- The Yersinia pestis Effector YopM Inhibits Pyrin Inflammasome Activation. [Journal Article]
- PPPLoS Pathog 2016; 12(12):e1006035
- Type III secretion systems (T3SS) are central virulence factors for many pathogenic Gram-negative bacteria, and secreted T3SS effectors can block key aspects of host cell signaling. To counter this, ...
Type III secretion systems (T3SS) are central virulence factors for many pathogenic Gram-negative bacteria, and secreted T3SS effectors can block key aspects of host cell signaling. To counter this, innate immune responses can also sense some T3SS components to initiate anti-bacterial mechanisms. The Yersinia pestis T3SS is particularly effective and sophisticated in manipulating the production of pro-inflammatory cytokines IL-1β and IL-18, which are typically processed into their mature forms by active caspase-1 following inflammasome formation. Some effectors, like Y. pestis YopM, may block inflammasome activation. Here we show that YopM prevents Y. pestis induced activation of the Pyrin inflammasome induced by the RhoA-inhibiting effector YopE, which is a GTPase activating protein. YopM blocks YopE-induced Pyrin-mediated caspase-1 dependent IL-1β/IL-18 production and cell death. We also detected YopM in a complex with Pyrin and kinases RSK1 and PKN1, putative negative regulators of Pyrin. In contrast to wild-type mice, Pyrin deficient mice were also highly susceptible to an attenuated Y. pestis strain lacking YopM, emphasizing the importance of inhibition of Pyrin in vivo. A complex interplay between the Y. pestis T3SS and IL-1β/IL-18 production is evident, involving at least four inflammasome pathways. The secreted effector YopJ triggers caspase-8- dependent IL-1β activation, even when YopM is present. Additionally, the presence of the T3SS needle/translocon activates NLRP3 and NLRC4-dependent IL-1β generation, which is blocked by YopK, but not by YopM. Taken together, the data suggest YopM specificity for obstructing the Pyrin pathway, as the effector does not appear to block Y. pestis-induced NLRP3, NLRC4 or caspase-8 dependent caspase-1 processing. Thus, we identify Y. pestis YopM as a microbial inhibitor of the Pyrin inflammasome. The fact that so many of the Y. pestis T3SS components are participating in regulation of IL-1β/IL-18 release suggests that these effects are essential for maximal control of innate immunity during plague.
- Prospects for biological soil-borne disease control: application of indigenous versus synthetic microbiomes. [Journal Article]
- PPhytopathology 2016 Nov 29
- Biological disease control of soil-borne plant diseases has traditionally employed the biopesticide approach whereby single strains or strain mixtures are introduced into production systems through i...
Biological disease control of soil-borne plant diseases has traditionally employed the biopesticide approach whereby single strains or strain mixtures are introduced into production systems through inundative/inoculative release. The approach has significant barriers that have long been recognized, including a generally limited spectrum of target pathogens for any given biocontrol agent andinadequate colonization of the host rhizosphere, which can plague progress in the utilization of this resource in commercial field-based crop production systems. Thus, although potential exists, this model has continued to lag in its application. New omics' tools have enabled more rapid screening of microbial populations allowing for the identification of strains with multiple functional attributes that may contribute to pathogen suppression. Similarly, these technologies also enable the characterization of consortia in natural systems which provide the framework for construction of synthetic microbiomes for disease control. Harnessing the potential of the microbiome indigenous to agricultural soils for disease suppression through application of specific management strategies has long been a goal of plant pathologists. Although this tactic also possesses limitation, our enhanced understanding of functional attributes of suppressive soil systems through application of community and metagenomic analysis methods provide opportunity to devise effective resource management schemes. As these microbial communities in large part are fostered by the resources endemic to soil and the rhizosphere, substrate mediated recruitment of disease suppressive microbiomes constitutes a practical means to foster their establishment in crop production systems.
- Secondary metabolites of endophytic Xylaria species with potential applications in medicine and agriculture. [Review]
- WJWorld J Microbiol Biotechnol 2017; 33(1):15
- Fungal endophytes are important sources of bioactive secondary metabolites. The genus Xylaria Hill (ex Schrank, 1789, Xylariaceae) comprises various endophytic species associated to both vascular and...
