The interplay between calcium and the in vitro lectin and chaperone activities of calreticulin

The ER resident protein calreticulin fulfills at least two important roles. It works as a chaperone preventing Golgi exit of non-native protein species and enhancing protein folding efficiency in either N-glycan-dependent, lectin chaperone, or classical chaperone, N-glycan-independent, modes and is one of the main calcium buffers in the cell. This last feature is independent from the lectin chaperone properties of the protein as this last activity is also observed in a CRT fragment lacking calcium buffer capacity. Here we study the interplay between calcium and the lectin and chaperone activities of CRT. The affinity of CRT for monoglucosylated glycans measured in solution by equilibrium dialysis and fluorescence anisotropy was not affected by the absence of calcium. Binding of CRT to monoglucosylated neoglycoproteins displaying either native or molten globule-like conformations was also independent of calcium concentration. Moreover, calcium and monoglucosylated glycans stabilized the CRT structure in an apparent additive, independent manner when the protein was subjected to thermal or urea-induced denaturation. In addition, the ability of CRT to decrease the level of aggregation of a chemically denatured monoglucosylated and nonglycosylated protein was also independent of calcium level.     

Screening of Exopolysaccharide-Producing Lactobacillus and Bifidobacterium Strains Isolated from the Human Intestinal Microbiota

Using phenotypic approaches, we have detected that 17% of human intestinal Lactobacillus and Bifidobacterium strains could be exopolysaccharide (EPS) producers. However, PCR techniques showed that only 7% harbored genes related to the synthesis of heteropolysaccharides. This is the first work to screen the human intestinal ecosystem for the detection of EPS-producing strains.     

Life expectancy in a western and immigrant receiving population (El Ejido, SE Spain)

This study deals with the mortality pattern of El Ejido population, an agricultural Spanish community with a sub-tropical climate, located on the western Mediterranean coast (Andalusia). Based on the incorporation of modern agrarian techniques, this region has experienced a great economic development. Its demographic consequences were relevant, such as the arrival of immigrants throughout the second half of the twentieth century. The analysis of several demographic parameters shown in the abridged life table has revealed a small but non-random decrease of mortality during the last two decades of the past century. Furthermore, from the low value reached by the current entropy coefficient (H = 0.131), and the comparison of El Ejido life-expectancy at birth (e0) with Spain and Andalusia, we concluded that: a) The current mortality of El Ejido has approached a theoretical situation, where all deaths tend to take place at the age of 78.09 (its e0), and the death probability is very low at earlier ages. b) Some peculiar characteristics of its immigration as well as the high influence of the great public health system reached currently in Spain, reveal that El Ejido mortality does not depend on its remarkable immigration.     

Adaptation and Response of Bifidobacterium animalis subsp. lactis to Bile: a Proteomic and Physiological Approach

Bile salts are natural detergents that facilitate the digestion and absorption of the hydrophobic components of the diet. However, their amphiphilic nature makes them very inhibitory for bacteria and strongly influences bacterial survival in the gastrointestinal tract. Adaptation to and tolerance of bile stress is therefore crucial for the persistence of bacteria in the human colonic niche. Bifidobacterium animalis subsp. lactis, a probiotic bacterium with documented health benefits, is applied largely in fermented dairy products. In this study, the effect of bile salts on proteomes of B. animalis subsp. lactis IPLA 4549 and its bile-resistant derivative B. animalis subsp. lactis 4549dOx was analyzed, leading to the identification of proteins which may represent the targets of bile salt response and adaptation in B. animalis subsp. lactis. The comparison of the wild-type and the bile-resistant strain responses allowed us to hypothesize about the resistance mechanisms acquired by the derivative resistant strain and about the bile salt response in B. animalis subsp. lactis. In addition, significant differences in the levels of metabolic end products of the bifid shunt and in the redox status of the cells were also detected, which correlate with some differences observed between the proteomes. These results indicate that adaptation and response to bile in B. animalis subsp. lactis involve several physiological mechanisms that are jointly dedicated to reduce the deleterious impact of bile on the cell's physiology.     

OPA1 processing reconstituted in yeast depends on the subunit composition of the m-AAA protease in mitochondria

The morphology of mitochondria in mammalian cells is regulated by proteolytic cleavage of OPA1, a dynamin-like GTPase of the mitochondrial inner membrane. The mitochondrial rhomboid protease PARL, and paraplegin, a subunit of the ATP-dependent m-AAA protease, were proposed to be involved in this process. Here, we characterized individual OPA1 isoforms by mass spectrometry, and we reconstituted their processing in yeast to identify proteases involved in OPA1 cleavage. The yeast homologue of OPA1, Mgm1, was processed both by PARL and its yeast homologue Pcp1. Neither of these rhomboid proteases cleaved OPA1. The formation of small OPA1 isoforms was impaired in yeast cells lacking the m-AAA protease subunits Yta10 and Yta12 and was restored upon expression of murine or human m-AAA proteases. OPA1 processing depended on the subunit composition of mammalian m-AAA proteases. Homo-oligomeric m-AAA protease complexes composed of murine Afg3l1, Afg3l2, or human AFG3L2 subunits cleaved OPA1 with higher efficiency than paraplegin-containing m-AAA proteases. OPA1 processing proceeded normally in murine cell lines lacking paraplegin or PARL. Our results provide evidence for different substrate specificities of m-AAA proteases composed of different subunits and reveal a striking evolutionary switch of proteases involved in the proteolytic processing of dynamin-like GTPases in mitochondria.     

Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation

Interstitial loss of all or part of the long arm of chromosome 5, or del(5q), is a frequent clonal chromosomal abnormality in human myelodysplastic syndrome (MDS, a preleukemic disorder) and acute myeloid leukemia (AML), and is thought to contribute to the pathogenesis of these diseases by deleting one or more tumor-suppressor genes. Although a major commonly deleted region (CDR) has been delineated on chromosome band 5q31.1 (refs. 3-7), attempts to identify tumor suppressors within this band have been unsuccessful. We focused our analysis of gene expression on RNA from primitive leukemia-initiating cells, which harbor 5q deletions, and analyzed 12 genes within the CDR that are expressed by normal hematopoietic stem cells. Here we show that the gene encoding alpha-catenin (CTNNA1) is expressed at a much lower level in leukemia-initiating stem cells from individuals with AML or MDS with a 5q deletion than in individuals with MDS or AML lacking a 5q deletion or in normal hematopoietic stem cells. Analysis of HL-60 cells, a myeloid leukemia line with deletion of the 5q31 region, showed that the CTNNA1 promoter of the retained allele is suppressed by both methylation and histone deacetylation. Restoration of CTNNA1 expression in HL-60 cells resulted in reduced proliferation and apoptotic cell death. Thus, loss of expression of the alpha-catenin tumor suppressor in hematopoietic stem cells may provide a growth advantage that contributes to human MDS or AML with del(5q).     

Increases in sampling support the southern Gondwanan hypothesis for the origin of dinosaurs

Dinosaurs were ubiquitous in terrestrial ecosystems through most of the Mesozoic and are still diversely represented in the modern fauna in the form of birds. Recent efforts to better understand the origins of the group have resulted in the discovery of many new species of early dinosaur and their closest relatives (dinosauromorphs). In addition, recent re‐examinations of early dinosaur phylogeny have highlighted uncertainties regarding the interrelationships of the main dinosaur lineages (Sauropodomorpha, Theropoda and Ornithischia), and questioned the traditional hypothesis that the group originated in South Gondwana and gradually dispersed over Pangaea. Here, we use an historical approach to examine the impact of new fossil discoveries and changing phylogenetic hypotheses on biogeographical scenarios for dinosaur origins over 20 years of research time, and analyse the results in the light of different fossil record sampling regimes. Our results consistently optimize South Gondwana as the ancestral area for Dinosauria, as well as for more inclusive clades including Dinosauromorpha, and show that this hypothesis is robust to increased taxonomic and geographic sampling and divergent phylogenetic results. Our results do not find any support for the recently proposed Laurasian origin of dinosaurs and suggest that a southern Gondwanan origin is by far the most plausible given our current knowledge of the diversity of early dinosaurs and non‐dinosaurian dinosauromorphs.     

Advances in novel vaccines for foot and mouth disease: focus on recombinant empty capsids

Foot and mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals, which causes severe economic losses in the livestock industry. Currently available vaccines are based on inactivated FMD virus (FMDV). Although inactivated virus vaccines have proved to be effective in FMD control, they have a number of disadvantages, including the need for high bio-containment production facilities and the lack of induction of immunological memory. Novel FMD vaccines based on the use of recombinant empty capsids have shown promising results. These recombinant empty capsids are attractive candidates because they avoid the use of virus in the production facilities but conserve its complete repertoire of conformational epitopes. However, many of these recombinant empty capsids require time-consuming procedures that are difficult to scale up. Achieving production of a novel and efficient FMD vaccine requires not only immunogenic antigens, but also industrially relevant processes. This review intends to summarize and compare the different strategies already published for the production of FMDV recombinant empty capsids, focusing on large-scale production.     

Declining population trends of European mountain birds

Mountain areas often hold special species communities, and they are high on the list of conservation concern. Global warming and changes in human land use, such as grazing pressure and afforestation, have been suggested to be major threats for biodiversity in the mountain areas, affecting species abundance and causing distribution shifts towards mountaintops. Population shifts towards poles and mountaintops have been documented in several areas, indicating that climate change is one of the key drivers of species’ distribution changes. Despite the high conservation concern, relatively little is known about the population trends of species in mountain areas due to low accessibility and difficult working conditions. Thanks to the recent improvement of bird monitoring schemes around Europe, we can here report a first account of population trends of 44 bird species from four major European mountain regions: Fennoscandia, UK upland, south‐western (Iberia) and south‐central mountains (Alps), covering 12 countries. Overall, the mountain bird species declined significantly (?7%) during 2002–2014, which is similar to the declining rate in common birds in Europe during the same period. Mountain specialists showed a significant ?10% decline in population numbers. The slope for mountain generalists was also negative, but not significantly so. The slopes of specialists and generalists did not differ from each other. Fennoscandian and Iberian populations were on average declining, while in United Kingdom and Alps, trends were nonsignificant. Temperature change or migratory behaviour was not significantly associated with regional population trends of species. Alpine habitats are highly vulnerable to climate change, and this is certainly one of the main drivers of mountain bird population trends. However, observed declines can also be partly linked with local land use practices. More efforts should be undertaken to identify the causes of decline and to increase conservation efforts for these populations.     

Occurrence of the black yeast Hortaea werneckii in the Mediterranean Sea

Extremophiles - The occurrence of cultivable fungi was investigated along the water column (25–2500 m depth) of four off-shore stations in the Mediterranean basin. An unexpected high...