Space exploration by dendritic cells requires maintenance of myosin II activity by IP3 receptor 1

Dendritic cells (DCs) patrol the interstitial space of peripheral tissues. The mechanisms that regulate their migration in such constrained environment remain unknown. We here investigated the role of calcium in immature DCs migrating in confinement. We found that they displayed calcium oscillations that were independent of extracellular calcium and more frequently observed in DCs undergoing strong speed fluctuations. In these cells, calcium spikes were associated with fast motility phases. IP₃ receptors (IP₃Rs) channels, which allow calcium release from the endoplasmic reticulum, were identified as required for immature DCs to migrate at fast speed. The IP₃R1 isoform was further shown to specifically regulate the locomotion persistence of immature DCs, that is, their capacity to maintain directional migration. This function of IP₃R1 results from its ability to control the phosphorylation levels of myosin II regulatory light chain (MLC) and the back/front polarization of the motor protein. We propose that by upholding myosin II activity, constitutive calcium release from the ER through IP₃R1 maintains DC polarity during migration in confinement, facilitating the exploration of their environment.     

The Mediterranean Sea under siege: spatial overlap between marine biodiversity,cumulative threats and marine reserves

Aim A large body of knowledge exists on individual anthropogenic threats that have an impact on marine biodiversity in the Mediterranean Sea, although we know little about how these threats accumulate and interact to affect marine species and ecosystems. In this context, we aimed to identify the main areas where the interaction between marine biodiversity and threats is more pronounced and to assess their spatial overlap with current marine protected areas in the Mediterranean. Location Mediterranean Sea. Methods We first identified areas of high biodiversity of marine mammals, marine turtles, seabirds, fishes and commercial or well‐documented invertebrates. We mapped potential areas of high threat where multiple threats are occurring simultaneously. Finally we quantified the areas of conservation concern for biodiversity by looking at the spatial overlap between high biodiversity and high cumulative threats, and we assessed the overlap with protected areas. Results Our results show that areas with high marine biodiversity in the Mediterranean Sea are mainly located along the central and north shores, with lower values in the south‐eastern regions. Areas of potential high cumulative threats are widespread in both the western and eastern basins, with fewer areas located in the south‐eastern region. The interaction between areas of high biodiversity and threats for invertebrates, fishes and large animals in general (including large fishes, marine mammals, marine turtles and seabirds) is concentrated in the coastal areas of Spain, Gulf of Lions, north‐eastern Ligurian Sea, Adriatic Sea, Aegean Sea, south‐eastern Turkey and regions surrounding the Nile Delta and north‐west African coasts. Areas of concern are larger for marine mammal and seabird species. Main conclusions These areas may represent good candidates for further research, management and protection activities, since there is only a maximum 2% overlap between existing marine protected areas (which cover 5% of the Mediterranean Sea) and our predicted areas of conservation concern for biodiversity.     

Connecting Proline and γ-Aminobutyric Acid in Stressed Plants through Non-Enzymatic Reactions

The accumulation of proline (Pro) in plants exposed to biotic/abiotic stress is a well-documented and conserved response in most vegetal species. Stress conditions induce the overproduction of reactive oxygen species which can lead to cellular damage. In vitro assays have shown that enzyme inactivation by hydroxyl radicals (^·OH) can be avoided in presence of Pro, suggesting that this amino acid could act as an ^·OH scavenger. We applied Density Functional Theory coupled with a polarizable continuum model to elucidate how Pro reacts with ^·OH. In this work we suggest that Pro reacts favourably with ^·OH by H–abstraction on the amine group. This reaction produces the spontaneous decarboxylation of Pro leading to the formation of pyrrolidin-1-yl. In turn, pyrrolidin-1-yl can easily be converted to Δ¹-pyrroline, the substrate of the enzyme Δ¹-pyrroline dehydrogenase, which produces γ-aminobutyric acid (GABA). GABA and Pro are frequently accumulated in stressed plants and several protective roles have been assigned to these molecules. Thereby we present an alternative non-enzymatic way to synthetize GABA under oxidative stress. Finally this work sheds light on a new beneficial role of Pro accumulation in the maintenance of photosynthetic activity.     

