32 research outputs found
Center-surround vs. distance-independent lateral connectivity in the olfactory bulb
Lateral neuronal interactions are known to play important roles in sensory information processing. A center-on surround-off local circuit arrangement has been shown to play a role in mediating contrast enhancement in the visual, auditory, and somatosensory systems. The lateral connectivity and the influence of those connections have been less clear for the olfactory system. A critical question is whether the synaptic connections between the primary projection neurons, mitral and tufted (M/T) cells, and their main inhibitory interneurons, the granule cells (GCs), can support a center-surround motif. Here, we study this question by injecting a ācenterā in the glomerular layer of the olfactory bulb (OB) with a marker of synaptic connectivity, the pseudorabies virus (PRV), then examines the distribution of labeling in the āsurroundā of GCs. We use a novel method to score the degree to which the data fits a center-surround model vs. distance-independent connectivity. Data from 22 injections show that M/T cells generally form lateral connections with GCs in patterns that lie between the two extremes
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A Framework for Exploring Functional Variability in Olfactory Receptor Genes
Background: Olfactory receptors (ORs) are the largest gene family in mammalian genomes. Since nearly all OR genes are orphan receptors, inference of functional similarity or differences between odorant receptors typically relies on sequence comparisons. Based on the alignment of entire coding region sequence, OR genes are classified into families and subfamilies, a classification that is believed to be a proxy for OR gene functional variability. However, the assumption that overall protein sequence diversity is a good proxy for functional properties is untested.Methodology: Here, we propose an alternative sequence-based approach to infer the similarities and differences in OR binding capacity. Our approach is based on similarities and differences in the predicted binding pockets of OR genes, rather than on the entire OR coding region.Conclusions: Interestingly, our approach yields markedly different results compared to the analysis based on the entire OR coding-regions. While neither approach can be tested at this time, the discrepancy between the two calls into question the assumption that the current classification reliably reflects OR gene functional variability.</p
Lateral Connectivity in the Olfactory Bulb is Sparse and Segregated
Lateral connections in the olfactory bulb were previously thought to be organized for centerāsurround inhibition. However, recent anatomical and physiological studies showed sparse and distributed interactions of inhibitory granule cells (GCs) which tended to be organized in columnar clusters. Little is known about how these distributed clusters are interconnected. In this study, we use transsynaptic tracing viruses bearing green or red fluorescent proteins to further elucidate mitral- and tufted-to-GC connectivity. Separate sites in the glomerular layer were injected with each virus. Columns with labeling from both viruses after transsynaptic spread show sparse red or green GCs which tended to be segregated. However, there was a higher incidence of co-labeled cells than chance would predict. Similar segregation of labeling is observed from dual injections into olfactory cortex. Collectively, these results suggest that neighboring mitral and tufted cells receive inhibitory inputs from segregated subsets of GCs, enabling inhibition of a center by specific and discontinuous lateral elements
Systematic first-principles study of impurity hybridization in NiAl
We have performed a systematic first-principles computational study of the
effects of impurity atoms (boron, carbon, nitrogen, oxygen, silicon, phosporus,
and sulfur) on the orbital hybridization and bonding properties in the
intermetallic alloy NiAl using a full-potential linear muffin-tin orbital
method. The matrix elements in momentum space were used to calculate real-space
properties: onsite parameters, partial densities of states, and local charges.
In impurity atoms that are empirically known to be embrittler (N and O) we
found that the 2s orbital is bound to the impurity and therefore does not
participate in the covalent bonding. In contrast, the corresponding 2s orbital
is found to be delocalized in the cohesion enhancers (B and C). Each of these
impurity atoms is found to acquire a net negative local charge in NiAl
irrespective of whether they sit in the Ni or Al site. The embrittler therefore
reduces the total number of electrons available for covalent bonding by
removing some of the electrons from the neighboring Ni or Al atoms and
localizing them at the impurity site. We show that these correlations also hold
for silicon, phosporus, and sulfur.Comment: Revtex, 8 pages, 7 eps figures, to appear in Phys. Rev.
