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At least 775 records · Page 43

Gravitational wave signatures of ab initio two-dimensional core collapse supernova explosion models for 12 – 25 M ⊙ stars

Here, we present the gravitational waveforms computed in ab initio two-dimensional core collapse supernova models evolved with the chimera code for progenitor masses between 12 and 25 M. For all models employ multifrequency neutrino transport in the ray-by-ray approximation, state-of-the-art weak interaction physics, relativistic transport corrections such as the gravitational redshift of neutrinos, two-dimensional hydrodynamics with the commensurate relativistic corrections, Newtonian self-gravity with a general-relativistic monopole correction, and the Lattimer-Swesty equation of state with 220 MeV compressibility, and begin with the most recent Woosley-Heger nonrotating progenitors in this mass range. All of our models exhibit robust explosions. Moreover, our waveforms capture all stages of supernova development: 1) a relatively short and weak prompt signal, 2) a quiescent stage, 3) a strong signal due to convection and standing accretion shock instability activity, 4) termination of active accretion onto the proto-neutron star, and 5) a slowly increasing tail that reaches a saturation value. Fourier decomposition shows that the gravitational wave signals we predict should be observable by AdvLIGO for Galactic events across the range of progenitors considered here. The fundamental limitation of these models is in their imposition of axisymmetry. Further progress will require counterpart three-dimensional models, which are underway.

79 ASTRONOMY AND ASTROPHYSICS↗

The TPR domain of PgaA is a multifunctional scaffold that binds PNAG and modulates PgaB-dependent polymer processing

The synthesis of exopolysaccharides as biofilm matrix components by pathogens is a crucial factor for chronic infections and antibiotic resistance. Many periplasmic proteins involved in polymer processing and secretion in Gram-negative synthase dependent exopolysaccharide biosynthetic systems have been individually characterized. The operons responsible for the production of PNAG, alginate, cellulose and the Pel polysaccharide each contain a gene that encodes an outer membrane associated tetratricopeptide repeat (TPR) domain containing protein. While the TPR domain has been shown to bind other periplasmic proteins, the functional consequences of these interactions for the polymer remain poorly understood. Herein, we show that the C-terminal TPR region of PgaA interacts with the de-N-acetylase domain of PgaB, and increases its deacetylase activity. Additionally, we found that when the two proteins form a complex, the glycoside hydrolase activity of PgaB is also increased. To better understand structure-function relationships we determined the crystal structure of a stable TPR module, which has a conserved groove formed by three repeat motifs. Tryptophan quenching, mass spectrometry analysis and molecular dynamics simulation studies suggest that the crystallized TPR module can bind PNAG/dPNAG via its electronegative groove on the concave surface, and potentially guide the polymer through the periplasm towards the porin for export. Our results suggest a scaffolding role for the TPR domain that combines PNAG/dPNAG translocation with the modulation of its chemical structure by PgaB.

59 BASIC BIOLOGICAL SCIENCES↗

Insights into the physiological and genomic characterization of three bacterial isolates from a highly alkaline, terrestrial serpentinizing system

The terrestrial serpentinite-hosted ecosystem known as “The Cedars” is home to a diverse microbial community persisting under highly alkaline (pH ~ 12) and reducing (Eh < -550 mV) conditions. This extreme environment presents particular difficulties for microbial life, and efforts to isolate microorganisms from The Cedars over the past decade have remained challenging. Herein, we report the initial physiological assessment and/or full genomic characterization of three isolates: Paenibacillus sp. Cedars (‘Paeni-Cedars’), Alishewanella sp. BS5-314 (‘Ali-BS5-314’), and Anaerobacillus sp. CMMVII (‘Anaero-CMMVII’). Paeni-Cedars is a Gram-positive, rod-shaped, mesophilic facultative anaerobe that grows between pH 7–10 (minimum pH tested was 7), temperatures 20–40°C, and 0–3% NaCl concentration. The addition of 10–20 mM CaCl 2 enhanced growth, and iron reduction was observed in the following order, 2-line ferrihydrite > magnetite > serpentinite ~ chromite ~ hematite. Genome analysis identified genes for flavin-mediated iron reduction and synthesis of a bacillibactin-like, catechol-type siderophore. Ali-BS5-314 is a Gram-negative, rod-shaped, mesophilic, facultative anaerobic alkaliphile that grows between pH 10–12 and temperatures 10–40°C, with limited growth observed 1–5% NaCl. Nitrate is used as a terminal electron acceptor under anaerobic conditions, which was corroborated by genome analysis. The Ali-BS5-314 genome also includes genes for benzoate-like compound metabolism. Anaero-CMMVII remained difficult to cultivate for physiological studies; however, growth was observed between pH 9–12, with the addition of 0.01–1% yeast extract. Anaero-CMMVII is a probable oxygen-tolerant anaerobic alkaliphile with hydrogenotrophic respiration coupled with nitrate reduction, as determined by genome analysis. Based on single-copy genes, ANI, AAI and dDDH analyses, Paeni-Cedars and Ali-BS5-314 are related to other species (P. glucanolyticus and A. aestuarii, respectively), and Anaero-CMMVII represents a new species. The characterization of these three isolates demonstrate the range of ecophysiological adaptations and metabolisms present in serpentinite-hosted ecosystems, including mineral reduction, alkaliphily, and siderophore production.

