441 research outputs found
Computational exploration of molecular receptive fields in the olfactory bulb reveals a glomerulus-centric chemical map
© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Progress in olfactory research is currently hampered by incomplete knowledge about chemical receptive ranges of primary receptors. Moreover, the chemical logic underlying the arrangement of computational units in the olfactory bulb has still not been resolved. We undertook a large-scale approach at characterising molecular receptive ranges (MRRs) of glomeruli in the dorsal olfactory bulb (dOB) innervated by the MOR18-2 olfactory receptor, also known as Olfr78, with human ortholog OR51E2. Guided by an iterative approach that combined biological screening and machine learning, we selected 214 odorants to characterise the response of MOR18-2 and its neighbouring glomeruli. We found that a combination of conventional physico-chemical and vibrational molecular descriptors performed best in predicting glomerular responses using nonlinear Support-Vector Regression. We also discovered several previously unknown odorants activating MOR18-2 glomeruli, and obtained detailed MRRs of MOR18-2 glomeruli and their neighbours. Our results confirm earlier findings that demonstrated tunotopy, that is, glomeruli with similar tuning curves tend to be located in spatial proximity in the dOB. In addition, our results indicate chemotopy, that is, a preference for glomeruli with similar physico-chemical MRR descriptions being located in spatial proximity. Together, these findings suggest the existence of a partial chemical map underlying glomerular arrangement in the dOB. Our methodology that combines machine learning and physiological measurements lights the way towards future high-throughput studies to deorphanise and characterise structure-activity relationships in olfaction.Peer reviewe
Detection of minimal residual disease identifies differences in treatment response between T-ALL and precursor B-ALL
We performed sensitive polymerase chain reaction-based minimal residual
disease (MRD) analyses on bone marrow samples at 9 follow-up time points
in 71 children with T-lineage acute lymphoblastic leukemia (T-ALL) and
compared the results with the precursor B-lineage ALL (B-ALL) results (n =
210) of our previous study. At the first 5 follow-up time points, the
frequency of MRD-positive patients and the MRD levels were higher in T-ALL
than in precursor-B-ALL, reflecting the more frequent occurrence of
resistant disease in T-ALL. Subsequently, patients were classified
according to their MRD level at time point 1 (TP1), taken at the end of
induction treatment (5 weeks), and at TP2 just before the start of
consolidation treatment (3 months). Patients were considered at low risk
if TP1 and TP2 were MRD negative and at high risk if MRD levels at TP1 and
TP2 were 10(-3) or higher; remaining patients were considered at
intermediate risk. The relative distribution of patients with T-ALL (n =
43) over the MRD-based risk groups differed significantly from that of
precursor B-ALL (n = 109). Twenty-three percent of patients with T-ALL and
46% of patients with precursor B-ALL were classified in the low-risk group
(P =.01) and had a 5-year relapse-free survival (RFS) rate of 98% or
greater. In contrast, 28% of patients with T-ALL were classified in the
MRD-based high-risk group compared to only 11% of patients with precursor
B-ALL (P =.02), and the RFS rates were 0% and 25%, respectively (P =.03).
Not only was the distribution of patients with T-ALL different over the
MRD-based risk groups, the prognostic value of MRD levels at TP1 and TP2
was higher in T-ALL (larger RFS gradient), and consistently higher RFS
rates were found for MRD-negative T-ALL patients at the first 5 follow-up
time points
Theory of the c-Axis Penetration Depth in the Cuprates
Recent measurements of the London penetration depth tensor in the cuprates
find a weak temperature dependence along the c-direction which is seemingly
inconsistent with evidence for d-wave pairing deduced from in-plane
measurements. We demonstrate in this paper that these disparate results are not
in contradiction, but can be explained within a theory based on incoherent
quasiparticle hopping between the CuO2 layers. By relating the calculated
temperature dependence of the penetration depth \lambda_c(T) to the c-axis
resistivity, we show how the measured ratio \lambda_c^2(0) / \lambda_c^2(T) can
provide insight into the behavior of c-axis transport below Tc and the related
issue of ``confinement.''Comment: 4 pages, REVTEX with psfig, 3 PostScript figures included in
compressed for
Frequency Characteristics of Visually Induced Motion Sickness
This article was published in the journal, Human Factors [Sage Publications / © Human Factors and Ergonomics Society.]. The definitive version is available at: http://dx.doi.org/10.1177/0018720812469046Objective: The aim of this study was to explore
the frequency response of visually induced motion
sickness (VIMS) for oscillating linear motion in the foreand-
aft axis.
