222 research outputs found
In Vivo Expansion of Co-Transplanted T Cells Impacts on Tumor Re-Initiating Activity of Human Acute Myeloid Leukemia in NSG Mice
Human cells from acute myeloid leukemia (AML) patients are frequently transplanted into immune-compromised mouse strains to provide an in vivo environment for studies on the biology of the disease. Since frequencies of leukemia re-initiating cells are low and a unique cell surface phenotype that includes all tumor re-initiating activity remains unknown, the underlying mechanisms leading to limitations in the xenotransplantation assay need to be understood and overcome to obtain robust engraftment of AML-containing samples. We report here that in the NSG xenotransplantation assay, the large majority of mononucleated cells from patients with AML fail to establish a reproducible myeloid engraftment despite high donor chimerism. Instead, donor-derived cells mainly consist of polyclonal disease-unrelated expanded co-transplanted human T lymphocytes that induce xenogeneic graft versus host disease and mask the engraftment of human AML in mice. Engraftment of mainly myeloid cell types can be enforced by the prevention of T cell expansion through the depletion of lymphocytes from the graft prior transplantation
Slowing and cooling molecules and neutral atoms by time-varying electric field gradients
A method of slowing, accelerating, cooling, and bunching molecules and
neutral atoms using time-varying electric field gradients is demonstrated with
cesium atoms in a fountain. The effects are measured and found to be in
agreement with calculation. Time-varying electric field gradient slowing and
cooling is applicable to atoms that have large dipole polarizabilities,
including atoms that are not amenable to laser slowing and cooling, to Rydberg
atoms, and to molecules, especially polar molecules with large electric dipole
moments. The possible applications of this method include slowing and cooling
thermal beams of atoms and molecules, launching cold atoms from a trap into a
fountain, and measuring atomic dipole polarizabilities.Comment: 13 pages, 10 figures. Scheduled for publication in Nov. 1 Phys. Rev.
Triadic (ecological, neural, cognitive) niche construction: a scenario of human brain evolution extrapolating tool use and language from the control of reaching actions
Hominin evolution has involved a continuous process of addition of new kinds of cognitive capacity, including those relating to manufacture and use of tools and to the establishment of linguistic faculties. The dramatic expansion of the brain that accompanied additions of new functional areas would have supported such continuous evolution. Extended brain functions would have driven rapid and drastic changes in the hominin ecological niche, which in turn demanded further brain resources to adapt to it. In this way, humans have constructed a novel niche in each of the ecological, cognitive and neural domains, whose interactions accelerated their individual evolution through a process of triadic niche construction. Human higher cognitive activity can therefore be viewed holistically as one component in a terrestrial ecosystem. The brain's functional characteristics seem to play a key role in this triadic interaction. We advance a speculative argument about the origins of its neurobiological mechanisms, as an extension (with wider scope) of the evolutionary principles of adaptive function in the animal nervous system. The brain mechanisms that subserve tool use may bridge the gap between gesture and language—the site of such integration seems to be the parietal and extending opercular cortices
The Educational and Professional Background of Central Bankers and its Effect on Inflation - An Empirical Analysis
Analysis of Area-Specific Expression Patterns of RORbeta, ER81 and Nurr1 mRNAs in Rat Neocortex by Double In Situ Hybridization and Cortical Box Method
BACKGROUND: The mammalian neocortex is subdivided into many areas, each of which exhibits distinctive lamina architecture. To investigate such area differences in detail, we chose three genes for comparative analyses, namely, RORbeta, ER81 and Nurr1, mRNAs of which have been reported to be mainly expressed in layers 4, 5 and 6, respectively. To analyze their qualitative and quantitative coexpression profiles in the rat neocortex, we used double in situ hybridization (ISH) histochemistry and cortical box method which we previously developed to integrate the data of different staining and individuals in a standard three-dimensional space. PRINCIPAL FINDINGS: Our new approach resulted in three main observations. First, the three genes showed unique area distribution patterns that are mostly complementary to one another. The patterns revealed by cortical box method matched well with the cytoarchitectonic areas defined by Nissl staining. Second, at single cell level, RORbeta and ER81 mRNAs were coexpressed in a subpopulation of layer 5 neurons, whereas Nurr1 and ER81 mRNAs were not colocalized. Third, principal component analysis showed that the order of hierarchical processing in the cortex correlates well with the expression profiles of these three genes. Based on this analysis, the dysgranular zone (DZ) in the somatosensory area was considered to exhibit a profile of a higher order area, which is consistent with previous proposal. CONCLUSIONS/SIGNIFICANCE: The tight relationship between the expression of the three layer specific genes and functional areas were revealed, demonstrating the usefulness of cortical box method in the study on the cerebral cortex. In particular, it allowed us to perform statistical evaluation and pattern matching, which would become important in interpreting the ever-increasing data of gene expression in the cortex
Frontal and insular input to the dorsolateral temporal pole in primates: Implications for auditory memory
The temporal pole (TP) has been involved in multiple functions from emotional and
social behavior, semantic processing,memory, language in humans and epilepsy surgery,
to the fronto-temporal neurodegenerative disorder (semantic) dementia. However, the
role of the TP subdivisions is still unclear, in part due to the lack of quantitative data
about TP connectivity. This study focuses in the dorsolateral subdivision of the TP:
area 38DL. Area 38DL main input originates in the auditory processing areas of the
rostral superior temporal gyrus. Among other connections, area 38DL conveys this
auditory highly processed information to the entorhinal, rostral perirhinal, and posterior
