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The role of juvenile hormone and insulin/TOR signaling in the growth of Manduca sexta
Get PDFIn many insect species, fitness trade-offs exist between maximizing body size and developmental speed. Understanding how various species evolve different life history strategies requires knowledge of the physiological mechanisms underlying the regulation of body size and developmental timing. Here the roles of juvenile hormone (JH) and insulin/target of rapamycin (TOR) signaling in the regulation of the final body size were examined in the tobacco hornworm, Manduca sexta.Wellesley College, National Science Foundation grants: (IOS-1027453, IOS-1354608), FCT fellowship: (SFRH/BPD/74313/2010)
Exosome Biogenesis, Regulation, and Function in Viral Infection
Get PDFExosomes are extracellular vesicles released upon fusion of multivesicular bodies(MVBs) with the cellular plasma membrane. They originate as intraluminal vesicles (ILVs) duringthe process of MVB formation. Exosomes were shown to contain selectively sorted functionalproteins, lipids, and RNAs, mediating cell-to-cell communications and hence playing a role in thephysiology of the healthy and diseased organism. Challenges in the field include the identificationof mechanisms sustaining packaging of membrane-bound and soluble material to these vesicles andthe understanding of the underlying processes directing MVBs for degradation or fusion with theplasma membrane. The investigation into the formation and roles of exosomes in viral infection is inits early years. Although still controversial, exosomes can, in principle, incorporate any functionalfactor, provided they have an appropriate sorting signal, and thus are prone to viral exploitation.This review initially focuses on the composition and biogenesis of exosomes. It then explores theregulatory mechanisms underlying their biogenesis. Exosomes are part of the endocytic system,which is tightly regulated and able to respond to several stimuli that lead to alterations in thecomposition of its sub-compartments. We discuss the current knowledge of how these changesaffect exosomal release. We then summarize how different viruses exploit specific proteins ofendocytic sub-compartments and speculate that it could interfere with exosome function, althoughno direct link between viral usage of the endocytic system and exosome release has yet beenreported. Many recent reports have ascribed functions to exosomes released from cells infectedwith a variety of animal viruses, including viral spread, host immunity, and manipulation of themicroenvironment, which are discussed. Given the ever-growing roles and importance of exosomesin viral infections, understanding what regulates their composition and levels, and defining theirfunctions will ultimately provide additional insights into the virulence and persistence of infections.FCT postdoctoral fellowship: (SFRH/BPD/62982/2009), FCT investigator fellowship of
the Principal Investigator: (IF/00899/2013)
Upscale and downscale energy transfer over the tropical Pacific revealed by scatterometer winds
Get PDFThe direction of the energy cascade in the mesoscales of atmospheric turbulence is investigated using near-surface winds over the tropical Pacific measured by satellite scatterometers SeaWinds (QuikSCAT) and ASCAT (MetOp-A). The tropical Pacific was subdivided into nine regions, classified as rainy or dry. Longitudinal third-order along-track structure functions inline image and skewness inline image were calculated as a function of separation inline image for each region and month during the period November 2008 to October 2009. We find that the results support both downscale and upscale interpretations, depending on region and month. The results indicate that normally energy cascades downscale, but cascades upscale over the cold tongue in the cold season and over the west Pacific in summer months. An explanation is offered based on the heating or cooling of the air by the underlying sea surface temperature. It is also found that the signature of intermittent small-scale (<100 km) events could be identified in graphs of inline image, implying that this diagnostic may be useful in the studies of tropical disturbances.EUMETSAT, NWP SAF part of the SAF network
REST mediates resolution of HIF-dependent gene expression in prolonged hypoxia
