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1.
Opt Express ; 31(16): 26854-26864, 2023 Jul 31.
Article in English | MEDLINE | ID: mdl-37710535

ABSTRACT

We report on the complete temporal characterization of ultrashort pulses, generated by resonant dispersive wave emission in gas-filled hollow-capillary fibers, with energy in the microjoule range and continuously tunable from the deep-ultraviolet to the ultraviolet. Temporal characterization of such ultrabroad pulses, particularly challenging in this spectral region, was performed using an all-in-vacuum setup for self-diffraction frequency resolved optical gating (SD-FROG). Sub-3-fs pulses were measured, tunable from 250 nm to 350 nm, with a minimum pulse duration of 2.4 ± 0.1 fs.

2.
Neuroscience ; 495: 115-125, 2022 07 15.
Article in English | MEDLINE | ID: mdl-35659639

ABSTRACT

Responses in the rostral (gustatory) nucleus of the solitary tract (rNST) are modified by synaptic interactions within the nucleus and the constitutive membrane properties of the neurons themselves. The potassium current IA is one potential source of modulation. In the caudal NST, projection neurons with IA show lower fidelity to afferent stimulation compared to cells without. We explored the role of an A-type K+ current (IA) in modulating the response to afferent stimulation and GABA-mediated inhibition in the rNST using whole cell patch clamp recording in transgenic mice that expressed channelrhodopsin (ChR2 H134R) in GABAergic neurons. The presence of IA was determined in current clamp and the response to electrical stimulation of afferent fibers in the solitary tract was assessed before and after treatment with the specific Kv4 channel blocker AmmTX3. Blocking IA significantly increased the response to afferent stimulation by 53%. Using dynamic clamp to create a synthetic IA conductance, we demonstrated a significant 14% decrease in responsiveness to afferent stimulation in cells lacking IA. Because IA reduced excitability and is hyperpolarization-sensitive, we examined whether IA contributed to the inhibition resulting from optogenetic release of GABA. Although blocking IA decreased the percent suppression induced by GABA, this effect was attributable to the increased responsiveness resulting from AmmTX3, not to a change in the absolute magnitude of suppression. We conclude that rNST responses to afferent input are regulated independently by IA and GABA.


Subject(s)
GABAergic Neurons , Solitary Nucleus , Animals , Electric Stimulation , Mice , Patch-Clamp Techniques , Taste/physiology , gamma-Aminobutyric Acid/pharmacology
3.
J Neurophysiol ; 124(6): 1727-1742, 2020 12 01.
Article in English | MEDLINE | ID: mdl-32997557

ABSTRACT

The rostral nucleus of the solitary tract (rNST) serves as the first central relay in the gustatory system. In addition to synaptic interactions, central processing is also influenced by the ion channel composition of individual neurons. For example, voltage-gated K+ channels such as outward K+ current (IA) can modify the integrative properties of neurons. IA currents are prevalent in rNST projection cells but are also found to a lesser extent in GABAergic interneurons. However, characterization of the kinetic properties of IA, the molecular basis of these currents, as well as the consequences of IA on spiking properties of identified rNST cells is lacking. Here, we show that IA in rNST GABAergic (G+) and non-GABAergic (G-) neurons share a common molecular basis. In both cell types, there was a reduction in IA following treatment with the specific Kv4 channel blocker AmmTx3. However, the kinetics of activation and inactivation of IA in the two cell types were different with G- neurons having significantly more negative half-maximal activation and inactivation values. Likewise, under current clamp, G- cells had significantly longer delays to spike initiation in response to a depolarizing stimulus preceded by a hyperpolarizing prepulse. Computational modeling and dynamic clamp suggest that differences in the activation half-maximum may account for the differences in delay. We further observed evidence for a window current under both voltage clamp and current clamp protocols. We speculate that the location of Kv4.3 channels on dendrites, together with a window current for IA at rest, serves to regulate excitatory afferent inputs.NEW & NOTEWORTHY Here, we demonstrate that the transient outward K+ current IA occurs in both GABAergic and non-GABAergic neurons via Kv4.3 channels in the rostral (gustatory) solitary nucleus. Although found in both cell types, IA is more prevalent in non-GABAergic cells; a larger conductance at more negative potentials leads to a greater impact on spike initiation compared with GABAergic neurons. An IA window current further suggests that IA can regulate excitatory afferent input to the nucleus.


