Endurance running is thought as critical for the evolutionary success of hominins. A new study analysing the running skills of the famous 'Lucy' - Australopithecus afarensis - finds that they performed poorer than modern humans, suggesting that key features of the human body plan evolved specifically to improve running performance.
View Article and Find Full Text PDFMono-ubiquitination of lysine 18 on histone H3 (H3K18ub), catalyzed by UHRF1, is a DNMT1 docking site that facilitates replication-coupled DNA methylation maintenance. Its functions beyond this are unknown. Here, we genomically map simultaneous increases in UHRF1-dependent H3K18ub and SUV39H1/H2-dependent H3K9me3 following DNMT1 inhibition.
View Article and Find Full Text PDFThe RING E3 ubiquitin ligase UHRF1 is an established cofactor for DNA methylation inheritance. The model posits that nucleosomal engagement through histone and DNA interactions directs UHRF1 ubiquitin ligase activity toward lysines on histone H3 tails, creating binding sites for DNMT1 through ubiquitin interacting motifs (UIM1 and UIM2). However, the extent to which DNMT1 relies on ubiquitin signaling through UHRF1 in support of DNA methylation maintenance remains unclear.
View Article and Find Full Text PDFBackground: BK polyomavirus-associated nephropathy (BKPyVAN) is an important cause of allograft dysfunction and failure in kidney transplant recipients (KTRs) and there are no proven effective treatments. Case reports and in vitro data support the potential activity of cidofovir against BK polyomavirus (BKPyV).
Methods: We report the results of a phase I/II, double-blind, placebo-controlled randomized dose-escalation trial of cidofovir in KTRs with biopsy-confirmed BKPyVAN and estimated glomerular filtration rate ≥30 mL/min.
DNA methyltransferase inhibitor (DNMTi) efficacy in solid tumors is limited. Colon cancer cells exposed to DNMTi accumulate lysine-27 trimethylation on histone H3 (H3K27me3). We propose this Enhancer of Zeste Homolog 2 (EZH2)-dependent repressive modification limits DNMTi efficacy.
View Article and Find Full Text PDFThe RING E3 ubiquitin ligase UHRF1 is an established cofactor for DNA methylation inheritance. Nucleosomal engagement through histone and DNA interactions directs UHRF1 ubiquitin ligase activity toward lysines on histone H3 tails, creating binding sites for DNMT1 through ubiquitin interacting motifs (UIM1 and UIM2). Here, we profile contributions of UHRF1 and DNMT1 to genome-wide DNA methylation inheritance and dissect specific roles for ubiquitin signaling in this process.
View Article and Find Full Text PDFPurpose Of Review: Kidney dysfunction is challenging in liver transplant candidates to determine whether it is reversible or not. This review focuses on the pertinent data on how to best approach liver transplant candidates with kidney dysfunction in the current era after implementing the simultaneous liver kidney (SLK) allocation policy and safety net.
Recent Findings: The implementation of the SLK policy inverted the steady rise in SLK transplants and improved the utilization of high-quality kidneys.
Background: BK polyomavirus (BKV) can cause permanent loss of allograft function due to BKV-associated nephropathy (BKVN) in kidney transplant recipients. Besides immunosuppression reduction, there are no consistently effective interventions for BKV infection. Study purpose was to define natural history of BKV infection, identify risk factors for BKV reactivation and BKVN in kidney transplant recipients, and inform the design/conduct of future clinical trials of BKV-targeted therapeutics.
View Article and Find Full Text PDFKidney transplant is not only the best treatment for patients with advanced kidney disease but it also reduces health care expenditure. The management of transplant patients is complex as they require special care by transplant nephrologists who have expertise in assessing transplant candidates, understand immunology and organ rejection, have familiarity with perioperative complications, and have the ability to manage the long-term effects of chronic immunosuppression. This skill set at the intersection of multiple disciplines necessitates additional training in Transplant Nephrology.
View Article and Find Full Text PDFThe force a muscle generates is dependent on muscle structure, in which fibre length, pennation angle and tendon slack length all influence force production. Muscles are not preserved in the fossil record and these parameters must be estimated when constructing a musculoskeletal model. Here, we test the capability of digitally reconstructed muscles of the model (specimen AL 288-1) to maintain an upright, single-support limb posture.
View Article and Find Full Text PDFA 39-year-old female with a history of kidney transplant presented to the endocrinology clinic for osteoporosis evaluation after sustaining an ankle fracture from a fall. Her kidney transplant regimen (mycophenolate mofetil 360 mg twice a day, tacrolimus 0.5 mg every morning and 0.
View Article and Find Full Text PDFWhile previous research has noted the large numbers of school personnel with exposure to potentially traumatic experiences and its relation to secondary traumatic stress, it is unclear how different patterns of adverse childhood experiences influence secondary traumatic stress. As such, the present study employed latent profile analysis to examine natural groups of adverse childhood experience (ACE) history in 218 school mental health professionals (65% female; 55% White, 17.9% Black; 39% early career, 34% midcareer, and 28% late career; = 32.
View Article and Find Full Text PDFTo understand how an extinct species may have moved, we first need to reconstruct the missing soft tissues of the skeleton, which rarely preserve, with an understanding of segmental volume and muscular composition within the body. The specimen AL 288-1 is one of the most complete hominin skeletons. Despite 40+ years of research, the frequency and efficiency of bipedal movement in this specimen is still debated.
View Article and Find Full Text PDFIntroduction: Significant center-to-center variation in attitudes and management of delayed graft function (DGF) remains common.
Methods: A survey to describe current DGF practices was developed by workgroup members sponsored by the National Kidney Foundation (NKF) and was distributed to both the NKF DGF workgroup members, kidney transplant program directors and the transplant community within the United States and Canada. Seventy-one percent of NKF workgroup members completed the survey along with 70 unique the United States and three Canadian kidney transplant programs.
Here, we review the modern interface of three-dimensional (3D) empirical (e.g. motion capture) and theoretical (e.
View Article and Find Full Text PDFOrgan procurement organizations (OPOs) play a central role in the recovery, preservation, and distribution of deceased donor kidneys for transplantation in the United States. We conducted a national survey to gather information on OPO practices and perceived barriers to efficient organ placement in the face of the new circle-based allocation and asked for suggestions to overcome them. Of the 57 OPOs, 44 responded (77%).
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is a chronic neurodegenerative disorder with a progressive loss of cognitive function. Currently, no effective treatment regimen is available. Lithium, a mood stabilizer for bipolar disorder, exerts broad neuroprotective and neurotrophic actions and improves cognitive function.
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