Antonseningram3092

Obtaining this higher level of detail is a step forward that now allows designers to inspect and refine their designs with base-pair level interventions.Radioprotectors for acute injuries caused by large doses of ionizing radiation are vital to national security, public health and future development of humankind. Selleckchem 6-Benzylaminopurine Here, we develop a strategy to explore safe and efficient radioprotectors by combining Hantzsch's reaction, high-throughput methods and polymer chemistry. A water-soluble polymer with low-cytotoxicity and an excellent anti-radiation capability has been achieved. In in vivo experiments, this polymer is even better than amifostine, which is the only approved radioprotector for clinical applications, in effectively protecting zebrafish embryos from fatally large doses of ionizing radiation (80 Gy X-ray). A mechanistic study also reveals that the radioprotective ability of this polymer originates from its ability to efficiently prevent DNA damage due to high doses of radiation. This is an initial attempt to explore polymer radioprotectors via a multi-component reaction. It allows exploiting functional polymers and provides the underlying insights to guide the design of radioprotective polymers.Transcription factor Rme1 is conserved among ascomycetes and regulates meiosis and pseudohyphal growth in Saccharomyces cerevisiae. The genome of the meiosis-defective pathogen Candida albicans encodes an Rme1 homolog that is part of a transcriptional circuitry controlling hyphal growth. Here, we use chromatin immunoprecipitation and genome-wide expression analyses to study a possible role of Rme1 in C. albicans morphogenesis. We find that Rme1 binds upstream and activates the expression of genes that are upregulated during chlamydosporulation, an asexual process leading to formation of large, spherical, thick-walled cells during nutrient starvation. RME1 deletion abolishes chlamydosporulation in three Candida species, whereas its overexpression bypasses the requirement for chlamydosporulation cues and regulators. RME1 expression levels correlate with chlamydosporulation efficiency across clinical isolates. Interestingly, RME1 displays a biphasic pattern of expression, with a first phase independent of Rme1 function and dependent on chlamydospore-inducing cues, and a second phase dependent on Rme1 function and independent of chlamydospore-inducing cues. Our results indicate that Rme1 plays a central role in chlamydospore development in Candida species.The KEOPS complex, which is conserved across archaea and eukaryotes, is composed of four core subunits; Pcc1, Kae1, Bud32 and Cgi121. KEOPS is crucial for the fitness of all organisms examined. In humans, pathogenic mutations in KEOPS genes lead to Galloway-Mowat syndrome, an autosomal-recessive disease causing childhood lethality. Kae1 catalyzes the universal and essential tRNA modification N6-threonylcarbamoyl adenosine, but the precise roles of all other KEOPS subunits remain an enigma. Here we show using structure-guided studies that Cgi121 recruits tRNA to KEOPS by binding to its 3' CCA tail. A composite model of KEOPS bound to tRNA reveals that all KEOPS subunits form an extended tRNA-binding surface that we have validated in vitro and in vivo to mediate the interaction with the tRNA substrate and its modification. These findings provide a framework for understanding the inner workings of KEOPS and delineate why all KEOPS subunits are essential.The fate of subducted CO2 remains the subject of widespread disagreement, with different models predicting either wholesale (up to 99%) decarbonation of the subducting slab or extremely limited carbon loss and, consequently, massive deep subduction of CO2. The fluid history of subducted rocks lies at the heart of this debate rocks that experience significant infiltration by a water-bearing fluid may release orders of magnitude more CO2 than rocks that are metamorphosed in a closed chemical system. Numerical models make a wide range of predictions regarding water mobility, and further progress has been limited by a lack of direct observations. Here we present a comprehensive field-based study of decarbonation efficiency in a subducting slab (Cyclades, Greece), and show that ~40% to ~65% of the CO2 in subducting crust is released via metamorphic decarbonation reactions at forearc depths. This result precludes extensive deep subduction of most CO2 and suggests that the mantle has become more depleted in carbon over geologic time.Using Hi-C, promoter-capture Hi-C (pCHi-C), and other genome-wide approaches in skeletal muscle progenitors that inducibly express a master transcription factor, Pax7, we systematically characterize at high-resolution the spatio-temporal re-organization of compartments and promoter-anchored interactions as a consequence of myogenic commitment and differentiation. We identify key promoter-enhancer interaction motifs, namely, cliques and networks, and interactions that are dependent on Pax7 binding. Remarkably, Pax7 binds to a majority of super-enhancers, and together with a cadre of interacting transcription factors, assembles feed-forward regulatory loops. During differentiation, epigenetic memory and persistent looping are maintained at a subset of Pax7 enhancers in the absence of Pax7. We also identify and functionally validate a previously uncharacterized Pax7-bound enhancer hub that regulates the essential myosin heavy chain cluster during skeletal muscle cell differentiation. Our studies lay the groundwork for understanding the role of Pax7 in orchestrating changes in the three-dimensional chromatin conformation in muscle progenitors.Expanded porphyrins have received considerable attention due to their unique optical, electrochemical and coordination properties. Here, we report benzene- and pyridine-incorporated octaphyrins(1.1.0.0.1.1.0.0), which are synthesized through Suzuki-Miyaura coupling of α,α'-diboryltripyrrane with m-dibromobenzene and 2,6-dibromopyridine, respectively, and subsequent oxidation with 2,3-dicyano-5,6-dichlorobenzoquinone. Both octaphyrins are nonaromatic and take on dumbbell structures. Upon treatment with Pd(OOCCH3)2, the benzene-incorporated one gives a Ci symmetric NNNC coordinated bis-PdII complex but the pyridine incorporated one gives Ci and Cs symmetric NNNC coordinated bis-PdII complexes along with an NNNN coordinated bis-PdII complex bearing a transannular C-C bond between the pyrrole α-positions. In addition, these two pyridine-containing NNNC PdII complexes undergo trifluoroacetic acid-induced clean interconversion.