Subject(s)
Electrophysiological Phenomena/physiology , GABAergic Neurons/physiology , Interneurons/physiology , Shal Potassium Channels/metabolism , Solitary Nucleus/physiology , Taste Perception/physiology , Animals , Female , GABAergic Neurons/metabolism , Interneurons/metabolism , Male , Mice , Mice, Transgenic , Shal Potassium Channels/antagonists & inhibitors , Solitary Nucleus/metabolism
4.
Oncogene ; 39(24): 4780, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32427987

ABSTRACT

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

6.
Sci Rep ; 7(1): 17563, 2017 12 14.
Article in English | MEDLINE | ID: mdl-29242581

ABSTRACT

The molecular and cellular etiology of eosinophilic esophagitis (EoE), an emerging tissue-specific allergic disease, involves dysregulated gene expression in esophageal epithelial cells. Herein, we assessed the esophageal expression of IL-33, an epithelium-derived alarmin cytokine, in patients with EoE. IL-33 protein was markedly overexpressed within the nuclei of a subpopulation of basal layer esophageal epithelial cells in patients with active EoE compared to control individuals. IL-33 exhibited dynamic expression as levels normalized upon EoE remission. IL-33-positive basal epithelial cells expressed E-cadherin and the undifferentiated epithelial cell markers keratin 5 and 14 but not the differentiation marker keratin 4. Moreover, the IL-33-positive epithelial cells expressed the epithelial progenitor markers p75 and p63 and lacked the proliferation markers Ki67 and phospho-histone H3. Additionally, the IL-33-positive cells had low expression of PCNA. IL-33 expression was detected in ex vivo-cultured primary esophageal epithelial cells in a subpopulation of cells lacking expression of proliferation markers. Collectively, we report that IL-33 expression is induced in an undifferentiated, non-dividing esophageal epithelial cell population in patients with active EoE.


Subject(s)
Eosinophilic Esophagitis/metabolism , Eosinophilic Esophagitis/pathology , Epithelial Cells/metabolism , Esophagus/pathology , Interleukin-33/metabolism , Epithelial Cells/pathology , Gene Expression Regulation , Humans
7.
Nat Commun ; 8(1): 813, 2017 10 09.
Article in English | MEDLINE | ID: mdl-28993618

ABSTRACT

Gas-filled hollow-core photonic crystal fibre is being used to generate ever wider supercontinuum spectra, in particular via dispersive wave emission in the deep and vacuum ultraviolet, with a multitude of applications. Dispersive waves are the result of nonlinear transfer of energy from a self-compressed soliton, a process that relies crucially on phase-matching. It was recently predicted that, in the strong-field regime, the additional transient anomalous dispersion introduced by gas ionization would allow phase-matched dispersive wave generation in the mid-infrared-something that is forbidden in the absence of free electrons. Here we report the experimental observation of such mid-infrared dispersive waves, embedded in a 4.7-octave-wide supercontinuum that uniquely reaches simultaneously to the vacuum ultraviolet, with up to 1.7 W of total average power.Dispersive wave emission in gas-filled hollow-core photonic crystal fibres has been possible in the visible and ultraviolet via the optical Kerr effect. Here, Köttig et al. demonstrate dispersive waves generated by an additional transient anomalous dispersion from gas ionization in the mid-infrared.

8.
Rev Sci Instrum ; 88(7): 073106, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28764547

ABSTRACT

A cross-correlation frequency-resolved optical gating (FROG) concept, potentially suitable for characterizing few or sub-cycle pulses in a single shot, is described in which a counter-propagating transient grating is used as both the gate and the dispersive element in a FROG spectrometer. An all-reflective setup, which can operate over the whole transmission range of the nonlinear medium, within the sensitivity range of the matrix sensor, is also proposed, and proof-of-principle experiments for the ultraviolet and visible-to-near-infrared spectral ranges are reported.

