Neurodevelopmental scaling is a major driver of brain-behavior differences in temperament across dog breeds.

Behavioral traits like aggression, anxiety, and trainability differ significantly across dog breeds and are highly heritable. However, the neural bases of these differences are unknown. Here we analyzed structural MRI scans of 62 dogs in relation to breed-average scores for the 14 major dimensions in the Canine Behavioral Assessment and Research Questionnaire, a well-validated measure of canine temperament. Several behavior categories showed significant relationships with morphologically covarying gray matter networks and regional volume changes. Networks involved in social processing and the flight-or-fight response were associated with stranger-directed fear and aggression, putatively the main behaviors under selection pressure during wolf-to-dog domestication. Trainability was significantly associated with expansion in broad regions of cortex, while fear, aggression, and other "problem" behaviors were associated with expansion in distributed subcortical regions. These results closely overlapped with regional volume changes with total brain size, in striking correspondence with models of developmental constraint on brain evolution. This suggests that the established link between dog body size and behavior is due at least in part to disproportionate enlargement of later-developing regions in larger brained dogs. We discuss how this may explain the known correlation of increasing reactivity with decreasing body size in dogs.

Anomalous Hydrodynamics in a One-Dimensional Electronic Fluid.

We construct multimode viscous hydrodynamics for one-dimensional spinless electrons. Depending on the scale, the fluid has six (shortest lengths), four (intermediate, exponentially broad regime), or three (asymptotically long scales) hydrodynamic modes. Interaction between hydrodynamic modes leads to anomalous scaling of physical observables and waves propagating in the fluid. In the four-mode regime, all modes are ballistic and acquire Kardar-Parisi-Zhang (KPZ)-like broadening with asymmetric power-law tails. "Heads" and "tails" of the waves contribute equally to thermal conductivity, leading to ω^{-1/3} scaling of its real part. In the three-mode regime, the system is in the universality class of a classical viscous fluid [O. Narayan and S. Ramaswamy, Anomalous Heat Conduction in One-Dimensional Momentum-Conserving Systems, Phys. Rev. Lett. 89, 200601 (2002).PRLTAO0031-900710.1103/PhysRevLett.89.200601, H. Spohn, Nonlinear fluctuating hydrodynamics for anharmonic chains, J. Stat. Phys. 154, 1191 (2014).JSTPBS0022-471510.1007/s10955-014-0933-y]. Self-interaction of the sound modes results in a KPZ-like shape, while the interaction with the heat mode results in asymmetric tails. The heat mode is governed by Levy flight distribution, whose power-law tails give rise to ω^{-1/3} scaling of heat conductivity.

Thermal Transport in One-Dimensional Electronic Fluids.

We study thermal conductivity for one-dimensional electronic fluids. The many-body Hilbert space is partitioned into bosonic and fermionic sectors that carry the thermal current in parallel. For times shorter than the bosonic umklapp time, the momenta of Bose and Fermi components are separately conserved, giving rise to the ballistic heat propagation and imaginary heat conductivity proportional to T/iω. The real part of thermal conductivity is controlled by decay processes of fermionic and bosonic excitations, leading to several regimes in frequency dependence. At lowest frequencies or longest length scales, the thermal transport is dominated by Lévy flights of low-momentum bosons that lead to a fractional scaling, ω^{-1/3} and L^{1/3}, of heat conductivity with the frequency ω and system size L, respectively.

Multiple periodicity in a nanoparticle-based single-electron transistor.

A single-electron transistor is a nano-device with large potential for low-power applications that can be used as logic elements in integrated circuits. In this device, the conductance oscillates with a well-defined period due to the Coulomb blockade effect. By using a unique technique, we explore single-electron transistors based on a single metallic nanoparticle with tunable coupling to electric leads. We demonstrate a unique regime in which the transistor is characterized by multi-periodic oscillations of the conductance with gate voltage where the additional periods are harmonics of the basic periodicity of the Coulomb blockade and their relative strength can be controllably tuned. These harmonics correspond to a charge change on the dot by a fraction of the electron charge. The presence of multiple harmonics makes these transistors potential elements in future miniaturization of nano-sized circuit elements.Single-electron transistors are elements for nanoscale electronics. Employing single-electron transistors based on gold nanoparticles, Bitton et al., report a fabrication technique that allows precise control over the coupling between a nanodot and leads, resulting in new transport characteristics.

