Brown Anole (Anolis sagrei) Hoxa5: Insights into the Divergence of Hoxa5 Gene Expression and Regulation Across Evolutionarily Divergent Gnathostome Vertebrates

Hox genes are evolutionarily conserved developmental regulatory genes that function, in part, to pattern the anterior-posterior (AP) axis of organs and organ systems during animal embryonic development. Hoxa5, specifically, is shown to be expressed in the spinal cord, somites, or transient compartments giving rise to the vertebrae and ribs, developing gut, lungs, and limbs of the mouse (Mus musculus). The cis-regulatory elements (CREs), or short DNA sequences, that direct Hoxa5 expression in these embryonic domains have been mapped and functionally tested in the mouse as well. Similar Hoxa5 expression patterns have been observed in chicken (Gallus gallus), American alligator (Alligator mississipiensis), and dogfish shark (Scyliorhinus canicular), but have shown divergence in the anterior limit of expression within the somites. Specifically, while mouse expression begins in somite 3, chicken, alligator, and shark begin in 8, 9, and 9, respectively. Further, no hoxa5 expression has been observed in the somites for teleost fish. Here, we present the embryonic Hoxa5 expression pattern within brown anole lizard (Anolis sagrei). Our data shows that Hoxa5 within the lizard has an anterior limit of expression in somite 6 and exhibits a more similar expression pattern to that of mouse, chicken, alligator, and shark than to teleost fishes. Furthermore, our comparative genomic DNA sequence analyses display that the functional CREs mapped in the mouse are conserved among the tetrapods, but not with the shark or teleost fishes. Our analyses suggest that divergent Hoxa5 expression patterns result from divergence within their respective CREs

Childhood height, adult height, and the risk of prostate cancer

PURPOSE: We previously showed that childhood height is positively associated with prostate cancer risk. It is, however, unknown whether childhood height exerts its effects independently of or through adult height. We investigated whether and to what extent childhood height has a direct effect on the risk of prostate cancer apart from adult height. METHODS: We included 5,871 men with height measured at ages 7 and 13 years in the Copenhagen School Health Records Register who also had adult (50–65 years) height measured in the Danish Diet, Cancer and Health study. Prostate cancer status was obtained through linkage to the Danish Cancer Registry. Direct and total effects of childhood height on prostate cancer risk were estimated from Cox regressions. RESULTS: From 1996 to 2012, 429 prostate cancers occurred. Child and adult heights were positively and significantly associated with prostate cancer risk. When adjusted for adult height, height at age 7 years was no longer significantly associated with the risk of prostate cancer. Height at 13 years was significantly and positively associated with prostate cancer risk even when adult height was adjusted for; per height z-score the hazard ratio was 1.15 [95 % confidence interval (CI) 1.01–1.32]. CONCLUSIONS: The effect of height at 13 years on the risk of prostate cancer was not entirely mediated through adult height, suggesting that child height and adult height may be associated with prostate cancer through different pathways

The stoichiometry of the outer kinetochore is modulated by microtubule-proximal regulatory factors

The kinetochore is a large molecular machine that attaches chromosomes to microtubules and facilitates chromosome segregation. The kinetochore includes submodules that associate with the centromeric DNA and submodules that attach to microtubules. Additional copies of several submodules of the kinetochore are added during anaphase, including the microtubule binding module Ndc80. While the factors governing plasticity are not known, they could include regulation based on microtubule–kinetochore interactions. We report that Fin1 localizes to the microtubule-proximal edge of the kinetochore cluster during anaphase based on single-particle averaging of super-resolution images. Fin1 is required for the assembly of normal levels of Dam1 and Ndc80 submodules. Levels of Ndc80 further depend on the Dam1 microtubule binding complex. Our results suggest the stoichiometry of outer kinetochore submodules is strongly influenced by factors at the kinetochore–microtubule interface such as Fin1 and Dam1, and phosphorylation by cyclin-dependent kinase. Outer kinetochore stoichiometry is remarkably plastic and responsive to microtubule-proximal regulation

Drug Use Behaviors: 2020 Treatment Providers Survey, Dataset, and Interview Final Reports

The purpose of this needs assessment is to deepen DOP’s (NE DHHS Drug Overdose Prevention (DOP) program) understanding of individuals’ drug use behaviors in Nebraska through the lens of treatment providers. The results of this study will aid DOP in providing training and other resources to treatment centers, focusing prevention efforts, and informing their strategic plan and future studies. Ultimately, this study will support DOP’s efforts to reduce opioid-involved fatal and non-fatal overdoses in Nebraska

Noninvasive evaluation of hand circulation before radial artery harvest for coronary artery bypass grafting

