Cyclin-Dependent Kinase 1 And Aurora Kinase Choreograph Mitotic Storage And Redistribution Of A Growth Factor Receptor

Endosomal trafficking of receptors and associated proteins plays a critical role in signal processing. Until recently, it was thought that trafficking was shut down during cell division. Thus, remarkably, the regulation of trafficking during division remains poorly characterized. Here we delineate the role of mitotic kinases in receptor trafficking during asymmetric division. Targeted perturbations reveal that Cyclin-dependent Kinase 1 (CDK1) and Aurora Kinase promote storage of Fibroblast Growth Factor Receptors (FGFRs) by suppressing endosomal degradation and recycling pathways. As cells progress through metaphase, loss of CDK1 activity permits differential degradation and targeted recycling of stored receptors, leading to asymmetric induction. Mitotic receptor storage, as delineated in this study, may facilitate rapid reestablishment of signaling competence in nascent daughter cells. However, mutations that limit or enhance the release of stored signaling components could alter daughter cell fate or behavior thereby promoting oncogenesis

Deploying Big Data To Crack The Genotype To Phenotype Code

Mechanistically connecting genotypes to phenotypes is a longstanding and central mission of biology. Deciphering these connections will unite questions and datasets across all scales from molecules to ecosystems. Although high-throughput sequencing has provided a rich platform on which to launch this effort, tools for deciphering mechanisms further along the genome to phenome pipeline remain limited. Machine learning approaches and other emerging computational tools hold the promise of augmenting human efforts to overcome these obstacles. This vision paper is the result of a Reintegrating Biology Workshop, bringing together the perspectives of integrative and comparative biologists to survey challenges and opportunities in cracking the genotype to phenotype code and thereby generating predictive frameworks across biological scales. Key recommendations include: promoting the development of minimum “best practices” for the experimental design and collection of data; fostering sustained and long-term data repositories; promoting programs that recruit, train, and retain a diversity of talent and providing funding to effectively support these highly cross-disciplinary efforts. We follow this discussion by highlighting a few specific transformative research opportunities that will be advanced by these efforts

An Atom Laser Based on Raman Transitions

In this paper we present an atom laser scheme using a Raman transition for the output coupling of atoms. A beam of thermal atoms (bosons) in a metastable atomic state $|1 >$ are pumped into a multimode atomic cavity. This cavity is coupled through spontaneous emission to a single mode of another cavity for the ground atomic state, $|2 >$. Above a certain threshold pumping rate a large number of atoms, $N_2$, builds up in this single quantum state and transitions to the ground state of the cavity become enhanced by a factor $(N_2 + 1)$. Atoms in this state are then coupled to the outside of the cavity with a Raman transition. This changes the internal state of the atom and imparts a momentum kick, allowing the atoms to leave the system.Comment: 8 pages, 4 postscript figures, uses RevTex, home page at http://online.anu.edu.au/Physics/Welcome.html (Some aspects of the exact physical model have changed from original version. Other general improvements included

Rotating Bose gas with hard-core repulsion in a quasi-2D harmonic trap: vortices in BEC

We consider a gas of N(=6, 10, 15) Bose particles with hard-core repulsion, contained in a quasi-2D harmonic trap and subjected to an overall angular velocity $\Omega$ about the z-axis. Exact diagonalization of the $n\times n$ many-body Hamiltonian matrix in given subspaces of the total (quantized) angular momentum L$_{z}$, with $n\sim 10^{5}$(e.g. for L$_{z}$=N=15, n =240782) was carried out using Davidson's algorithm. The many-body variational ground state wavefunction, as also the corresponding energy and the reduced one-particle density-matrix were calculated. With the usual identification of $\Omega$ as the Lagrange multiplier associated with L$_{z}$ for a rotating system, the $L_{z}-\Omega$ phase diagram (or the stability line) was determined that gave a number of critical angular velocities $\Omega_{{\bf c}i}, i=1,2,3,... ,$ at which the ground state angular momentum and the associated condensate fraction undergo abrupt jumps. A number of (total) angular momentum states were found to be stable at successively higher critical angular velocities $\Omega_{{\bf c}i}, \ i=1,2,3,...$for a given N. For$L_{z}>N$, the condensate was strongly depleted. The critical$\Omega_{{\bf c}i}$values, however, decreased with increasing interaction strength as well as the particle number, and were systematically greater than the non-variational Yrast-state values for the single vortex state with L$_{z}$=N. We have also observed that the condensate fraction for the single vortex state (as also for the higher vortex states) did not change significantly even as the 2-body interaction strength was varied over several$(\sim 4)$ orders of magnitude in the moderately to the weakly interacting regime.Comment: Revtex, 11 pages, 1 table as ps file, 4 figures as ps file

Resolved-sideband Raman cooling to the ground state of an optical lattice

We trap neutral Cs atoms in a two-dimensional optical lattice and cool them close to the zero-point of motion by resolved-sideband Raman cooling. Sideband cooling occurs via transitions between the vibrational manifolds associated with a pair of magnetic sublevels and the required Raman coupling is provided by the lattice potential itself. We obtain mean vibrational excitations \bar{n}_x \approx \bar{n}_y \approx 0.01, corresponding to a population \sim 98% in the vibrational ground state. Atoms in the ground state of an optical lattice provide a new system in which to explore quantum state control and subrecoil laser coolingComment: PDF file, 13 pages including 3 figure

