Small molecule screen in zebrafish and HSC expansion

The zebrafish (Danio rerio) has emerged as a valuable model organism that is amenable for large-scale chemical and genetic screens. The ability of zebrafish to produce large quantities of synchronized, externally fertilized, transparent embryos makes them ideal for screens, which often are not possible in mammalian models. Signaling pathways important for hematopoiesis are well conserved between zebrafish and mammals, making many targets identified in zebrafish screens applicable to mammals. Hematopoiesis in zebrafish occurs in two waves: the primitive or embryonic wave and the definitive or adult wave. Definitive hematopoietic stem cells arise in the aorta-gonad-mesonephros region (AGM) and express conserved markers such as runx1 and c-myb that allow for the detection of stem cells by whole-mount in situ hybridization (WISH). In this protocol, we will discuss a chemical screen in zebrafish embryos to detect compounds that expand or deplete hematopoietic stem cells (HSCs) in vivo. This type of screen represents a powerful tool to study HSCs in zebrafish

Controlling Molecular Scattering by Laser-Induced Field-Free Alignment

We consider deflection of polarizable molecules by inhomogeneous optical fields, and analyze the role of molecular orientation and rotation in the scattering process. It is shown that molecular rotation induces spectacular rainbow-like features in the distribution of the scattering angle. Moreover, by preshaping molecular angular distribution with the help of short and strong femtosecond laser pulses, one may efficiently control the scattering process, manipulate the average deflection angle and its distribution, and reduce substantially the angular dispersion of the deflected molecules. We provide quantum and classical treatment of the deflection process. The effects of strong deflecting field on the scattering of rotating molecules are considered by the means of the adiabatic invariants formalism. This new control scheme opens new ways for many applications involving molecular focusing, guiding and trapping by optical and static fields

Клінічні ознаки у собак, що позитивно реагують на антиген Yersinia enterocolitica 0:9

Canine yersiniosis is currently a scantily researched disease. Two agents predominately cause yersiniosis: Y. enterocolitica (gut yersiniosis), Y. preudotuberculosis (yersiniosis). There are three clinical forms of the disease: intestinal, generalized and secondary-focal. Current available research states the prevalence of Y. enterocolitica against other biovariants in canine infections. The majority of infected dogs demonstrate both asymptomatic clinical course and unspecific symptoms or serve as a carrier. Meanwhile yersiniosis pose a threat to human health causing a severe complex of symptoms. In some cases the disease can be lethal, thus the disease has both epizootological and epidemiological value. The goal of this paper was to generalize clinical signs in dogs that demonstrated positive reaction to Y. enterocolitica antigen 0:9, which is a dominant causative agent of yersiniosis in the northeastern region of Ukraine. The study was conducted based on clinical data, biochemical and hematological laboratory studies. Contamination of canine subjects with Y. enterocolitica 0:9 was conducted using agglutination reaction using respective antigen. The research showed, that the dominant symptoms in canines, affected by Yersinia serovariant 0:9 were gastrointestinal lesions in 100 % of the cases. The clinical signs included melena or bloody stool, general depression, anorexia, cachexia, more rarely – vomiting, tachypnea and breathing irregularities. The results of biochemical blood assays and CBC were heterogeneous and cannot be used as a specific marker of Yersinia infection. The main method of confirmation for Yersinia infection would be a serological agglutination reaction, which can identify positive diagnostic titers in animal blood samples. Further research is planned to study mono- and concurrent course of Yersiniosis with different infectious diseases.Ієрсиніоз собак досі маловивчене захворювання. Найчастіше його викликають два збудники – Y. enterocolitica (кишковий ієрсиніоз) і Y. pseudotuberculosis (ієрсиніоз). Виділяють три клінічні форми хвороби: кишкову, генералізовану, вторинно-вогнещеву. Відомі дослідження вказують на превалювання Y. enterocolitica над іншими біоварами в інфекційному процесі у собак. У більшості інфікованих собак захворювання перебігає безсимптомно з неспецифічною клінічною картиною або у вигляді бактеріоносійства. Водночас ієрсиніози становляють загрозу здоров’ю людини, проявляючись складним симптомокомплексом, а в окремих випадках закінчуються летально. Тому ієрсиніоз має як епізоотологічне, так і епідеміологічне значення. Мета роботи – узагальнити клінічні ознаки у собак, які в діагностичних титрах реагували на ієрсиніозний антиген Y. enterocolitica 0:9, домінуючий збудник кишкового ієрсиніозу собак в північно-східному регіоні України. У роботі використовували клінічні, гематологічні та біохімічні дослідження. Позитивні реакції на контамінацію організму собак Y. enterocolitica 0:9 визначали в реакції аглютинації з відповідним антигеном. Дослідження показали, що домінуючими симптомами при ураженні собак сероваром 0:9 у 100 % випадків було ураження шлунково-кишкового тракту з діареєю, з домішками крові у фекаліях, на тлі пригнічення, анорексії, кахексії. Рідше хвороба супроводжувалася блюванням і порушенням ритму дихання. Результати гематологічних та біохімічних досліджень у собак з позитивною реакцією на іерсініозной антиген 0:9 характеризувалися різноманітністю і не можуть служити діагностичним маркером ієрсиниозної інфекції. Основною підозрою на захворювання кишковим ієрсинізом може слугувати серологічна реакція аглютинації з виявленням позитивно реагуючих тварин в діагностичних титрах. Подальші дослідження планується спрямувати на вивчення моно- і асоційованого перебігу ієрсиніозу з іншими захворюваннями собак інфекційної природи