Post‐fire recovery occurs overwhelmingly by resprouting in the Chaco Serrano forest of Central Argentina

In fire‐prone landscapes, differences in post‐fire regeneration by resprouting between species or sites could be far more important in explaining vegetation physiognomy and composition than seed regeneration. This is the first study exploring the relative contribution of tree resprouts and seeds to post‐fire crown volume in the Chaco Serrano forest of South America. Additionally, we compare the resprouting response among species and quantify post‐fire changes in tree composition among sites. We established 290 permanent plots distributed in three sites affected by wildfires in 2005. For all tree species in all plots we recorded survival of every individual 1 year after the fire; at the plot level, we recorded the above‐ground tree volume before and 3 years after the fire. Resprouting from the base was the main resprouting type. Survival varied between species from 73% to 100% for native species and from 7% to 100% for non‐natives. Before the fire, crown volume was similar in the three sites, and was completely lost after the fire in 92% of the plots. Three years after the fire, between 8% and 58% of crown volume was recovered. The ratio of crown recovery because of resprouts and seedlings was 1562:1. Tree composition exhibited few changes because of the high post‐fire survival of most native species. We conclude that in the semiarid Chaco Serrano ecosystem tree species regenerate mainly by resprouting. This regeneration mode should be taken into account to better understand post‐fire successional pathways of these forests, their management and the restoration of burnt forest areas.     

Type designation of the oaks Quercus ballota and Q. rotundifolia (Fagaceae)

The names Quercus ballota and Q. rotundifolia (Fagaceae), referring to taxa sometimes considered conspecific with the widely distributed Q. ilex, are discussed and typified. A specimen preserved at MPU is designated as the lectotype of Desfontaines's name Q. ballota. Lamarck's name Q. rotundifolia is neotypified using a specimen preserved at VAL, with several duplicates in other European herbaria.     

Inflammatory cytokines in vitro production are associated with Ala16Val superoxide dismutase gene polymorphism of peripheral blood mononuclear cells

Obesity is considered a chronic low-grade inflammatory state associated with a chronic oxidative stress caused by superoxide production (O(2)(-)). The superoxide dismutase manganese dependent (SOD2) catalyzes O(2)(-) in H(2)O(2) into mitochondria and is encoded by a single gene that presents a common polymorphism that results in the replacement of alanine (A) with a valine (V) in the 16 codon. This polymorphism has been implicated in a decreased efficiency of SOD2 transport into targeted mitochondria in V allele carriers. Previous studies described an association between VV genotype and metabolic diseases, including obesity and diabetes. However, the causal mechanisms to explain this association need to be more elucidated. We postulated that the polymorphism could influence the inflammatory response. To test our hypothesis, we evaluated the in vitro cytokines production by human peripheral blood mononuclear cells (PBMCs) carrier's different Ala16Val-SOD2 genotypes (IL-1, IL-6, IL-10, TNF-α, IFN-γ). Additionally, we evaluated if the culture medium glucose, enriched insulin, could influence the cytokine production. Higher levels of proinflammatory cytokines were observed in VV-PBMCs when compared to AA-PBMCs. However, the culture medium glucose and enriched insulin did not affect cytokine production. The results suggest that Ala16Val-SOD2 gene polymorphism could trigger the PBMCs proinflammatory cytokines level. However, discerning if a similar mechanism occurs in fat cells is an open question.     

Pandemic influenza due to pH1N1/2009 virus: estimation of infection burden in Reunion Island through a prospective serosurvey, austral winter 2009

Background

To date, there is little information that reflects the true extent of spread of the pH1N1/2009v influenza pandemic at the community level as infection often results in mild or no clinical symptoms. This study aimed at assessing through a prospective study, the attack rate of pH1N1/2009 virus in Reunion Island and risk factors of infection, during the 2009 season.

Methodology/Principal Findings

A serosurvey was conducted during the 2009 austral winter, in the frame of a prospective population study. Pairs of sera were collected from 1687 individuals belonging to 772 households, during and after passage of the pandemic wave. Antibodies to pH1N1/2009v were titered using the hemagglutination inhibition assay (HIA) with titers ≥1/40 being considered positive. Seroprevalence during the first two weeks of detection of pH1N1/2009v in Reunion Island was 29.8% in people under 20 years of age, 35.6% in adults (20–59 years) and 73.3% in the elderly (≥60 years) (P<0.0001). Baseline corrected cumulative incidence rates, were 42.9%, 13.9% and 0% in these age groups respectively (P<0.0001). A significant decline in antibody titers occurred soon after the passage of the epidemic wave. Seroconversion rates to pH1N1/2009 correlated negatively with age: 63.2%, 39.4% and 16.7%, in each age group respectively (P<0.0001). Seroconversion occurred in 65.2% of individuals who were seronegative at inclusion compared to 6.8% in those who were initially seropositive.

Conclusions

Seroincidence of pH1N1/2009v infection was three times that estimated from clinical surveillance, indicating that almost two thirds of infections occurring at the community level have escaped medical detection. People under 20 years of age were the most affected group. Pre-epidemic titers ≥1/40 prevented seroconversion and are likely protective against infection. A concern was raised about the long term stability of the antibody responses.     

