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Low-frequency normal modes that describe allosteric transitions in biological nanomachines are robust to sequence variations

Zheng, Wenjun; Brooks, Bernard R.; Thirumalai, D.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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By representing the high-resolution crystal structures of a number of enzymes using the elastic network model, it has been shown that only a few low-frequency normal modes are needed to describe the large-scale domain movements that are triggered by ligand binding. Here we explore a link between the nearly invariant nature of the modes that describe functional dynamics at the mesoscopic level and the large evolutionary sequence variations at the residue level. By using a structural perturbation method (SPM), which probes the residue-specific response to perturbations (or mutations), we identify a sparse network of strongly conserved residues that transmit allosteric signals in three structurally unrelated biological nanomachines, namely, DNA polymerase, myosin motor, and the Escherichia coli chaperonin. Based on the response of every mode to perturbations, which are generated by interchanging specific sequence pairs in a multiple sequence alignment, we show that the functionally relevant low-frequency modes are most robust to sequence variations. Our work shows that robustness of dynamical modes at the mesoscopic level is encoded in the structure through a sparse network of residues that transmit allosteric signals.

Plant-derived anti-Lewis Y mAb exhibits biological activities for efficient immunotherapy against human cancer cells

Brodzik, Robert; Glogowska, Magdalena; Bandurska, Katarzyna; Okulicz, Monika; Deka, Deepali; Ko, Kisung; van der Linden, Joke; Leusen, Jeanette H. W.; Pogrebnyak, Natalia; Golovkin, Maxim; Steplewski, Zenon; Koprowski, Hilary
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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Although current demands for therapeutic mAbs are growing quickly, production methods to date, including in vitro mammalian tissue culture and transgenic animals, provide only limited quantities at high cost. Several tumor-associated antigens in tumor cells have been identified as targets for therapeutic mAbs. Here we describe the production of mAb BR55-2 (IgG2a) in transgenic plants that recognizes the nonprotein tumor-associated antigen Lewis Y oligosaccharide overexpressed in human carcinomas, particularly breast and colorectal cancers. Heavy and light chains of mAb BR55-2 were expressed separately and assembled in plant cells of low-alkaloid tobacco transgenic plants (Nicotiana tabacum cv. LAMD609). Expression levels of plant-derived mAb (mAbP) were high (30 mg/kg of fresh leaves) in T1 generation plants. Like the mammalian-derived mAbM, the plant mAbP bound specifically to both SK-BR3 breast cancer cells and SW948 colorectal cancer cells. The Fc domain of both mAbP and mAbM showed the similar binding to FcγRI receptor (CD64). Comparable levels of cytotoxicity against SK-BR3 cells were also shown for both mAbs in antibody-dependent cell-mediated cytotoxicity assay. Furthermore, plant-derived BR55-2 efficiently inhibited SW948 tumor growth xenografted in nude mice. Altogether...

Biological versus nonbiological older brothers and men’s sexual orientation

Bogaert, Anthony F.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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The most consistent biodemographic correlate of sexual orientation in men is the number of older brothers (fraternal birth order). The mechanism underlying this effect remains unknown. In this article, I provide a direct test pitting prenatal against postnatal (e.g., social/rearing) mechanisms. Four samples of homosexual and heterosexual men (total n = 944), including one sample of men raised in nonbiological and blended families (e.g., raised with half- or step-siblings or as adoptees) were studied. Only biological older brothers, and not any other sibling characteristic, including nonbiological older brothers, predicted men’s sexual orientation, regardless of the amount of time reared with these siblings. These results strongly suggest a prenatal origin to the fraternal birth-order effect.

Intracellular IL-1α-binding proteins contribute to biological functions of endogenous IL-1α in systemic sclerosis fibroblasts