Background: Simulators, virtual environments,
and commercially available video games that create an
illusion of self-motion are often reported to induce
the symptoms seen in response to true motion. Often
this human response can be the limiting factor in the
acceptability and usability of such systems. Whereas
motion sickness in physically moving environments
is known to peak at an oscillation frequency around
0.2 Hz, it has recently been suggested that VIMS peaks
at around 0.06 Hz following the proposal that the
summed response of the visual and vestibular selfmotion
systems is maximized at this frequency. Methods: We exposed 24 participants to random
dot optical flow patterns simulating oscillating foreand-
aft motion within the frequency range of 0.025 to
1.6 Hz. Before and after each 20-min exposure, VIMS was
assessed with the Simulator Sickness Questionnaire.
Also, a standard motion sickness scale was used to rate
symptoms at 1-min intervals during each trial.
Results: VIMS peaked between 0.2 and 0.4 Hz with
a reducing effect at lower and higher frequencies.
Conclusion: The numerical prediction of the
“crossover frequency” hypothesis, and the design
guidance curve previously proposed, cannot be accepted
when the symptoms are purely visually induced.
Application: In conditions in which stationary
observers are exposed to optical flow that simulates
oscillating fore-and-aft motion, frequencies around 0.2
to 0.4 Hz should be avoided
Regulation of PTEN expression by the SWI/SNF chromatin-remodelling protein BRG1 in human colorectal carcinoma cells
Amiloride-sensitive channels in type I fungiform taste cells in mouse
<p>Abstract</p> <p>Background</p> <p>Taste buds are the sensory organs of taste perception. Three types of taste cells have been described. Type I cells have voltage-gated outward currents, but lack voltage-gated inward currents. These cells have been presumed to play only a support role in the taste bud. Type II cells have voltage-gated Na<sup>+ </sup>and K<sup>+ </sup>current, and the receptors and transduction machinery for bitter, sweet, and umami taste stimuli. Type III cells have voltage-gated Na<sup>+</sup>, K<sup>+</sup>, and Ca<sup>2+ </sup>currents, and make prominent synapses with afferent nerve fibers. Na<sup>+ </sup>salt transduction in part involves amiloride-sensitive epithelial sodium channels (ENaCs). In rodents, these channels are located in taste cells of fungiform papillae on the anterior part of the tongue innervated by the chorda tympani nerve. However, the taste cell type that expresses ENaCs is not known. This study used whole cell recordings of single fungiform taste cells of transgenic mice expressing GFP in Type II taste cells to identify the taste cells responding to amiloride. We also used immunocytochemistry to further define and compare cell types in fungiform and circumvallate taste buds of these mice.</p> <p>Results</p> <p>Taste cell types were identified by their response to depolarizing voltage steps and their presence or absence of GFP fluorescence. TRPM5-GFP taste cells expressed large voltage-gated Na<sup>+ </sup>and K<sup>+ </sup>currents, but lacked voltage-gated Ca<sup>2+ </sup>currents, as expected from previous studies. Approximately half of the unlabeled cells had similar membrane properties, suggesting they comprise a separate population of Type II cells. The other half expressed voltage-gated outward currents only, typical of Type I cells. A single taste cell had voltage-gated Ca<sup>2+ </sup>current characteristic of Type III cells. Responses to amiloride occurred only in cells that lacked voltage-gated inward currents. Immunocytochemistry showed that fungiform taste buds have significantly fewer Type II cells expressing PLC signalling components, and significantly fewer Type III cells than circumvallate taste buds.</p> <p>Conclusion</p> <p>The principal finding is that amiloride-sensitive Na<sup>+ </sup>channels appear to be expressed in cells that lack voltage-gated inward currents, likely the Type I taste cells. These cells were previously assumed to provide only a support function in the taste bud.</p
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