Publications by authors named "Llewellyn T"

(3-(pyrimidin-4-yl)-7-azaindoles) are synthetic hybrids of the naturally occurring alkaloids and and display a strong cytotoxic potential. We have recently shown that the novel derivative is highly cytotoxic in several lymphoma and leukemia cell lines as well as in primary patient-derived lymphoma and leukemia cells and predominantly targets cyclin-dependent kinases (CDKs). Here, we efficiently synthesized nine novel 2-aminopyridyl congeners (-), i.

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Outbreaks of fungal diseases have devastated plants and animals throughout history. Over the past century, the repeated emergence of coffee wilt disease caused by the fungal pathogen Fusarium xylarioides severely impacted coffee production across sub-Saharan Africa. To improve the disease management of such pathogens, it is crucial to understand their genetic structure and evolutionary potential.

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Article Synopsis
  • * The authors suggest new metrics to measure how well vaccines stimulate CD8 T cells and identify key viral parts that trigger immune response, considering genetic differences among people and viral changes.
  • * The proposed methods were tested successfully using proteins from the Ebola virus and SARS-CoV-2 vaccines, showing the effectiveness of their approach.
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Nanodiscs are discoidal lipoproteins that have often been used as vehicles to study membrane proteins in their native configuration. Nanodiscs have been primarily made from synthetic lipids. However, nanodiscs also offer a format by which native lipids can be studied in their natural configuration.

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Universal and early recognition of pathogens occurs through recognition of evolutionarily conserved pathogen associated molecular patterns (PAMPs) by innate immune receptors and the consequent secretion of cytokines and chemokines. The intrinsic complexity of innate immune signaling and associated signal transduction challenges our ability to obtain physiologically relevant, reproducible and accurate data from experimental systems. One of the reasons for the discrepancy in observed data is the choice of measurement strategy.

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Meriolin derivatives represent a new class of kinase inhibitors with a pronounced cytotoxic potential. Here, we investigated a newly synthesized meriolin derivative (termed meriolin 16) that displayed a strong apoptotic potential in Jurkat leukemia and Ramos lymphoma cells. Meriolin 16 induced apoptosis in rapid kinetics (within 2-3 h) and more potently (IC: 50 nM) than the previously described derivatives meriolin 31 and 36 [1].

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Lichen-forming fungi are a diverse and ecologically important group of obligate mutualistic symbionts. Due to difficulties with maintaining them in culture and their extremely slow growth, lichenologists are increasingly opting for metagenomic sequencing followed by symbiont genome separation using bioinformatic pipelines. However, without knowing the true genome size of the lichen-forming fungus, we cannot quantify the completeness of the genome assembly and the efficacy of the bioinformatic filtering.

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The root systems of most plant species are aided by the soil-foraging capacities of symbiotic arbuscular mycorrhizal (AM) fungi of the Glomeromycotina subphylum. Despite recent advances in our knowledge of the ecology and molecular biology of this mutualistic symbiosis, our understanding of the AM fungi genome biology is just emerging. Presented here is a close to T2T genome assembly of the model AM fungus Rhizophagus irregularis DAOM197198, achieved through Nanopore long-read DNA sequencing and Hi-C data.

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Fungi produce a vast number of secondary metabolites that shape their interactions with other organisms and the environment. Characterizing the genes underpinning metabolite synthesis is therefore key to understanding fungal evolution and adaptation. Lichenized fungi represent almost one-third of Ascomycota diversity and boast impressive secondary metabolites repertoires.

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Unlabelled: Mental Fatigue (MF) has been associated with reduced physical performance but the mechanisms underlying this result are unclear. A reduction in excitability of the corticomotor system is a way mental fatigue could negatively impact physical performance. Carbohydrate (CHO) mouth rinse (MR) has been shown to increase corticomotor excitability.

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Seed banks were first established to conserve crop genetic diversity, but seed banking has more recently been extended to wild plants, particularly crop wild relatives (CWRs) (e.g., by the Millennium Seed Bank (MSB), Royal Botanic Gardens Kew).

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Objective: We would like to determine whether electrotherapy, specifically microcurrent therapy, increases function and decreases pain in people who have acute knee pain.

Design: Randomized, double-blinded, placebo-controlled clinical trial.

Setting: University laboratory and patient home.

