Lymphocytic myocarditis remains a poorly characterized disorder. Approximately 10 percent of patients with cardiomyopathy of recent onset who undergo endomyocardial biopsy have this condition, which ...is presumed to be caused by viral infection.
1
,
2
The clinical course of patients with lymphocytic myocarditis varies; some patients have subclinical disease,
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some present with fulminant disease, which is frequently fatal,
4
–
6
and others have indolent disease that progresses to dilated cardiomyopathy.
7
,
8
Although a histopathological classification system, referred to as the Dallas criteria, has been widely applied in the diagnosis of myocarditis since 1987,
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whether these criteria alone can be used to predict . . .
Burn wounds can create significant damage to human skin, compromising one of the key barriers to infection. The leading cause of death among burn wound patients is infection. Even in the patients ...that survive, infections can be notoriously difficult to treat and can cause lasting damage, with delayed healing and prolonged hospital stays. Biofilm formation in the burn wound site is a major contributing factor to the failure of burn treatment regimens and mortality as a result of burn wound infection. Bacteria forming a biofilm or a bacterial community encased in a polysaccharide matrix are more resistant to disinfection, the rigors of the host immune system, and critically, more tolerant to antibiotics. Burn wound-associated biofilms are also thought to act as a launchpad for bacteria to establish deeper, systemic infection and ultimately bacteremia and sepsis. In this review, we discuss some of the leading burn wound pathogens and outline how they regulate biofilm formation in the burn wound microenvironment. We also discuss the new and emerging models that are available to study burn wound biofilm formation in vivo.
The purification and characterization of Gram-negative bacterial lipid A is tedious and time-consuming. Herein we report a rapid and sensitive method to identify lipid A directly on intact bacteria ...without any chemical treatment or purification, using an atypical solvent system to solubilize the matrix combined with MALDI-TOF mass spectrometry.
•Gram-negative bacterial lipid A can be directly detected on intact bacteria by MALDI-TOF MS.•No extractions or purification steps are required.•The method is rapid (<5min), and only requires about 104–105 bacteria.
To compare the potency of mesenchymal stem cells between the cells derived from the subacromial bursa to concentrated bone marrow aspirate (cBMA) taken from patients undergoing rotator cuff (RC) ...repair.
Subacromial bursa and cBMA were harvested arthroscopically from 13 patients (age 57.4 ± 5.2 years, mean ± standard deviation) undergoing arthroscopic primary RC repair. Bone marrow was aspirated from the proximal humerus and concentrated using an automated system (Angel System; Arthrex). Subacromial bursa was collected from 2 sites (over the RC tendon and muscle) and digested with collagenase to isolate a single cellular fraction. Proliferation, number of colony-forming units, differentiation potential, and gene expression were compared among the cells derived from each specimen.
The cells derived from subacromial bursa showed significantly higher proliferation compared with the cells derived from cBMA after 5, 7, and 10 days (P = .018). Regarding colony-forming units, the subacromial bursa had significantly more colonies than cBMA (P = .002). Subacromial bursal cells over the RC tendon produced significantly more colonies than cells over both the RC muscle and cBMA (P = .033 and P = .028, respectively). Moreover, when compared with cBMA, cells derived from subacromial bursa showed significantly higher differentiation ability and higher gene expression indicative of chondrogenesis, osteogenesis, and adipogenesis.
The subacromial bursa is an easily accessible tissue that can be obtained during RC repair, with significant pluripotent stem cell potency for tendon healing. Compared with cBMA taken from the proximal humerus, bursal cells showed significantly increased differentiation ability and gene expression over time.
Failed RC repairs have been partly attributed to a poor healing environment. Biologic augmentation of the repair site may help increase healing potential and incorporation of the cuff at the tendon–bone interface.
