The postcranial anatomy of Brasilodon quadrangularis and the acquisition of mammaliaform traits among non-mammaliaform cynodonts

Brasilodon quadrangularis (Cynodontia, Probainognathia) is an iconic non-mammaliaform cynodont from the Late Triassic of Brazil (Riograndia Assemblage Zone, Candelária Sequence), being considered as the sister taxon of Mammaliaformes. Although its phylogenetic position is very important, several aspects of its postcranial anatomy remain unclear or unstudied. Here, we present a detailed description of the postcranial elements referred to Brasilodon, including previously mentioned specimens and new ones, which add relevant information about its postcranial morphology and provide a new insight into the anatomical transition between advanced non-mammaliaform cynodonts and early mammaliaforms. Functional and ecological implications are also investigated, based on the postcranial morphology and muscular reconstructions. The postcranium of Brasilodon differs from most non-mammaliaform cynodonts and presents similarities with tritylodontids, early mammaliaforms and extant therians, such as a ventrally oriented scapular glenoid facet, a distinct and ossified greater humeral tubercle, lack of ectepicondylar foramen, olecranon process, hemispherical humeral and femoral heads and a prominent intertrochanteric crest. The humeral torsion, the length of the deltopectoral crest, the large bicipital groove and the well-developed lesser tubercle, indicate that the forelimb of Brasilodon was hold in a semi-sprawling position, with well-developed adductor muscles to maintain the body off the ground. The short femoral neck and the strong medial projection of the femoral head indicate the femur was held in a more erect posture than in basal non-mammaliaform cynodonts. The anterodorsally projected iliac blade with reduced postacetabular process, reduction of the anterior part of the pubis, medially located lesser trochanter indicate a basically mammalian pattern of pelvic musculature, able to swing the femur in a nearly parasagittal plane.Fil: Guignard, Morgan L.. Universidade Federal do Rio Grande do Sul; BrasilFil: Martinelli, Agustín Guillermo. Universidade Federal do Rio Grande do Sul; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Soares, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentina. Universidade Federal do Rio Grande do Sul; Brasi

Structural basis of complement membrane attack complex formation

In response to complement activation, the membrane attack complex (MAC) assembles from fluid-phase proteins to form pores in lipid bilayers. MAC directly lyses pathogens by a ‘multi-hit’ mechanism; however, sublytic MAC pores on host cells activate signalling pathways. Previous studies have described the structures of individual MAC components and subcomplexes; however, the molecular details of its assembly and mechanism of action remain unresolved. Here we report the electron cryo-microscopy structure of human MAC at subnanometre resolution. Structural analyses define the stoichiometry of the complete pore and identify a network of interaction interfaces that determine its assembly mechanism. MAC adopts a ‘split-washer’ configuration, in contrast to the predicted closed ring observed for perforin and cholesterol-dependent cytolysins. Assembly precursors partially penetrate the lipid bilayer, resulting in an irregular β-barrel pore. Our results demonstrate how differences in symmetric and asymmetric components of the MAC underpin a molecular basis for pore formation and suggest a mechanism of action that extends beyond membrane penetration

Travel philanthropy and sustainable development: the case of the Plymouth–Banjul Challenge

Travel philanthropy is an evolving phenomenon. It owes its origins to rising frustrations with conventional aid and traditional philanthropic giving and is seen as development assistance enabling resources to flow directly from the tourism industry into community development and conservation initiatives. Philanthropists have long sought to achieve social transformation, and travel philanthropy in all its forms has evolved through the democratization of charity, as a kind of “doing good” through “giving back” whilst travelling. This paper evaluates values, practices and impacts of traditional, modern and post-modern philanthropy. Drawing upon evidence emerging from a longitudinal study, which involved the retrospective evaluation of personal diary entries, participant observations and semi-structured interviews about the transcontinental Plymouth–Banjul (car) Challenge (PBC), it exemplifies how an initiative can evolve across all three philanthropic approaches. It further debates critical understandings of the problematic travel philanthropy concept and its role in stimulating sustainable development in sub-Saharan Africa

Kumanoa mahlacensis (Batrachospermales, Rhodophyta) en un marjal costero mediterráneo, una nueva especie para la flora ficológica contiental europea

Morphological characters and molecular sequence data of the plastid-encoded RUBISCO large subunit gen (rbcL) confirmed the first record of Kumanoa mahlacensis (S. Kumano & W.A. Bowden-Kerby) Entwisle, M.L. Vis, W.B. Chiasson, Necchi & A.R. Sherwood in Europe from a Spanish Mediterranean coastal wetland. The genus Kumanoa has a worldwide distribution and inhabits in both lotic and lentic habitats, but information about the ecological requirements of species is scarce. In this study, the morphology and ecology of Spanish material is described in order to gain a broader insight of the distribution of species from Mediterranean areas.El estudio de los caracteres morfológicos y las secuencias del gen plastidial (rbcL) que codifica la subunidad mayor de la enzima RUBISCO han confirmado la presencia de Kumanoa mahlacensis (S. Kumano & W.A. Bowden-Kerby) Entwisle, M.L. Vis, W.B. Chiasson, Necchi & A.R. Sherwood en Europa, en un marjal costero mediterráneo del levante español. El género Kumanoa presenta una distribución mundial y habita tanto en ambientes lóticos como leníticos; sin embargo existe poca información sobre los requerimientos ecológicos de esta especie. En este trabajo se describe la morfología y ecología del material recolectado en España con el objetivo de obtener una visión más amplia de su distribución y de su presencia en áreas mediterráneas

Fbxw7 Deletion Accelerates KrasG12D-Driven Pancreatic Tumorigenesis via Yap Accumulation

AbstractPancreatic cancers driven by KRAS mutations require additional mutations for tumor progression. The tumor suppressor FBXW7 is altered in pancreatic cancers, but its contribution to pancreatic tumorigenesis is unknown. To determine potential cooperation between Kras mutation and Fbxw7 inactivation in pancreatic tumorigenesis, we generated P48-Cre;LSL-KrasG12D;Fbxw7fl/fl (KFCfl/fl) compound mice. We found that KFCfl/fl mice displayed accelerated tumorigenesis: all mice succumbed to pancreatic ductal adenocarcinoma (PDA) by 40 days of age, with PDA onset occurring by 2 weeks of age. PDA in KFCfl/fl mice was preceded by earlier onset of acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) lesions, and associated with chromosomal instability and the accumulation of Fbxw7 substrates Yes-associated protein (Yap), c-Myc, and Notch. Using KFCfl/fl and FBXW7-deficient human pancreatic cancer cells, we found that Yap silencing attenuated growth promotion by Fbxw7 deletion. Our data demonstrate that Fbxw7 is a potent suppressor of KrasG12D-induced pancreatic tumorigenesis due, at least in part, to negative regulation of Yap