Kawaguchi, Yasushi; Nishimagi, Emi; Tochimoto, Akiko; Kawamoto, Manabu; Katsumata, Yasuhiro; Soejima, Makoto; Kanno, Tokiko; Kamatani, Naoyuki; Hara, Masako
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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The aberrant production of precursor IL-1α (pre-IL-1α) in skin fibroblasts that are derived from systemic sclerosis (SSc) is associated with the induction of IL-6 and procollagen, which contributes to the fibrosis of SSc. However, little is understood about how intracellular pre-IL-1α regulates the expression of the other molecules in fibroblasts. We report here that pre-IL-1α can form a complex with IL-1α-binding proteins that is translocated into the nuclei of fibroblasts. Immunoprecipitation that used anti-human IL-1α Ab and 35S-labeled nuclear extracts of fibroblasts showed three specific bands (≈31, 35, and 65 kDa). The 31-kDa molecule was identified as pre-IL-1α, and the 35- and 65-kDa molecules might be pre-IL-1α-binding proteins. A partial sequencing for the 10 aa from the N-terminals of the molecules showed 100% homology for HAX-1 (HS1-associated protein X-1) and IL-1 receptor type II (IL-1RII). Suppression of the genes of HAX-1 or IL-1RII induced the inhibitory effects of IL-1 signal transduction, including production of IL-6 and procollagen, by fibroblasts. In particular, pre-IL-1α was not translocated into the nucleus by an inhibition of HAX-1. These findings reveal that nuclear localization of pre-IL-1α depends on the binding to HAX-1 and that biological activities might be elicited by the binding to both HAX-1 and IL-1RII in SSc fibroblasts.

Localized proton microcircuits at the biological membrane–water interface

Brändén, Magnus; Sandén, Tor; Brzezinski, Peter; Widengren, Jerker
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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Cellular processes such as nerve conduction, energy metabolism, and import of nutrients into cells all depend on transport of ions across biological membranes through specialized membrane-spanning proteins. Understanding these processes at a molecular level requires mechanistic insights into the interaction between these proteins and the membrane itself. To explore the role of the membrane in ion translocation we used an approach based on fluorescence correlation spectroscopy. Specifically, we investigated exchange of protons between the water phase and the membrane surface, as well as diffusion of protons along membrane surfaces, at a single-molecule level. We show that the lipid head groups collectively act as a proton-collecting antenna, dramatically accelerating proton uptake from water to a membrane-anchored proton acceptor. Furthermore, the results show that proton transfer along the surface can be significantly faster than that between the lipid head groups and the surrounding water phase. Thus, ion translocation across membranes and between the different membrane protein components is a complex interplay between the proteins and the membrane itself, where the membrane acts as a proton-conducting link between membrane-spanning proton transporters.

Proteomics of specific treatment-related alterations in Fabry disease: A strategy to identify biological abnormalities

Moore, David F.; Krokhin, Oleg V.; Beavis, Ronald C.; Ries, Markus; Robinson, Chevalia; Goldin, Ehud; Brady, Roscoe O.; Wilkins, John A.; Schiffmann, Raphael
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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Fabry disease is inherited as an X-linked disorder secondary to deficiency of α-galactosidase A, resulting in abnormal metabolism of substances containing α-d-galactosyl moieties. As a consequence, a multisystem disorder develops, culminating in strokes, progressive renal, and cardiac dysfunction. Signs and symptoms of Fabry disease become manifest in childhood, but diagnosis is often delayed. Thirteen children with Fabry disease (age range, 6.5–17 years) were studied as part of a 6-month open-label study of enzyme replacement therapy (ERT) with agalsidase alfa. Paired serum samples were drawn at the start of the study and after 6 months of ERT. Global protein changes in paired samples were compared by using differential stable isotope labeling of peptide lysine residues with O-methylisourea and subsequent nanoHPLC–tandem MS. Statistically significant decreases were observed for five proteins following ERT: α2-HS glycoprotein, vitamin D-binding protein, transferrin, Ig-α-2 C chain, and α-2-antiplasmin. The presence of low levels of α-2-antiplasmin and plasminogen was confirmed by alternate means in 34 consecutive patients, including four of five ERT-naïve subjects. Decreased α-2-antiplasmin was associated with a parallel increase in circulating VEGF. Soluble VEGF receptor-2 was significantly elevated in plasma of patients compared with pediatric controls and decreased with ERT. These results suggest previously unknown abnormalities of fibrinolysis and angiogenesis factors in Fabry disease. We demonstrated the feasibility of identifying treatment-specific alterations in a small number of subjects that point to previously unsuspected disease-related biological abnormalities.