59 BASIC BIOLOGICAL SCIENCES↗

Three-dimensional Features of the Outer Heliosphere Due to Coupling between the Interstellar and Heliospheric Magnetic Field. V. The Bow Wave, Heliospheric Boundary Layer, Instabilities, and Magnetic Reconnection

The heliosphere is formed due to interaction between the solar wind (SW) and local interstellar medium (LISM). The shape and position of the heliospheric boundary, the heliopause, in space depend on the parameters of interacting plasma flows. The interplay between the asymmetrizing effect of the interstellar magnetic field and charge exchange between ions and neutral atoms plays an important role in the SW–LISM interaction. By performing three-dimensional, MHD plasma/kinetic neutral atom simulations, we determine the width of the outer heliosheath—the LISM plasma region affected by the presence of the heliosphere—and analyze quantitatively the distributions in front of the heliopause. It is shown that charge exchange modifies the LISM plasma to such extent that the contribution of a shock transition to the total variation of plasma parameters becomes small even if the LISM velocity exceeds the fast magnetosonic speed in the unperturbed medium. By performing adaptive mesh refinement simulations, we show that a distinct boundary layer of decreased plasma density and enhanced magnetic field should be observed on the interstellar side of the heliopause. We show that this behavior is in agreement with the plasma oscillations of increasing frequency observed by the plasma wave instrument onboard Voyager 1. We also demonstrate that Voyager observations in the inner heliosheath between the heliospheric termination shock and the heliopause are consistent with dissipation of the heliospheric magnetic field. The choice of LISM parameters in this analysis is based on the simulations that fit observations of energetic neutral atoms performed by Interstellar Boundary Explorer .

79 ASTRONOMY AND ASTROPHYSICS↗

Fluoride-Mediated Capture of a Noncovalent Bound State of a Reversible Covalent Enzyme Inhibitor: X-ray Crystallographic Analysis of an Exceptionally Potent [alpha]-Ketoheterocycle Inhibitor of Fatty Acid Amide Hydrolase

Two cocrystal X-ray structures of the exceptionally potent {alpha}-ketoheterocycle inhibitor 1 (K{sub i} = 290 pM) bound to a humanized variant of rat fatty acid amide hydrolase (FAAH) are disclosed, representing noncovalently and covalently bound states of the same inhibitor with the enzyme. Key to securing the structure of the noncovalently bound state of the inhibitor was the inclusion of fluoride ion in the crystallization conditions that is proposed to bind the oxyanion hole precluding inhibitor covalent adduct formation with stabilization of the tetrahedral hemiketal. This permitted the opportunity to detect important noncovalent interactions stabilizing the binding of the inhibitor within the FAAH active site independent of the covalent reaction. Remarkably, noncovalently bound 1 in the presence of fluoride appears to capture the active site in the same 'in action' state with the three catalytic residues Ser241-Ser217-Lys142 occupying essentially identical positions observed in the covalently bound structure of 1, suggesting that this technique of introducing fluoride may have important applications in structural studies beyond inhibiting substrate or inhibitor oxyanion hole binding. Key insights to emerge from the studies include the observations that noncovalently bound 1 binds in its ketone (not gem diol) form, that the terminal phenyl group in the acyl side chain of the inhibitor serves as the key anchoring interaction overriding the intricate polar interactions in the cytosolic port, and that the role of the central activating heterocycle is dominated by its intrinsic electron-withdrawing properties. These two structures are also briefly compared with five X-ray structures of {alpha}-ketoheterocycle-based inhibitors bound to FAAH recently disclosed.

