148 research outputs found
Follicular lymphoma, a B cell malignancy addicted to epigenetic mutations
K Korfi, S Ali, J Heward and J Fitzgibbon are supported by Cancer Research UK Programme Grant
[C15966/A15968] and Bloodwise Programme Grant [15002]. S Ali is also a recipient of Cancer
Research UK Clinical Careers Committee research bursary [C56515/A21397]
Surgical and Obstetric Outcomes in Adults with Sickle Cell Disease
Sickle cell disease patients are more likely than the general population to undergo surgery and usually do so at a younger age. Female sickle cell disease patients also have special gynecological and obstetric issues related to their disease
Factors associated with survival in a contemporary adult sickle cell disease cohort: Factors Associated with Survival in Sickle Cell Disease
We examined the relationship of clinical differences among sickle cell disease (SCD) patients in order to understand the major contributors to early mortality in a contemporary cohort
Plant mitochondrial introns as genetic markers - conservation and variation
Plant genomes are comprised of nuclear, plastid and mitochondrial components characterized by different patterns of inheritance and evolution. Genetic markers from the three genomes provide complementary tools for investigations of inheritance, genetic relationships and phenotypic contributions. Plant mitochondrial genomes are challenging for universal marker development because they are highly variable in terms of size, gene order and intergenic sequences and highly conserved with respect to protein-coding sequences. PCR amplification of introns with primers that anneal to conserved, flanking exons is effective for the development of polymorphic nuclear genome markers. The potential for plant mitochondrial intron polymorphisms to distinguish between congeneric species or intraspecific varieties has not been systematically investigated and is possibly constrained by requirements for intron secondary structure and interactions with co-evolved organelle intron splicing factors. To explore the potential for broadly applicable plant mitochondrial intron markers, PCR primer sets based upon conserved sequences flanking 11 introns common to seven angiosperm species were tested across a range of plant orders. PCR-amplified introns were screened for indel polymorphisms among a group of cross-compatible Citrus species and relatives; two Raphanus sativus mitotypes; representatives of the two Phaseolus vulgaris gene pools; and congeneric pairs of Cynodon, Cenchrus, Solanum, and Vaccinium species. All introns were successfully amplified from each plant entry. Length polymorphisms distinguishable by gel electrophoresis were common among genera but infrequent within genera. Sequencing of three introns amplified from 16 entries identified additional short indel polymorphisms and nucleotide substitutions that separated Citrus, Cynodon, Cenchrus and Vaccinium congeners, but failed to distinguish Solanum congeners or representatives of the Phaseolus vulgaris major gene pools. The ability of primer sets to amplify a wider range of plant speciesβ introns and the presence of intron polymorphisms that distinguish congeners was confirmed by in silico analysis. While mitochondrial intron variation is limited in comparison to nuclear introns, these exon-based primer sets provide robust tools for the amplification of mitochondrial introns across a wide range of plant species wherein useful polymorphisms can be identified
MYH9 and APOL1 are both associated with sickle cell disease nephropathy
Renal failure occurs in 5β18% of sickle cell disease (SCD) patients and is associated with early mortality. At risk SCD patients cannot be identified prior to the appearance of proteinuria and the pathobiology is not well understood. The MYH9 and APOL1 genes have been associated with risk for focal segmental glomerulosclerosis and end-stage renal disease in African Americans
Rate-Induced Transitions in Networked Complex Adaptive Systems: Exploring Dynamics and Management Implications Across Ecological, Social, and Socioecological Systems
Complex adaptive systems (CASs), from ecosystems to economies, are open
systems and inherently dependent on external conditions. While a system can
transition from one state to another based on the magnitude of change in
external conditions, the rate of change -- irrespective of magnitude -- may
also lead to system state changes due to a phenomenon known as a rate-induced
transition (RIT). This study presents a novel framework that captures RITs in
CASs through a local model and a network extension where each node contributes
to the structural adaptability of others. Our findings reveal how RITs occur at
a critical environmental change rate, with lower-degree nodes tipping first due
to fewer connections and reduced adaptive capacity. High-degree nodes tip later
as their adaptability sources (lower-degree nodes) collapse. This pattern
persists across various network structures. Our study calls for an extended
perspective when managing CASs, emphasizing the need to focus not only on
thresholds of external conditions but also the rate at which those conditions
change, particularly in the context of the collapse of surrounding systems that
contribute to the focal system's resilience. Our analytical method opens a path
to designing management policies that mitigate RIT impacts and enhance
resilience in ecological, social, and socioecological systems. These policies
could include controlling environmental change rates, fostering system
adaptability, implementing adaptive management strategies, and building
capacity and knowledge exchange. Our study contributes to the understanding of
RIT dynamics and informs effective management strategies for complex adaptive
systems in the face of rapid environmental change.Comment: 25 pages, 4 figures, 1 box, supplementary informatio
Identifying Defects in Li-Ion Cells Using Ultrasound Acoustic Measurements
Identification of the state-of-health (SoH) of Li-ion cells is a vital tool to protect operating battery packs against accelerated degradation and failure. This is becoming increasingly important as the energy and power densities demanded by batteries and the economic costs of packs increase. Here, ultrasonic time-of-flight analysis is performed to demonstrate the technique as a tool for the identification of a range of defects and SoH in Li-ion cells. Analysis of large, purpose-built defects across multiple length scales is performed in pouch cells. The technique is then demonstrated to detect a microscale defect in a commercial cell, which is validated by examining the acoustic transmission signal through the cell. The location and scale of the defects are confirmed using X-ray computed tomography, which also provides information pertaining to the layered structure of the cells. The demonstration of this technique as a methodology for obtaining direct, non-destructive, depth-resolved measurements of the condition of electrode layers highlights the potential application of acoustic methods in real-time diagnostics for SoH monitoring and manufacturing processes
Runx1 Loss Minimally Impacts Long-Term Hematopoietic Stem Cells
RUNX1 encodes a DNA binding subunit of the core-binding transcription factors and is frequently mutated in acute leukemia, therapy-related leukemia, myelodysplastic syndrome, and chronic myelomonocytic leukemia. Mutations in RUNX1 are thought to confer upon hematopoietic stem cells (HSCs) a pre-leukemic state, but the fundamental properties of Runx1 deficient pre-leukemic HSCs are not well defined. Here we show that Runx1 deficiency decreases both apoptosis and proliferation, but only minimally impacts the frequency of long term repopulating HSCs (LT-HSCs). It has been variously reported that Runx1 loss increases LT-HSC numbers, decreases LT-HSC numbers, or causes age-related HSC exhaustion. We attempt to resolve these discrepancies by showing that Runx1 deficiency alters the expression of several key HSC markers, and that the number of functional LT-HSCs varies depending on the criteria used to score them. Finally, we identify genes and pathways, including the cell cycle and p53 pathways that are dysregulated in Runx1 deficient HSCs
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