Deep Underground Science and Engineering Laboratory - Preliminary Design Report
The DUSEL Project has produced the Preliminary Design of the Deep Underground
Science and Engineering Laboratory (DUSEL) at the rehabilitated former
Homestake mine in South Dakota. The Facility design calls for, on the surface,
two new buildings - one a visitor and education center, the other an experiment
assembly hall - and multiple repurposed existing buildings. To support
underground research activities, the design includes two laboratory modules and
additional spaces at a level 4,850 feet underground for physics, biology,
engineering, and Earth science experiments. On the same level, the design
includes a Department of Energy-shepherded Large Cavity supporting the Long
Baseline Neutrino Experiment. At the 7,400-feet level, the design incorporates
one laboratory module and additional spaces for physics and Earth science
efforts. With input from some 25 science and engineering collaborations, the
Project has designed critical experimental space and infrastructure needs,
including space for a suite of multidisciplinary experiments in a laboratory
whose projected life span is at least 30 years. From these experiments, a
critical suite of experiments is outlined, whose construction will be funded
along with the facility. The Facility design permits expansion and evolution,
as may be driven by future science requirements, and enables participation by
other agencies. The design leverages South Dakota's substantial investment in
facility infrastructure, risk retirement, and operation of its Sanford
Laboratory at Homestake. The Project is planning education and outreach
programs, and has initiated efforts to establish regional partnerships with
underserved populations - regional American Indian and rural populations
The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe
The preponderance of matter over antimatter in the early Universe, the
dynamics of the supernova bursts that produced the heavy elements necessary for
life and whether protons eventually decay --- these mysteries at the forefront
of particle physics and astrophysics are key to understanding the early
evolution of our Universe, its current state and its eventual fate. The
Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed
plan for a world-class experiment dedicated to addressing these questions. LBNE
is conceived around three central components: (1) a new, high-intensity
neutrino source generated from a megawatt-class proton accelerator at Fermi
National Accelerator Laboratory, (2) a near neutrino detector just downstream
of the source, and (3) a massive liquid argon time-projection chamber deployed
as a far detector deep underground at the Sanford Underground Research
Facility. This facility, located at the site of the former Homestake Mine in
Lead, South Dakota, is approximately 1,300 km from the neutrino source at
Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino
charge-parity symmetry violation and mass ordering effects. This ambitious yet
cost-effective design incorporates scalability and flexibility and can
accommodate a variety of upgrades and contributions. With its exceptional
combination of experimental configuration, technical capabilities, and
potential for transformative discoveries, LBNE promises to be a vital facility
for the field of particle physics worldwide, providing physicists from around
the globe with opportunities to collaborate in a twenty to thirty year program
of exciting science. In this document we provide a comprehensive overview of
LBNE's scientific objectives, its place in the landscape of neutrino physics
worldwide, the technologies it will incorporate and the capabilities it will
possess.Comment: Major update of previous version. This is the reference document for
LBNE science program and current status. Chapters 1, 3, and 9 provide a
comprehensive overview of LBNE's scientific objectives, its place in the
landscape of neutrino physics worldwide, the technologies it will incorporate
and the capabilities it will possess. 288 pages, 116 figure
A Framework for Exploring Functional Variability in Olfactory Receptor Genes
BACKGROUND: Olfactory receptors (ORs) are the largest gene family in mammalian genomes. Since nearly all OR genes are orphan receptors, inference of functional similarity or differences between odorant receptors typically relies on sequence comparisons. Based on the alignment of entire coding region sequence, OR genes are classified into families and subfamilies, a classification that is believed to be a proxy for OR gene functional variability. However, the assumption that overall protein sequence diversity is a good proxy for functional properties is untested. METHODOLOGY: Here, we propose an alternative sequence-based approach to infer the similarities and differences in OR binding capacity. Our approach is based on similarities and differences in the predicted binding pockets of OR genes, rather than on the entire OR coding region. CONCLUSIONS: Interestingly, our approach yields markedly different results compared to the analysis based on the entire OR coding-regions. While neither approach can be tested at this time, the discrepancy between the two calls into question the assumption that the current classification reliably reflects OR gene functional variability
Fluorescence Resonance Energy Transfer Microscopy of the Helicobacter pylori Vacuolating Cytotoxin within Mammalian Cells
The Helicobacter pylori vacuolating cytotoxin (VacA) binds and enters mammalian cells to induce cellular vacuolation. To investigate the quaternary structure of VacA within the intracellular environment where toxin cytotoxicity is elaborated, we employed fluorescence resonance energy transfer (FRET) microscopy. HeLa cells coexpressing full-length and truncated forms of VacA fused to cyan fluorescent protein (CFP) or yellow fluorescent protein (YFP) were analyzed for FRET to indicate direct associations. These studies revealed that VacA-CFP and VacA-YFP interact within vacuolated cells, supporting the belief that monomer associations at an intracellular site are important for the toxin's vacuolating activity. In addition, the two fragments of proteolytically nicked VacA, p37 and p58, interact when coexpressed within mammalian cells. Because p37 and p58 function in trans when expressed separately within mammalian cells, these data suggest that the mechanism by which these two fragments induce vacuolation requires direct association. FRET microscopy also demonstrated interactions between mutant forms of VacA, as well as wild-type VacA with mutant forms of the toxin within vacuolated cells. Finally, a dominant-negative form of the toxin directly associates with wild-type VacA in cells where vacuolation was not detectable, suggesting that the formation of complexes comprising wild-type and dominant-negative forms of toxin acts to block intracellular toxin function