Characterization of T-bet and eomes in peripheral human immune cells.

The T-box transcription factors T-bet and Eomesodermin (Eomes) have been well defined as key drivers of immune cell development and cytolytic function. While the majority of studies have defined the roles of these factors in the context of murine T-cells, recent results have revealed that T-bet, and possibly Eomes, are expressed in other immune cell subsets. To date, the expression patterns of these factors in subsets of human peripheral blood mononuclear cells beyond T-cells remain relatively uncharacterized. In this study, we used multiparametric flow cytometry to characterize T-bet and Eomes expression in major human blood cell subsets, including total CD4(+) and CD8(+) T-cells, γδ T-cells, invariant NKT cells, natural killer cells, B-cells, and dendritic cells. Our studies identified novel cell subsets that express T-bet and Eomes and raise implications for their possible functions in the context of other human immune cell subsets besides their well-known roles in T-cells. The corrigendum regards data and text for the final figure of the manuscript, Figure 7: Subsequent analysis of T-bet levels in human lymphocytes comparing different permeabilization procedures (eBioscience FoxP3 transcription factor kit, BD Pharmingen Cytofix/Cytoperm) has revealed variable findings in the level of T-bet expression detected within certain lymphocyte populations. While this does not change our conclusions for the majority of the populations assessed in this study, B cells in particular show differences under these conditions. Specifically, permeabilization via the eBioscience FoxP3 transcription factor staining buffer set indicates that subpopulations of memory B cells express significantly higher levels of T-bet (MFI) compared to plasmablasts, and that plasmablasts express T-bet only at low levels. Subsequent RNA transcript analysis confirms that plasmablasts express T-bet RNA at a level comparable to naïve B cells. Together, in combination with fluorescence-minus-one and isotype control studies, these new findings suggest that subsets memory B cells, not plasmablasts, express the highest levels of T-bet in the B cell compartment and plasmablasts express T-bet at a lower frequency than is reported in Figure 7. Figure 7 Legend should read: (C) Histograms depicting T-bet expression levels in B-cells and NK cells from a representative donor. Histograms represent the following subsets: naïve B-cells (thick black line), memory B-cells (shaded gray), plasmablasts (thin black line), CD56bright NK cells (gray line), and CD56dim NK cells (shaded black). B-cell results section should be titled T-bet is predominantly expressed in mature memory B-cells and should read: While Eomes was undetectable in B-cells (data not shown), we found T-bet in ~10% of B-cells (Figure 7B). This T-bet expression was largely relegated to memory B-cells, with significantly lower amounts observed in transitional/immature B-cells, naïve B-cells, and plasmablasts (Figure 7B). Greater than 15% of memory B-cells expressed T-bet, a significantly higher frequency than that of all other B-cell populations, suggesting that T-bet may play a particularly important role in memory B-cell function. The discussion related to T-bet expression in plasmablasts should be reconsidered as follows: We found that T-bet is not significantly expressed in transitional/immature B-cells, naïve B-cells, and plasmablasts, but is highly expressed in subsets of memory-B cells. Reduced frequencies of T-bet expression in plasmablasts indicate a specific role for T-bet at the memory B-cell stage of development, which may no longer be necessary after further differentiation to the plasmablast stage. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest

Multiple scattering and attenuation corrections in Deep Inelastic Neutron Scattering experiments

Multiple scattering and attenuation corrections in Deep Inelastic Neutron Scattering experiments are analyzed. The theoretical basis is stated, and a Monte Carlo procedure to perform the calculation is presented. The results are compared with experimental data. The importance of the accuracy in the description of the experimental parameters is tested, and the implications of the present results on the data analysis procedures is examined.Comment: 19 pages, 8 figure

Follow-Up Observations of PTFO 8-8695: A 3 MYr Old T-Tauri Star Hosting a Jupiter-mass Planetary Candidate