Voxel-based morphometry predicts shifts in dendritic spine density and morphology with auditory fear conditioning.

Neuroimaging has provided compelling data about the brain. Yet the underlying mechanisms of many neuroimaging techniques have not been elucidated. Here we report a voxel-based morphometry (VBM) study of Thy1-YFP mice following auditory fear conditioning complemented by confocal microscopy analysis of cortical thickness, neuronal morphometric features and nuclei size/density. Significant VBM results included the nuclei of the amygdala, the insula and the auditory cortex. There were no significant VBM changes in a control brain area. Focusing on the auditory cortex, confocal analysis showed that fear conditioning led to a significantly increased density of shorter and wider dendritic spines, while there were no spine differences in the control area. Of all the morphology metrics studied, the spine density was the only one to show significant correlation with the VBM signal. These data demonstrate that learning-induced structural changes detected by VBM may be partially explained by increases in dendritic spine density.

Acquisition of Paleolithic toolmaking abilities involves structural remodeling to inferior frontoparietal regions.

Human ancestors first modified stones into tools 2.6 million years ago, initiating a cascading increase in technological complexity that continues today. A parallel trend of brain expansion during the Paleolithic has motivated over 100 years of theorizing linking stone toolmaking and human brain evolution, but empirical support remains limited. Our study provides the first direct experimental evidence identifying likely neuroanatomical targets of natural selection acting on toolmaking ability. Subjects received MRI and DTI scans before, during, and after a 2-year Paleolithic toolmaking training program. White matter fractional anisotropy (FA) showed changes in branches of the superior longitudinal fasciculus leading into left supramarginal gyrus, bilateral ventral precentral gyri, and right inferior frontal gyrus pars triangularis. FA increased from Scan 1-2, a period of intense training, and decreased from Scan 2-3, a period of reduced training. Voxel-based morphometry found a similar trend toward gray matter expansion in the left supramarginal gyrus from Scan 1-2 and a reversal of this effect from Scan 2-3. FA changes correlated with training hours and with motor performance, and probabilistic tractography confirmed that white matter changes projected to gray matter changes and to regions that activate during Paleolithic toolmaking. These results show that acquisition of Paleolithic toolmaking skills elicits structural remodeling of recently evolved brain regions supporting human tool use, providing a mechanistic link between stone toolmaking and human brain evolution. These regions participate not only in toolmaking, but also in other complex functions including action planning and language, in keeping with the hypothesized co-evolution of these functions.

Correlations in nonequilibrium Luttinger liquid and singular Fredholm determinants.

We study interaction-induced correlations in Luttinger liquid with multiple Fermi edges. Many-particle correlation functions are expressed in terms of Fredholm determinants det(1+ÂB[over ^]), where A(ε) and B(t) have multiple discontinuities in energy and time spaces. We propose a general asymptotic formula for this class of determinants and provide analytical and numerical support to this conjecture. This allows us to establish nonequilibrium Fermi-edge singularities of many-particle correlation functions. As an example, we calculate a two-particle distribution function characterizing genuinely nonequilibrium quantum correlations between left- and right-moving fermions that have left the interaction region.

Coexistence of Coulomb blockade and zero bias anomaly in a strongly coupled nanodot.

The current-voltage characteristics through a metallic nanoparticle which is well coupled to a metallic lead are measured. It is shown that the I-V curves are composed of two contributions. One is a suppression of the tunneling conductivity at the Fermi level, and the second is an oscillating feature which shifts with gate voltage. The results indicate that zero-bias anomaly and Coulomb blockade phenomena coexist in an asymmetric strongly coupled zero-dimensional system.

Route of administration-dependent anti-inflammatory effect of liposomal alendronate.

Innate immunity and inflammation are of major importance in various pathological conditions. Intravenous (IV) and intraperitoneal (IP) liposomal alendronate (LA) treatments have been shown to deplete circulating monocytes and peritoneal macrophages resulting in the inhibition of restenosis and endometriosis (EM), respectively. Nevertheless, the correlation between the extent of circulating monocyte depletion and liposome biodistribution is unknown, and the route of administration-dependent bioactivity in restenosis and EM has not been determined. We found that, LA treatment resulted in a dose-response modified biodistribution following both IV and IP administrations. The biodistribution of high-dose LA (10mg/kg), but not that of the low-dose (1mg/kg), was similar in healthy and diseased animals. It is concluded that LA impedes its own elimination from the circulation by depleting circulating monocytes and/or inhibiting their endocytic activity, in a dose-dependent manner. Both IV and IP administration of LA mediated by the partial and transient depletion of circulating monocytes effected inhibition of restenosis. Inhibition of EM was effected only by IP administration, which depleted both intraperitoneal and circulating monocytes. Thus, EM should be considered as a local inflammatory condition with systemic manifestations as opposed to restenosis, a systemic inflammatory disease.

