Penicillium spp. occupy many diverse biological niches that include plant pathogens, opportunistic human pathogens, saprophytes, indoor air contaminants, and those selected specifically for ...industrial applications to produce secondary metabolites and lifesaving antibiotics. Recent phylogenetic studies have established Penicillium fuscoglaucum as a synonym for Penicillium commune, which is an indoor air contaminant and toxin producer and can infect apple fruit during storage. During routine culturing on selective media in the lab, we obtained an isolate of P. fuscoglaucum Pf_T2 and sequenced its genome. The Pf_T2 genome is far superior to available genomic resources for the species. Our assembly exhibits a length of 35.1 Mb, a BUSCO score of 97.9% complete, and consists of five scaffolds/contigs representing the four expected chromosomes. It was determined that the Pf_T2 genome was colinear with a type specimen P. fuscoglaucum and contained a lineage-specific, intact cyclopiazonic acid (CPA) gene cluster. For comparison, a highly virulent postharvest apple pathogen, P. expansum strain TDL 12.1, was included and showed a similar growth pattern in culture to our Pf_T2 isolate but was far more aggressive in apple fruit than P. fuscoglaucum. The genome of Pf_T2 serves as a major improvement over existing resources, has superior annotation, and can inform forthcoming omics-based work and functional genetic studies to probe secondary metabolite production and disparities in aggressiveness during apple fruit decay.
Cytokine-induced memory-like natural killer cells Cooper, Megan A; Elliott, Julie M; Keyel, Peter A ...
Proceedings of the National Academy of Sciences - PNAS,
02/2009, Letnik:
106, Številka:
6
Journal Article
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Odprti dostop
The mammalian immune response to infection is mediated by 2 broad arms, the innate and adaptive immune systems. Innate immune cells are a first-line defense against pathogens and are thought to ...respond consistently to infection, regardless of previous exposure, i.e., they do not exhibit memory of prior activation. By contrast, adaptive immune cells display immunologic memory that has 2 basic characteristics, antigen specificity and an amplified response upon subsequent exposure. Whereas adaptive immune cells have rearranged receptor genes to recognize the universe of antigens, natural killer (NK) cells are innate immune lymphocytes with a limited repertoire of germ-line encoded receptors for target recognition. NK cells also produce cytokines such as IFN-gamma (IFN-γ) to protect the host during the innate response to infection. Herein, we show that cytokine-activated NK cells transferred into naïve hosts can be specifically detected 7-22 days later when they are phenotypically similar to naïve cells and are not constitutively producing IFN-γ. However, they produce significantly more IFN-γ when restimulated. This memory-like property is intrinsic to the NK cell. By contrast, memory-like NK cells do not express granzyme B protein and kill targets similarly to naïve NK cells. Thus, these experiments identify an ability of innate immune cells to retain an intrinsic memory of prior activation, a function until now attributed only to antigen-specific adaptive immune cells.
Bacteria in the class Alphaproteobacteria have a wide variety of lifestyles and physiologies. They include pathogens of humans and livestock, agriculturally valuable strains, and several highly ...abundant marine groups. The ancestor of mitochondria also originated in this clade. Despite significant effort to investigate the phylogeny of the Alphaproteobacteria with a variety of methods, there remains considerable disparity in the placement of several groups. Recent emphasis on phylogenies derived from multiple protein-coding genes remains contentious due to disagreement over appropriate gene selection and the potential influences of systematic error. We revisited previous investigations in this area using concatenated alignments of the small and large subunit (SSU and LSU) rRNA genes, as we show here that these loci have much lower GC bias than whole genomes. This approach has allowed us to update the canonical 16S rRNA gene tree of the Alphaproteobacteria with additional important taxa that were not previously included, and with added resolution provided by concatenating the SSU and LSU genes. We investigated the topological stability of the Alphaproteobacteria by varying alignment methods, rate models, taxon selection and RY-recoding to circumvent GC content bias. We also introduce RYMK-recoding and show that it avoids some of the information loss in RY-recoding. We demonstrate that the topology of the Alphaproteobacteria is sensitive to inclusion of several groups of taxa, but it is less affected by the choice of alignment and rate methods. The majority of topologies and comparative results from Approximately Unbiased tests provide support for positioning the Rickettsiales and the mitochondrial branch within a clade. This composite clade is a sister group to the abundant marine SAR11 clade (Pelagibacterales). Furthermore, we add support for taxonomic assignment of several recently sequenced taxa. Accordingly, we propose three subclasses within the Alphaproteobacteria: the Caulobacteridae, the Rickettsidae, and the Magnetococcidae.
