Live Hot, Die Young: Transmission Distortion in Recombination Hotspots

There is strong evidence that hotspots of meiotic recombination in humans are transient features of the genome. For example, hotspot locations are not shared between human and chimpanzee. Biased gene conversion in favor of alleles that locally disrupt hotspots is a possible explanation of the short lifespan of hotspots. We investigate the implications of such a bias on human hotspots and their evolution. Our results demonstrate that gene conversion bias is a sufficiently strong force to produce the observed lack of sharing of intense hotspots between species, although sharing may be much more common for weaker hotspots. We investigate models of how hotspots arise, and find that only models in which hotspot alleles do not initially experience drive are consistent with observations of rather hot hotspots in the human genome. Mutations acting against drive cannot successfully introduce such hotspots into the population, even if there is direct selection for higher recombination rates, such as to ensure correct segregation during meiosis. We explore the impact of hotspot alleles on patterns of haplotype variation, and show that such alleles mask their presence in population genetic data, making them difficult to detect.</p

Live Hot, Die Young: Transmission Distortion in Recombination Hotspots

There is strong evidence that hotspots of meiotic recombination in humans are transient features of the genome. For example, hotspot locations are not shared between human and chimpanzee. Biased gene conversion in favor of alleles that locally disrupt hotspots is a possible explanation of the short lifespan of hotspots. We investigate the implications of such a bias on human hotspots and their evolution. Our results demonstrate that gene conversion bias is a sufficiently strong force to produce the observed lack of sharing of intense hotspots between species, although sharing may be much more common for weaker hotspots. We investigate models of how hotspots arise, and find that only models in which hotspot alleles do not initially experience drive are consistent with observations of rather hot hotspots in the human genome. Mutations acting against drive cannot successfully introduce such hotspots into the population, even if there is direct selection for higher recombination rates, such as to ensure correct segregation during meiosis. We explore the impact of hotspot alleles on patterns of haplotype variation, and show that such alleles mask their presence in population genetic data, making them difficult to detect

Isolation and identification of ER associated proteins with unique expression changes specific to the V144D SPTLC1 mutations in HSN-I

Axonal degeneration is the final common path in many neurological disorders. Hereditary sensory neuropathies (HSN) are a group of neuropathies involving the sensory neurons. The most common subtype is autosomal dominant hereditary sensory neuropathy type I (HSN-I). Progressive degeneration of the dorsal root ganglion (DRG) neuron with an onset of clinical symptoms between the second or third decade of life characterises HSN-I. Mutations in the serine palmitoyltransferase (SPT) long chain subunit 1 (SPTLC1) gene cause HSN-I. The endoplasmic reticulum (ER) is a dynamic organelle that houses the SPTLC1 protein. Ultra structural analysis has shown the ER in the HSN-I mutant cells to wrap around dysfunctional mitochondria and tethers them to the perinucleus. This investigation establishes that the V144D mutant of SPTLC1 alters the expression of and potentially interacts with a set of proteins within the ER. Using ER protein lysates from HSN-I patient and control lymphoblasts: we have identified a change in regulation of five proteins; Hypoxia Up regulated Protein 1: Chloride intracellular channel protein 1: Ubiqutin-40s Ribosomal protein S27a: Coactosin and Ig Kappa chain C. The expression and regulation of these proteins may help to establish a link between the ER and the ‘dying back’ process of the DRG neuron

Compilation of algorithm-specific graph states for quantum circuits

We present a quantum circuit compiler that prepares an algorithm-specific graph state from quantum circuits described in high level languages, such as Cirq and Q#. The computation can then be implemented using a series of non-Pauli measurements on this graph state. By compiling the graph state directly instead of starting with a standard lattice cluster state and preparing it over the course of the computation, we are able to better understand the resource costs involved and eliminate wasteful Pauli measurements on the actual quantum device. Access to this algorithm-specific graph state also allows for optimisation over locally equivalent graph states to implement the same quantum circuit. The compiler presented here finds ready application in measurement based quantum computing, NISQ devices and logical level compilation for fault tolereant implementations

Garvey-Kelson Relations for Nuclear Charge Radii

The Garvey-Kelson relations (GKRs) are algebraic expressions originally developed to predict nuclear masses. In this letter we show that the GKRs provide a fruitful framework for the prediction of other physical observables that also display a slowly-varying dynamics. Based on this concept, we extend the GKRs to the study of nuclear charge radii. The GKRs are tested on 455 out of the approximately 800 nuclei whose charge radius is experimentally known. We find a rms deviation between the GK predictions and the experimental values of only 0.01 fm. This should be contrasted against some of the most successful microscopic models that yield rms deviations almost three times as large. Predictions - with reliable uncertainties - are provided for 116 nuclei whose charge radius is presently unknown.Comment: 4 pages and 3 figure

Supergravity Null Scissors and Super-Crosses

In this paper we construct the supergravity solutions for the orthogonally intersecting null scissors and the fluxed D-strings. We name the latter as the super-crosses according to their shape. It turns out that the smeared solutions are U-dual related to the intersecting $(p,q)$-strings. Their open string properties are also studied. As a by-product, we clarify the supersymmetry conditions of D2-D2 pairs with most generic fluxes.Comment: 16 pages, 1 figure;v2. minor comment revised;v3. references added, final to JHE

A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis.