Fungal endophytes are important sources of bioactive secondary metabolites. The genus Xylaria Hill (ex Schrank, 1789, Xylariaceae) comprises various endophytic species associated to both vascular and non vascular plants. The secondary metabolites produced by Xylaria species include a variety of volatile and non-volatile compounds. Examples of the former are sesquiterpenoids, esters, and alcohols, among others; and of the latter we find terpenoids, cytochalasins, mellein, alkaloids, polyketides, and aromatic compounds. Some of these metabolites have shown potential activity as herbicides, fungicides, and insecticides; others possess antibacterial, antimalarial, and antifungal activities, or α-glucosidase inhibitory activity. Thus metabolites from Xylaria are promising compounds for applications in agriculture for plague control as biopesticides, and biocontrol agents; and in medicine, for example as drugs for the treatment of infectious and non-infectious diseases. This review seeks to show the great value of the secondary metabolites of Xylaria, particularly in the agriculture and medicine fields.
- Vaccination via Chloroplast Genetics: Affordable Protein Drugs for the Prevention and Treatment of Inherited or Infectious Human Diseases. [Journal Article]
- ARAnnu Rev Genet 2016 Nov 23; 50:595-618
- Plastid-made biopharmaceuticals treat major metabolic or genetic disorders, including Alzheimer's, diabetes, hypertension, hemophilia, and retinopathy. Booster vaccines made in chloroplasts prevent g...
Plastid-made biopharmaceuticals treat major metabolic or genetic disorders, including Alzheimer's, diabetes, hypertension, hemophilia, and retinopathy. Booster vaccines made in chloroplasts prevent global infectious diseases, such as tuberculosis, malaria, cholera, and polio, and biological threats, such as anthrax and plague. Recent advances in this field include commercial-scale production of human therapeutic proteins in FDA-approved cGMP facilities, development of tags to deliver protein drugs to targeted human cells or tissues, methods to deliver precise doses, and long-term stability of protein drugs at ambient temperature, maintaining their efficacy. Codon optimization utilizing valuable information from sequenced chloroplast genomes enhanced expression of eukaryotic human or viral genes in chloroplasts and offered unique insights into translation in chloroplasts. Support from major biopharmaceutical companies, development of hydroponic production systems, and evaluation by regulatory agencies, including the CDC, FDA, and USDA, augur well for advancing this novel concept to the clinic and revolutionizing affordable healthcare.
- Enhanced control of cortical pyramidal neurons with micro-magnetic stimulation. [Journal Article]
- ITIEEE Trans Neural Syst Rehabil Eng 2016 Nov 22
- Magnetic stimulation is less sensitive to the inflammatory reactions that plague conventional electrode-based cortical implants and therefore may be useful as a next-generation (implanted) cortical p...
Magnetic stimulation is less sensitive to the inflammatory reactions that plague conventional electrode-based cortical implants and therefore may be useful as a next-generation (implanted) cortical prosthetic. The fields arising from micro-coils are quite small however and thus, their ability to modulate cortical activity must first be established. Here, we show that layer V pyramidal neurons (PNs) can be strongly activated by micro-coil stimulation and further, the asymmetric fields arising from such coils do not simultaneously activate horizontally -oriented axon fibers, thus confining activation to a focal region around the coil. The spatially-narrow fields from micro-coils allowed the sensitivity of different regions within a single PN to be compared: while the proximal axon was most sensitive in naïve cells, repetitive stimulation over the apical dendrite led to a change in state of the neuron that reduced thresholds there to below those of the axon. Thus, our results raise the possibility that regardless of the mode of stimulation, penetration depths that target specific portions of the apical dendrite may actually be more effective than those that target Layer 6. Interestingly, the state change had similar properties to state changes described previously at the systems level, suggesting a possible neuronal mechanism underlying such responses.
- Vaccine-Preventable Diseases In Pediatric Patients: A Review Of Measles, Mumps, Rubella, And Varicella. [Journal Article]
- PEPediatr Emerg Med Pract 2016; 13(12):1-20
- Vaccine-preventable diseases such as measles, mumps, rubella, and varicella continue to plague children and adults worldwide. Although public health programs have helped decrease the prevalence and s...
Vaccine-preventable diseases such as measles, mumps, rubella, and varicella continue to plague children and adults worldwide. Although public health programs have helped decrease the prevalence and sequelae of these diseases, outbreaks still occur. To limit the spread of these diseases, emergency clinicians must be able to readily identify the characteristic presentations of the rashes associated with measles, rubella, and varicella, as well as the common presenting features associated with mumps. Diagnostic laboratory studies are not usually necessary, as a complete history and physical examination usually lead to an accurate diagnosis. Treatment for these vaccine-preventable diseases usually consists of supportive care, but, in some cases, severe complications and death may occur. This issue provides a review of the clinical features, differential diagnoses, potential complications, and treatment options for measles, mumps, rubella, and varicella.
