El autor propone como ámbito de ese diálogo el campo de la vida humana. La bioética con su actualidad, su complejidad y su metodología transdisciplinar surge como posibilidad de un diálogo respetuoso y ordenado, llamado a dar muchos frutos

Teología, 1981, Tomo XVIII nº 038 (número completo)

“Resonancias marianas en los Catecismos Hispanoamericanos del Siglo XVI” (Continuación) / Juan Guillermo Durán -- Obispos y religiosos. Disposiciones pastorales organizativas / Emilio Barcelón -- “Fe y Cultura: Hermenéutica Cultural en América Latina” / Pablo Sudar -- Libros recibidos -- Crónica de la Facultad -- Índice Volumen XVIII

Evaluación de técnicas de defensa y de la densidad en el cultivo de una nueva hortaliza : Cucúrbita pepo var. vegetable spaghetti

El zapallo Spaghetti, cultivo vigoroso de clima templado, constituye una alternativa productiva interesante y novedosa para nuestro país. El objetivo de este estudio fue evaluar el efecto del mulching y de la densidad sobre el rendimiento total, el peso medio y el calibre de los frutos. El estudio se llevó a cabo en Azul sobre un suelo Argiudol típico en camellones de 0,80 m de ancho con diferentes densidades de siembra. Se realizó una fertilización profunda en bandas de 0,80 m con fosfato diamónico, controlando las malezas en forma química, manual y mecánicamente, y las plagas haciendo aplicaciones preventivas de insecticidas y fungicidas. La siembra manual se efectuó el 2 de noviembre y los tratamientos fueron: densidades de siembra de 20, 15, 10 y 5 mil pl/ha (D1, D2, D3 y D4), con y sin mulching. Se trabajó con 32 parcelas y cada una tenía tres surcos de seis metros de longitud separados entre si por 2m. Se realizaron cuatro cosechas al llegar a la madurez completa (15/2, 29/2, 7/3 y 3/4). Los calibres evaluados fueron: (1) 2,2 kg, (2) 1,7 kg; (3) 1,3 kg y (4) 0,8 kg / fruto. Para el análisis de los datos se utilizó un modelo de bloques completamente aleatorizados con parcelas sub-divididas. En la parcela principal se evaluó el efecto del mulching, en la subparcela la densidad y la interacción de mulching por densidad, y en la subsubparcelas las diferentes cosechas. La cosecha total mostró diferencias significativas para el efecto del mulching, obteniéndose 71,90 t/ha (a) (con mulching) y 62,02 t/ha (b) (sin mulching); para cada densidad se detectaron diferencias significativas para el efecto mulching: D1: 84,45 t/ha (a), D2: 76,47 t/ha (ab); D3: 65,14 t/ha (b) y D4: 61,55 t/ha (b). Se observaron diferencias significativas en el número de frutos cosechados: con mulching (51.667 frutos/ha) y sin mulching (44.167 frutos/ha), y para las diferentes densidades: D1: 54.167 (a); D2: 50.000 (ab); D3: 47.700 (ab) y D4: 40.833 (b) t/ha. La composición de calibres de frutos cosechados fue el mismo para todos los tratamientos y cosechas.

Sapientia, 1963, Vol. XVIII, nº 69-70 (número completo)

Contenido: Materialismo dialéctico y totalitarismo / Octavio N. Derisi – Luis Lavelle / Regis Jolivet – La continuidad entre la dogmática jurídica, la teoría general y la filosofía del derecho / Avelino M. Quintas – Lógica y logística / Carlos A. Lungarzo Melcon – La ética existencialista y marxista / Octavio N. Derisi – Ontología del arte moderno / Ángel T. Lo Celso – Notas y comentarios -- Bibliografía

Poner el cuerpo. Mujeres y política estatal en Mari (Siglo XVIII a.c.)

Women and men are subjects defined both by their physical-natural reality and their socio-cultural environment. In this way they are reified, and many such examples can be found throughout history. We are interested in the situation of women in Ancient Mesopotamia, particularly the daughters of Zimrî-Lîm, king of the city of Mari, the archaeological site of Tell Hariri, modern Syria, during the 18th century BC. Zimrî- Lîm made marriages a policy of the state. He himself married foreign women and married their joint daughters to other important kings as well. This marital policy was another, more extended, way of dominion where women were a nexus between Mari and other states. In this paper, we will analyze the roles which were assigned and developed by royal women from a political level via a comprehensive approach. These women are presented generally as political objects, though, in extreme cases also they were taking forward actions as subjects and by it they were visualized as “the other,” the foreigner and, in some cases, the enemy.

En defensa de la moralidad del derecho

En la primera lectio con la que iniciamos el año académico 2013 expuse sobre el tema: “En defensa de la racionalidad del Derecho”. Cicerón ya decía que la naturaleza del Derecho debíamos buscarla en la naturaleza del hombre, y ésta justamente en su especificidad es racional (lo que nos permite distinguirnos de los otros seres irracionales), por eso el Derecho debe fundarse en su ser racional. Por su parte, en el inicio del año académico 2014 expuse: “En defensa de la politicidad del Derecho”, en consonancia con la defensa de su racionalidad que hicimos aquella primera vez. Esto es posible por la estrecha relación que existe entre ambas dimensiones (la racionalidad y la politicidad), debido a que el hombre es un animal político, como decía Aristóteles (zoom politykon), porque es un animal racional (zoom logotykon). A diferencia de otros animales, donde lo gregario se da en el orden instintivo, en el hombre la sociabilidad y la politicidad suponen la racionalidad. Siguiendo la misma línea, este año voy a referirme a la moralidad del Derecho, a fin de completar la trilogía (racionalidad, politicidad y moralidad). De ahí el título de la presente lectio: “En defensa de la moralidad del Derecho”. Esto es así porque de la misma manera que el hombre es también un animal ético (zoom ethykon), es racional y así todo su obrar ético se funda en su racionalidad, por aquello de que el obrar sigue al ser (operari sequitur esse). De esta manera, lo que pretendo demostrar en la presente tesis es que tanto la politicidad del Derecho a la que me referí el año pasado, como a la moralidad del Derecho a la que me referiré en esta disertación se fundan en la racionalidad del Derecho abordada en la primera lectio. Por eso, en algunas partes de esta disertación me remitiré a las dos anteriores ya que las tres lecciones forman un conjunto...