A stressful event may be sufficient to challenge a strongly held set of assumptions about the world and the self. In some people this may lead to post-traumatic stress disorder (PTSD) and in others ...to positive psychological change (PPC), whereby a person’s reactions to the challenge are beneficial. Little research has investigated PPC in people who have had head and neck cancer (HNC). The aim of this study was to identify demographic, clinical, and psychological factors associated with PPC over time. A cross-sequential study collected data over 5 years. Participants were sent the Silver Lining Questionnaire (SLQ; a measure of PPC), the University of Washington HNC quality of life measure, and the Medical Outcomes Short-Form 12 each year. Additional data were collected from clinical records. Analysis using linear mixed-effects modelling revealed that participants with lower stage tumours and those who only had a surgical intervention reported greater PPC over time. Multivariable modelling adjusting for psychosocial variables found that PPC had a quadratic relationship with time since diagnosis, increasing initially and levelling off after 18 months. These findings build on the minimal PPC research with people following HNC. In particular it demonstrates a model of trajectories for the development of PPC longitudinally over time.
We present a combined experimental and theoretical investigation of formaldehyde ($H_{2}CO$) dissociation to H2and CO at energies just above the threshold for competing H elimination. High-resolution ...state-resolved imaging measurements of the CO velocity distributions reveal two dissociation pathways. The first proceeds through a well-established transition state to produce rotationally excited CO and vibrationally cold H2. The second dissociation pathway yields rotationally cold CO in conjunction with highly vibrationally excited H2. Quasiclassical trajectory calculations performed on a global potential energy surface for$H_{2}CO$suggest that this second channel represents an intramolecular hydrogen abstraction mechanism: One hydrogen atom explores large regions of the potential energy surface before bonding with the second H atom, bypassing the saddle point entirely.
The Human Cell Atlas is a large international collaborative effort to map all cell types of the human body. Single-cell RNA sequencing can generate high-quality data for the delivery of such an ...atlas. However, delays between fresh sample collection and processing may lead to poor data and difficulties in experimental design.
This study assesses the effect of cold storage on fresh healthy spleen, esophagus, and lung from ≥ 5 donors over 72 h. We collect 240,000 high-quality single-cell transcriptomes with detailed cell type annotations and whole genome sequences of donors, enabling future eQTL studies. Our data provide a valuable resource for the study of these 3 organs and will allow cross-organ comparison of cell types. We see little effect of cold ischemic time on cell yield, total number of reads per cell, and other quality control metrics in any of the tissues within the first 24 h. However, we observe a decrease in the proportions of lung T cells at 72 h, higher percentage of mitochondrial reads, and increased contamination by background ambient RNA reads in the 72-h samples in the spleen, which is cell type specific.
In conclusion, we present robust protocols for tissue preservation for up to 24 h prior to scRNA-seq analysis. This greatly facilitates the logistics of sample collection for Human Cell Atlas or clinical studies since it increases the time frames for sample processing.
Because lignin limits the use of wood for fiber, chemical, and energy production, strategies for its downregulation are of considerable interest. We have produced transgenic aspen (Populus ...tremuloides Michx.) trees in which expression of a lignin biosynthetic pathway gene Pt4CL1 encoding 4-coumarate:coenzyme A ligase (4CL) has been downregulated by antisense inhibition. Trees with suppressed Pt4CL1 expression exhibited up to a 45% reduction of lignin, but this was compensated for by a 15% increase in cellulose. As a result, the total lignin-cellulose mass remained essentially unchanged. Leaf, root, and stem growth were substantially enhanced, and structural integrity was maintained both at the cellular and whole-plant levels in the transgenic lines. Our results indicate that lignin and cellulose deposition could be regulated in a compensatory fashion, which may contribute to metabolic flexibility and a growth advantage to sustain the long-term structural integrity of woody perennials.
