Landscape genetics reveal broad and fine‐scale population structure due to landscape features and climate history in the northern leopard frog (Rana pipiens) in North Dakota

Prehistoric climate and landscape features play large roles structuring wildlife populations. The amphibians of the northern Great Plains of North America present an opportunity to investigate how these factors affect colonization, migration, and current population genetic structure. This study used 11 microsatellite loci to genotype 1,230 northern leopard frogs (Rana pipiens) from 41 wetlands (30 samples/wetland) across North Dakota. Genetic structure of the sampled frogs was evaluated using Bayesian and multivariate clustering methods. All analyses produced concordant results, identifying a major east–west split between two R. pipiens population clusters separated by the Missouri River. Substructuring within the two major identified population clusters was also found. Spatial principal component analysis (sPCA) and variance partitioning analysis identified distance, river basins, and the Missouri River as the most important landscape factors differentiating R. pipiens populations across the state. Bayesian reconstruction of coalescence times suggested the major east– west split occurred ~13–18 kya during a period of glacial retreat in the northern Great Plains and substructuring largely occurred ~5–11 kya during a period of extreme drought cycles. A range‐wide species distribution model (SDM) for R. pipiens was developed and applied to prehistoric climate conditions during the Last Glacial Maximum (21 kya) and the mid‐Holocene (6 kya) from the CCSM4 climate model to identify potential refugia. The SDM indicated potential refugia existed in South Dakota or further south in Nebraska. The ancestral populations of R. pipiens in North Dakota may have inhabited these refugia, but more sampling outside the state is needed to reconstruct the route of colonization. Using microsatellite genotype data, this study determined that colonization from glacial refugia, drought dynamics in the northern Great Plains, and major rivers acting as barriers to gene flow were the defining forces shaping the regional population structure of R. pipiens in North Dakota

Persistence of RNAi-Mediated Knockdown in Drosophila Complicates Mosaic Analysis Yet Enables Highly Sensitive Lineage Tracing.

RNA interference (RNAi) has emerged as a powerful way of reducing gene function in Drosophila melanogaster tissues. By expressing synthetic short hairpin RNAs (shRNAs) using the Gal4/UAS system, knockdown is efficiently achieved in specific tissues or in clones of marked cells. Here we show that knockdown by shRNAs is so potent and persistent that even transient exposure of cells to shRNAs can reduce gene function in their descendants. When using the FLP-out Gal4 method, in some instances we observed unmarked "shadow RNAi" clones adjacent to Gal4-expressing clones, which may have resulted from brief Gal4 expression following recombination but prior to cell division. Similarly, Gal4 driver lines with dynamic expression patterns can generate shadow RNAi cells after their activity has ceased in those cells. Importantly, these effects can lead to erroneous conclusions regarding the cell autonomy of knockdown phenotypes. We have investigated the basis of this phenomenon and suggested experimental designs for eliminating ambiguities in interpretation. We have also exploited the persistence of shRNA-mediated knockdown to design a sensitive lineage-tracing method, i-TRACE, which is capable of detecting even low levels of past reporter expression. Using i-TRACE, we demonstrate transient infidelities in the expression of some cell-identity markers near compartment boundaries in the wing imaginal disc