HIV-mediated phosphatidylinositol 3-kinase/serine-threonine kinase activation in APCs leads to programmed death-1 ligand upregulation and suppression of HIV-specific CD8 T cells

Recent evidence demonstrates that HIV-1 infection leads to the attenuation of cellular immune responses, which has been correlated with the increased expression of programmed death (PD)-1 on virus-specific CD8(+) T cells. PD-1 is induced upon T cell activation, and its prolonged expression facilitates CD8(+) T cell inhibitory signals when bound to its B7 family ligands, PD-ligand (L)1/2, which are expressed on APCs. Importantly, early reports demonstrated that blockade of the PD-1/PD-L interaction by Abs may help to counter the development of immune exhaustion driven by HIV viral persistence. To better understand the regulation of the PD-1 pathway during HIV infection, we examined the ability of the virus to induce PD-L expression on macrophages and dendritic cells. We found a direct relationship between the infection of APCs and the expression of PD-L1 in which virus-mediated upregulation induced a state of nonresponsiveness in uninfected HIV-specific T cells. Furthermore, this exhaustion phenotype was revitalized by the blockade of PD-L1, after which T cells regained their capacity for proliferation and the secretion of proinflammatory cytokines IFN-γ, IL-2, and IL-12 upon restimulation. In addition, we identify a critical role for the PI3K/serine-threonine kinase signaling pathway in PD-L1 upregulation of APCs by HIV, because inhibition of these intracellular signal transducer enzymes significantly reduced PD-L1 induction by infection. These data identify a novel mechanism by which HIV exploits the immunosuppressive PD-1 pathway and suggest a new role for virus-infected cells in the local corruption of immune responses required for viral suppression.     

Cellular nucleic acid binding protein binds G-rich single-stranded nucleic acids and may function as a nucleic acid chaperone

Cellular nucleic acid binding protein (CNBP) is a small single-stranded nucleic acid binding protein made of seven Zn knuckles and an Arg-Gly rich box. CNBP is strikingly conserved among vertebrates and was reported to play broad-spectrum functions in eukaryotic cells biology. Neither its biological function nor its mechanisms of action were elucidated yet. The main goal of this work was to gain further insights into the CNBP biochemical and molecular features. We studied Bufo arenarum CNBP (bCNBP) binding to single-stranded nucleic acid probes representing the main reported CNBP putative targets. We report that, although bCNBP is able to bind RNA and single-stranded DNA (ssDNA) probes in vitro, it binds RNA as a preformed dimer whereas both monomer and dimer are able to bind to ssDNA. A systematic analysis of variant probes shows that the preferred bCNBP targets contain unpaired guanosine-rich stretches. These data expand the knowledge about CNBP binding stoichiometry and begins to dissect the main features of CNBP nucleic acid targets. Besides, we show that bCNBP presents a highly disordered predicted structure and promotes the annealing and melting of nucleic acids in vitro. These features are typical of proteins that function as nucleic acid chaperones. Based on these data, we propose that CNBP may function as a nucleic acid chaperone through binding, remodeling, and stabilizing nucleic acids secondary structures. This novel CNBP biochemical activity broadens the field of study about its biological function and may be the basis to understand the diverse ways in which CNBP controls gene expression.     

Relevance of forage fish in the diet of Magellanic penguins breeding in northern Patagonia,Argentina

We quantified the trophic niche of Magellanic penguins (Spheniscus magellanicus) breeding and moulting in Golfo San Jorge, Argentina, through conventional stomach content and stable isotope analysis. A total of 112 adults were flushed during the early and late chick stages of 2011 and 2012 at Isla Vernacci Norte, and at least 15 prey taxa were found, including fishes, cephalopods, crustaceans and polychaetes. Overall, Argentine anchovy (Engraulis anchoita) showed the highest contribution in terms of importance by mass (68.1–85.3%, depending on chick stage and year), except for the old chick stage in 2011 when the shortfin squid (Illex argentinus) was the main prey consumed (56.0%). Based on carbon and nitrogen isotopic values from a total of 256 blood samples, corresponding to young and old chicks and to adults of both sexes sampled throughout the incubation, chick and moult stages at the above mentioned colony and years, Bayesian mixing model outputs showed that Argentine anchovy was always the main prey (48–86%). Bayesian mixing model outputs obtained from adults of both sexes and their chicks during the late chick stage of 2013 at Isla Vernacci Norte, Isla Tova and Isla Leones also showed that Argentine anchovy was the main prey consumed. This is the first comprehensive assessment of Magellanic penguin diet composition in northern Patagonia, quantifying the relative contribution of prey in the diet of adults and chicks at different stages of the annual cycle and years, and confirms the relevance of a forage fish such as the Argentine anchovy in its trophic ecology.