Starch grain evidence for the preceramic dispersals of maize and root crops into tropical dry and humid forests of Panama

Dickau, Ruth; Ranere, Anthony J.; Cooke, Richard G.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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The Central American isthmus was a major dispersal route for plant taxa originally brought under cultivation in the domestication centers of southern Mexico and northern South America. Recently developed methodologies in the archaeological and biological sciences are providing increasing amounts of data regarding the timing and nature of these dispersals and the associated transition to food production in various regions. One of these methodologies, starch grain analysis, recovers identifiable microfossils of economic plants directly off the stone tools used to process them. We report on new starch grain evidence from Panama demonstrating the early spread of three important New World cultigens: maize (Zea mays), manioc (Manihot esculenta), and arrowroot (Maranta arundinacea). Maize starch recovered from stone tools at a site located in the Pacific lowlands of central Panama confirms previous archaeobotanical evidence for the use of maize there by 7800–7000 cal BP. Starch evidence from preceramic sites in the less seasonal, humid premontane forests of Chiriquí province, western Panama, shows that maize and root crops were present by 7400–5600 cal BP, several millennia earlier than previously documented. Several local starchy resources...

Coupling of protein and hydration-water dynamics in biological membranes

Wood, K.; Plazanet, M.; Gabel, F.; Kessler, B.; Oesterhelt, D.; Tobias, D. J.; Zaccai, G.; Weik, M.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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The dynamical coupling between proteins and their hydration water is important for the understanding of macromolecular function in a cellular context. In the case of membrane proteins, the environment is heterogeneous, composed of lipids and hydration water, and the dynamical coupling might be more complex than in the case of the extensively studied soluble proteins. Here, we examine the dynamical coupling between a biological membrane, the purple membrane (PM), and its hydration water by a combination of elastic incoherent neutron scattering, specific deuteration, and molecular dynamics simulations. Examining completely deuterated PM, hydrated in H2O, allowed the direct experimental exploration of water dynamics. The study of natural abundance PM in D2O focused on membrane dynamics. The temperature-dependence of atomic mean-square displacements shows inflections at 120 K and 260 K for the membrane and at 200 K and 260 K for the hydration water. Because transition temperatures are different for PM and hydration water, we conclude that ps–ns hydration water dynamics are not directly coupled to membrane motions on the same time scale at temperatures <260 K. Molecular-dynamics simulations of hydrated PM in the temperature range from 100 to 296 K revealed an onset of hydration-water translational diffusion at ≈200 K...

Alternative translation of osteopontin generates intracellular and secreted isoforms that mediate distinct biological activities in dendritic cells

Shinohara, Mari L.; Kim, Hye-Jung; Kim, June-Ho; Garcia, Virgilio A.; Cantor, Harvey
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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Osteopontin (Opn) contributes to diverse biological processes that include immune responses, vascularization, and bone formation. Until recently, studies describing the activities of Opn have focused on the cytokine-like properties of the secreted protein. Here, we show that alternative translation of a single Opn mRNA species generates a secreted and intracellular isoform. Utilization of a 5′ canonical translation start site generates a protein that includes an N-terminal signal sequence allowing targeting to secretory vesicles and cytokine secretion, whereas usage of a downstream start site generates a shortened protein that lacks the N-terminal signal sequence and localizes mainly to cytoplasm. The coordinated action of these Opn gene products regulates the functional phenotype of subsets of dendritic cells.

Brain systems mediating semantic and syntactic processing in deaf native signers: Biological invariance and modality specificity

Capek, Cheryl M.; Grossi, Giordana; Newman, Aaron J.; McBurney, Susan L.; Corina, David; Roeder, Brigitte; Neville, Helen J.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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Studies of written and spoken language suggest that nonidentical brain networks support semantic and syntactic processing. Event-related brain potential (ERP) studies of spoken and written languages show that semantic anomalies elicit a posterior bilateral N400, whereas syntactic anomalies elicit a left anterior negativity, followed by a broadly distributed late positivity. The present study assessed whether these ERP indicators index the activity of language systems specific for the processing of aural-oral language or if they index neural systems underlying any natural language, including sign language. The syntax of a signed language is mediated through space. Thus the question arises of whether the comprehension of a signed language requires neural systems specific for this kind of code. Deaf native users of American Sign Language (ASL) were presented signed sentences that were either correct or that contained either a semantic or a syntactic error (1 of 2 types of verb agreement errors). ASL sentences were presented at the natural rate of signing, while the electroencephalogram was recorded. As predicted on the basis of earlier studies, an N400 was elicited by semantic violations. In addition, signed syntactic violations elicited an early frontal negativity and a later posterior positivity. Crucially...