A paperfluidic platform to detect Neisseria gonorrhoeae in clinical samples

Globally, the microbe Neisseria gonorrhoeae (NG) causes 106 million newly documented sexually transmitted infections each year. Once appropriately diagnosed, NG infections can be readily treated with antibiotics, but high-risk patients often do not return to the clinic for treatment if results are not provided at the point of care. A rapid, sensitive molecular diagnostic would help increase NG treatment and reduce the prevalence of this sexually transmitted disease. Here, we report on the design and development of a rapid, highly sensitive, paperfluidic device for point-of-care diagnosis of NG. The device integrates patient swab sample lysis, nucleic acid extraction, thermophilic helicase-dependent amplification (tHDA), an internal amplification control (NGIC), and visual lateral flow detection within an 80 min run time. Limits of NG detection for the NG/NGIC multiplex tHDA assay were determined within the device, and clinical performance was validated retroactively against qPCR-quantified patient samples in a proof-of-concept study. This paperfluidic diagnostic has a clinically relevant limit of detection of 500 NG cells per device with analytical sensitivity down to 10 NG cells per device. In triplicate testing of 40 total urethral and vaginal swab samples, the device had 95% overall sensitivity and 100% specificity, approaching current laboratory-based molecular NG diagnostics. This diagnostic platform could increase access to accurate NG diagnoses to those most in need.This work was funded by the National Institute of Health National Institute of Allergy and Infectious Diseases award number R01 AI113927 to Boston University and the NIH National Institute of Biomedical and Bioengineering award number U54 EB007958 to Johns Hopkins University. (R01 AI113927 - National Institute of Health National Institute of Allergy and Infectious Diseases; U54 EB007958 - NIH National Institute of Biomedical and Bioengineering)Accepted manuscrip

On the sign of kurtosis near the QCD critical point

We point out that the quartic cumulant (and kurtosis) of the order parameter fluctuations is universally negative when the critical point is approached on the crossover side of the phase separation line. As a consequence, the kurtosis of a fluctuating observable, such as, e.g., proton multiplicity, may become smaller than the value given by independent Poisson statistics. We discuss implications for the Beam Energy Scan program at RHIC.Comment: 4 pages, 2 figure

The two-point correlation function of three-dimensional O(N) models: critical limit and anisotropy

In three-dimensional O(N) models, we investigate the low-momentum behavior of the two-point Green's function G(x) in the critical region of the symmetric phase. We consider physical systems whose criticality is characterized by a rotational-invariant fixed point. Several approaches are exploited, such as strong-coupling expansion of lattice non-linear O(N) sigma models, 1/N-expansion, field-theoretical methods within the phi^4 continuum formulation. In non-rotational invariant physical systems with O(N)-invariant interactions, the vanishing of space-anisotropy approaching the rotational-invariant fixed point is described by a critical exponent rho, which is universal and is related to the leading irrelevant operator breaking rotational invariance. At N=\infty one finds rho=2. We show that, for all values of $N\geq 0$, $\rho\simeq 2$. Non-Gaussian corrections to the universal low-momentum behavior of G(x) are evaluated, and found to be very small.Comment: 65 pages, revte

Kraichnan model of passive scalar advection

A simple model of a passive scalar quantity advected by a Gaussian non-solenoidal ("compressible") velocity field is considered. Large order asymptotes of quantum-field expansions are investigated by instanton approach. The existence of finite convergence radius of the series is proved, a position and a type of the corresponding singularity of the series in the regularization parameter are determined. Anomalous exponents of the main contributions to the structural functions are resummed using new information about the series convergence and two known orders of the expansion.Comment: 21 page

Thermodynamic Analysis of Interacting Nucleic Acid Strands

Motivated by the analysis of natural and engineered DNA and RNA systems, we present the first algorithm for calculating the partition function of an unpseudoknotted complex of multiple interacting nucleic acid strands. This dynamic program is based on a rigorous extension of secondary structure models to the multistranded case, addressing representation and distinguishability issues that do not arise for single-stranded structures. We then derive the form of the partition function for a fixed volume containing a dilute solution of nucleic acid complexes. This expression can be evaluated explicitly for small numbers of strands, allowing the calculation of the equilibrium population distribution for each species of complex. Alternatively, for large systems (e.g., a test tube), we show that the unique complex concentrations corresponding to thermodynamic equilibrium can be obtained by solving a convex programming problem. Partition function and concentration information can then be used to calculate equilibrium base-pairing observables. The underlying physics and mathematical formulation of these problems lead to an interesting blend of approaches, including ideas from graph theory, group theory, dynamic programming, combinatorics, convex optimization, and Lagrange duality

rLOAD: does sex mediate the effect of acute antiplatelet loading on stroke outcome.