9.
J Intellect Disabil Res ; 61(11): 1011-1020, 2017 11.
Article in English | MEDLINE | ID: mdl-28836311

ABSTRACT

BACKGROUND: Little research exists on suspension of students with autism or intellectual disabilities. We examined suspension rates of students with autism or intellectual disability in Maryland from 2004 to 2015 to understand whether race and disability status predicted the odds of being suspended. METHOD: We used school enrollment data and school suspension data in Maryland for analysis. Descriptive statistics by race and disability category were calculated. Logistic regression was used to examine differences in odds of suspension by race and by disability (ID and autism) each year. RESULTS: Suspension rates in Maryland decreased overall from 2004 to 2015, but African American students with intellectual disability or no disability were significantly more likely to be suspended. White students with autism and White students with intellectual disability had significantly higher odds of suspension than White students without a disability. CONCLUSIONS: Overall risk for suspension in Maryland decreased over time. African American students with autism or intellectual disability, as well as white students with autism or intellectual disability, experienced significantly higher odds of suspension when compared to their White students without a disability. This relatively unexplored issue commands attention from researchers and policymakers alike.


Subject(s)
Autism Spectrum Disorder , Black or African American/statistics & numerical data , Disabled Persons/statistics & numerical data , Intellectual Disability , Schools/statistics & numerical data , Students/statistics & numerical data , White People/statistics & numerical data , Adolescent , Child , Disabled Children/statistics & numerical data , Female , Humans , Male , Maryland , Mentally Ill Persons/statistics & numerical data , Persons with Mental Disabilities/statistics & numerical data
10.
Phys Rev Lett ; 118(26): 263902, 2017 Jun 30.
Article in English | MEDLINE | ID: mdl-28707928

ABSTRACT

We identify a novel regime of soliton-plasma interactions in which high-intensity ultrashort pulses of intermediate soliton order undergo coherent plasma-induced fission. Experimental results obtained in gas-filled hollow-core photonic crystal fiber are supported by rigorous numerical simulations. In the anomalous dispersion regime, the cumulative blueshift of higher-order input solitons with ionizing intensities results in pulse splitting before the ultimate self-compression point, leading to the generation of robust pulse pairs with PHz bandwidths. The novel dynamics closes the gap between plasma-induced adiabatic soliton compression and modulational instability.

11.
J Neurophysiol ; 116(2): 391-403, 2016 08 01.
Article in English | MEDLINE | ID: mdl-27146980

ABSTRACT

Inhibition is presumed to play an important role in gustatory processing in the rostral nucleus of the solitary tract (rNST). One source of inhibition, GABA, is abundant within the nucleus and comes both from local, intrasolitary sources and from outside the nucleus. In addition to the receptor-mediated effects of GABA on rNST neurons, the hyperpolarization-sensitive currents, Ih and IA, have the potential to further modulate afferent signals. To elucidate the effects of GABAergic modulation on solitary tract (ST)-evoked responses in phenotypically defined rNST neurons and to define the presence of IA and Ih in the same cells, we combined in vitro recording and optogenetics in a transgenic mouse model. This mouse expresses channelrhodopsin 2 (ChR2) in GAD65-expressing GABAergic neurons throughout the rNST. GABA positive (GABA+) neurons differed from GABA negative (GABA-) neurons in their response to membrane depolarization and ST stimulation. GABA+ neurons had lower thresholds to direct membrane depolarization compared with GABA- neurons, but GABA- neurons responded more faithfully to ST stimulation. Both IA and Ih were present in subsets of GABA+ and GABA- neurons. Interestingly, GABA+ neurons with Ih were more responsive to afferent stimulation than inhibitory neurons devoid of these currents, whereas GABA- neurons with IA were more subject to inhibitory modulation. These results suggest that the voltage-gated channels underlying IA and Ih play an important role in modulating rNST output through a circuit of feedforward inhibition.


