Hematopoietic stem cells are responsible for generating all types of blood cells. As such they are under a high degree of regulation, both internal and external. With the identification of the ...hematopoietic stem cell niche, there has been increased investigation into extrinsic regulation of hematopoietic stem cells with emphasis on developmental signaling pathways. The purpose of this review is to discuss recent advances and findings in how these different pathways interact to achieve a balanced control of these stem cells.
Studies indicating the importance of pathways such as Wnt, Notch, bone morphogenic protein, Sonic hedgehog and fibroblast growth factor in controlling the fate of hematopoietic stem cells are the most significant recent findings. These pathways have been implicated to affect various aspects of hematopoietic stem cells, including self-renewal, proliferation and lineage determination. Equally important are studies showing, by inactivation of various pathway components, the complexity of signal integration at the stem cell level in vivo. Additionally, some recent reports have provided evidence for direct interaction or cross-talk between different signaling pathways in this regulation.
We review highlights of the recent advances made toward resolving the mechanisms of external regulation of hematopoietic stem cells. Understanding the interaction of different signaling pathways in the context of the hematopoietic stem cell niche is essential for increasing their therapeutic potential.
•Presents maps of methane equivalent width (of the 890 nm band) and spectral slope based on data from the New Horizons Ralph/MVIC instrument.•Plutoś surface shows a diverse and complicated ...distribution of methane abundance and colors.•The broadest diversity occurs between 30 degrees North and 30 degrees South.•Equivalent Width shows some dependence on elevation, while spectral slope does not.
The data returned from NASA’s New Horizons spacecraft have given us an unprecedented, detailed look at the Pluto system. New Horizons' Ralph/MVIC (Multispectral Visible Imaging Camera) is composed of 7 independent CCD arrays on a single substrate. Among these are a red channel (540–700 nm), near-infrared channel (780–975 nm), and narrow band methane channel (860–910 nm). By comparing the relative reflectance of these channels we are able to produce high-resolution methane “equivalent width” (based on the 890 nm absorption band) and spectral slope maps of Pluto’s surface. From these maps we can then quantitatively study the relationships between methane distribution, redness, and other parameters like latitude and elevation. We find Pluto’s surface to show a great diversity of terrains, particularly in the equatorial region between 30°N and 30°S latitude. Methane “equivalent width” also shows some dependence on elevation (while spectral slope shows very little).
The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network has yielded neuroimaging and urinary biomarker findings that highlight unique alterations in brain structure ...and in urinary proteins related to tissue remodeling and vascular structure in patients with Urological Chronic Pelvic Pain Syndrome (UCPPS). We hypothesized that localized changes in diffusion tensor imaging (DTI) measurements might be associated with corresponding changes in urinary protein levels in UCPPS. To test this hypothesis, we created statistical parameter maps depicting the linear correlation between DTI measurements (fractional anisotropy (FA) and apparent diffusion coefficient (ADC)) and urinary protein quantification (MMP2, MMP9, NGAL, MMP9/NGAL complex, and VEGF) in 30 UCPPS patients from the MAPP Research Network, after accounting for clinical covariates. Results identified a brainstem region that showed a strong correlation between both ADC (R2 = 0.49, P<0.0001) and FA (R2 = 0.39, P = 0.0002) with urinary MMP9 levels as well as a correlation between both ADC (R2 = 0.42, P = 0.0001) and FA (R2 = 0.29, P = 0.0020) and urinary MMP9/NGAL complex. Results also identified significant correlations between FA and urinary MMP9 in white matter adjacent to sensorimotor regions (R2 = 0.30, P = 0.002; R2 = 0.36, P = 0.0005, respectively), as well as a correlation in similar sensorimotor regions when examining ADC and urinary MMP2 levels (R2 = 0.42, P<0.0001) as well as FA and urinary MMP9/NGAL complex (R2 = 0.33, P = 0.0008). A large, diffuse cluster of white matter was identified as having a strong correlation between both ADC (R2 = 0.35, P = 0.0006) and FA (R2 = 0.43, P<0.0001) with urinary NGAL levels. In contrast, no significant association between DTI measurements and VEGF was observed. Results suggest that elevated MMP9 or MMP9/NGAL in UCPPS may be related to degenerative neuronal changes in brainstem nuclei through excitotoxicity, while also facilitating synaptic plasticity in sensorimotor regions.