BackgroundBiologic sex can influence response to pharmacologic therapy. The purpose of this proof-of-concept study was to evaluate the medicating effects of estrogen in the efficacy of acute antiplatelet loading therapy on stroke outcome in the rabbit small clot embolic model.MethodsFemale and male (20/group) New Zealand White rabbits were embolized to produce embolic stroke by injecting small blood clots into the middle cerebral artery via an internal carotid artery catheter. Two hours after embolization, rabbits were treated with standard dose antiplatelet loading (aspirin 10 mg/kg plus clopidogrel 10 mg/kg). Primary outcome measures were platelet inhibition, behavioral outcome P 50 (the weight of microclots (mg) that produces neurologic dysfunction in 50% of a group of animals), and effect of endogenous estrogen on outcome.ResultsFor the first time in a non-rodent model of stroke, it was found that higher endogenous estrogen levels resulted in significantly better behavioral outcome in female subjects (r s -0.70, p < 0.011). Platelet inhibition in response to collagen, arachidonic acid, and adenosine diphosphate (ADP) was not significantly different in females with higher vs. lower estrogen levels.ConclusionsBehavioral outcomes are improved with females with higher endogenous estrogen levels treated with standard dose antiplatelet loading. This is the first non-rodent study to demonstrate that higher endogenous estrogen levels in female rabbits appear to be neuroprotective in ischemic stroke. This research supports the further study of the effect of endogenous estrogen levels on outcome with standard dose antiplatelet loading in stroke patients not eligible for revascularization therapies

Extending the Globular Cluster System-Halo Mass Relation to the Lowest Galaxy Masses

High mass galaxies, with halo masses $M_{200} \ge 10^{10} M_{\odot}$, reveal a remarkable near-linear relation between their globular cluster (GC) system mass and their host galaxy halo mass. Extending this relation to the mass range of dwarf galaxies has been problematic due to the difficulty in measuring independent halo masses. Here we derive new halo masses based on stellar and HI gas kinematics for a sample of nearby dwarf galaxies with GC systems. We find that the GC system mass--halo mass relation for galaxies populated by GCs holds from halo masses of $M_{200} \sim 10^{14} M_{\odot}$ down to below $M_{200}$ $\sim 10^9 M_{\odot}$, although there is a substantial increase in scatter towards low masses. In particular, three well-studied ultra diffuse galaxies, with dwarf-like stellar masses, reveal a wide range in their GC-to-halo mass ratios. We compare our GC system--halo mass relation to the recent model of El Badry et al., finding that their fiducial model does not reproduce our data in the low mass regime. This may suggest that GC formation needs to be more efficient than assumed in their model, or it may be due to the onset of stochastic GC occupation in low mass halos. Finally, we briefly discuss the stellar mass-halo mass relation for our low mass galaxies with GCs, and we suggest some nearby dwarf galaxies for which searches for GCs may be fruitful.Comment: 16 pages, 5 figures, accepted for publication in MNRA

Quantum Knizhnik-Zamolodchikov equation, generalized Razumov-Stroganov sum rules and extended Joseph polynomials

We prove higher rank analogues of the Razumov--Stroganov sum rule for the groundstate of the O(1) loop model on a semi-infinite cylinder: we show that a weighted sum of components of the groundstate of the A_{k-1} IRF model yields integers that generalize the numbers of alternating sign matrices. This is done by constructing minimal polynomial solutions of the level 1 U_q(\hat{sl(k)}) quantum Knizhnik--Zamolodchikov equations, which may also be interpreted as quantum incompressible q-deformations of fractional quantum Hall effect wave functions at filling fraction nu=1/k. In addition to the generalized Razumov--Stroganov point q=-e^{i pi/k+1}, another combinatorially interesting point is reached in the rational limit q -> -1, where we identify the solution with extended Joseph polynomials associated to the geometry of upper triangular matrices with vanishing k-th power.Comment: v3: misprint fixed in eq (2.1