Cellular restriction factors, which render cells intrinsically resistant to viruses, potentially impose genetic barriers to cross-species transmission and emergence of viral pathogens in nature. One ...such factor is APOBEC3G. To overcome APOBEC3G-mediated restriction, many lentiviruses encode Vif, a protein that targets APOBEC3G for degradation. As with many restriction factor genes, primate APOBEC3G displays strong signatures of positive selection. This is interpreted as evidence that the primate APOBEC3G locus reflects a long-term evolutionary "arms-race" between retroviruses and their primate hosts. Here, we provide direct evidence that APOBEC3G has functioned as a barrier to cross-species transmission, selecting for viral resistance during emergence of the AIDS-causing pathogen SIVmac in captive colonies of Asian macaques in the 1970s. Specifically, we found that rhesus macaques have multiple, functionally distinct APOBEC3G alleles, and that emergence of SIVmac and simian AIDS required adaptation of the virus to evade APOBEC3G-mediated restriction. Our evidence includes the first comparative analysis of APOBEC3G polymorphism and function in both a reservoir and recipient host species (sooty mangabeys and rhesus macaques, respectively), and identification of adaptations unique to Vif proteins of the SIVmac lineage that specifically antagonize rhesus APOBEC3G alleles. By demonstrating that interspecies variation in a known restriction factor selected for viral counter-adaptations in the context of a documented case of cross-species transmission, our results lend strong support to the evolutionary "arms-race" hypothesis. Importantly, our study confirms that APOBEC3G divergence can be a critical determinant of interspecies transmission and emergence of primate lentiviruses, including viruses with the potential to infect and spread in human populations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Histone methyl transferase EZH2 (Enhancer of Zeste Homolog 2) is generally associated with H3K27 methylation and gene silencing, as a member of the polycomb repressor 2 (PRC2) complex. ...Immunoprecipitation and mass spectrometry of the EZH2-protein interactome in estrogen receptor positive, breast cancer-derived MCF7 cells revealed EZH2 interactions with subunits of chromatin remodeler SWI/SNF complex and TRIM28, which formed a complex with EZH2 distinct from PRC2. Unexpectedly, transcriptome profiling showed that EZH2 primarily activates, rather than represses, transcription in MCF7 cells and with TRIM28 co-regulates a set of genes associated with stem cell maintenance and poor survival of breast cancer patients. TRIM28 depletion repressed EZH2 recruitment to chromatin and expression of this gene set, in parallel with decreased CD44
/CD24
mammosphere formation. Mammosphere formation, inhibited by EZH2 depletion, was rescued by ectopic expression of EZH2 but not by TRIM28 expression or by EZH2 mutated at the region (pre-SET domain) of TRIM28 interaction. These results support PRC2-independent functions of EZH2 and TRIM28 in activation of gene expression that promotes mammary stem cell enrichment and maintenance.
Plastic pollution is an increasing worldwide problem urgently requiring a solution. While recycling rates are increasing globally, only 9% of all plastic waste has been recycled, and with the cost ...and limited downstream uses of recycled plastic, an alternative is needed. Here, we found that expanded polystyrene (EPS) promoted high levels of bacterial biofilm formation and sought out environmental EPS waste to characterize these native communities. We demonstrated that the EPS attached communities had limited plastic degrading activity. We then performed a long‐term enrichment experiment where we placed a robust selection pressure on these communities by limiting carbon availability such that the waste plastic was the only carbon source. Seven of the resulting enriched bacterial communities had increased plastic degrading activity compared to the starting bacterial communities. Pseudomonas stutzeri was predominantly identified in six of the seven enriched communities as the strongest polyester degrader. Sequencing of one isolate of P. stutzeri revealed two putative polyesterases and one putative MHETase. This indicates that waste plastic‐associated biofilms are a source for bacteria that have plastic‐degrading potential, and that this potential can be unlocked through selective pressure and further in vitro enrichment experiments, resulting in biodegradative communities that are better than nature.
In this work, we demonstrate an approach to unlock the plastic‐degrading potential of marine plastic‐associated biofilms. We also identify Pseudomonas stutzeri as a plastic degrading species and discover three new enzymes potentially linked to polyester degradation.