In this report the Heisenberg pyrochlore antiferromagnet Gd2Pt2O7 is one of a series of gadolinium pyrochlore compounds with a variety of B-site cations. Despite the expected simplicity of a ...spin-only Gd3+ Heisenberg interaction model, the gadolinium pyrochlore series exhibits various complex magnetic ground states at low temperature. Gd2Pt2O7 displays the highest temperature magnetic order of the series with $T_N$=1.6 K, which has been attributed to enhanced superexchange pathways facilitated by empty $5d$ $e_g$ Pt orbitals. In this study, we use various neutron scattering techniques on an isotopically enriched polycrystalline 160Gd2Pt2O7 sample to examine the magnetic structure and spin-wave excitation spectrum below $T_N$ in order to extract the dominant exchange interactions. We find that the ground-state magnetic structure is the Palmer-Chalker state previously seen in Gd2Sn2O7 with an associated gapped excitation spectrum consistent with enhanced exchange interactions between further near-neighbor Gd3+ ions. We confirm this exchange model with analysis of the magnetic diffuse scattering in the paramagnetic regime using polarized neutrons.
Health care personnel (HCP) are at high risk for exposure to the SARS-CoV-2 virus. While personal protective equipment (PPE) may mitigate this risk, prospective data collection on its use and other ...risk factors for seroconversion in this population is needed.
The primary objectives of this study are to (1) determine the incidence of, and risk factors for, SARS-CoV-2 infection among HCP at a tertiary care medical center and (2) actively monitor PPE use, interactions between study participants via electronic sensors, secondary cases in households, and participant mental health and well-being.
To achieve these objectives, we designed a prospective, observational study of SARS-CoV-2 infection among HCP and their household contacts at an academic tertiary care medical center in North Carolina, USA. Enrolled HCP completed frequent surveys on symptoms and work activities and provided serum and nasal samples for SARS-CoV-2 testing every 2 weeks. Additionally, interactions between participants and their movement within the clinical environment were captured with a smartphone app and Bluetooth sensors. Finally, a subset of participants' households was randomly selected every 2 weeks for further investigation, and enrolled households provided serum and nasal samples via at-home collection kits.
As of December 31, 2020, 211 HCP and 53 household participants have been enrolled. Recruitment and follow-up are ongoing and expected to continue through September 2021.
Much remains to be learned regarding the risk of SARS-CoV-2 infection among HCP and their household contacts. Through the use of a multifaceted prospective study design and a well-characterized cohort, we will collect critical information regarding SARS-CoV-2 transmission risks in the health care setting and its linkage to the community.
DERR1-10.2196/25410.
Recent soils research has shown that important chemical soil characteristics can change in less than a decade, often the result of broad environmental changes. Repeated sampling to monitor these ...changes in forest soils is a relatively new practice that is not well documented in the literature and has only recently been broadly embraced by the scientific community. The objective of this protocol is therefore to synthesize the latest information on methods of soil resampling in a format that can be used to design and implement a soil monitoring program. Successful monitoring of forest soils requires that a study unit be defined within an area of forested land that can be characterized with replicate sampling locations. A resampling interval of 5 years is recommended, but if monitoring is done to evaluate a specific environmental driver, the rate of change expected in that driver should be taken into consideration. Here, we show that the sampling of the profile can be done by horizon where boundaries can be clearly identified and horizons are sufficiently thick to remove soil without contamination from horizons above or below. Otherwise, sampling can be done by depth interval. Archiving of sample for future reanalysis is a key step in avoiding analytical bias and providing the opportunity for additional analyses as new questions arise.
Background & Aims:
Previously identified clinical risk factors such as sex, alcohol consumption, and age at infection do not accurately predict which patients with chronic hepatitis C (CHC) will ...develop advanced fibrosis (bridging fibrosis and cirrhosis). The aim of this study was to identify genetic polymorphisms that can predict the risk of advanced fibrosis in patients with CHC.
Methods:
A total of 916 subjects with CHC was enrolled from 2 centers. A gene-centric disease association study of 24,832 putative functional, single nucleotide polymorphisms (SNPs) was performed. Of the 1609 SNPs that were significantly associated (
P ≤ .05) with advanced fibrosis in the discovery cohort (University of California San Francisco UCSF, N = 433), the first batch of 100 SNPs were selected for validation in the replication cohort (Virginia Commonwealth University VCU, N = 483).
Results:
A missense SNP in the DEAD box polypeptide 5 (DDX5) gene was significantly associated with an increased risk of advanced fibrosis in both the UCSF and the VCU cohorts (OR, 1.8 and 2.2, respectively). Two diplotype groups, carrying the haplotypes composed of the DDX5 SNP and 2 neighboring POLG2 SNPs were also significantly associated with an increased risk of advanced fibrosis and had comparable or better risk estimates. In addition, a missense SNP in the carnitine palmitoyltransferase 1A (CPT1A) gene was associated with a decreased risk of advanced fibrosis in both the UCSF and the VCU cohorts (OR, 0.3 and 0.6, respectively).
Conclusions:
Subjects with CHC carrying DDX5 minor allele or DDX5-POLG2 haplotypes are at an increased risk of developing advanced fibrosis, whereas those carrying the CPT1A minor allele are at a decreased risk.
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