Biological and immunological characteristics of hepatitis E virus-like particles based on the crystal structure

Yamashita, Tetsuo; Mori, Yoshio; Miyazaki, Naoyuki; Cheng, R. Holland; Yoshimura, Masato; Unno, Hideaki; Shima, Ryoichi; Moriishi, Kohji; Tsukihara, Tomitake; Li, Tian Cheng; Takeda, Naokazu; Miyamura, Tatsuo; Matsuura, Yoshiharu
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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Hepatitis E virus (HEV) is a causative agent of acute hepatitis. The crystal structure of HEV-like particles (HEV-LP) consisting of capsid protein was determined at 3.5-Å resolution. The capsid protein exhibited a quite different folding at the protruding and middle domains from the members of the families of Caliciviridae and Tombusviridae, while the shell domain shared the common folding. Tyr-288 at the 5-fold axis plays key roles in the assembly of HEV-LP, and aromatic amino acid residues are well conserved among the structurally related viruses. Mutational analyses indicated that the protruding domain is involved in the binding to the cells susceptive to HEV infection and has some neutralization epitopes. These structural and biological findings are important for understanding the molecular mechanisms of assembly and entry of HEV and also provide clues in the development of preventive and prophylactic measures for hepatitis E.

Evidence for biological nitrification inhibition in Brachiaria pastures

Subbarao, G. V.; Nakahara, K.; Hurtado, M. P.; Ono, H.; Moreta, D. E.; Salcedo, A. F.; Yoshihashi, A. T.; Ishikawa, T.; Ishitani, M.; Ohnishi-Kameyama, M.; Yoshida, M.; Rondon, M.; Rao, I. M.; Lascano, C. E.; Berry, W. L.; Ito, O.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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Nitrification, a key process in the global nitrogen cycle that generates nitrate through microbial activity, may enhance losses of fertilizer nitrogen by leaching and denitrification. Certain plants can suppress soil-nitrification by releasing inhibitors from roots, a phenomenon termed biological nitrification inhibition (BNI). Here, we report the discovery of an effective nitrification inhibitor in the root-exudates of the tropical forage grass Brachiaria humidicola (Rendle) Schweick. Named “brachialactone,” this inhibitor is a recently discovered cyclic diterpene with a unique 5-8-5-membered ring system and a γ-lactone ring. It contributed 60–90% of the inhibitory activity released from the roots of this tropical grass. Unlike nitrapyrin (a synthetic nitrification inhibitor), which affects only the ammonia monooxygenase (AMO) pathway, brachialactone appears to block both AMO and hydroxylamine oxidoreductase enzymatic pathways in Nitrosomonas. Release of this inhibitor is a regulated plant function, triggered and sustained by the availability of ammonium (NH4+) in the root environment. Brachialactone release is restricted to those roots that are directly exposed to NH4+. Within 3 years of establishment, Brachiaria pastures have suppressed soil nitrifier populations (determined as amoA genes; ammonia-oxidizing bacteria and ammonia-oxidizing archaea)...

Origin and temperature dependence of radiation damage in biological samples at cryogenic temperatures

Meents, Alke; Gutmann, Sascha; Wagner, Armin; Schulze-Briese, Clemens
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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Radiation damage is the major impediment for obtaining structural information from biological samples by using ionizing radiation such as x-rays or electrons. The knowledge of underlying processes especially at cryogenic temperatures is still fragmentary, and a consistent mechanism has not been found yet. By using a combination of single-crystal x-ray diffraction, small-angle scattering, and qualitative and quantitative radiolysis experiments, we show that hydrogen gas, formed inside the sample during irradiation, rather than intramolecular bond cleavage between non-hydrogen atoms, is mainly responsible for the loss of high-resolution information and contrast in diffraction experiments and microscopy. The experiments that are presented in this paper cover a temperature range between 5 and 160 K and reveal that the commonly used temperature in x-ray crystallography of 100 K is not optimal in terms of minimizing radiation damage and thereby increasing the structural information obtainable in a single experiment. At 50 K, specific radiation damage to disulfide bridges is reduced by a factor of 4 compared to 100 K, and samples can tolerate a factor of 2.6 and 3.9 higher dose, as judged by the increase of Rfree values of elastase and cubic insulin crystals...

Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs

Hanna, Jacob; Cheng, Albert W.; Saha, Krishanu; Kim, Jongpil; Lengner, Christopher J.; Soldner, Frank; Cassady, John P.; Muffat, Julien; Carey, Bryce W.; Jaenisch, Rudolf
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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Human and mouse embryonic stem cells (ESCs) are derived from blastocyst-stage embryos but have very different biological properties, and molecular analyses suggest that the pluripotent state of human ESCs isolated so far corresponds to that of mouse-derived epiblast stem cells (EpiSCs). Here we rewire the identity of conventional human ESCs into a more immature state that extensively shares defining features with pluripotent mouse ESCs. This was achieved by ectopic induction of Oct4, Klf4, and Klf2 factors combined with LIF and inhibitors of glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase (ERK1/2) pathway. Forskolin, a protein kinase A pathway agonist which can induce Klf4 and Klf2 expression, transiently substitutes for the requirement for ectopic transgene expression. In contrast to conventional human ESCs, these epigenetically converted cells have growth properties, an X-chromosome activation state (XaXa), a gene expression profile, and a signaling pathway dependence that are highly similar to those of mouse ESCs. Finally, the same growth conditions allow the derivation of human induced pluripotent stem (iPS) cells with similar properties as mouse iPS cells. The generation of validated “naïve” human ESCs will allow the molecular dissection of a previously undefined pluripotent state in humans and may open up new opportunities for patient-specific...

Disentangling the role of environmental and human pressures on biological invasions across Europe

Pyšek, Petr; Jarošík, Vojtěch; Hulme, Philip E.; Kühn, Ingolf; Wild, Jan; Arianoutsou, Margarita; Bacher, Sven; Chiron, Francois; Didžiulis, Viktoras; Essl, Franz; Genovesi, Piero; Gherardi, Francesca; Hejda, Martin; Kark, Salit; Lambdon, Philip W.;
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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The accelerating rates of international trade, travel, and transport in the latter half of the twentieth century have led to the progressive mixing of biota from across the world and the number of species introduced to new regions continues to increase. The importance of biogeographic, climatic, economic, and demographic factors as drivers of this trend is increasingly being realized but as yet there is no consensus regarding their relative importance. Whereas little may be done to mitigate the effects of geography and climate on invasions, a wider range of options may exist to moderate the impacts of economic and demographic drivers. Here we use the most recent data available from Europe to partition between macroecological, economic, and demographic variables the variation in alien species richness of bryophytes, fungi, vascular plants, terrestrial insects, aquatic invertebrates, fish, amphibians, reptiles, birds, and mammals. Only national wealth and human population density were statistically significant predictors in the majority of models when analyzed jointly with climate, geography, and land cover. The economic and demographic variables reflect the intensity of human activities and integrate the effect of factors that directly determine the outcome of invasion such as propagule pressure...

Correct biological timing in Arabidopsis requires multiple light-signaling pathways

Dalchau, Neil; Hubbard, Katharine E.; Robertson, Fiona C.; Hotta, Carlos T.; Briggs, Helen M.; Stan, Guy-Bart; Gonçalves, Jorge M.; Webb, Alex A. R.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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Circadian oscillators provide rhythmic temporal cues for a range of biological processes in plants and animals, enabling anticipation of the day/night cycle and enhancing fitness-associated traits. We have used engineering models to understand the control principles of a plant’s response to seasonal variation. We show that the seasonal changes in the timing of circadian outputs require light regulation via feed-forward loops, combining rapid light-signaling pathways with entrained circadian oscillators. Linear time-invariant models of circadian rhythms were computed for 3,503 circadian-regulated genes and for the concentration of cytosolic-free calcium to quantify the magnitude and timing of regulation by circadian oscillators and light-signaling pathways. Bioinformatic and experimental analysis show that rapid light-induced regulation of circadian outputs is associated with seasonal rephasing of the output rhythm. We identify that external coincidence is required for rephasing of multiple output rhythms, and is therefore important in general phase control in addition to specific photoperiod-dependent processes such as flowering and hypocotyl elongation. Our findings uncover a fundamental design principle of circadian regulation...

