126 research outputs found
Rising from the Sea: Correlations between Sulfated Polysaccharides and Salinity in Plants
High salinity soils inhibit crop production worldwide and represent a serious agricultural problem. To meet our ever-increasing demand for food, it is essential to understand and engineer salt-resistant crops. In this study, we evaluated the occurrence and function of sulfated polysaccharides in plants. Although ubiquitously present in marine algae, the presence of sulfated polysaccharides among the species tested was restricted to halophytes, suggesting a possible correlation with salt stress or resistance. To test this hypothesis, sulfated polysaccharides from plants artificially and naturally exposed to different salinities were analyzed. Our results revealed that the sulfated polysaccharide concentration, as well as the degree to which these compounds were sulfated in halophytic species, were positively correlated with salinity. We found that sulfated polysaccharides produced by Ruppia maritima Loisel disappeared when the plant was cultivated in the absence of salt. However, subjecting the glycophyte Oryza sativa Linnaeus to salt stress did not induce the biosynthesis of sulfated polysaccharides but increased the concentration of the carboxylated polysaccharides; this finding suggests that negatively charged cell wall polysaccharides might play a role in coping with salt stress. These data suggest that the presence of sulfated polysaccharides in plants is an adaptation to high salt environments, which may have been conserved during plant evolution from marine green algae. Our results address a practical biological concept; additionally, we suggest future strategies that may be beneficial when engineering salt-resistant crops
Phagosomal Rupture by Mycobacterium tuberculosis Results in Toxicity and Host Cell Death
Survival within macrophages is a central feature of Mycobacterium tuberculosis pathogenesis. Despite significant advances in identifying new immunological parameters associated with mycobacterial disease, some basic questions on the intracellular fate of the causative agent of human tuberculosis in antigen-presenting cells are still under debate. To get novel insights into this matter, we used a single-cell fluorescence resonance energy transfer (FRET)-based method to investigate the potential cytosolic access of M. tuberculosis and the resulting cellular consequences in an unbiased, quantitative way. Analysis of thousands of THP-1 macrophages infected with selected wild-type or mutant strains of the M. tuberculosis complex unambiguously showed that M. tuberculosis induced a change in the FRET signal after 3 to 4 days of infection, indicating phagolysosomal rupture and cytosolic access. These effects were not seen for the strains M. tuberculosisΔRD1 or BCG, both lacking the ESX-1 secreted protein ESAT-6, which reportedly shows membrane-lysing properties. Complementation of these strains with the ESX-1 secretion system of M. tuberculosis restored the ability to cause phagolysosomal rupture. In addition, control experiments with the fish pathogen Mycobacterium marinum showed phagolysosomal translocation only for ESX-1 intact strains, further validating our experimental approach. Most importantly, for M. tuberculosis as well as for M. marinum we observed that phagolysosomal rupture was followed by necrotic cell death of the infected macrophages, whereas ESX-1 deletion- or truncation-mutants that remained enclosed within phagolysosomal compartments did not induce such cytotoxicity. Hence, we provide a novel mechanism how ESX-1 competent, virulent M. tuberculosis and M. marinum strains induce host cell death and thereby escape innate host defenses and favor their spread to new cells. In this respect, our results also open new research directions in relation with the extracellular localization of M. tuberculosis inside necrotic lesions that can now be tackled from a completely new perspective
Sleep-disordered breathing-do we have to change gears in heart failure?
The majority of patients with heart failure have sleep-disordered breathing (SDB)-with central (rather than obstructive) sleep apnoea becoming the predominant form in those with more severe disease. Cyclical apnoeas and hypopnoeas are associated with sleep disturbance, hypoxaemia, haemodynamic changes, and sympathetic activation. Such patients have a worse prognosis than those without SDB. Mask-based therapies of positive airway pressure targeted at SDB can improve measures of sleep quality and partially normalise the sleep and respiratory physiology, but recent randomised trials of cardiovascular outcomes in central sleep apnoea have been neutral or suggested the possibility of harm, likely from increased sudden death. Further randomised outcome studies (with cardiovascular mortality and hospitalisation endpoints) are required to determine whether mask-based treatment for SDB is appropriate for patients with chronic systolic heart failure and obstructive sleep apnoea, for those with heart failure with preserved ejection fraction, and for those with decompensated heart failure. New therapies for sleep apnoea-such as implantable phrenic nerve stimulators-also require robust assessment. No longer can the surrogate endpoints of improvement in respiratory and sleep metrics be taken as adequate therapeutic outcome measures in patients with heart failure and sleep apnoea
Virulence Regulator EspR of Mycobacterium tuberculosis Is a Nucleoid-Associated Protein