59 BASIC BIOLOGICAL SCIENCES↗

Epitaxial growth of highly-crystalline spinel ferrite thin films on perovskite substrates for all-oxide devices

The potential growth modes for epitaxial growth of Fe 3 O 4 on SrTiO 3 (001) are investigated through control of the energetics of the pulsed-laser deposition growth process (via substrate temperature and laser fluence). We find that Fe 3 O 4 grows epitaxially in three distinct growth modes: 2D-like, island and 3D-to-2D, the last of which is characterized by films that begin growth in an island growth mode before progressing to a 2D growth mode. Films grown in the 2D-like and 3D-to-2D growth modes are atomically flat and partially strained, while films grown in the island growth mode are terminated in islands and fully relaxed. We find that the optimal structural, transport and magnetic properties are obtained for films grown on the 2D-like/3D-to-2D growth regime boundary. The viability for including such thin films in perovskite-based all-oxide devices is demonstrated by growing a Fe 3 O 4 /La 0.7 Sr 0.3 MnO 3 spin valve epitaxially on SrTiO 3 .

Science & Technology - Other Topics↗

Skip residues modulate the structural properties of the myosin rod and guide thick filament assembly

The rod of sarcomeric myosins directs thick filament assembly and is characterized by the insertion of four skip residues that introduce discontinuities in the coiled-coil heptad repeats. We report in this paper that the regions surrounding the first three skip residues share high structural similarity despite their low sequence homology. Near each of these skip residues, the coiled-coil transitions to a nonclose-packed structure inducing local relaxation of the superhelical pitch. Moreover, molecular dynamics suggest that these distorted regions can assume different conformationally stable states. In contrast, the last skip residue region constitutes a true molecular hinge, providing C-terminal rod flexibility. Assembly of myosin with mutated skip residues in cardiomyocytes shows that the functional importance of each skip residue is associated with rod position and reveals the unique role of the molecular hinge in promoting myosin antiparallel packing. By defining the biophysical properties of the rod, the structures and molecular dynamic calculations presented here provide insight into thick filament formation, and highlight the structural differences occurring between the coiled-coils of myosin and the stereotypical tropomyosin. Finally, in addition to extending our knowledge into the conformational and biological properties of coiled-coil discontinuities, the molecular characterization of the four myosin skip residues also provides a guide to modeling the effects of rod mutations causing cardiac and skeletal myopathies.

59 BASIC BIOLOGICAL SCIENCES↗

Evolving Outer Heliosphere: Tracking Solar Wind Transients from 1 au to the VLISM with IBEX and Voyager 1

Abstract Interstellar Boundary Explorer (IBEX) observations of energetic neutral atom (ENA) fluxes from the heliosphere have greatly enriched our understanding of the interaction of the solar wind (SW) with the local interstellar medium (LISM). However, there has been recent controversy surrounding the inability of most ENA models to produce as high an intensity of ∼0.5–6 keV ENAs as IBEX observes at 1 au, especially as a function of time. In our previous study (E. J. Zirnstein et al.), we introduced a new model that utilizes a data-driven magnetohydrodynamic simulation of the SW–LISM interaction to propagate pickup ions through the heliosheath (HS) after they are nonadiabatically heated at the heliospheric termination shock. E. J. Zirnstein et al. only simulated and analyzed IBEX observations from the direction of Voyager 2. In this study, we expand our model to include fluxes from the direction of Voyager 1, as well as in the low-latitude part (middle) of the ribbon (10° below the ecliptic plane). We show that the model results at Voyager 1 are consistent with E. J. Zirnstein et al.’s results at Voyager 2 in terms of a secondary ENA source contribution of ≲20% from both directions. Our results in the middle of the ribbon also reproduce the data, when including a time-dependent secondary ENA source. Finally, we demonstrate with our simulation that three large pressure waves likely merged in the VLISM and were observed by Voyager 1 as “pf2,” while at least one of the wave’s effects in the HS was observed by IBEX as a brief enhancement in ENA flux in early 2016.