Episodic radiations in the fly tree of life

Wiegmann, Brian M.; Trautwein, Michelle D.; Winkler, Isaac S.; Barr, Norman B.; Kim, Jung-Wook; Lambkin, Christine; Bertone, Matthew A.; Cassel, Brian K.; Bayless, Keith M.; Heimberg, Alysha M.; Wheeler, Benjamin M.; Peterson, Kevin J.; Pape, Thomas; Sinc
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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Flies are one of four superradiations of insects (along with beetles, wasps, and moths) that account for the majority of animal life on Earth. Diptera includes species known for their ubiquity (Musca domestica house fly), their role as pests (Anopheles gambiae malaria mosquito), and their value as model organisms across the biological sciences (Drosophila melanogaster). A resolved phylogeny for flies provides a framework for genomic, developmental, and evolutionary studies by facilitating comparisons across model organisms, yet recent research has suggested that fly relationships have been obscured by multiple episodes of rapid diversification. We provide a phylogenomic estimate of fly relationships based on molecules and morphology from 149 of 157 families, including 30 kb from 14 nuclear loci and complete mitochondrial genomes combined with 371 morphological characters. Multiple analyses show support for traditional groups (Brachycera, Cyclorrhapha, and Schizophora) and corroborate contentious findings, such as the anomalous Deuterophlebiidae as the sister group to all remaining Diptera. Our findings reveal that the closest relatives of the Drosophilidae are highly modified parasites (including the wingless Braulidae) of bees and other insects. Furthermore...

Dynamics and biological relevance of DNA demethylation in Arabidopsis antibacterial defense

Yu, Agnès; Lepère, Gersende; Jay, Florence; Wang, Jingyu; Bapaume, Laure; Wang, Yu; Abraham, Anne-Laure; Penterman, Jon; Fischer, Robert L.; Voinnet, Olivier; Navarro, Lionel
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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DNA methylation is an epigenetic mark that silences transposable elements (TEs) and repeats. Whereas the establishment and maintenance of DNA methylation are relatively well understood, little is known about their dynamics and biological relevance in plant and animal innate immunity. Here, we show that some TEs are demethylated and transcriptionally reactivated during antibacterial defense in Arabidopsis. This effect is correlated with the down-regulation of key transcriptional gene silencing factors and is partly dependent on an active demethylation process. DNA demethylation restricts multiplication and vascular propagation of the bacterial pathogen Pseudomonas syringae in leaves and, accordingly, some immune-response genes, containing repeats in their promoter regions, are negatively regulated by DNA methylation. This study provides evidence that DNA demethylation is part of a plant-induced immune response, potentially acting to prime transcriptional activation of some defense genes linked to TEs/repeats.

Polaro–cryptic mirror of the lookdown as a biological model for open ocean camouflage

Brady, Parrish C.; Travis, Kort A.; Maginnis, Tara; Cummings, Molly E.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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With no object to hide behind in 3D space, the open ocean represents a challenging environment for camouflage. Conventional strategies for reflective crypsis (e.g., standard mirror) are effective against axially symmetric radiance fields associated with high solar altitudes, yet ineffective against asymmetric polarized radiance fields associated with low solar inclinations. Here we identify a biological model for polaro–crypsis. We measured the surface-reflectance Mueller matrix of live open ocean fish (lookdown, Selene vomer) and seagrass-dwelling fish (pinfish, Lagodon rhomboides) using polarization-imaging and modeling polarization camouflage for the open ocean. Lookdowns occupy the minimization basin of our polarization-contrast space, while pinfish and standard mirror measurements exhibit higher contrast values than optimal. The lookdown reflective strategy achieves significant gains in polaro–crypsis (up to 80%) in comparison with nonpolarization sensitive strategies, such as a vertical mirror. Lookdowns achieve polaro–crypsis across solar altitudes by varying reflective properties (described by 16 Mueller matrix elements mij) with incident illumination. Lookdowns preserve reflected polarization aligned with principle axes (dorsal–ventral and anterior–posterior...

Implementation of cell-free biological networks at steady state

Niederholtmeyer, Henrike; Stepanova, Viktoria; Maerkl, Sebastian J.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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Transcription and translation can be performed in vitro, outside of cells, allowing the assembly of artificial genetic networks. This bottom-up approach to engineering biological networks in a completely defined and minimal environment is instructive to define the rules and limitations of network construction. It is, however, still challenging to implement complex genetic networks in vitro because the reactions are usually performed in a batch format, where reaction products accumulate and synthesis rates decline over time. Here, we addressed this problem by developing a microfluidic device to perform in vitro transcription and translation reactions in continuous mode, where synthesis rates stay constant. This allowed us to build and implement a genetic oscillator that showed sustained oscillations for extended periods of times.