Subject(s)
Action Potentials/physiology , Neural Inhibition/physiology , Neurons/classification , Neurons/physiology , Optogenetics , Solitary Nucleus/cytology , 4-Aminopyridine/pharmacology , Action Potentials/drug effects , Animals , Channelrhodopsins , Female , Glutamate Decarboxylase/genetics , Glutamate Decarboxylase/metabolism , In Vitro Techniques , Male , Mice , Mice, Transgenic , Microscopy, Confocal , Neural Inhibition/drug effects , Neurons/drug effects , Potassium Channel Blockers/pharmacology , Receptors, Purinergic P2X2/metabolism , Sodium Channel Blockers/pharmacology , Tetrodotoxin/pharmacology , Vesicular Inhibitory Amino Acid Transport Proteins/genetics , Vesicular Inhibitory Amino Acid Transport Proteins/metabolism
13.
Phys Rev Lett ; 115(3): 033901, 2015 Jul 17.
Article in English | MEDLINE | ID: mdl-26230794

ABSTRACT

We propose a scheme for the emission of few-cycle dispersive waves in the midinfrared using hollow-core photonic crystal fibers filled with noble gas. The underlying mechanism is the formation of a plasma cloud by a self-compressed, subcycle pump pulse. The resulting free-electron population modifies the fiber dispersion, allowing phase-matched access to dispersive waves at otherwise inaccessible frequencies, well into the midinfrared. Remarkably, the pulses generated turn out to have durations of the order of two optical cycles. In addition, this ultrafast emission, which occurs even in the absence of a zero dispersion point between pump and midinfrared wavelengths, is tunable over a wide frequency range simply by adjusting the gas pressure. These theoretical results pave the way to a new generation of compact, fiber-based sources of few-cycle midinfrared radiation.

14.
Physiol Behav ; 152(Pt B): 329-39, 2015 Dec 01.
Article in English | MEDLINE | ID: mdl-26216080

ABSTRACT

Bariatric surgery is an effective treatment for obesity that involves both peripheral and central mechanisms. To elucidate central pathways by which oral and visceral signals are influenced by high-fat diet (HFD) and Roux-en-Y gastric bypass (RYGB) surgery, we recorded from neurons in the caudal visceral nucleus of the solitary tract (cNST, N=287) and rostral gustatory NST (rNST,N=106) in rats maintained on a HFD and lab chow (CHOW) or CHOW alone, and subjected to either RYGB or sham surgery. Animals on the HFD weighed significantly more than CHOW rats and RYGB reversed and then blunted weight gain regardless of diet. Using whole-cell patch clamp recording in a brainstem slice, we determined the membrane properties of cNST and rNST neurons associated with diet and surgery. We could not detect differences in rNST neurons associated with these manipulations. In cNST neurons, neither the threshold for solitary tract stimulation nor the amplitude of evoked EPSCs at threshold varied by condition; however suprathreshold EPSCs were larger in HFD compared to chow-fed animals. In addition, a transient outward current, most likely an IA current, was increased with HFD and RYGB reduced this current as well as a sustained outward current. Interestingly, hypothalamic projecting cNST neurons preferentially express IA and modulate transmission of afferent signals (Bailey, '07). Thus, diet and RYGB have multiple effects on the cellular properties of neurons in the visceral regions of NST, with potential to influence inputs to forebrain feeding circuits.


Subject(s)
Diet, High-Fat/adverse effects , Gastric Bypass , Neurons/physiology , Solitary Nucleus/physiopathology , Afferent Pathways/physiopathology , Animals , Body Weight , Disease Models, Animal , Gastric Bypass/adverse effects , Male , Membrane Potentials/physiology , Overweight/physiopathology , Overweight/surgery , Patch-Clamp Techniques , Rats, Sprague-Dawley , Tissue Culture Techniques
15.
Opt Lett ; 40(7): 1238-41, 2015 Apr 01.
Article in English | MEDLINE | ID: mdl-25831302

ABSTRACT

Compression of 250-fs, 1-µJ pulses from a KLM Yb:YAG thin-disk oscillator down to 9.1 fs is demonstrated. A kagomé-PCF with a 36-µm core-diameter is used with a pressure gradient from 0 to 40 bar of krypton. Compression to 22 fs is achieved by 1200 fs2 group-delay-dispersion provided by chirped mirrors. By coupling the output into a second kagomé-PCF with a pressure gradient from 0 to 25 bar of argon, octave spanning spectral broadening via the soliton-effect is observed at 18-W average output power. Self-compression to 9.1 fs is measured, with compressibility to 5 fs predicted. Also observed is strong emission in the visible via dispersive wave generation, amounting to 4% of the total output power.