Get PDFThe hypoxia-inducible factor (HIF) is a key regulator of the cellular response to hypoxia which promotes oxygen delivery and metabolic adaptation to oxygen deprivation. However, the degree and duration of HIF-1α expression in hypoxia must be carefully balanced within cells in order to avoid unwanted side effects associated with excessive activity. The expression of HIF-1α mRNA is suppressed in prolonged hypoxia, suggesting that the control of HIF1A gene transcription is tightly regulated by negative feedback mechanisms. Little is known about the resolution of the HIF-1α protein response and the suppression of HIF-1α mRNA in prolonged hypoxia. Here, we demonstrate that the Repressor Element 1-Silencing Transcription factor (REST) binds to the HIF-1α promoter in a hypoxia-dependent manner. Knockdown of REST using RNAi increases the expression of HIF-1α mRNA, protein and transcriptional activity. Furthermore REST knockdown increases glucose consumption and lactate production in a HIF-1α- (but not HIF-2α-) dependent manner. Finally, REST promotes the resolution of HIF-1α protein expression in prolonged hypoxia. In conclusion, we hypothesize that REST represses transcription of HIF-1α in prolonged hypoxia, thus contributing to the resolution of the HIF-1α response.Science Foundation Ireland grant numnber: (06/CE/B1129)
Decrease of CD68 Synovial Macrophages in Celastrol Treated Arthritic Rats
Get PDFRheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease characterized by cellular infiltration into the joints, hyperproliferation of synovial cells and bone damage. Available treatments for RA only induce remission in around 30% of the patients, have important adverse effects and its use is limited by their high cost. Therefore, compounds that can control arthritis, with an acceptable safety profile and low production costs are still an unmet need. We have shown, in vitro, that celastrol inhibits both IL-1β and TNF, which play an important role in RA, and, in vivo, that celastrol has significant anti-inflammatory properties. Our main goal in this work was to test the effect of celastrol in the number of sublining CD68 macrophages (a biomarker of therapeutic response for novel RA treatments) and on the overall synovial tissue cellularity and joint structure in the adjuvant-induced rat model of arthritis (AIA).FCT fellowship: (SFRH/BPD/92860/2013)
The Araguaia River as an Important Biogeographical Divide for Didelphid Marsupials in Central Brazil
Get PDFThe riverine barrier model suggests that rivers play a significant role in separating widespread organisms into isolated populations. In this study, we used a comparative approach to investigate the phylogeography of 6 didelphid marsupial species in central Brazil. Specifically, we evaluate the role of the mid-Araguaia River in differentiating populations and estimate divergence time among lineages to assess the timing of differentiation of these species, using mitochondrial DNA sequence data. The 6 didelphid marsupials revealed different intraspecific genetic patterns and structure. The 3 larger and more generalist species, Didelphis albiventris, Didelphis marsupialis, and Philander opossum, showed connectivity across the Araguaia River. In contrast the genetic structure of the 3 smaller and specialist species, Gracilinanus agilis, Marmosa (Marmosa) murina, and Marmosa (Micoureus) demerarae was shaped by the mid-Araguaia. Moreover, the split of eastern and western bank populations of the 2 latter species is consistent with the age of Araguaia River sediments formation. We hypothesize that the role of the Araguaia as a riverine barrier is linked to the level of ecological specialization among the 6 didelphid species and differences in their ability to cross rivers or disperse through the associated habitat types.FCT PhD grants: (SFRH/BD/24767/2005, SFRH/BD/23191/2005); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) PhD scholarship; Conselho Nacional de Desenvolvimento Científico e Tenológico (CNPq, Brazil) research grants; European Funds (COMPETE)
To err is robotic, to tolerate immunological: fault detection in multirobot systems