Despite anticoagulation therapy, up to one-half of patients with deep vein thrombosis (DVT) will develop the post-thrombotic syndrome (PTS). Improving the long-term outcome of DVT patients at risk ...for PTS will therefore require new approaches. Here we investigate the effects of statins--lipid-lowering agents with anti-thrombotic and anti-inflammatory properties--in decreasing thrombus burden and decreasing vein wall injury, mediators of PTS, in established murine stasis and non-stasis chemical-induced venous thrombosis (N = 282 mice). Treatment of mice with daily atorvastatin or rosuvastatin significantly reduced stasis venous thrombus burden by 25% without affecting lipid levels, blood coagulation parameters, or blood cell counts. Statin-driven reductions in VT burden (thrombus mass for stasis thrombi, intravital microscopy thrombus area for non-stasis thrombi) compared similarly to the therapeutic anticoagulant effects of low molecular weight heparin. Blood from statin-treated mice showed significant reductions in platelet aggregation and clot stability. Statins additionally reduced thrombus plasminogen activator inhibitor-1 (PAI-1), tissue factor, neutrophils, myeloperoxidase, neutrophil extracellular traps (NETs), and macrophages, and these effects were most notable in the earlier timepoints after DVT formation. In addition, statins reduced DVT-induced vein wall scarring by 50% durably up to day 21 in stasis VT, as shown by polarized light microscopy of picrosirius red-stained vein wall collagen. The overall results demonstrate that statins improve VT resolution via profibrinolytic, anticoagulant, antiplatelet, and anti-vein wall scarring effects. Statins may therefore offer a new pharmacotherapeutic approach to improve DVT resolution and to reduce the post-thrombotic syndrome, particularly in subjects who are ineligible for anticoagulation therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diagnosis and therapy in one: Many prevalent diseases, such as atherosclerosis, could be efficiently treated by localized, macrophage‐targeted therapies. A biocompatible nanoparticle with high ...macrophage avidity is presented; the nanoparticle has magnetic and fluorescence, as well as therapeutic, imaging functionalities. Multimodal detection and exquisite phototoxicity to macrophages under appropriate illumination is shown (see image).
Trees in urban ecosystems are valued for shade and cooling effects, reduction of CO
2
emissions and pollution, and aesthetics, among other benefits. However, in arid and semiarid regions, urban trees ...must be maintained through supplemental irrigation. In these regions it is desirable to identify tree species that are especially efficient in the balance between water loss and carbon uptake. We used a common-garden approach to compare water-use efficiency (WUE) at leaf and tree scales for commonly planted, nonnative tree species in the Los Angeles Basin (California, USA), in order to evaluate WUE as a metric of the trade-off between water use and growth in urban trees. Leaf-level gas exchange, sap flux density, leaf δ
13
C, and stem growth measurements were conducted on eight species within the Los Angeles County Arboretum:
Brachychiton discolor
,
B. populneus
,
Eucalyptus grandis
,
Ficus microcarpa
,
Jacaranda chelonia
,
Gleditsia triacanthos
,
Lagerstroemia indica
,
and
Koelreuteria paniculata
. We found species with high instantaneous WUE also had the highest tree-level seasonal WUE (stem basal-area increment (BAI)/total transpiration). High tree-level WUE resulted from low water use in
B. discolor
,
B. populneus
, and
E. grandis
. In contrast, high basal-area growth explained moderately high WUE in
F. microcarpa
. Notably, high WUE was not associated with low BAI. At a monthly time scale, nearly all species showed the highest WUE during late spring/early summer, when the majority of basal-area growth occurred. Although leaf- and tree-level WUE were reasonably well correlated, leaf δ
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C was not significantly related to leaf- or tree-level WUE. Overall, the most water-efficient species were evergreen, or from regions that experience high vapor-pressure deficit (VPD). These results suggest that whole-tree WUE is a useful measure of the balance between some critical costs and benefits of irrigated urban trees and may be helpful in determining which trees should be planted to maximize growth while conserving water. Although measuring whole-tree WUE directly provides the most complete understanding of urban tree costs and benefits, this study suggests that leaf-level instantaneous measurements of WUE and knowledge of species native climates may be reasonable proxies.
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