Skovsgaardlowry1113

The human β-globin locus control region (LCR) hypersensitive site 2 (HS2) is one of enhancers for transcription of the β-like globin genes in erythroid cells. Our previous study showed that the LCR HS2 has active chromatin structure before transcriptional induction of the β-globin gene, while another enhancer LCR HS3 is activated by the induction. To compare functional difference between them, we deleted each HS (ΔHS2 and ΔHS3) from the human β-globin locus in hybrid MEL/ch11 cells. Deletion of either HS2 or HS3 dramatically diminished the β-globin transcription and disrupted locus-wide histone H3K27ac and chromatin interaction between LCR HSs and gene. Surprisingly, ΔHS2 weakened interactions between CTCF sites forming the β-globin topologically associating domain (TAD), while ΔHS3 did not. CTCF occupancy and chromatin accessibility were reduced at the CTCF sites in the ΔHS2 locus. To further characterize the HS2, we deleted the maf-recognition elements for erythroid activator NF-E2 at HS2. This deletion decreased the β-globin transcription and enhancer-promoter interaction, but did not affect interactions between CTCF sites for the TAD. In light of these results, we propose that the HS2 has a role in forming a β-globin TAD by activating neighboring CTCF sites and this role is beyond typical enhancer activity.

Obesity was suggested to increase the incidence of gastric cancer (GC) in women, but results from previous studies were inconsistent. We investigated the relationship between obesity and the risk of GC according to menopausal status.

We enrolled 1418180 premenopausal and 4854187 postmenopausal women aged≥40years using the Korean National Health Insurance System Cohort (2009-2014). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for GC incidence according to body mass index (BMI) and waist circumference (WC) using the Cox proportional hazards models.

During the mean follow-up period of 7.2years, 42441 women were newly diagnosed with GC. Compared with the group with BMI 18.5-22.9kg/m

, the adjusted HRs (95% CIs) for GC in the groups with BMI<18.5, 23-24.9, 25-29.9, and ≥30kg/m

were 1.12 (0.95-1.33), 0.96 (0.89-1.04), 1.02 (0.94-1.11), and 0.99 (0.83-1.18), respectively, for premenopausal women and 1.07 (1.00-1.14), 1.01 (0.99-1.04), 1.03 (1.00-1.05), and 1.11 (1.10-1.16), respectively, for postmenopausal women. Compared with the group with WC 65-74.9cm, the adjusted HRs (95% CIs) for GC for the groups with WC<65, 75-84.9, 85-94.9, and ≥90cm were 1.00 (0.88-1.15), 1.03 (0.96-1.11), 1.10 (0.99-1.22), and 1.02 (0.81-1.27), respectively, for premenopausal women and 1.01 (0.94-1.09), 1.01 (0.99-1.04), 1.09 (1.06-1.13), and 1.14 (1.09-1.19), respectively, for postmenopausal women.

We found a positive association between the highest BMI and WC category and risk of GC in postmenopausal women; however, such an association was not evident in premenopausal women.

We found a positive association between the highest BMI and WC category and risk of GC in postmenopausal women; however, such an association was not evident in premenopausal women.Fertilization is commonly used to increase growth in forest plantations, but it may also affect tree water relations and responses to drought. Here, we measured changes in biomass, transpiration, sapwood-to-leaf area ratio (As Al ) and sap flow driving force (ΔΨ) during the 6-year rotation of tropical plantations of Eucalyptus grandis under controlled conditions for throughfall and potassium (K) fertilization. K fertilization increased final tree height by 8 m. Throughfall exclusion scarcely affected tree functioning because of deep soil water uptake. Tree growth increased in K-supplied plots and remained stable in K-depleted plots as tree height increased, while growth per unit leaf area increased in all plots. Stand transpiration and hydraulic conductance standardized per leaf area increased with height in K-depleted plots, but remained stable or decreased in K-supplied plots. Greater Al in K-supplied plots increased the hydraulic constraints on water use. This involved a direct mechanism through halved As Al in K-supplied plots relative to K-depleted plots, and an indirect mechanism through deteriorated water status in K-supplied plots, which prevented the increase in ΔΨ with tree height. K fertilization in tropical plantations reduces the hydraulic compensation to growth, which could increase the risk of drought-induced dieback under climate change.We describe a case of pacemaker implant guided by intracardiac echocardiography and three-dimensional anatomical mapping in a pregnant patient, with no peri-procedural use of radiation.Mesenchymal stromal cells in solid tumors have emerged as important mediators of immune function and response to immunotherapies. As such, comprehensive insights into their biology may reveal new predictors of drug response and new drug targets. While our understanding of mesenchymal biology in cancer is nascent, it is rapidly evolving, driven by advances in single-cell technologies. These studies reveal distinct subclasses of cancer-associated fibroblasts (CAFs) with unique properties for immune regulation and control of leukocyte activity. While these studies have revealed several similarities across distinct types of cancer, they still face key challenges in nomenclature. Single-cell analysis of tumors has also revealed an abundance of perivascular cells with unique biology and associations with immune infiltration. They are often misclassified, likely confounding previous bulk studies, revealing a distinct lineage of cells that remain to be fully characterized. These studies have also shed light on the discrete cell types or transient cell states that shape mesenchymal heterogeneity in tumors, offering insights into new therapeutic strategies to modulate stromal cell differentiation. In this review, we will address how recent advances in single-cell technologies have shaped our understanding of stromal heterogeneity and their coordination of immune responses in cancer.

Quantitative muscle ultrasound offers biomarkers that aid in the diagnosis, detection, and follow-up of neuromuscular disorders. At present, quantitative muscle ultrasound methods are 2D and are often operator and device dependent. The aim of this study was to combine an existing device independent method with an automated ultrasound machine and perform 3D quantitative muscle ultrasound, providing new normative data of healthy controls.

In total, 123 healthy volunteers were included. read more After physical examination, 3D ultrasound scans of the tibialis anterior muscle were acquired using an automated ultrasound scanner. Image postprocessing was performed to obtain calibrated echo intensity values based on a phantom reference.

Tibialis anterior muscle volumes of 61.2 ± 24.1mL and 53.7 ± 22.7mL were scanned in males and females, respectively. Echo intensity correlated with gender**, age**, fat fraction*, histogram kurtosis**, skewness* and standard deviation** (*P < .05, **P < .01). Outcome measures did not differ significantly for different acquisition presets.