Accurate Determination of Phenotypic Information from Historic Thoroughbred Horses by Single Base Extension

Historic DNA have the potential to identify phenotypic information otherwise invisible in the historical, archaeological and palaeontological record. In order to determine whether a single nucleotide polymorphism typing protocol based on single based extension (SNaPshot™) could produce reliable phenotypic data from historic samples, we genotyped three coat colour markers for a sample of historic Thoroughbred horses for which both phenotypic and correct geotypic information were known from pedigree information in the General Stud Book. Experimental results were consistent with the pedigrees in all cases. Thus we demonstrate that historic DNA techniques can produce reliable phenotypic information from museum specimens.© 2010 Campana et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

A novel experimental technique and its application to study the effects of particle density and flow submergence on bed particle saltation

This research was sponsored by EPSRC grant EP/G056404/1 which is greatly appreciated.Peer reviewedPublisher PD

Association of Social Risk Factors With Mortality among Us adults With a New Cancer Diagnosis

This cohort study examines the associations of multiple social risk factors with mortality risk among patients newly diagnosed with cancer in the US

Phosphatidylethanolamine N-methyltransferase (PEMT) Knockout Mice Exhibit Worse Alcohol-Induced Liver Injury than Wildtype Mice

Phosphatidylethanolamine N-methyltransferase (PEMT) is an enzyme that catalyzes the successive transfer of 3 methyl groups from S-adenosylmethionine (SAM) to phosphatidylethanolamine (PE) to generate phosphatidylcholine (PC). PC is vital for exporting fat out of the liver, ultimately preventing hepatic steatosis. Alcohol also induces steatosis partly through damaging this pathway, so the purpose of this study was to investigate the relationship between alcohol and PEMT in the liver. PEMT -/- (KO) and wild-type (WT) mice were subjected to a chronic + binge alcohol treatment, and both serum and liver samples were analyzed. Triglyceride quantification, SAM and S-adenosylhomocysteine (SAH) levels, and histological analyses were performed on liver samples, while ALT levels were determined from serum samples. Our study showed that ethanol-fed PEMT KO mice exhibited worse liver injury compared to other treatment groups. Our results show increased triglyceride levels, increased ALT levels, decreased SAM:SAH ratio, and increased liver to body weight ratio. From these findings, we conclude that additional liver damage is observed with the combination of alcohol feeding and absence of the PEMT enzyme. The mechanism by which these two factors affect one another is a key area of future study.https://digitalcommons.unmc.edu/surp2021/1016/thumbnail.jp

Crosslinking and Mechanical Properties Significantly Influence Cell Attachment, Proliferation, and Migration Within Collagen Glycosaminoglycan Scaffolds.

Crosslinking and the resultant changes in mechanical properties have been shown to influence cellular activity within collagen biomaterials. With this in mind, we sought to determine the effects of crosslinking on both the compressive modulus of collagen-glycosaminoglycan scaffolds and the activity of osteoblasts seeded within them. Dehydrothermal, 1-ethyl-3-3-dimethyl aminopropyl carbodiimide and glutaraldehyde crosslinking treatments were first investigated for their effect on the compressive modulus of the scaffolds. After this, the most promising treatments were used to study the effects of crosslinking on cellular attachment, proliferation, and infiltration. Our experiments have demonstrated that a wide range of scaffold compressive moduli can be attained by varying the parameters of the crosslinking treatments. 1-Ethyl-3-3-dimethyl aminopropyl carbodiimide and glutaraldehyde treatments produced the stiffest scaffolds (fourfold increase when compared to dehydrothermal crosslinking). When cells were seeded onto the scaffolds, the stiffest scaffolds also showed increased cell number and enhanced cellular distribution when compared to the other groups. Taken together, these results indicate that crosslinking can be used to produce collagen-glycosaminoglycan scaffolds with a range of compressive moduli, and that increased stiffness enhances cellular activity within the scaffolds

Potential Impact of Revised Nci Eligibility Criteria Guidance: Prior Malignancy Exclusion in Breast Cancer Clinical Trials

