The F-type 5′ motif of mouse L1 elements: a major class of L1 termini similar to the A-type in organization but unrelated in sequence

It has previously been shown that the L1 family in the mouse (L1Md) contains two alternative 5' ends called the A- and F-type sequences (1,2). We show here that the F-type element is a major class of murine L1 elements and report on the details of organization of the 5' motif of these F-type elements. Although the A- and F-type 5' sequences share no detectable sequence homology the organization of an F-type 5' end is strikingly similar to that of an A-type. That is, the F-type 5' sequences consist of a tandem array of a small number of 206 bp monomers while the A-type 5' motif consists of a tandem array of 208 bp monomers. All of the A-type elements characterized to date have a truncated monomer at the 5' end of the array. Many of the F-type elements are also terminated at the 5' end by a truncated copy but unlike the A-type elements some F-type elements terminate with a monomer which is within a few nucleotides of being complete. In addition the F-type consensus sequence, in contrast to the A-type sequence, shows homology (70%) to the body of the L1Md starting at the position where the monomer joins the rest of the L1 element

The diagonal-traverse homology search algorithm for locating similarities between two sequences

We present a fast computer algorithm for finding homology between two DNA sequences. It generates a two-dimensional display in which a diagonal string of dots represents a stretch of homology between the two sequences. Our algorithm performs the search very rapidly, and has no internal data storage requirement except for the sequences themselves. These characteristics make it particularly well suited for execution on microcomputers. Without slowing execution, the matching criterion can be that a specified fraction of contiguous bases must be identical. Even with gapped sequences, we have found large search windows to be surprisingly good for detecting poor homologies with nearly complete background suppression. A diagonal search pattern is used that reports the finds in a compact and logically ordered form. A simple and rapid plotting algorithm for unsophisticated printers is also reported

Locations of three repetitive sequence families found in BALB/c adult β-globin clones

Three different repeat sequences have been mapped within the cloned EcoRI fragments that Contain the adult β-globin genes from the BALB/c (Hd

Dynamic Coupling and Allosteric Behavior in a Nonallosteric Protein †

Long-range intraprotein interactions give rise to many important protein behaviors. Understanding how energy is transduced through protein structures to either transmit a signal or elicit conformational changes is therefore a current challenge in structural biology. In an effort to understand such linkages, multiple V→A mutations were made in the small globular protein eglin c. The physical responses, as mapped by NMR spin relaxation, residual dipolar couplings (RDCs), and scalar couplings, illustrate that the interior of this non-allosteric protein forms a dynamic network and that local perturbations are transmitted as dynamic and structural changes to distal sites as far as 16 Å away. Two basic types of propagation responses were observed: contiguous pathways of enhanced (attenuated) dynamics with no change in structure; and dispersed (non-contiguous) changes in methyl rotation rates that appear to result from subtle deformation of backbone structure. In addition, energy transmission is found to be unidirectional. In one mutant, an allosteric conformational change of a side chain is seen in the context of a pathway of propagated changes in ps-ns dynamics. The observation of so many long-range interactions in a small, rigid system lends experimental weight to the idea that all well-folded proteins inherently possess allosteric features [Gunasekaran et al. (2004) Proteins 57, 433−443], and that dynamics are a rich source of information for mapping and gaining mechanistic insight into communication pathways in individual proteins

The L1Md long interspersed repeat family in the mouse: almost all examples are truncated at one end

Caractérisation d'un grand élément répétitif détecté en sept localisations différentes dans le locus globine β de la souris Balb/C. Cette répétition possède la même extrémité de l'élément conservé alors que l'autre extrémité se termine en un point différent chez chaque membre de cette famille de répétitions

Mutational analysis of human immunodeficiency virus type 1 protease suggests functional homology with aspartic proteinases.