- Host transcriptomic responses to pneumonic plague reveal that Yersinia pestis inhibits both the initial adaptive and innate immune responses in mice. [Journal Article]
- IJInt J Med Microbiol 2016 Nov 14
- Pneumonic plague is the most deadly form of infection caused by Yersinia pestis and can progress extremely fast. However, our understanding on the host transcriptomic response to pneumonic plague is ...
Pneumonic plague is the most deadly form of infection caused by Yersinia pestis and can progress extremely fast. However, our understanding on the host transcriptomic response to pneumonic plague is insufficient. Here, we used RNA-sequencing technology to analyze transcriptomic responses in mice infected with fully virulent strain 201 or EV76, a live attenuated vaccine strain lacking the pigmentation locus. Approximately 600 differentially expressed genes (DEGs) were detected in lungs from both 201- and EV76-infected mice at 12h post-infection (hpi). DEGs in lungs of 201-infected mice exceeded 2000 at 48hpi, accompanied by sustained large numbers of DEGs in the liver and spleen; however, limited numbers of DEGs were detected in those organs of EV-infected mice. Remarkably, DEGs in lungs were significantly enriched in critical immune responses pathways in EV76-infected but not 201-infected mice, including antigen processing and presentation, T cell receptor signaling among others. Pathological and bacterial load analyses confirmed the rapid systemic dissemination of 201-infection and the confined EV76-infection in lungs. Our results suggest that fully virulent Y. pestis inhibits both the innate and adaptive immune responses that are substantially stimulated in a self-limited infection, which update our holistic views on the transcriptomic response to pneumonic plague.
- On the Mechanics of Transcatheter Aortic Valve Replacement. [Journal Article]
- ABAnn Biomed Eng 2016 Nov 21
- Transcatheter aortic valves (TAVs) represent the latest advances in prosthetic heart valve technology. TAVs are truly transformational as they bring the benefit of heart valve replacement to patients...
Transcatheter aortic valves (TAVs) represent the latest advances in prosthetic heart valve technology. TAVs are truly transformational as they bring the benefit of heart valve replacement to patients that would otherwise not be operated on. Nevertheless, like any new device technology, the high expectations are dampened with growing concerns arising from frequent complications that develop in patients, indicating that the technology is far from being mature. Some of the most common complications that plague current TAV devices include malpositioning, crimp-induced leaflet damage, paravalvular leak, thrombosis, conduction abnormalities and prosthesis-patient mismatch. In this article, we provide an in-depth review of the current state-of-the-art pertaining the mechanics of TAVs while highlighting various studies guiding clinicians, regulatory agencies, and next-generation device designers.
- Investigation of and Response to 2 Plague Cases, Yosemite National Park, California, USA, 2015. [Journal Article]
- EIEmerg Infect Dis 2016; 22(12)
- In August 2015, plague was diagnosed for 2 persons who had visited Yosemite National Park in California, USA. One case was septicemic and the other bubonic. Subsequent environmental investigation ide...
In August 2015, plague was diagnosed for 2 persons who had visited Yosemite National Park in California, USA. One case was septicemic and the other bubonic. Subsequent environmental investigation identified probable locations of exposure for each patient and evidence of epizootic plague in other areas of the park. Transmission of Yersinia pestis was detected by testing rodent serum, fleas, and rodent carcasses. The environmental investigation and whole-genome multilocus sequence typing of Y. pestis isolates from the patients and environmental samples indicated that the patients had been exposed in different locations and that at least 2 distinct strains of Y. pestis were circulating among vector-host populations in the area. Public education efforts and insecticide applications in select areas to control rodent fleas probably reduced the risk for plague transmission to park visitors and staff.
New Search Next
- Innovative solutions in bariatric surgery. [Review]
- GSGland Surg 2016; 5(5):529-536
- Nowadays all over the world the rising plague of obesity can be observed. The obesity was recognized as "an epidemic of XXI century" in 1997 by World Health Organization. The change of eating habits,...
Nowadays all over the world the rising plague of obesity can be observed. The obesity was recognized as "an epidemic of XXI century" in 1997 by World Health Organization. The change of eating habits, active lifestyle or pharmacological curation are often insufficient to fight against obesity. Nowadays, there are not any guidelines about gold standard for curing obese patients is bariatric surgery. At the moment, two types of bariatric procedures: laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy, are most commonly used. There are also some other new approaches, which are still being investigated. The mechanism of losing weight in bariatric surgery is based on restriction, malabsorption and neurohormonal effect. Not only is the surgery technique very important to succeed, but also the postoperative care in the outpatient clinic. This article reviews the new possibilities in obesity treatment.