The principal virulence determinant of Mycobacterium tuberculosis (Mtb), the ESX-1 protein secretion system, is positively controlled at the transcriptional level by EspR. Depletion of EspR reportedly affects a small number of genes, both positively or negatively, including a key ESX-1 component, the espACD operon. EspR is also thought to be an ESX-1 substrate. Using EspR-specific antibodies in ChIP-Seq experiments (chromatin immunoprecipitation followed by ultra-high throughput DNA sequencing) we show that EspR binds to at least 165 loci on the Mtb genome. Included in the EspR regulon are genes encoding not only EspA, but also EspR itself, the ESX-2 and ESX-5 systems, a host of diverse cell wall functions, such as production of the complex lipid PDIM (phenolthiocerol dimycocerosate) and the PE/PPE cell-surface proteins. EspR binding sites are not restricted to promoter regions and can be clustered. This suggests that rather than functioning as a classical regulatory protein EspR acts globally as a nucleoid-associated protein capable of long-range interactions consistent with a recently established structural model. EspR expression was shown to be growth phase-dependent, peaking in the stationary phase. Overexpression in Mtb strain H37Rv revealed that EspR influences target gene expression both positively or negatively leading to growth arrest. At no stage was EspR secreted into the culture filtrate. Thus, rather than serving as a specific activator of a virulence locus, EspR is a novel nucleoid-associated protein, with both architectural and regulatory roles, that impacts cell wall functions and pathogenesis through multiple genes
Push-out bond strength of fiber posts to root dentin using glass ionomer and resin modified glass ionomer cements
Decreased olfactory discrimination is associated with impulsivity in healthy volunteers
In clinical populations, olfactory abilities parallel executive function, implicating shared
neuroanatomical substrates within the ventral prefrontal cortex. In healthy individuals, the relationship
between olfaction and personality traits or certain cognitive and behavioural characteristics remains
unexplored. We therefore tested if olfactory function is associated with trait and behavioural impulsivity
in nonclinical individuals. Eighty-three healthy volunteers (50 females) underwent quantitative
assessment of olfactory function (odour detection threshold, discrimination, and identifcation). Each
participant was rated for trait impulsivity index using the Barratt Impulsiveness Scale and performed
a battery of tasks to assess behavioural impulsivity (Stop Signal Task, SST; Information Sampling
Task, IST; Delay Discounting). Lower odour discrimination predicted high ratings in non-planning
impulsivity (Barratt Non-Planning impulsivity subscale); both, lower odour discrimination and detection
threshold predicted low inhibitory control (SST; increased motor impulsivity). These fndings extend
clinical observations to support the hypothesis that defcits in olfactory ability are linked to impulsive
tendencies within the healthy population. In particular, the relationship between olfactory abilities and
behavioural inhibitory control (in the SST) reinforces evidence for functional overlap between neural
networks involved in both processes. These fndings may usefully inform the stratifcation of people at
risk of impulse-control-related problems and support planning early clinical interventions
A randomised controlled trial of sensory awareness training and additional motor practice for learning scalpel skills in podiatry students
Systematic Genetic Nomenclature for Type VII Secretion Systems
CITATION: Bitter, W., et al. 2009. Systematic genetic nomenclature for type VII secretion systems. PLoS Pathogens, 5(10): 1-6, doi: 10.1371/journal.ppat.1000507.The original publication is available at http://journals.plos.org/plospathogensMycobacteria, such as the etiological
agent of human tuberculosis, Mycobacterium
tuberculosis, are protected by an impermeable
cell envelope composed of an inner
cytoplasmic membrane, a peptidoglycan
layer, an arabinogalactan layer, and an
outer membrane. This second membrane
consists of covalently linked, tightly packed
long-chain mycolic acids [1,2] and noncovalently
bound shorter lipids involved in
pathogenicity [3–5]. To ensure protein
transport across this complex cell envelope,
mycobacteria use various secretion pathways,
such as the SecA1-mediated general
secretory pathway [6,7], an alternative
SecA2-operated pathway [8], a twin-arginine
translocation system [9,10], and a
specialized secretion pathway variously
named ESAT-6-, SNM-, ESX-, or type
VII secretion [11–16]. The latter pathway,
hereafter referred to as type VII secretion
(T7S), has recently become a large and
competitive research topic that is closely
linked to studies of host–pathogen interactions
of M. tuberculosis [17] and other
pathogenic mycobacteria [16]. Molecular
details are just beginning to be revealed
[18–22] showing that T7S systems are
complex machineries with multiple components
and multiple substrates. Despite
their biological importance, there has been
a lack of a clear naming policy for the
components and substrates of these systems.
As there are multiple paralogous T7S
systems within the Mycobacteria and
orthologous systems in related bacteria,
we are concerned that, without a unified
nomenclature system, a multitude of redundant
and obscure gene names will be
used that will inevitably lead to confusion
and hinder future progress. In this opinion
piece we will therefore propose and introduce
a systematic nomenclature with
guidelines for name selection of new
components that will greatly facilitate
communication and understanding in this
rapidly developing field of research.http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1000507Publisher's versio
- …