Get PDFFault detection and fault tolerance represent two of the most important and largely unsolved issues in the field of multirobot systems (MRS). Efficient, long-term operation requires an accurate, timely detection, and accommodation of abnormally behaving robots. Most existing approaches to fault-tolerance prescribe a characterization of normal robot behaviours, and train a model to recognize these behaviours. Behaviours unrecognized by the model are consequently labelled abnormal or faulty. MRS employing these models do not transition well to scenarios involving temporal variations in behaviour (e.g., online learning of new behaviours, or in response to environment perturbations). The vertebrate immune system is a complex distributed system capable of learning to tolerate the organism's tissues even when they change during puberty or metamorphosis, and to mount specific responses to invading pathogens, all without the need of a genetically hardwired characterization of normality. We present a generic abnormality detection approach based on a model of the adaptive immune system, and evaluate the approach in a swarm of robots. Our results reveal the robust detection of abnormal robots simulating common electro-mechanical and software faults, irrespective of temporal changes in swarm behaviour. Abnormality detection is shown to be scalable in terms of the number of robots in the swarm, and in terms of the size of the behaviour classification space
Reassessing the Evolutionary History of the 17q21 Inversion Polymorphism
Get PDFA polymorphic inversion that lies on chromosome 17q21 comprises two major haplotype families (H1 and H2) that not only differ in orientation but also in copy-number. Although the processes driving the spread of the inversion-associated lineage (H2) in humans remain unclear, a selective advantage has been proposed for one of its subtypes. Here, we genotyped a large panel of individuals from previously overlooked populations using a custom array with a unique panel of H2-specific single nucleotide polymorphisms and found a patchy distribution of H2 haplotypes in Africa, with North Africans displaying a higher frequency of inverted subtypes, when compared with Sub-Saharan groups. Interestingly, North African H2s were found to be closer to "non-African" chromosomes further supporting that these populations may have diverged more recently from groups outside Africa. Our results uncovered higher diversity within the H2 family than previously described, weakening the hypothesis of a strong selective sweep on all inverted chromosomes and suggesting a rather complex evolutionary history at this locus.FEDER funds: (Operational Programme for Competitiveness Factors—COMPETE); Fundação para a Ciência e a Tecnologia grants: (IF/01262/2014); Programa Operacional Regional do Norte grants: (NORTE-07-0162-FEDER-00018, NORTE-07-0162-FEDER-000067); Quadro de Referência Estratégica Nacional (QREN); EMBO short-term fellowship: (ASFT 520-2013); Spanish MINECO project: (CGL2013-44351-P); Laboratoire d’Excellence (LABEX) TULIP:(ANR-10-LABX-41)
Computational fact checking from knowledge networks
Get PDFTraditional fact checking by expert journalists cannot keep up with the
enormous volume of information that is now generated online. Computational fact
checking may significantly enhance our ability to evaluate the veracity of
dubious information. Here we show that the complexities of human fact checking
can be approximated quite well by finding the shortest path between concept
nodes under properly defined semantic proximity metrics on knowledge graphs.
Framed as a network problem this approach is feasible with efficient
computational techniques. We evaluate this approach by examining tens of
thousands of claims related to history, entertainment, geography, and
biographical information using a public knowledge graph extracted from
Wikipedia. Statements independently known to be true consistently receive
higher support via our method than do false ones. These findings represent a
significant step toward scalable computational fact-checking methods that may
one day mitigate the spread of harmful misinformation.Swiss National Science Foundation fellowship: (142353), Lilly Endowment, the James S. McDonnell Foundation, National Science Foundation grant: (CCF-1101743), Department of Defense grant: (W911NF-12-1-0037)
The importance of iron in pathophysiologic conditions
Get PDFBiological iron is necessary for vital functions and also potentially toxic to the organisms. This dual effect raised the interest of many investigators to study the mechanisms controlling its homeostasis that are altered in many pathologic conditions. Recently the understanding of iron metabolism significantly improved with the discovery of genes responsible for genetic disorders, such as hemochromatosis, the IRE/IRPs machinery and the hepcidin-ferroportin axis, which allowed to elucidate the basis of cellular and systemic iron homeostasis. In addition, these advances disclosed a causal link between deregulation of iron homeostasis, inflammation and oxidative stress, often induced by the iron accumulation that is commonly observed in many pathologic conditions