79 ASTRONOMY AND ASTROPHYSICS↗

Structural Mechanisms of Allostery and Autoinhibition in JNK Family Kinases

c-Jun N-terminal (JNK) family kinases have a common peptide-docking site used by upstream activating kinases, substrates, scaffold proteins, and phosphatases, where the ensemble of bound proteins determines signaling output. Although there are many JNK structures, little is known about mechanisms of allosteric regulation between the catalytic and peptide-binding sites, and the activation loop, whose phosphorylation is required for catalytic activity. Here, we compare three structures of unliganded JNK3 bound to different peptides. These were compared as a class to structures that differ in binding of peptide, small molecule ligand, or conformation of the kinase activation loop. Peptide binding induced an inhibitory interlobe conformer that was reversed by alterations in the activation loop. Structure class analysis revealed the subtle structural mechanisms for allosteric signaling between the peptide-binding site and activation loop. Biochemical data from isothermal calorimetry, fluorescence energy transfer, and enzyme inhibition demonstrated affinity differences among the three peptides that were consistent with structural observations.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Fireworks on Weather Radar and Camera

High-sensitivity weather radars easily detect nonmeteorological phenomena characterized by weak radar returns. Fireworks are the example presented here. To understand radar observations, an experiment was conducted in which the National Severe Storms Laboratory (NSSL)’s research (3-cm wavelength) dual-polarization radar and a video camera were located at 1 km from fireworks in Norman, Oklahoma. The fireworks from the 4 July 2017 celebration were recorded by both instruments. The experiment is described. Few bursts recorded by the camera are analyzed to obtain the height of the explosion, its maximum diameter, number of stars, and the duration of the visible image. Radar volume scans are examined to characterize the height of the observation, the maximum reflectivity, and its distribution with height. The fireworks location is close to the Terminal Doppler Weather Radar (TDWR) that operates in single polarization at a 5-cm wavelength and monitors hazardous weather over the Oklahoma City airport. A third radar with data from the event is the Weather Surveillance Radar-1988 Doppler (WSR-88D) located in Norman. It has a wavelength of 10 cm and supports technical developments at the Radar Operation Center. Reflectivity factors measured by the three radars are compared to infer the size of dominant scatterers. The polarimetric characteristics of fireworks returns are analyzed. Although these differ from those of precipitation, they are indistinguishable from insect returns. Radar observation of larger fireworks in Fort Worth, Texas, with a WSR-88D is included and compared with the observations of the smaller fireworks in Norman. We expect the detectability of explosions would be similar as of fireworks. Pinpointing locations would be useful to first responders, or air quality forecasters. We note a benefit of fireworks recognition in weather radar data is that it can prevent contamination of precipitation accumulations.

54 ENVIRONMENTAL SCIENCES↗

Structural Insights into the Functional Role of the Hcn Sub-domain of the Receptor-Binding Domain of the Botulinum Neurotoxin Mosaic Serotype C/D

Botulinum neurotoxin (BoNT), the causative agent of the deadly neuroparalytic disease botulism, is the most poisonous protein known for humans. Produced by different strains of the anaerobic bacterium Clostridium botulinum, BoNT effects cellular intoxication via a multistep mechanism executed by the three modules of the activated protein. Endocytosis, the first step of cellular intoxication, is triggered by the ~50 kDa, heavy-chain receptor-binding module (HCR) that is specific for a ganglioside and a protein receptor on neuronal cell surfaces. This dual receptor recognition mechanism between BoNT and the host cell’s membrane is well documented and occurs via specific intermolecular interactions with the C-terminal sub-domain, Hcc, of BoNT-HCR. The N-terminal sub-domain of BoNT-HCR, Hcn, comprises ~50% of BoNT-HCR and adopts a B-sheet jelly roll fold. While suspected in assisting cell surface recognition, no unambiguous function for the Hcn sub-domain in BoNT has been indentified. To obtain insights into the potential function of the Hcn sub-domain in BoNT, the first crystal structure of a BoNT with an organic ligand bound to the Hcn sub-domain has been obtained. Here, we describe the crystal structure of BoNT/CD-HCR determined at 1.70 Å resolution with a tetraethylene glycol (PG4) molecule bound in an hydrophobic cleft between B-strands in the B-sheet jelly fold roll of the Hcn sub-domain. The molecule is completely engulfed in the cleft, making numerous hydrophobic (Y932, S959, W966, and D1042) and hydrophilic (S935, W977, L979, N1013, and I1066) contacts with the protein’s side chain and backbone that may mimic in vivo interactions with the phospholipid membranes on neuronal cell surfaces. A sulfate ion was also observed bound to residues T1176, D1177, K1196, and R1243 in the Hcc sub-domain of BoNT/CD-HCR. In the crystal structure of a similar protein, BoNT/D-HCR, a sialic acid