Onsager-Machlup theory and work fluctuation theorem for a harmonically driven Brownian particle

We extend Tooru-Cohen analysis for nonequilirium steady state(NSS) of a Brownian particle to nonequilibrium oscillatory state (NOS) of Brownian particle by considering time dependent external drive protocol. We consider an unbounded charged Brownian particle in the presence of an oscillating electric field and prove work fluctuation theorem, which is valid for any initial distribution and at all times. For harmonically bounded and constantly dragged Brownian particle considered by Tooru and Cohen, work fluctuation theorem is valid for any initial condition(also NSS), but only in large time limit. We use Onsager-Machlup Lagrangian with a constraint to obtain frequency dependent work distribution function, and describe entropy production rate and properties of dissipation functions for the present system using Onsager-Machlup functional.Comment: 6 pages, 1 figur

Effective pair potentials for spherical nanoparticles

An effective description for spherical nanoparticles in a fluid of point particles is presented. The points inside the nanoparticles and the point particles are assumed to interact via spherically symmetric additive pair potentials, while the distribution of points inside the nanoparticles is taken to be spherically symmetric and smooth. The resulting effective pair interactions between a nanoparticle and a point particle, as well as between two nanoparticles, are then given by spherically symmetric potentials. If overlap between particles is allowed, the effective potential generally has non-analytic points, but for each effective potential the expressions for different overlapping cases can be written in terms of one analytic auxiliary potential. Effective potentials for hollow nanoparticles (appropriate e.g. for buckyballs) are also considered, and shown to be related to those for solid nanoparticles. Finally, explicit expressions are given for the effective potentials derived from basic pair potentials of power law and exponential form, as well as from the commonly used London-Van der Waals, Morse, Buckingham, and Lennard-Jones potential. The applicability of the latter is demonstrated by comparison with an atomic description of nanoparticles with an internal face centered cubic structure.Comment: 27 pages, 12 figures. Unified description of overlapping and nonoverlapping particles added, as well as a comparison with an idealized atomic descriptio

Histocompatibility and Hematopoietic Transplantation in the Zebrafish

The zebrafish has proven to be an excellent model for human disease, particularly hematopoietic diseases, since these fish make similar types of blood cells as humans and other mammals. The genetic program that regulates the development and differentiation of hematopoietic cells is highly conserved. Hematopoietic stem cells (HSCs) are the source of all the blood cells needed by an organism during its lifetime. Identifying an HSC requires a functional assay, namely, a transplantation assay consisting of multilineage engraftment of a recipient and subsequent serial transplant recipients. In the past decade, several types of hematopoietic transplant assays have been developed in the zebrafish. An understanding of the major histocompatibility complex (MHC) genes in the zebrafish has lagged behind transplantation experiments, limiting the ability to perform unbiased competitive transplantation assays. This paper summarizes the different hematopoietic transplantation experiments performed in the zebrafish, both with and without immunologic matching, and discusses future directions for this powerful experimental model of human blood diseases

Crucial role of sidewalls in velocity distributions in quasi-2D granular gases

Our experiments and three-dimensional molecular dynamics simulations of particles confined to a vertical monolayer by closely spaced frictional walls (sidewalls) yield velocity distributions with non-Gaussian tails and a peak near zero velocity. Simulations with frictionless sidewalls are not peaked. Thus interactions between particles and their container are an important determinant of the shape of the distribution and should be considered when evaluating experiments on a tightly constrained monolayer of particles.Comment: 4 pages, 4 figures, Added reference, model explanation charified, other minor change

An Extension of the Fluctuation Theorem

Heat fluctuations are studied in a dissipative system with both mechanical and stochastic components for a simple model: a Brownian particle dragged through water by a moving potential. An extended stationary state fluctuation theorem is derived. For infinite time, this reduces to the conventional fluctuation theorem only for small fluctuations; for large fluctuations, it gives a much larger ratio of the probabilities of the particle to absorb rather than supply heat. This persists for finite times and should be observable in experiments similar to a recent one of Wang et al.Comment: 12 pages, 1 eps figure in color (though intelligible in black and white

Extended Heat-Fluctuation Theorems for a System with Deterministic and Stochastic Forces

Heat fluctuations over a time \tau in a non-equilibrium stationary state and in a transient state are studied for a simple system with deterministic and stochastic components: a Brownian particle dragged through a fluid by a harmonic potential which is moved with constant velocity. Using a Langevin equation, we find the exact Fourier transform of the distribution of these fluctuations for all \tau. By a saddle-point method we obtain analytical results for the inverse Fourier transform, which, for not too small \tau, agree very well with numerical results from a sampling method as well as from the fast Fourier transform algorithm. Due to the interaction of the deterministic part of the motion of the particle in the mechanical potential with the stochastic part of the motion caused by the fluid, the conventional heat fluctuation theorem is, for infinite and for finite \tau, replaced by an extended fluctuation theorem that differs noticeably and measurably from it. In particular, for large fluctuations, the ratio of the probability for absorption of heat (by the particle from the fluid) to the probability to supply heat (by the particle to the fluid) is much larger here than in the conventional fluctuation theorem.Comment: 23 pages, 6 figures. Figures are now in color, Eq. (67) was corrected and a footnote was added on the d-dimensional cas