We describe the design and performance of the near-infrared (1.51-1.70 m), fiber-fed, multi-object (300 fibers), high resolution (R = λ/Δλ ∼ 22,500) spectrograph built for the Apache Point ...Observatory Galactic Evolution Experiment (APOGEE). APOGEE is a survey of ∼105 red giant stars that systematically sampled all Milky Way populations (bulge, disk, and halo) to study the Galaxy's chemical and kinematical history. It was part of the Sloan Digital Sky Survey III (SDSS-III) from 2011 to 2014 using the 2.5 m Sloan Foundation Telescope at Apache Point Observatory, New Mexico. The APOGEE-2 survey is now using the spectrograph as part of SDSS-IV, as well as a second spectrograph, a close copy of the first, operating at the 2.5 m du Pont Telescope at Las Campanas Observatory in Chile. Although several fiber-fed, multi-object, high resolution spectrographs have been built for visual wavelength spectroscopy, the APOGEE spectrograph is one of the first such instruments built for observations in the near-infrared. The instrument's successful development was enabled by several key innovations, including a "gang connector" to allow simultaneous connections of 300 fibers; hermetically sealed feedthroughs to allow fibers to pass through the cryostat wall continuously; the first cryogenically deployed mosaic volume phase holographic grating; and a large refractive camera that includes mono-crystalline silicon and fused silica elements with diameters as large as ∼400 mm. This paper contains a comprehensive description of all aspects of the instrument including the fiber system, optics and opto-mechanics, detector arrays, mechanics and cryogenics, instrument control, calibration system, optical performance and stability, lessons learned, and design changes for the second instrument.
Anemia is common among people living with HIV infection (PLWH) and is associated with adverse health outcomes. Information on risk factors for anemia incidence in the current antiretroviral therapy ...(ART) era is lacking.
Within a prospective clinical cohort of adult PLWH receiving care at eight sites across the United States between 1/2010-3/2018, Cox proportional hazards regression analyses were conducted among a) PLWH free of anemia at baseline and b) PLWH free of severe anemia at baseline to determine associations between time-updated patient characteristics and development of anemia (hemoglobin < 10 g/dL), or severe anemia (hemoglobin < 7.5 g/dL). Linear mixed effects models were used to examine relationships between patient characteristics and hemoglobin levels during follow-up. Hemoglobin levels were ascertained using laboratory data from routine clinical care. Potential risk factors included: age, sex, race/ethnicity, body mass index, smoking status, hazardous alcohol use, illicit drug use, hepatitis C virus (HCV) coinfection, estimated glomerular filtration rate (eGFR), CD4 cell count, viral load, ART use and time in care at CNICS site.
This retrospective cohort study included 15,126 PLWH. During a median follow-up of 6.6 (interquartile range IQR 4.3-7.6) years, 1086 participants developed anemia and 465 participants developed severe anemia. Factors that were associated with incident anemia included: older age, female sex, black race, HCV coinfection, lower CD4 cell counts, VL ≥400 copies/ml and lower eGFR.
Because anemia is a treatable condition associated with increased morbidity and mortality among PLWH, hemoglobin levels should be monitored routinely, especially among PLWH who have one or more risk factors for anemia.
The detection of diffuse radio emission associated with clusters of galaxies indicates populations of relativistic leptons infusing the intracluster medium (ICM). Those electrons and positrons are ...either injected into and accelerated directly in the ICM, or produced as secondary pairs by cosmic-ray ions scattering on ambient protons. Radiation mechanisms involving the energetic leptons together with the decay of neutral pions produced by hadronic interactions have the potential to produce abundant GeV photons. Here, we report on the search for GeV emission from clusters of galaxies using data collected by the Large Area Telescope on the Fermi Gamma-ray Space Telescope from 2008 August to 2010 February. Thirty-three galaxy clusters have been selected according to their proximity and high mass, X-ray flux and temperature, and indications of non-thermal activity for this study. We report upper limits on the photon flux in the range 0.2-100 GeV toward a sample of observed clusters (typical values (1-5) x 10(-9) photon cm(-2) s(-1)) considering both point-like and spatially resolved models for the high-energy emission and discuss how these results constrain the characteristics of energetic leptons and hadrons, and magnetic fields in the ICM. The volume-averaged relativistic-hadron-to-thermal energy density ratio is found to be <5%-10% in several clusters.