botulinum neurotoxin↗

The Spectrin-Actin-Based Periodic Cytoskeleton as a Conserved Nanoscale Scaffold and Ruler of the Neural Stem Cell Lineage

Through three-dimensional STORM super-resolution microscopy, we resolve the spectrin-actin-based membrane cytoskeleton of neural stem cells (NSCs) and NSC-derived neurons, astrocytes, and oligodendrocytes. We show that undifferentiated NSCs are capable of forming patches of locally periodic, one-dimensional (1D) membrane cytoskeleton with ~180 nm periodicity. Such periodic structures become increasingly ordered and long-ranging as the NSCs mature into terminally differentiated neuronal and glial cell types, and, during this process, distinct 1D periodic “strips” dominate the flat 2D membranes. Moreover, we report remarkable alignment of the periodic cytoskeletons between abutting cells at axon-axon and axon-oligodendrocyte contacts and identify two adhesion molecules, neurofascin and L1CAM, as candidates to drive this nanoscale alignment. We thus show that a conserved 1D periodic membrane cytoskeletal motif serves as a nanoscale scaffold and ruler to mediate the physical interactions between cell types of the NSC lineage.

59 BASIC BIOLOGICAL SCIENCES↗

The Structure of an As(III) S -Adenosylmethionine Methyltransferase with 3-Coordinately Bound As(III) Depicts the First Step in Catalysis

Arsenic is a ubiquitous environmental toxic substance and a Class 1 human carcinogen. Arsenic methylation by the enzyme As(III) $S$-adenosylmethionine (SAM) methyltransferase (ArsM in microbes or AS3MT in animals) detoxifies As(III) in microbes but transforms it into more toxic and potentially more carcinogenic methylated species in humans. We previously proposed a reaction pathway for ArsM/AS3MT that involves initial 3-coordinate binding of As(III). To date, reported structures have had only 2-coordinately bound trivalent arsenicals. In this work we report a crystal structure of CmArsM from Cyanidioschyzon sp.5508 in which As(III) is 3-coordinately bound to three conserved cysteine residues with a molecule of the product $S$-adenosyl- L -homocysteine bound in the SAM binding site. We propose that this structure represents the first step in the catalytic cycle. In a previously reported SAM-bound structure, a disulfide bond is formed between two conserved cysteine residues. Comparison of these two structures indicates that there is a conformational change in the N-terminal domain of CmArsM that moves a loop to allow formation of the 3-coordinate As(III) binding site. We propose that this conformational change is an initial step in the As(III) SAM methyltransferase catalytic cycle.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Structure of an Odorant-Vinding Protein form the Mosquito Aedes aegypti Suggests a Binding Pocket Covered by a pH-Sensitive

The yellow fever mosquito, Aedes aegypti, is the primary vector for the viruses that cause yellow fever, mostly in tropical regions of Africa and in parts of South America, and human dengue, which infects 100 million people yearly in the tropics and subtropics. A better understanding of the structural biology of olfactory proteins may pave the way for the development of environmentally-friendly mosquito attractants and repellents, which may ultimately contribute to reduction of mosquito biting and disease transmission. Previously, we isolated and cloned a major, female-enriched odorant-binding protein (OBP) from the yellow fever mosquito, AaegOBP1, which was later inadvertently renamed AaegOBP39. We prepared recombinant samples of AaegOBP1 by using an expression system that allows proper formation of disulfide bridges and generates functional OBPs, which are indistinguishable from native OBPs. We crystallized AaegOBP1 and determined its three-dimensional structure at 1.85 {angstrom} resolution by molecular replacement based on the structure of the malaria mosquito OBP, AgamOBP1, the only mosquito OBP structure known to date. The structure of AaegOBP1 (= AaegOBP39) shares the common fold of insect OBPs with six {alpha}-helices knitted by three disulfide bonds. A long molecule of polyethylene glycol (PEG) was built into the electron-density maps identified in a long tunnel formed by a crystallographic dimer of AaegOBP1. Circular dichroism analysis indicated that delipidated AaegOBP1 undergoes a pH-dependent conformational change, which may lead to release of odorant at low pH (as in the environment in the vicinity of odorant receptors). A C-terminal loop covers the binding cavity and this 'lid' may be opened by disruption of an array of acid-labile hydrogen bonds thus explaining reduced or no binding affinity at low pH.