Summary Background Multipotent adult progenitor cells are a bone marrow-derived, allogeneic, cell therapy product that modulates the immune system, and represents a promising therapy for acute ...stroke. We aimed to identify the highest, well-tolerated, and safest single dose of multipotent adult progenitor cells, and if they were efficacious as a treatment for stroke recovery. Methods We did a phase 2, randomised, double-blind, placebo-controlled, dose-escalation trial of intravenous multipotent adult progenitor cells in 33 centres in the UK and the USA. We used a computer-generated randomisation sequence and interactive voice and web response system to assign patients aged 18–83 years with moderately severe acute ischaemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 8–20 to treatment with intravenous multipotent adult progenitor cells (400 million or 1200 million cells) or placebo between 24 h and 48 h after symptom onset. Patients were ineligible if there was a change in NIHSS of four or more points during at least a 6 h period between screening and randomisation, had brainstem or lacunar infarct, a substantial comorbid disease, an inability to undergo an MRI scan, or had a history of splenectomy. In group 1, patients were enrolled and randomly assigned in a 3:1 ratio to receive 400 million cells or placebo and assessed for safety through 7 days. In group 2, patients were randomly assigned in a 3:1 ratio to receive 1200 million cells or placebo and assessed for safety through the first 7 days. In group 3, patients were enrolled, randomly assigned, and stratified by baseline NIHSS score to receive 1200 million cells or placebo in a 1:1 ratio within 24–48 h. Patients, investigators, and clinicians were masked to treatment assignment. The primary safety outcome was dose-limiting toxicity effects. The primary efficacy endpoint was global stroke recovery, which combines dichotomised results from the modified Rankin scale, change in NIHSS score from baseline, and Barthel index at day 90. Analysis was by intention to treat (ITT) including all patients in groups 2 and 3 who received the investigational agent or placebo. This study is registered with ClinicalTrials.gov , number NCT01436487. Findings The study was done between Oct 24, 2011, and Dec 7, 2015. After safety assessments in eight patients in group 1, 129 patients were randomly assigned (67 to receive multipotent adult progenitor cells and 62 to receive placebo) in groups 2 and 3 (1200 million cells). The ITT populations consisted of 65 patients who received multipotent adult progenitor cells and 61 patients who received placebo. There were no dose-limiting toxicity events in either group. There were no infusional or allergic reactions and no difference in treatment-emergent adverse events between the groups (64 99% of 65 patients in the multipotent adult progenitor cell group vs 59 97% of 61 in the placebo group). There was no difference between the multipotent adult progenitor cell group and placebo groups in global stroke recovery at day 90 (odds ratio 1·08 95% CI 0·55–2·09, p=0·83). Interpretation Administration of multipotent adult progenitor cells was safe and well tolerated in patients with acute ischaemic stroke. Although no significant improvement was observed at 90 days in neurological outcomes with multipotent adult progenitor cells treatment, further clinical trials evaluating the efficacy of the intervention in an earlier time window after stroke (<36 h) are planned. Funding Athersys Inc.
...a robust literature has shown that treating oneself with interest, kindness, and acceptance (i.e., self-compassion) correlates strongly with emotional stability, resilience, ability to sustain ...motivation during difficult times, less brooding anxiety and depression, and higher spouse ratings of marital quality (4). ...we showed that the physician’s mood upon returning home is the strongest predictor of mate satisfaction with the physician’s work/life integration; which, in turn, affects the physician’s attitude toward work. ...we showed that the self-reported frequency with which life mates discuss their respective meta-reactions to their daily experiences correlated strongly with overall marital satisfaction.