Many autoimmune and infectious diseases are characterized by the formation of granulomas which are inflammatory lesions that consist of spatially organized immune cells. These sites protect the host ...and control pathogens like Mycobacterium tuberculosis (Mtb), but are highly inflammatory and cause pathology. Using bacille Calmette-Guerin (BCG) and Mtb infection in mice that induce sarcoid or caseating granulomas, we show that a subpopulation of granuloma macrophages produces vascular endothelial growth factor (VEGF-A), which recruits immune cells to the granuloma by a non-angiogenic pathway. Selective blockade of VEGF-A in myeloid cells, combined with granuloma transplantation, shows that granuloma VEGF-A regulates granulomatous inflammation. The severity of granuloma-related inflammation can be ameliorated by pharmaceutical or genetic inhibition of VEGF-A, which improves survival of mice infected with virulent Mtb without altering host protection. These data show that VEGF-A inhibitors could be used as a host-directed therapy against granulomatous diseases like tuberculosis and sarcoidosis, thereby expanding the value of already existing and approved anti-VEGF-A drugs.
Display omitted
•Mycobacterial granulomas contain a subpopulation of VEGF-A-producing macrophages•VEGF-A recruits macrophages to the granuloma via a non-angiogenic pathway•VEGF-A inhibition reduces granulomatous inflammation with limited effect on protection•Mice with myeloid-specific deletion of VEGF-A are more resistant to Mtb infection
Harding et al. show that VEGF-A inhibitors reduce granuloma-associated pathologies, including mycobacterial-based infections. Granulomas contain a heterogeneous inflammatory cell population, including macrophages that produce VEGF-A during periods of cell death. VEGF-A potentiates excessive inflammation by recruiting macrophages to the granuloma. FDA-approved VEGF-A inhibitors exist and could help limit tuberculosis-associated inflammation.
Several scaffolds and cell sources are being investigated for cartilage regeneration. The aim of the study was to prepare nanocellulose-based thermosensitive injectable hydrogel scaffolds and assess ...their potential as 3D scaffolds allowing the chondrogenic differentiation of embedded human dental pulp stem and progenitor cells (hDPSCs).
The hydrogel-forming solutions were prepared by adding β-glycerophosphate (GP) to chitosan (CS) at different ratios. Nanocellulose (NC) suspension was produced from hemp hurd then added dropwise to the CS/GP mixture. In vitro characterization of the prepared hydrogels involved optimizing gelation and degradation time, mass-swelling ratio, and rheological properties. The hydrogel with optimal characteristics, NC-CS/GP-21, was selected for further investigation including assessment of biocompatibility. The chondrogenesis ability of hDPSCs embedded in NC-CS/GP-21 hydrogel was investigated in vitro and compared to that of bone marrow-derived mesenchymal stem cells (BMSCs), then was confirmed in vivo in 12 adult Sprague Dawley rats.
The selected hydrogel showed stability in culture media, had a gelation time of 2.8 minutes, showed a highly porous microstructure by scanning electron microscope, and was morphologically intact in vivo for 14 days after injection. Histological and immunohistochemical analyses and real-time PCR confirmed the chondrogenesis ability of hDPSCs embedded in NC-CS/GP-21 hydrogel.
Our results suggest that nanocellulose-chitosan thermosensitive hydrogel is a biocompatible, injectable, mechanically stable and slowly degradable scaffold. hDPSCs embedded in NC-CS/GP-21 hydrogel is a promising, minimally invasive, stem cell-based strategy for cartilage regeneration.
We report on the first detection of GeV high-energy gamma-ray emission from a young supernova remnant with the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope. These observations ...reveal a source with no discernible spatial extension detected at a significance level of 12.2$\sigma$ above 500 MeV at a location that is consistent with the position of the remnant of the supernova explosion that occurred around 1680 in the Cassiopeia constellation - Cassiopeia A. The gamma-ray flux and spectral shape of the source are consistent with a scenario in which the gamma-ray emission originates from relativistic particles accelerated in the shell of this remnant. The total content of cosmic rays (electrons and protons) accelerated in Cas A can be estimated as $W_{\mathrm{CR}} \approx (1-4) \times 10^{49}$ erg thanks to the well-known density in the remnant assuming that the observed gamma-ray originates in the SNR shell(s). The magnetic field in the radio-emitting plasma can be robustly constrained as B $\gt 0.1$ mG, providing new evidence of the magnetic field amplification at the forward shock and the strong field in the shocked ejecta.
PDF