Processing of the retroviral gag and pol gene products is mediated by a viral protease. Bacterial expression systems have been developed which permit genetic analysis of the human immunodeficiency virus type 1 protease as measured by cleavage of the pol protein precursor. Deletion analysis of the pol reading frame locates the sequences required to encode a protein with appropriate proteolytic activity near the left end of the pol reading frame but largely outside the gag-pol overlap region, which is at the extreme left end of pol. Most missense mutations within an 11-amino-acid domain highly conserved among retroviral proteases and with sequence similarity to the active site of aspartic proteinases abolish appropriate processing, suggesting that the retrovirus proteases share a catalytic mechanism with aspartic proteinases. Substitution of the amino acids flanking the scissile bond at three of the processing sites encoded by pol demonstrates distinct sequence requirements for cleavage at these different sites. The inclusion of a charged amino acid at the processing site blocks cleavage. A subset of these substitutions also inhibits processing at the nonmutated sites

Detection of Native-State Nonadditivity in Double Mutant Cycles via Hydrogen Exchange

Proteins have evolved to exploit long-range structural and dynamic effects as a means of regulating function. Understanding communication between sites in proteins is therefore vital to our comprehension of such phenomena as allostery, catalysis, and ligand binding/ejection. Double mutant cycle analysis has long been used to determine the existence of communication between pairs of sites—proximal or distal—in proteins. Typically, non-additivity (or “thermodynamic coupling”) is measured from global transitions in concert with a single probe. Here, we have applied the atomic resolution of NMR in tandem with native-state hydrogen exchange (HX) to probe the structure/energy landscape for information transduction between a large number of distal sites in a protein. Considering the event of amide proton exchange as an energetically quantifiable structural perturbation, m n-dimensional cycles can be constructed from mutation of n-1 residues, where m is the number of residues for which HX data is available. Thus, efficient mapping of a large number of couplings is made possible. We have applied this technique to one additive and two non-additive double mutant cycles in a model system, eglin c. We find heterogeneity of HX-monitored couplings for each cycle, yet, averaging results in strong agreement with traditionally measured values. Furthermore, long-range couplings observed at locally exchanging residues indicate that the basis for communication can occur within the native state ensemble, a conclusion which is not apparent from traditional measurements. We propose that higher-order couplings can be obtained and show that such couplings provide a mechanistic basis for understanding lower-order couplings, via “spheres of perturbation”. The method is presented as an additional tool for identifying a large number of couplings with greater coverage of the protein of interest

Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA

A record fuel hot-spot pressure P[subscript hs] = 56±7  Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium–tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility, these implosions achieved a Lawson parameter ∼60% of the value required for ignition [A. Bose et al., Phys. Rev. E 93, LM15119ER (2016)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure is approximately 40% lower. Three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.United States. Department of Energy (DE-NA0001944

Cryogneic-Target Performance and Implosion Physics Studies on OMEGA

Recent progress in direct-drive cryogenic implosions on the OMEGA Laser Facility [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)] is reviewed. Ignition-relevant areal densities of ~200 mg/cm^2 in cryogenic D2 implosions with peak laser-drive intensities of ~5 x 10^14 W/cm^2 were previously reported [T. C. Sangster et al., Phys. Rev. Lett. 100, 185006 (2008)]. The laser intensity is increased to ~10^15 W/cm^2 to demonstrate ignition-relevant implosion velocities of 3–4 x 10^7 cm/ s, providing an understanding of the relevant target physics. Planar-target acceleration experiments show the importance of the nonlocal electron-thermal-transport effects for modeling the laser drive. Nonlocal and hot-electron preheat is observed to stabilize the Rayleigh–Taylor growth at a peak drive intensity of ~10^15 W/cm^2. The shell preheat caused by hot electrons generated by two-plasmon-decay instability was reduced by using Si-doped ablators. The measured compressibility of planar plastic targets driven with high-compression shaped pulses agrees well with one-dimensional simulations at these intensities. Shock mistiming has contributed to compression degradation of recent cryogenic implosions driven with continuous pulses. Multiple-picket (shock-wave) target designs make it possible for a more robust tuning of the shock-wave arrival times. Cryogenic implosions driven with double-picket pulses demonstrate somewhat improved compression performance at a peak drive intensity of ~10^15 W/cm^2