Project description:Escherichia coli is both a commensal and a pathogen in humans and other animals. Here, we describe the isolation of E. coli strain 4s bacteriophage Paul. The complete 79,429-bp genome was annotated and demonstrates similarity with phieco32viruses, as does its prolate podophage morphology.
Project description:We experimentally demonstrate the feasibility of an aqueous Paul trap using a proof-of-principle planar device. Radio frequency voltages are used to generate an alternating focusing/defocusing potential well in two orthogonal directions. Individual charged particles are dynamically confined into nanometer scale in space. Compared with conventional Paul traps working in frictionless vacuum, the aqueous environment associated with damping forces and thermally induced fluctuations (Brownian noise) exerts a fundamental influence on the underlying physics. We investigate the impact of these two effects on the confining dynamics, with the aim to reduce the rms value of the positional fluctuations. We find that the rms fluctuations can be modulated by adjusting the voltages and frequencies. This technique provides an alternative for the localization and control of charged particles in an aqueous environment.
Project description:BackgroundMango, Mangifera indica L., an important tropical fruit crop, is grown for its sweet and aromatic fruits. Past improvement of this species has predominantly relied on chance seedlings derived from over 1000 cultivars in the Indian sub-continent with a large variation for fruit size, yield, biotic and abiotic stress resistance, and fruit quality among other traits. Historically, mango has been an orphan crop with very limited molecular information. Only recently have molecular and genomics-based analyses enabled the creation of linkage maps, transcriptomes, and diversity analysis of large collections. Additionally, the combined analysis of genomic and phenotypic information is poised to improve mango breeding efficiency.ResultsThis study sequenced, de novo assembled, analyzed, and annotated the genome of the monoembryonic mango cultivar 'Tommy Atkins'. The draft genome sequence was generated using NRGene de-novo Magic on high molecular weight DNA of 'Tommy Atkins', supplemented by 10X Genomics long read sequencing to improve the initial assembly. A hybrid population between 'Tommy Atkins' x 'Kensington Pride' was used to generate phased haplotype chromosomes and a highly resolved phased SNP map. The final 'Tommy Atkins' genome assembly was a consensus sequence that included 20 pseudomolecules representing the 20 chromosomes of mango and included ~?86% of the ~?439?Mb haploid mango genome. Skim sequencing identified ~?3.3?M SNPs using the 'Tommy Atkins' x 'Kensington Pride' mapping population. Repeat masking identified 26,616 genes with a median length of 3348?bp. A whole genome duplication analysis revealed an ancestral 65 MYA polyploidization event shared with Anacardium occidentale. Two regions, one on LG4 and one on LG7 containing 28 candidate genes, were associated with the commercially important fruit size characteristic in the mapping population.ConclusionsThe availability of the complete 'Tommy Atkins' mango genome will aid global initiatives to study mango genetics.
Project description:Relict woolly mammoth (Mammuthus primigenius) populations survived on several small Beringian islands for thousands of years after mainland populations went extinct. Here we present multiproxy paleoenvironmental records to investigate the timing, causes, and consequences of mammoth disappearance from St. Paul Island, Alaska. Five independent indicators of extinction show that mammoths survived on St. Paul until 5,600 ± 100 y ago. Vegetation composition remained stable during the extinction window, and there is no evidence of human presence on the island before 1787 CE, suggesting that these factors were not extinction drivers. Instead, the extinction coincided with declining freshwater resources and drier climates between 7,850 and 5,600 y ago, as inferred from sedimentary magnetic susceptibility, oxygen isotopes, and diatom and cladoceran assemblages in a sediment core from a freshwater lake on the island, and stable nitrogen isotopes from mammoth remains. Contrary to other extinction models for the St. Paul mammoth population, this evidence indicates that this mammoth population died out because of the synergistic effects of shrinking island area and freshwater scarcity caused by rising sea levels and regional climate change. Degradation of water quality by intensified mammoth activity around the lake likely exacerbated the situation. The St. Paul mammoth demise is now one of the best-dated prehistoric extinctions, highlighting freshwater limitation as an overlooked extinction driver and underscoring the vulnerability of small island populations to environmental change, even in the absence of human influence.
Project description:Mitochondrial myopathy (MM) with progressive external ophthalmoplegia (PEO) is a common manifestation of mitochondrial disease in adulthood, for which there is no curative therapy. In mice with MM, ketogenic diet significantly delayed progression of the disease. We asked in this pilot study what effects high-fat, low-carbohydrate "modified Atkins" diet (mAD) had for PEO/MM patients and control subjects and followed up the effects by clinical, morphological, transcriptomic, and metabolomic analyses. All of our five patients, irrespective of genotype, showed a subacute response after 1.5-2 weeks of diet, with progressive muscle pain and leakage of muscle enzymes, leading to premature discontinuation of the diet. Analysis of muscle ultrastructure revealed selective fiber damage, especially in the ragged-red-fibers (RRFs), a MM hallmark. Two years of follow-up showed improvement of muscle strength, suggesting activation of muscle regeneration. Our results indicate that (i) nutrition can modify mitochondrial disease progression, (ii) dietary counseling should be part of MM care, (iii) short mAD is a tool to induce targeted RRF lysis, and (iv) mAD, a common weight-loss method, may induce muscle damage in a population subgroup.
Project description:Mast cells are tissue resident, innate immune cells with heterogenous phenotypes tuned by cytokines and other microenvironmental stimuli. Playing a protective role in parasitic, bacterial, and viral infections, mast cells are also known for their role in the pathogenesis of allergy, asthma, and autoimmune diseases. Here, we review factors controlling mast cell activation, with a focus on receptor signaling and potential therapies for allergic disease. Specifically, we will discuss our work with Fc?RI and F?R signaling, IL-4, IL-10, and TGF-?1 treatment, and Stat5. We conclude with potential therapeutics for allergic disease. Much of these efforts have been influenced by the work of Bill Paul. With many mechanistic targets for mast cell activation and different classes of therapeutics being studied, there is reason to be hopeful for continued clinical progress in this area.
Project description:BackgroundIn an effort to improve stroke quality of care and patient outcomes, quality of care metrics are monitored to assess utilization of evidence-based stroke care processes as part of the Paul Coverdell National Acute Stroke Program (PCNASP). We aimed to assess temporal trends in defect-free care (DFC) received by stroke patients in the PCNASP between 2008 and 2018.MethodsQuality of care data for 10 performance measures were available for 849,793 patients aged ≥18 years who were admitted to a participating hospital with a clinical diagnosis of stroke between 2008 and 2018. A patient who receives care according to all performance measures for which they are eligible, receives "defect-free care" (DFC) (eg, appropriate medications, assessments, and education). Generalized estimating equations were used to examine the factors associated with receipt of DFC.ResultsDFC among ischemic stroke patients increased from 38.0% in 2008 to 80.8% in 2018 (P < .0001), with the largest improvement seen in receipt of stroke education (relative percent change, RPC = 64%). Similarly, DFC for hemorrhagic stroke and transient ischemic attack patients increased from 46.7% to 82.6% (RPC = 76.9%) and 39.9% to 85.0% (RPC = 113.0%) (P < .001), respectively. Among ischemic stroke patients, the adjusted odds for receiving DFC were lower for women, patients aged 18 to 54 years, Medicaid or Medicare participants, and patients with atrial fibrillation (P < .05).ConclusionsFrom 2008 to 2018, receipt of DFC by ischemic stroke patients significantly increased in the PCNASP; however certain subgroups were less likely to receive this level of care. Targeted quality improvement initiatives could result in even further improvements among all stroke patients and help reduce disparities in care.