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Mevalonate Kinase Deficiency (MKD) is an autoinflammatory disease caused by mutations in the mevalonate kinase gene, which produces an enzyme responsible for the production of isoprenoids in the mevalonate pathway. Patient data indicate that MKD is a multicytokine disease with increased plasma levels of cytokines such as tumor necrosis factor-α, interleukin (IL)-6, and interferon (IFN)-γ. To study the mechanisms responsible for these changes, the mevalonate pathway was inhibited with lovastatin in peripheral blood mononuclear cells (PBMCs) and monocytes isolated from the blood of healthy donors followed by stimulation with lipopolysaccharide (LPS) to induce an inflammatory response.

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Exercise training (ExT) is an established non-pharmacological therapy that improves the health and quality of life in patients with chronic heart failure (CHF). Exaggerated sympathetic drive characterizes CHF due to an imbalance of the autonomic nervous system. Neuronal nitric oxide synthase (nNOS) in the paraventricular nucleus (PVN) produce nitric oxide (NO•), which is known to regulate the sympathetic tone.

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The purpose of this study was to examine heart rate variability (HRV) at rest, and during submaximal (100 bpm) and maximal exercise in collegiate distance runners. We predicted there would be less HRV during exercise. Eight collegiate runners (19-22 yrs) were recruited for participation.

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Good balance, flexibility, and strength are all required to maintain a steady stance during the kinematic chain to produce successful golf shots. When the body can produce more power, more club head speed is generated. This formation of power translates into greater distance and accuracy.

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Pedometers are a popular way for people to track if they have reached the recommended 10,000 daily steps. Therefore, the purpose of this study was to determine the accuracy of four brands of pedometers at measuring steps, and to determine if a relationship exists between pedometer cost and accuracy. The hypothesis was that the more expensive brands of pedometers (the Fitbit Charge™ and Omron HJ-303™) would yield more accurate step counts than less expensive brands (the SmartHealth - Walking FIT™ and Sportline™).

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The purpose of this study was to determine if combining velocity-based training with eccentric focus (VEB) and velocity-based training (VBT) results in power and strength gains. Nineteen men and women collegiate track and field athletes participated in this study. The subjects completed a 12-week intervention with either a VEB program or a VBT program.

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Background: Concussions have been associated with elevated musculoskeletal injury risk; however, the influence of unreported and unrecognized concussions has not been investigated.

Hypothesis: The purpose of this study was to examine the association between concussion and lower extremity musculoskeletal injury rates across a diverse array of sports among collegiate student-athletes at the conclusion of their athletic career. The hypothesis was that there will be a positive association between athletes who reported a history of concussions and higher rates of lower extremity injuries.

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Exercise training (ExT) has been shown to reduce sympathetic drive during heart failure (HF). The subfornical organ (SFO) is involved in the neural control of sympathetic drive. We hypothesized that an activated SFO contributes to enhanced sympathetic activity in HF.

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Objective: The purpose of this study was to explore the current reported, unreported, and potentially unrecognized concussion rates among collegiate student-athletes who have completed their collegiate athletic career.

Design: Retrospective survey.

Setting: College and University athletic training rooms.

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An increased sympathetic drive is an adverse characteristic in chronic heart failure (CHF). The protein expression of neuronal nitric oxide synthase (nNOS)- and hence nitric oxide (NO)-mediated sympathoinhibition is reduced in the paraventricular nucleus (PVN) of rats with CHF. However, the molecular mechanism(s) of nNOS downregulation remain(s) unclear.

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Aim: Endothelial function is a predictor of cardiovascular health and is improved with exercise training. However, it is not clear how exercise acutely affects endothelial function. Previous studies present conflicting results, resulting from varied exercise protocols and ambiguity in data analysis after exercise.

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The purpose of this study was to determine if a difference in interleukin-6 (IL-6) and delayed onset muscles soreness (DOMS) exists in two different phases of the menstrual cycle. Nine runners performed one 75-min high-intensity interval running session during the early follicular (EF) phase and once during the midluteal (ML) phase of the menstrual cycle. Estrogen and progesterone levels were significantly reduced in the EF phase when compared to the ML phase.

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The paraventricular nucleus (PVN) of the hypothalamus is involved in the neural control of sympathetic drive, but the precise mechanism(s) that influences the PVN is not known. The activation of the PVN may be influenced by input from higher forebrain areas, such as the median preoptic nucleus (MnPO) and the subfornical organ (SFO). We hypothesized that activation of the MnPO or SFO would drive the PVN through a glutamatergic pathway.

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