Mycotoxins are a prevalent problem for stored fruits, grains, and vegetables. Alternariol, aflatoxin, and patulin, produced by
spp.,
spp., and
spp., are the major mycotoxins that negatively affect ...human and animal health and reduce fruit and produce quality. Control strategies for these toxins are varied, but one method that is increasing in interest is through host microbiome manipulation, mirroring a biocontrol approach. While the majority of mycotoxins and other secondary metabolites (SM) produced by fungi impact host-fungal interactions, there is also an interplay between the various organisms within the host microbiome. In addition to SMs, these interactions involve compounds such as signaling molecules, plant defense and growth hormones, and metabolites produced by both the plants and microbial community. Therefore, studies to understand the impact of the various toxins impacting the beneficial and harmful microorganisms that reside within the microbiome is warranted, and could lead to identification of safe analogs for antimicrobial activity to reduce fruit decay. Additionally, exploring the composition of the microbial carposphere of host plants is likely to shed light on developing a microbial consortium to maintain quality during storage and abate mycotoxin contamination.
Localized ecological systems are known to shift abruptly and irreversibly from one state to another when they are forced across critical thresholds. Here we review evidence that the global ecosystem ...as a whole can react in the same way and is approaching a planetary-scale critical transition as a result of human influence. The plausibility of a planetary-scale 'tipping point' highlights the need to improve biological forecasting by detecting early warning signs of critical transitions on global as well as local scales, and by detecting feedbacks that promote such transitions. It is also necessary to address root causes of how humans are forcing biological changes.
Identification of type 1 innate lymphoid cells (ILC1s) has been problematic. The transcription factor Hobit encoded by
has been proposed as a major driver of ILC1 programs. Using
reporter mice, we ...showed that correlation of Hobit expression with ILC1s is tissue- and context-dependent. In liver and intestinal mucosa,
expression correlated well with ILC1s; in salivary glands,
was coexpressed with the natural killer (NK) master transcription factors Eomes and TCF1 in a unique cell population, which we call ILC1-like NK cells; during viral infection,
was induced in conventional NK cells of spleen and liver. The impact of
deletion on ILC1s and NK cells was also multifaceted, including a marked decrease in granzyme- and interferon-gamma (IFNγ)-producing ILC1s in the liver, slightly fewer ILC1s and more Eomes
TCF1
ILC1-like NK cells in salivary glands, and only reduced production of granzyme B by ILC1 in the intestinal mucosa. NK cell-mediated control of viral infection was unaffected. We conclude that Hobit has two major impacts on ILC1s: It sustains liver ILC1 numbers, while promoting ILC1 functional maturation in other tissues by controlling TCF1, Eomes, and granzyme expression.
Blue mold, caused primarily by
, is a significant postharvest disease of apples. It not only causes economic losses but also produces mycotoxins that contaminate processed fruit products, which ...contributes to food waste and loss. Previous research has shown that packing and storage bins harbor
spores and that steam and hot water efficiently reduce spore inoculum levels. However, studies using wooden and plastic bins regarding their ability to harbor spores, the effect of chemical sanitation treatments on spore levels, and the impact of rinsate from treated bins on apple fruit decay have not been investigated for the Mid-Atlantic area (Okull et al. 2006; Rosenberger 2009). We evaluated different sanitation treatments (chemical and physical) to reduce
inoculum levels on wooden and plastic bins. We determined that wooden bins bound
spores four orders of magnitude higher than plastic. When both bin types were treated with steam (wooden) or sterile hot water (plastic), Thyme Guard, or Academy, all treatments resulted in significantly (
< 0.05) lower spore levels compared to untreated controls. Although, plastic bins retained lower numbers of spores after inoculation with contaminated spore rinsate and required much higher concentrations of
spores in rinsate to retain spores at levels that would lead to decay on apple fruit. Overall, we demonstrated that plastic bins retain fewer spores than wooden bins and that both can be sanitized by various physical or chemical treatments. We envision that our findings will be applicable in the future as the techniques implemented in this study were used to investigate industry-relevant questions. Our goal is that the research techniques and findings become feasible with advancements in technology and/or accompany other shifts in existing processes in commercial pome fruit packing and storage facilities.
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