PRDM9 binding localizes almost all meiotic recombination sites in humans and mice. However, most PRDM9-bound loci do not become recombination hotspots. To explore factors that affect binding and subsequent recombination outcomes, we mapped human PRDM9 binding sites in a transfected human cell line and measured PRDM9-induced histone modifications. These data reveal varied DNA-binding modalities of PRDM9. We also find that human PRDM9 frequently binds promoters, despite their low recombination rates, and it can activate expression of a small number of genes including CTCFL and VCX. Furthermore, we identify specific sequence motifs that predict consistent, localized meiotic recombination suppression around a subset of PRDM9 binding sites. These motifs strongly associate with KRAB-ZNF protein binding, TRIM28 recruitment, and specific histone modifications. Finally, we demonstrate that, in addition to binding DNA, PRDM9's zinc fingers also mediate its multimerization, and we show that a pair of highly diverged alleles preferentially form homo-multimers

Higher Derivative Corrections to R-charged Black Holes: Boundary Counterterms and the Mass-Charge Relation

We carry out the holographic renormalization of Einstein-Maxwell theory with curvature-squared corrections. In particular, we demonstrate how to construct the generalized Gibbons-Hawking surface term needed to ensure a perturbatively well-defined variational principle. This treatment ensures the absence of ghost degrees of freedom at the linearized perturbative order in the higher-derivative corrections. We use the holographically renormalized action to study the thermodynamics of R-charged black holes with higher derivatives and to investigate their mass to charge ratio in the extremal limit. In five dimensions, there seems to be a connection between the sign of the higher derivative couplings required to satisfy the weak gravity conjecture and that violating the shear viscosity to entropy bound. This is in turn related to possible constraints on the central charges of the dual CFT, in particular to the sign of c-a.Comment: 30 pages. v2: references added, some equations simplifie

Hamiltonian thermodynamics of a Lovelock black hole

We consider the Hamiltonian dynamics and thermodynamics of spherically symmetric spacetimes within a one-parameter family of five-dimensional Lovelock theories. We adopt boundary conditions that make every classical solution part of a black hole exterior, with the spacelike hypersurfaces extending from the horizon bifurcation three-sphere to a timelike boundary with fixed intrinsic metric. The constraints are simplified by a Kucha\v{r}-type canonical transformation, and the theory is reduced to its true dynamical degrees of freedom. After quantization, the trace of the analytically continued Lorentzian time evolution operator is interpreted as the partition function of a thermodynamical canonical ensemble. Whenever the partition function is dominated by a Euclidean black hole solution, the entropy is given by the Lovelock analogue of the Bekenstein-Hawking entropy; in particular, in the low temperature limit the system exhibits a dominant classical solution that has no counterpart in Einstein's theory. The asymptotically flat space limit of the partition function does not exist. The results indicate qualitative robustness of the thermodynamics of five-dimensional Einstein theory upon the addition of a nontrivial Lovelock term.Comment: 22 pages, REVTeX v3.

First results from a VLBA proper motion survey of H2O masers in low-mass YSOs: the Serpens core and RNO15-FIR

This article reports first results of a long-term observational program aimed to study the earliest evolution of jet/disk systems in low-mass YSOs by means of VLBI observations of the 22.2 GHz water masers. We report here data for the cluster of low-mass YSOs in the Serpens molecular core and for the single object RNO~15-FIR. Towards Serpens SMM1, the most luminous sub-mm source of the Serpens cluster, the water maser emission comes from two small (< 5 AU in size) clusters of features separated by ~25 AU, having line of sight velocities strongly red-shifted (by more than 10 km/s) with respect to the LSR velocity of the molecular cloud. The two maser clusters are oriented on the sky along a direction that is approximately perpendicular to the axis of the radio continuum jet observed with the VLA towards SMM1. The spatial and velocity distribution of the maser features lead us to favor the interpretation that the maser emission is excited by interaction of the receding lobe of the jet with dense gas in the accretion disk surrounding the YSO in SMM1. Towards RNO~15-FIR, the few detected maser features have both positions and (absolute) velocities aligned along a direction that is parallel to the axis of the molecular outflow observed on much larger angular scales. In this case the maser emission likely emerges from dense, shocked molecular clumps displaced along the axis of the jet emerging from the YSO. The protostar in Serpens SMM1 is more massive than the one in RNO~15-FIR. We discuss the case where a high mass ejection rate can generate jets sufficiently powerful to sweep away from their course the densest portions of circumstellar gas. In this case, the excitation conditions for water masers might preferably occur at the interface between the jet and the accretion disk, rather than along the jet axis.Comment: 18 pages (postscript format); 9 figures; to be published into Astronomy & Astrophysics, Main Journa