BACKGROUND: Many individuals with cancer have survived a prior cancer and for this reason may have been excluded from clinical trials. Recent NCI guidance recommends including these individuals, especially when the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low. Using breast cancer as an example, we determined the potential effect this policy change may have on clinical trial accrual. PATIENTS AND METHODS: We reviewed protocols of NCI-sponsored breast cancer clinical trials activated in 1991 through 2016. We quantified prevalence of prior cancer-related exclusion criteria and assessed the association with trial characteristics using Fisher\u27s exact tests. Using SEER data, we estimated the prevalence and timing of prior primary (nonbreast) cancer diagnoses among patients with breast cancer. RESULTS: Among 87 clinical trials (total target enrollment, 137,253 patients), 77% excluded individuals with prior cancer, most commonly (79%) within the preceding 5 years. Among trials with radiographic response or toxicity endpoints, 69% excluded prior cancer. In SEER data, the prevalence of a prior (nonbreast) cancer diagnosis ranged from 5.7% to 7.7%, depending on breast cancer stage, of which 39% occurred within 5 years of the incident breast cancer. For trials excluding prior cancer, the estimated proportion of patients excluded for this reason ranged from 1.3% to 5.8%, with the estimated number of excluded patients ranging from 1 to 288. CONCLUSIONS: More than three-fourths of NCI-sponsored breast cancer clinical trials exclude patients with prior cancer, including almost 70% of trials with response or toxicity endpoints. Given that \u3e5% of patients with breast cancer have a history of prior cancer, in large phase III trials this practice may exclude hundreds of patients. Following recent NCI eligibility guidance, the inclusion of patients with prior cancer on breast cancer trials may have a meaningful impact on accrual

Knockdown of Ant2 Reduces Adipocyte Hypoxia And Improves Insulin Resistance in Obesity.

Decreased adipose tissue oxygen tension and increased HIF-1α expression can trigger adipose tissue inflammation and dysfunction in obesity. Our current understanding of obesity-associated decreased adipose tissue oxygen tension is mainly focused on changes in oxygen supply and angiogenesis. Here, we demonstrate that increased adipocyte O2 demand, mediated by ANT2 activity, is the dominant cause of adipocyte hypoxia. Deletion of adipocyte Ant2 improves obesity-induced intracellular adipocyte hypoxia by decreasing obesity-induced adipocyte oxygen demand, without effects on mitochondrial number or mass, or oligomycin-sensitive respiration. This led to decreased adipose tissue HIF-1α expression and inflammation with improved glucose tolerance and insulin resistance in both a preventative or therapeutic setting. Our results suggest that ANT2 may be a target for the development of insulin sensitizing drugs and that ANT2 inhibition might have clinical utility

Acute effects of an Avena sativa herb extract on responses to the Stroop Color-Word test

Background and aims: Extracts from oat (Avena sativa) herb may benefit cognitive performance. This study investigated whether Neuravena®, an oat herb extract, could acutely improve responses to the Stroop Color–Word test, a measure of attention and concentration and the ability to maintain task focus.  Subjects and methods: Elderly volunteers with below-average cognitive performance consumed single doses (0, 1600, and 2400 mg) of oat herb extract at weekly intervals in a double-blind, randomized, crossover comparison. Resting blood pressure (BP) was assessed before and after supplementation, and a Stroop test was performed.  Results: Significantly fewer errors were made during the color-naming component of the Stroop test after consuming the 1600-mg dose than after the 0-mg or 2400-mg doses (F (1,36)=18.85, p<0.001). In 7 subjects with suspected cognitive impairment, Stroop interference score was also improved by the 1600-mg dose compared to 0- and 2400-mg doses (F (1, 34)=2.40, p<0.01). Resting BP was unaffected by supplementation.  Conclusions: Taking 1600 mg of oat herb extract may acutely improve attention and concentration and the ability to maintain task focus in older adults with differing levels of cognitive status

Murine Ultrasound-Guided Transabdominal Para-Aortic Injections of Self-Assembling Type I Collagen Oligomers

Abdominal aortic aneurysms (AAAs) represent a potentially life-threatening condition that predominantly affects the infrarenal aorta. Several preclinical murine models that mimic the human condition have been developed and are now widely used to investigate AAA pathogenesis. Cell- or pharmaceutical-based therapeutics designed to prevent AAA expansion are currently being evaluated with these animal models, but more minimally invasive strategies for delivery could improve their clinical translation. The purpose of this study was to investigate the use of self-assembling type I collagen oligomers as an injectable therapeutic delivery vehicle in mice. Here we show the success and reliability of a para-aortic, ultrasound-guided technique for injecting quickly-polymerizing collagen oligomer solutions into mice to form a collagen-fibril matrix at body temperature. A commonly used infrarenal mouse AAA model was used to determine the target location of these collagen injections. Ultrasound-guided, closed-abdominal injections supported consistent delivery of collagen to the area surrounding the infrarenal abdominal aorta halfway between the right renal artery and aortic trifurcation into the iliac and tail arteries. This minimally invasive approach yielded outcomes similar to open-abdominal injections into the same region. Histological analysis on tissue removed on day 14 post-operatively showed minimal in vivo degradation of the self-assembled fibrillar collagen and the majority of implants experienced minimal inflammation and cell invasion, further confirming this material's potential as a method for delivering therapeutics. Finally, we showed that the typical length and position of this infrarenal AAA model was statistically similar to the length and targeted location of the injected collagen, increasing its feasibility as a localized therapeutic delivery vehicle. Future preclinical and clinical studies are needed to determine if specific therapeutics incorporated into the self-assembling type I collagen matrix described here can be delivered near the aorta and locally limit AAA expansion.