parahippocampal cortices, presumably for storage in long-term memory (Muñoz-López
et al., 2015). However, the connections of the TP with cortical areas beyond the temporal
cortex suggest that this area is part of a wider network. With the aim to quantitatively
determine the topographical, laminar pattern and weighting of the lateral TP afferents
from the frontal and insular cortices, we placed a total of 11 tracer injections of the
fluorescent retrograde neuronal tracers Fast Blue and Diamidino Yellow at different levels
of the lateral TP in rhesus monkeys. The results showed that circa 50% of the total
cortical input to area 38DL originates in medial frontal areas 14, 25, 32, and 24 (25%);
orbitofrontal areas Pro and PAll (15%); and the agranular, parainsular and disgranular
insula (10%). This study sets the anatomical bases to better understand the function of
the dorsolateral division of the TP. More specifically, these results suggest that area 38DL
forms part of the wider limbic circuit that might contribute, among other functions, with
an auditory component to multimodal memory processing
Feed-Forward Segmentation of Figure-Ground and Assignment of Border-Ownership
Figure-ground is the segmentation of visual information into objects and their surrounding backgrounds. Two main processes herein are boundary assignment and surface segregation, which rely on the integration of global scene information. Recurrent processing either by intrinsic horizontal connections that connect surrounding neurons or by feedback projections from higher visual areas provide such information, and are considered to be the neural substrate for figure-ground segmentation. On the contrary, a role of feedforward projections in figure-ground segmentation is unknown. To have a better understanding of a role of feedforward connections in figure-ground organization, we constructed a feedforward spiking model using a biologically plausible neuron model. By means of surround inhibition our simple 3-layered model performs figure-ground segmentation and one-sided border-ownership coding. We propose that the visual system uses feed forward suppression for figure-ground segmentation and border-ownership assignment
Comprehensive in vivo Mapping of the Human Basal Ganglia and Thalamic Connectome in Individuals Using 7T MRI
Basal ganglia circuits are affected in neurological disorders such as Parkinson's disease (PD), essential tremor, dystonia and Tourette syndrome. Understanding the structural and functional connectivity of these circuits is critical for elucidating the mechanisms of the movement and neuropsychiatric disorders, and is vital for developing new therapeutic strategies such as deep brain stimulation (DBS). Knowledge about the connectivity of the human basal ganglia and thalamus has rapidly evolved over recent years through non-invasive imaging techniques, but has remained incomplete because of insufficient resolution and sensitivity of these techniques. Here, we present an imaging and computational protocol designed to generate a comprehensive in vivo and subject-specific, three-dimensional model of the structure and connections of the human basal ganglia. High-resolution structural and functional magnetic resonance images were acquired with a 7-Tesla magnet. Capitalizing on the enhanced signal-to-noise ratio (SNR) and enriched contrast obtained at high-field MRI, detailed structural and connectivity representations of the human basal ganglia and thalamus were achieved. This unique combination of multiple imaging modalities enabled the in-vivo visualization of the individual human basal ganglia and thalamic nuclei, the reconstruction of seven white-matter pathways and their connectivity probability that, to date, have only been reported in animal studies, histologically, or group-averaged MRI population studies. Also described are subject-specific parcellations of the basal ganglia and thalamus into sub-territories based on their distinct connectivity patterns. These anatomical connectivity findings are supported by functional connectivity data derived from resting-state functional MRI (R-fMRI). This work demonstrates new capabilities for studying basal ganglia circuitry, and opens new avenues of investigation into the movement and neuropsychiatric disorders, in individual human subjects
Population Genomics of Parallel Adaptation in Threespine Stickleback using Sequenced RAD Tags
Next-generation sequencing technology provides novel opportunities for gathering genome-scale sequence data in natural populations, laying the empirical foundation for the evolving field of population genomics. Here we conducted a genome scan of nucleotide diversity and differentiation in natural populations of threespine stickleback (Gasterosteus aculeatus). We used Illumina-sequenced RAD tags to identify and type over 45,000 single nucleotide polymorphisms (SNPs) in each of 100 individuals from two oceanic and three freshwater populations. Overall estimates of genetic diversity and differentiation among populations confirm the biogeographic hypothesis that large panmictic oceanic populations have repeatedly given rise to phenotypically divergent freshwater populations. Genomic regions exhibiting signatures of both balancing and divergent selection were remarkably consistent across multiple, independently derived populations, indicating that replicate parallel phenotypic evolution in stickleback may be occurring through extensive, parallel genetic evolution at a genome-wide scale. Some of these genomic regions co-localize with previously identified QTL for stickleback phenotypic variation identified using laboratory mapping crosses. In addition, we have identified several novel regions showing parallel differentiation across independent populations. Annotation of these regions revealed numerous genes that are candidates for stickleback phenotypic evolution and will form the basis of future genetic analyses in this and other organisms. This study represents the first high-density SNP–based genome scan of genetic diversity and differentiation for populations of threespine stickleback in the wild. These data illustrate the complementary nature of laboratory crosses and population genomic scans by confirming the adaptive significance of previously identified genomic regions, elucidating the particular evolutionary and demographic history of such regions in natural populations, and identifying new genomic regions and candidate genes of evolutionary significance
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