Full counting statistics of a Luttinger liquid conductor.

Nonequilibrium bosonization technique is used to study current fluctuations of interacting electrons in a single-channel quantum wire representing a Luttinger liquid (LL) conductor. An exact expression for the time resolved full counting statistics of the transmitted charge is derived. It is given by the Fredholm determinant of the counting operator with a time-dependent scattering phase. The result has a form of counting statistics of noninteracting particles with fractional charges, induced by scattering off the boundaries between the LL wire and the noninteracting leads.

Nonequilibrium Luttinger liquid: zero-bias anomaly and dephasing.

A one-dimensional system of interacting electrons out of equilibrium is studied in the framework of the Luttinger liquid model. We analyze several setups and develop a theory of tunneling into such systems. A remarkable property of the problem is the absence of relaxation in energy distribution functions of left and right movers yet the presence of the finite dephasing rate due to electron-electron scattering, which smears zero-bias-anomaly singularities in the tunneling density of states.

Nonequilibrium zero-bias anomaly in disordered metals.

We extend the theory of a zero-bias anomaly (ZBA) in the tunneling density of states of a diffusive metallic film to out-of-equilibrium conditions. An effective action describing virtual fluctuations out of equilibrium is derived. The singular behavior of the equilibrium ZBA is smoothed out by real processes of inelastic scattering.

Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimulation for treatment-resistant depression.

Chronic deep brain stimulation (DBS) of subgenual cingulate white matter results in dramatic remission of symptoms in some previously treatment-resistant depression patients. The effects of stimulation may be mediated locally or via corticocortical or corticosubcortical connections. We use tractography to define the likely connectivity of cingulate regions stimulated in DBS-responsive patients using diffusion imaging data acquired in healthy control subjects. We defined 2 distinct regions within anterior cingulate cortex based on anatomical connectivity: a pregenual region strongly connected to medial prefrontal and anterior midcingulate cortex and a subgenual region with strongest connections to nucleus accumbens, amygdala, hypothalamus, and orbitofrontal cortex. The location of electrode contact points from 9 patients successfully treated with DBS lies within this subgenual region. The anatomical connectivity of the subgenual cingulate region targeted with DBS for depression supports the hypothesis that treatment efficacy is mediated via effects on a distributed network of frontal, limbic, and visceromotor brain regions. At present, targeting of DBS for depression is based on landmarks visible in conventional magnetic resonance imaging. Preoperatively acquired diffusion imaging for connectivity-based cortical mapping could improve neurosurgical targeting. We hypothesize that the subgenual region with greatest connectivity across the distributed network described here may prove most effective.

Anomalous c-axis transport in layered metals.

Transport in metals with a strongly anisotropic single-particle spectrum is studied. Coherent band transport in all directions, described by the standard Boltzmann equation, is shown to withstand both elastic and inelastic scattering as long as EFtau >> 1. A model of phonon-assisted tunneling via resonant states located in between the layers is suggested to explain a nonmonotonic temperature dependence of the c-axis resistivity observed in experiments.

Structural features of a zinc binding site in the superantigen strepococcal pyrogenic exotoxin A (SpeA1): implications for MHC class II recognition.

Streptococcal pyrogenic exotoxin A (SpeA) is produced by Streptococcus pyogenes, and has been associated with severe infections such as scarlet fever and Streptococcal Toxic Shock Syndrome (STSS). In this study, the crystal structure of SpeA1 (the product of speA allele 1) in the presence of 2.5 mM zinc was determined at 2.8 A resolution. The protein crystallizes in the orthorhombic space group P2(1)2(1)2, with four molecules in the crystallographic asymmetric unit. The final structure has a crystallographic R-factor of 21.4% for 7,031 protein atoms, 143 water molecules, and 4 zinc atoms (one zinc atom per molecule). Four protein ligands-Glu 33, Asp 77, His 106, and His 110-form a zinc binding site that is similar to the one observed in a related superantigen, staphylococcoal enterotoxin C2. Mutant toxin forms substituting Ala for each of the zinc binding residues were generated. The affinity of these mutants for zinc ion confirms the composition of this metal binding site. The implications of zinc binding to SpeA1 for MHC class II recognition are explored using a molecular modeling approach. The results indicate that, despite their common overall architecture, superantigens appear to have multiple ways of complex formation with MHC class II molecules.

Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials.

Testing the therapeutic potential of transcranial magnetic stimulation (TMS) in controlled trials requires a valid sham condition. Sham TMS is typically administered by tilting the coil 45--90 degrees off the scalp, with one or two wings of the coil touching the scalp. Lack of cortical effects has not been verified. We compared sham manipulations in their thresholds for eliciting motor-evoked potentials (MEPs) in human volunteers and in intracerebral measurements of voltage induced in the prefrontal cortex of a rhesus monkey. Three types of sham (one-wing 45 degrees and 90 degrees and two-wing 90 degrees tilt) induced much lower voltage in the brain than active TMS (67--73% reductions). However, the two-wing 45 degrees sham induced values just 24% below active TMS. This sham was about half as potent in inducing MEPs over the motor cortex as active TMS. Some sham TMS conditions produce substantial cortical stimulation, making it critical to carefully select the sham manipulation for clinical trials.

Neural correlates of maternal separation in rhesus monkeys.

BACKGROUND: The neurobiological basis of stress and anxiety in primates remains poorly understood. In this study, we examined the neural response to a naturalistic social stressor: maternal separation. We used rhesus monkeys as an animal model because of their close phylogenetic affinity with humans. METHODS: Six juvenile rhesus monkeys received [(18)F]-fluorodeoxyglucose positron emission tomography scans following 1) a period together with their mothers and again after separation from their mothers 2) with or 3) without visual contact. Image subtraction revealed brain regions that exhibited altered activity during separation. In addition, plasma cortisol concentrations obtained following each condition were tested for correlations with regional brain activity. RESULTS: Maternal separation activated the right dorsolateral prefrontal cortex and the right ventral temporal/occipital lobe. There was also decreased activity in left dorsolateral prefrontal cortex associated with separation stress. Correlational analyses demonstrated these activated and deactivated regions to be positively and negatively correlated with cortisol, respectively. Additionally, correlational analyses revealed cortisol-related activation in brainstem areas previously implicated in stress and anxiety. CONCLUSIONS: In juvenile rhesus monkeys, the stress of maternal separation is associated with activation in the right dorsolateral prefrontal cortex and ventral temporal/occipital lobes and decreased activity in the left dorsolateral prefrontal cortex.

Recombinant Staphylococcus aureus exfoliative toxins are not bacterial superantigens.

Staphylococcal scalded-skin syndrome is an exfoliative dermatitis characterized by the separation of the epidermis at the stratum granulosum. This disruption is mediated by one of two Staphylococcus aureus exotoxins, exfoliative toxins A and B (ETA and ETB). Both ETA and ETB have been reported to be bacterial superantigens. A controversy exists, however, as other data indicate that these exotoxins are not superantigens. Here we demonstrate that recombinant exfoliative toxins produced in Escherichia coli do not act as T-cell mitogens and thus are not bacterial superantigens. These data fit the clinical profile of the disease, which is not associated with the classic symptoms of a superantigen-mediated syndrome.

Health promotion practices of emergency physicians.

In this article we describe health promotion practices of emergency physicians (EPs). A survey was mailed to members of the West Virginia American College of Emergency Physicians. Main outcomes included the EP's beliefs regarding health promotion, perceived roles in health promotion, and perceived effectiveness in modifying the behavior of patients. Over 90% of respondents routinely asked about cigarette smoking and half about alcohol use. A minority routinely asked about illicit drug use, diet, exercise, domestic violence, or stress. The majority stated they were the main person responsible for patient health education in their emergency department (ED). Most felt prepared to counsel patients about smoking (68%) and alcohol (59%), although very few described themselves as successful in helping patients change their behavior. Although EPs feel responsible for promoting the health of their patients, only a minority reported routinely screening and counseling patients about prevention and most were not confident in their ability to help patients change their health-related behaviors.