We present Spitzer 4.5\micron\ light curve observations, Keck NIRSPEC radial velocity observations, and LCOGT optical light curve observations of PTFO~8-8695, which may host a Jupiter-sized planet in a very short orbital period (0.45 days). Previous work by \citet{vaneyken12} and \citet{barnes13} predicts that the stellar rotation axis and the planetary orbital plane should precess with a period of $300 - 600$ days. As a consequence, the observed transits should change shape and depth, disappear, and reappear with the precession. Our observations indicate the long-term presence of the transit events ($>3$ years), and that the transits indeed do change depth, disappear and reappear. The Spitzer observations and the NIRSPEC radial velocity observations (with contemporaneous LCOGT optical light curve data) are consistent with the predicted transit times and depths for the $M_\star = 0.34\ M_\odot$ precession model and demonstrate the disappearance of the transits. An LCOGT optical light curve shows that the transits do reappear approximately 1 year later. The observed transits occur at the times predicted by a straight-forward propagation of the transit ephemeris. The precession model correctly predicts the depth and time of the Spitzer transit and the lack of a transit at the time of the NIRSPEC radial velocity observations. However, the precession model predicts the return of the transits approximately 1 month later than observed by LCOGT. Overall, the data are suggestive that the planetary interpretation of the observed transit events may indeed be correct, but the precession model and data are currently insufficient to confirm firmly the planetary status of PTFO~8-8695b.Comment: Accepted for publication in The Astrophysical Journa

Optical-Model Description of Time-Reversal Violation

A time-reversal-violating spin-correlation coefficient in the total cross section for polarized neutrons incident on a tensor rank-2 polarized target is calculated by assuming a time-reversal-noninvariant, parity-conserving ``five-fold" interaction in the neutron-nucleus optical potential. Results are presented for the system $n + {^{165}{\rm Ho}}$ for neutron incident energies covering the range 1--20 MeV. From existing experimental bounds, a strength of $2 \pm 10$ keV is deduced for the real and imaginary parts of the five-fold term, which implies an upper bound of order $10^{-4}$ on the relative $T$-odd strength when compared to the central real optical potential.Comment: 11 pages (Revtex

Effect of P to A Mutation of the N-Terminal Residue Adjacent to the Rgd Motif on Rhodostomin: Importance of Dynamics in Integrin Recognition

Rhodostomin (Rho) is an RGD protein that specifically inhibits integrins. We found that Rho mutants with the P48A mutation 4.4–11.5 times more actively inhibited integrin α5β1. Structural analysis showed that they have a similar 3D conformation for the RGD loop. Docking analysis also showed no difference between their interactions with integrin α5β1. However, the backbone dynamics of RGD residues were different. The values of the R2 relaxation parameter for Rho residues R49 and D51 were 39% and 54% higher than those of the P48A mutant, which caused differences in S2, Rex, and τe. The S2 values of the P48A mutant residues R49, G50, and D51 were 29%, 14%, and 28% lower than those of Rho. The Rex values of Rho residues R49 and D51 were 0.91 s−1 and 1.42 s−1; however, no Rex was found for those of the P48A mutant. The τe values of Rho residues R49 and D51 were 9.5 and 5.1 times lower than those of P48A mutant. Mutational study showed that integrin α5β1 prefers its ligands to contain (G/A)RGD but not PRGD sequences for binding. These results demonstrate that the N-terminal proline residue adjacent to the RGD motif affect its function and dynamics, which suggests that the dynamic properties of the RGD motif may be important in Rho's interaction with integrin α5β1

What have transgenic and knockout animals taught us about respiratory disease?

Over the past decade there has been a significant shift to the use of murine models for investigations into the molecular basis of respiratory diseases, including asthma and chronic obstructive pulmonary disease. These models offer the exciting prospect of dissecting the complex interaction between cytokines, chemokines and growth related peptides in disease pathogenesis. Furthermore, the receptors and the intracellular signalling pathways that are subsequently activated are amenable for study because of the availability of monoclonal antibodies and techniques for targeted gene disruption and gene incorporation for individual mediators, receptors and proteins. However, it is clear that extrapolation from these models to the human condition is not straightforward, as reflected by some recent clinical disappointments. This is not necessarily a problem with the use of mice itself, but results from our continued ignorance of the disease process and how to improve the modelling of complex interactions between different inflammatory mediators that underlie clinical pathology. This review highlights some of the strengths and weaknesses of murine models of respiratory disease

Interaction and efficacy of Keigai-rengyo-to extract and acupuncture in male patients with acne vulgaris: A study protocol for a randomized controlled pilot trial