AbstractObjective: Radial artery harvesting for coronary artery bypass may lead to digit ischemia if collateral hand circulation is inadequate. The modified Allen's test is the most common preoperative screening test used. Unfortunately, this test has high false-positive and false-negative rates. The purpose of this study was to compare the results of a modified Allen's test with digit pressure change during radial artery compression for assessing collateral circulation before radial artery harvest. Methods: One hundred twenty-nine consecutive patients were studied before coronary artery bypass operations. A modified Allen's test was performed with Doppler ultrasound to assess blood flow in the superficial palmar arch before and during radial artery compression. A decreased audible Doppler signal after radial artery compression was considered a positive modified Allen's test. First and second digit pressures were measured before and during radial artery compression. A decrease in digit pressure of 40 mm Hg or more (digit ΔP) with radial artery compression was considered positive. Results: Seven of 14 dominant extremities (50%) and 8 of the 16 nondominant extremities (50%) with a positive modified Allen's test had a digit ΔP of less than 40 mm Hg (false positive). Sixteen of 115 dominant extremities (14%) and 5 of 112 nondominant extremities (4%) with a negative Allen's test had a digit ΔP of 40 mm Hg or more with radial artery compression (false negative). Conclusion: Use of the modified Allen's test for screening before radial artery harvest may unnecessarily exclude some patients from use of this conduit and may also place a number of patients at risk for digit ischemia from such harvest. Direct digit pressure measurement is a simple, objective method that may more precisely select patients for radial artery harvest. Additional studies are needed to define objective digital pressure criteria that will accurately predict patients at risk for hand ischemia after radial harvest. (J Thorac Cardiovasc Surg 1999;117:261-6

Genetic variation in Glutathione S-Transferase Omega-1, Arsenic Methyltransferase and Methylene-tetrahydrofolate Reductase, arsenic exposure and bladder cancer: a case–control study

Abstract Background Ingestion of groundwater with high concentrations of inorganic arsenic has been linked to adverse health outcomes, including bladder cancer, however studies have not consistently observed any elevation in risk at lower concentrations. Genetic variability in the metabolism and clearance of arsenic is an important consideration in any investigation of its potential health risks. Therefore, we examined the association between genes thought to play a role in the metabolism of arsenic and bladder cancer. Methods Single nucleotide polymorphisms (SNPs) in GSTO-1, As3MT and MTHFR were genotyped using DNA from 219 bladder cancer cases and 273 controls participating in a case–control study in Southeastern Michigan and exposed to low to moderate (\u3c50 μg/L) levels of arsenic in their drinking water. A time-weighted measure of arsenic exposure was constructed using measures from household water samples combined with past residential history, geocoded and merged with archived arsenic data predicted from multiple resources. Results While no single SNP in As3MT was significantly associated with bladder cancer overall, several SNPs were associated with bladder cancer among those exposed to higher arsenic levels. Individuals with one or more copies of the C allele in rs11191439 (the Met287Thr polymorphism) had an elevated risk of bladder cancer (OR = 1.17; 95% CI = 1.04-1.32 per 1 μg/L increase in average exposure). However, no association was observed between average arsenic exposure and bladder cancer among TT homozygotes in the same SNP. Bladder cancer cases were also 60% less likely to be homozygotes for the A allele in rs1476413 in MTHFR compared to controls (OR = 0.40; 95% CI = 0.18-0.88). Conclusions Variation in As3MT and MTHFR is associated with bladder cancer among those exposed to relatively low concentrations of inorganic arsenic. Further investigation is warranted to confirm these findings

3C. 3-Ketosteroid receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Steroid hormone receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [65, 193]) are nuclear hormone receptors of the NR3 class, with endogenous agonists that may be divided into 3-hydroxysteroids (estrone and 17β-estradiol) and 3-ketosteroids (dihydrotestosterone [DHT], aldosterone, cortisol, corticosterone, progesterone and testosterone)

Genetic variation in Glutathione S-Transferase Omega-1, Arsenic Methyltransferase and Methylene-tetrahydrofolate Reductase, arsenic exposure and bladder cancer: a case–control study

Abstract Background Ingestion of groundwater with high concentrations of inorganic arsenic has been linked to adverse health outcomes, including bladder cancer, however studies have not consistently observed any elevation in risk at lower concentrations. Genetic variability in the metabolism and clearance of arsenic is an important consideration in any investigation of its potential health risks. Therefore, we examined the association between genes thought to play a role in the metabolism of arsenic and bladder cancer. Methods Single nucleotide polymorphisms (SNPs) in GSTO-1, As3MT and MTHFR were genotyped using DNA from 219 bladder cancer cases and 273 controls participating in a case–control study in Southeastern Michigan and exposed to low to moderate (<50 μg/L) levels of arsenic in their drinking water. A time-weighted measure of arsenic exposure was constructed using measures from household water samples combined with past residential history, geocoded and merged with archived arsenic data predicted from multiple resources. Results While no single SNP in As3MT was significantly associated with bladder cancer overall, several SNPs were associated with bladder cancer among those exposed to higher arsenic levels. Individuals with one or more copies of the C allele in rs11191439 (the Met287Thr polymorphism) had an elevated risk of bladder cancer (OR = 1.17; 95% CI = 1.04-1.32 per 1 μg/L increase in average exposure). However, no association was observed between average arsenic exposure and bladder cancer among TT homozygotes in the same SNP. Bladder cancer cases were also 60% less likely to be homozygotes for the A allele in rs1476413 in MTHFR compared to controls (OR = 0.40; 95% CI = 0.18-0.88). Conclusions Variation in As3MT and MTHFR is associated with bladder cancer among those exposed to relatively low concentrations of inorganic arsenic. Further investigation is warranted to confirm these findings.http://deepblue.lib.umich.edu/bitstream/2027.42/112833/1/12940_2012_Article_570.pd