16.
Opt Lett ; 40(6): 1026-9, 2015 Mar 15.
Article in English | MEDLINE | ID: mdl-25768173

ABSTRACT

A noise-seeded transient comb of Raman sidebands spanning three octaves from 180 to 2400 nm, is generated by pumping a hydrogen-filled hollow-core photonic crystal fiber with 26-µJ, 300-fs pulses at 800 nm. The pump pulses are spectrally broadened by both Kerr and Raman-related self-phase modulation (SPM), and the broadening is then transferred to the Raman lines. In spite of the high intensity, and in contrast to bulk gas-cell based experiments, neither SPM broadening nor ionization are detrimental to comb formation.

17.
Mucosal Immunol ; 8(3): 464-75, 2015 May.
Article in English | MEDLINE | ID: mdl-25807184

ABSTRACT

Eosinophils, multifunctional cells that contribute to both innate and adaptive immunity, are involved in the initiation, propagation, and resolution of immune responses, including tissue repair. They achieve this multifunctionality by expression of a diverse set of activation receptors, including those that directly recognize pathogens and opsonized targets, and by their ability to store and release preformed cytotoxic mediators that participate in host defense, to produce a variety of de novo pleotropic mediators and cytokines, and to interact directly and indirectly with diverse cell types, including adaptive and innate immunocytes and structural cells. Herein, we review the basic biology of eosinophils and then focus on new emerging concepts about their role in mucosal immune homeostasis, particularly maintenance of intestinal IgA. We review emerging data about their development and regulation and describe new concepts concerning mucosal eosinophilic diseases. We describe recently developed therapeutic strategies to modify eosinophil levels and function and provide collective insight about the beneficial and detrimental functions of these enigmatic cells.


Subject(s)
Asthma/immunology , Enteritis/immunology , Eosinophilia/immunology , Eosinophilic Esophagitis/immunology , Eosinophils/immunology , Gastritis/immunology , Immunity, Mucosal , Inflammatory Bowel Diseases/immunology , Adaptive Immunity , Animals , Antibodies, Monoclonal/therapeutic use , Asthma/drug therapy , Asthma/pathology , Cytokines/genetics , Cytokines/immunology , Enteritis/drug therapy , Enteritis/pathology , Eosinophilia/drug therapy , Eosinophilia/pathology , Eosinophilic Esophagitis/drug therapy , Eosinophilic Esophagitis/pathology , Eosinophils/drug effects , Eosinophils/pathology , Gastritis/drug therapy , Gastritis/pathology , Gene Expression , Homeostasis/drug effects , Homeostasis/immunology , Humans , Immunity, Innate , Immunologic Factors/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/pathology
18.
19.
Opt Lett ; 39(6): 1398-401, 2014 Mar 15.
Article in English | MEDLINE | ID: mdl-24690797

ABSTRACT

By modeling giant chirped pulse formation in ultra-long, normally dispersive, mode-locked fiber lasers, we verify convergence to a steady-state consisting of highly chirped and coherent, nanosecond-scale pulses, which is in good agreement with recent experimental results. Numerical investigation of the transient dynamics reveals the existence of dark soliton-like structures within the envelope of the initial noisy pulse structure. Quasi-stationary dark solitons can persist throughout a large part of the evolution from noise to a stable dissipative soliton solution of the mode-locked laser cavity.

20.
Opt Lett ; 38(16): 2984-7, 2013 Aug 15.
Article in English | MEDLINE | ID: mdl-24104627

ABSTRACT

We numerically investigate self-frequency blueshifting of a fundamental soliton in a gas-filled hollow-core photonic crystal fiber. Because of the changing underlying soliton parameters, the blueshift gives rise to adiabatic soliton compression. Based on these features, we propose a device that enables frequency shifting over an octave and pulse compression from 30 fs down to 2.3 fs.


Subject(s)
Gases , Optical Fibers , Photons , Time Factors
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