59 BASIC BIOLOGICAL SCIENCES↗

Characterization of individual mouse cerebrospinal fluid proteomes

Analysis of cerebrospinal fluid (CSF) offers key insight into the status of the central nervous system. Characterization of murine CSF proteomes can provide a valuable resource for studying central nervous system injury and disease in animal models. However, the small volume of CSF in mice has thus far limited individual mouse proteome characterization. Through non-terminal CSF extractions in C57Bl/6 mice and high-resolution liquid chromatography-mass spectrometry analysis of individual murine samples, we report the most comprehensive proteome characterization of individual murine CSF to date. Utilizing stringent protein inclusion criteria that required the identification of at least two unique peptides (1% false discovery rate at the peptide level) we identified a total of 566 unique proteins, including 128 proteins from three individual CSF samples that have been previously identified in brain tissue. Our methods and analysis provide a mechanism for individual murine CSF proteome analysis.

Cerebrospinal fluid↗

A Fine-grained Asynchronous Bulk Synchronous parallelism model for PGAS applications

The Partitioned Global Address Space (PGAS) model is well suited for executing irregular applications on cluster-based systems, due to its efficient support for short, one-sided messages. Separately, the actor model has been gaining popularity as a productive asynchronous message-passing approach for distributed objects in enterprise and cloud computing platforms, typically implemented in languages such as Erlang, Scala or Rust. To the best of our knowledge, there has been no past work on using the actor model to deliver both productivity and scalability to irregular PGAS applications with large number of small messages. In this paper, we introduce a new programming system for PGAS applications, in which point-to-point remote operations can be expressed as fine-grained asynchronous actor messages. In our approach, the programmer does not need to worry about programming complexities related to message aggregation and termination detection. Our approach can be viewed as extending the classical Bulk Synchronous Parallelism model with fine-grained asynchronous communications within a phase or superstep. Here, we believe that our approach offers a desirable point in the productivity-performance space for PGAS applications, with more scalable performance and higher productivity relative to past approaches. Specifically, for seven irregular mini-applications from the Bale Kernels and three graph kernels executed using 2048 cores in the NERSC Cori system, our approach shows geometric mean performance improvements of ≥ 20X relative to standard PGAS versions (UPC and OpenSHMEM) while maintaining comparable productivity to those versions.

97 MATHEMATICS AND COMPUTING↗

Architecture of the Mediator head module

Mediator is a key regulator of eukaryotic transcription, connecting activators and repressors bound to regulatory DNA elements with RNA polymerase II (Pol II). In the yeast Saccharomyces cerevisiae, Mediator comprises 25 subunits with a total mass of more than one megadalton (refs 5, 6) and is organized into three modules, called head, middle/arm and tail. Our understanding of Mediator assembly and its role in regulating transcription has been impeded so far by limited structural information. Here we report the crystal structure of the essential Mediator head module (seven subunits, with a mass of 223 kilodaltons) at a resolution of 4.3 angstroms. Our structure reveals three distinct domains, with the integrity of the complex centred on a bundle of ten helices from five different head subunits. An intricate pattern of interactions within this helical bundle ensures the stable assembly of the head subunits and provides the binding sites for general transcription factors and Pol II. Our structural and functional data suggest that the head module juxtaposes transcription factor IIH and the carboxy-terminal domain of the largest subunit of Pol II, thereby facilitating phosphorylation of the carboxy-terminal domain of Pol II. Our results reveal architectural principles underlying the role of Mediator in the regulation of gene expression.

59 BASIC BIOLOGICAL SCIENCES↗