<p>Abstract</p> <p>Background</p> <p>In consideration of patients seeking to use traditional Chinese medicine, an evidence-based potentiality for safe and effective use of herbal medicine and acupuncture in treatment of acne vulgaris has been suggested. However, despite common use of a combination of herbal medicine and acupuncture in clinical practice, the current level of evidence is insufficient to draw a conclusion for an interaction and efficacy of herbal medicine and acupuncture. Therefore, considering these methodological flaws, this study was designed to assess the interaction and efficacy of an available herbal medicine, Keigai-rengyo-to extract (KRTE), and acupuncture for treatment of acne using the 2 × 2 factorial design and the feasibility of a large clinical trial.</p> <p>Methods/Design</p> <p>A randomized, assessor single blinded, 2 × 2 factorial pilot trial will be conducted. Forty four participants with acne vulgaris will be randomized into one of four groups: waiting list group (WL), KRTE only group (KO), acupuncture only group (AO), and KRTE and acupuncture combined treatment group (KA). After randomization, a total of 8 sessions of acupuncture treatment will be performed twice a week in the AO- and KA groups, respectively. Patients in the KO- and KA groups will be prescribed KRTE 3 times a day at a dose of 7.4 g after meals for 4 weeks. The following outcome measurements will be used in examination of subjects: the mean percentage change and the count change of inflammatory and non-inflammatory acne lesions, the Skindex 29, visual analogue scale (VAS) and investigator global assessment (IGA) from baseline to the end of the trial.</p> <p>Trial Registration</p> <p>The trial is registered with the Clinical Research Information Service (CRiS), Republic of Korea: KCT0000071.</p

Long-term multiwavelength monitoring and reverberation mapping of NGC 2617 during a changing-look event

We present the results of photometric and spectroscopic monitoring campaigns of the changing look AGN NGC~2617 carried out from 2016 until 2022 and covering the wavelength range from the X-ray to the near-IR. The facilities included the telescopes of the SAI MSU, MASTER Global Robotic Net, the 2.3-m WIRO telescope, Swift, and others. We found significant variability at all wavelengths and, specifically, in the intensities and profiles of the broad Balmer lines. We measured time delays of ~ 6 days (~ 8 days) in the responses of the H-beta (H-alpha) line to continuum variations. We found the X-ray variations to correlate well with the UV and optical (with a small time delay of a few days for longer wavelengths). The K-band lagged the B band by 14 +- 4 days during the last 3 seasons, which is significantly shorter than the delays reported previously by the 2016 and 2017--2019 campaigns. Near-IR variability arises from two different emission regions: the outer part of the accretion disc and a more distant dust component. The HK-band variability is governed primarily by dust. The Balmer decrement of the broad-line components is inversely correlated with the UV flux. The change of the object's type, from Sy1 to Sy1.8, was recorded over a period of ~ 8 years. We interpret these changes as a combination of two factors: changes in the accretion rate and dust recovery along the line of sight.Comment: 14 pages, 15 figures, accepted by the MNRA

Broad-line region in NGC 4151 monitored by two decades of reverberation mapping campaigns. I. Evolution of structure and kinematics

We report the results of long-term reverberation mapping (RM) campaigns of the nearby active galactic nuclei (AGN) NGC 4151, spanning from 1994 to 2022, based on archived observations of the FAST Spectrograph Publicly Archived Programs and our new observations with the 2.3m telescope at the Wyoming Infrared Observatory. We reduce and calibrate all the spectra in a consistent way, and derive light curves of the broad H$\beta$ line and 5100\,{\AA} continuum. Continuum light curves are also constructed using public archival photometric data to increase sampling cadences. We subtract the host galaxy contamination using {\it HST} imaging to correct fluxes of the calibrated light curves. Utilizing the long-term archival photometric data, we complete the absolute flux-calibration of the AGN continuum. We find that the H$\beta$ time delays are correlated with the 5100\,{\AA} luminosities as $\tau_{\rm H\beta}\propto L_{5100}^{0.46\pm0.16}$. This is remarkably consistent with Bentz et al. (2013)'s global size-luminosity relationship of AGNs. Moreover, the data sets for five of the seasons allow us to obtain the velocity-resolved delays of the H$\beta$ line, showing diverse structures (outflows, inflows and disks). Combining our results with previous independent measurements, we find the measured dynamics of the H$\beta$ broad-line region (BLR) are possibly related to the long-term trend of the luminosity. There is also a possible additional $\sim$1.86 years time lag between the variation in BLR radius and luminosity. These results suggest that dynamical changes in the BLR may be driven by the effects of radiation pressure.Comment: Accepted for publication in MNRAS; comments welcome