The prevalence and incidence of mental ill-health in adults with autism and intellectual disabilities

The prevalence, and incidence, of mental ill-health in adults with intellectual disabilities and autism were compared with the whole population with intellectual disabilities, and with controls, matched individually for age, gender, ability-level, and Down syndrome. Although the adults with autism had a higher point prevalence of problem behaviours compared with the whole adult population with intellectual disabilities, compared with individually matched controls there was no difference in prevalence, or incidence of either problem behaviours or other mental ill-health. Adults with autism who had problem behaviours were less likely to recover over a two-year period than were their matched controls. Apparent differences in rates of mental ill-health are accounted for by factors other than autism, including Down syndrome and ability level

Energy spectrum of a 2D Dirac electron in the presence of a constant magnetic field

In this paper we obtain exact solutions of a 2D relativistic Dirac oscillator in the presence of a constant magnetic field. We compute the energy spectrum and discuss its dependence on the spin and magnetic field strength.Comment: 7 page

Amygdala-prefrontal coupling underlies individual differences in emotion regulation

Despite growing evidence on the neural bases of emotion regulation, little is known about the mechanisms underlying individual differences in cognitive regulation of negative emotion, and few studies have used objective measures to quantify regulatory success. Using a trait-like psychophysiological measure of emotion regulation, corrugator electromyography, we obtained an objective index of the ability to cognitively reappraise negative emotion in 56 healthy men (session 1), who returned 1.3 years later to perform the same regulation task using fMRI (session 2). Results indicated that the corrugator measure of regulatory skill predicted amygdala-prefrontal functional connectivity. Individuals with greater ability to down-regulate negative emotion as indexed by corrugator at session 1 showed not only greater amygdala attenuation but also greater inverse connectivity between the amygdala and several sectors of the prefrontal cortex while down-regulating negative emotion at session 2. Our results demonstrate that individual differences in emotion regulation are stable over time and underscore the important role of amygdala-prefrontal coupling for successful regulation of negative emotion

Enhancing the genome editing toolbox: genome wide CRISPR arrayed libraries.

CRISPR-Cas9 technology has accelerated biological research becoming routine for many laboratories. It is rapidly replacing conventional gene editing techniques and has high utility for both genome-wide and gene-focussed applications. Here we present the first individually cloned CRISPR-Cas9 genome wide arrayed sgRNA libraries covering 17,166 human and 20,430 mouse genes at a complexity of 34,332 sgRNAs for human and 40,860 sgRNAs for the mouse genome. For flexibility in generating stable cell lines the sgRNAs have been cloned in a lentivirus backbone containing PiggyBac transposase recognition elements together with fluorescent and drug selection markers. Over 95% of tested sgRNA induced specific DNA cleavage as measured by CEL-1 assays. Furthermore, sgRNA targeting GPI anchor protein pathway genes induced loss of function mutations in human and mouse cell lines measured by FLAER labelling. These arrayed libraries offer the prospect for performing screens on individual genes, combinations as well as larger gene sets. They also facilitate rapid deconvolution of signals from genome-wide screens. This set of vectors provide an organized comprehensive gene editing toolbox of considerable scientific value

We are all one together : peer educators\u27 views about falls prevention education for community-dwelling older adults - a qualitative study

Background: Falls are common in older people. Despite strong evidence for effective falls prevention strategies, there appears to be limited translation of these strategies from research to clinical practice. Use of peers in delivering falls prevention education messages has been proposed to improve uptake of falls prevention strategies and facilitate translation to practice. Volunteer peer educators often deliver educational presentations on falls prevention to community-dwelling older adults. However, research evaluating the effectiveness of peer-led education approaches in falls prevention has been limited and no known study has evaluated such a program from the perspective of peer educators involved in delivering the message. The purpose of this study was to explore peer educators’ perspective about their role in delivering peer-led falls prevention education for community-dwelling older adults. Methods: A two-stage qualitative inductive constant comparative design was used.In stage one (core component) focus group interviews involving a total of eleven participants were conducted. During stage two (supplementary component) semi-structured interviews with two participants were conducted. Data were analysed thematically by two researchers independently. Key themes were identified and findings were displayed in a conceptual framework. Results: Peer educators were motivated to deliver educational presentations and importantly, to reach an optimal peer connection with their audience. Key themes identified included both personal and organisational factors that impact on educators’ capacity to facilitate their peers’ engagement with the message. Personal factors that facilitated message delivery and engagement included peer-to-peer connection and perceived credibility, while barriers included a reluctance to accept the message that they were at risk of falling by some members in the audience. Organisational factors, including ongoing training for peer educators and formative feedback following presentations, were perceived as essential because they affect successful message delivery. Conclusions: Peer educators have the potential to effectively deliver falls prevention education to older adults and influence acceptance of the message as they possess the peer-to-peer connection that facilitates optimal engagement. There is a need to consider incorporating learnings from this research into a formal large scale evaluation of the effectiveness of the peer education approach in reducing falls in older adults