The type III secretion (T3S) injectisome is a specialized protein nanomachine that is critical for the pathogenicity of many Gram-negative bacteria, including purveyors of plague, typhoid fever, ...whooping cough, sexually transmitted infections and major nosocomial infections. This syringe-shaped 3.5-MDa macromolecular assembly spans both bacterial membranes and that of the infected host cell. The internal channel formed by the injectisome allows for the direct delivery of partially unfolded virulence effectors into the host cytoplasm. The structural foundation of the injectisome is the basal body, a molecular lock-nut structure composed predominantly of three proteins that form highly oligomerized concentric rings spanning the inner and outer membranes. Here we present the structure of the prototypical Salmonella enterica serovar Typhimurium pathogenicity island 1 basal body, determined using single-particle cryo-electron microscopy, with the inner-membrane-ring and outer-membrane-ring oligomers defined at 4.3 Å and 3.6 Å resolution, respectively. This work presents the first, to our knowledge, high-resolution structural characterization of the major components of the basal body in the assembled state, including that of the widespread class of outer-membrane portals known as secretins.
The loss of organic and inorganic carbon from roots into soil underpins nearly all the major changes that occur in the rhizosphere. In this review we explore the mechanistic basis of organic carbon ...and nitrogen flow in the rhizosphere. It is clear that C and N flow in the rhizosphere is extremely complex, being highly plant and environment dependent and varying both spatially and temporally along the root. Consequently, the amount and type of rhizodeposits (e.g. exudates, border cells, mucilage) remains highly context specific. This has severely limited our capacity to quantify and model the amount of rhizodeposition in ecosystem processes such as C sequestration and nutrient acquisition. It is now evident that C and N flow at the soil-root interface is bidirectional with C and N being lost from roots and taken up from the soil simultaneously. Here we present four alternative hypotheses to explain why high and low molecular weight organic compounds are actively cycled in the rhizosphere. These include: (1) indirect, fortuitous root exudate recapture as part of the root's C and N distribution network, (2) direct re-uptake to enhance the plant's C efficiency and to reduce rhizosphere microbial growth and pathogen attack, (3) direct uptake to recapture organic nutrients released from soil organic matter, and (4) for inter-root and root-microbial signal exchange. Due to severe flaws in the interpretation of commonly used isotopic labelling techniques, there is still great uncertainty surrounding the importance of these individual fluxes in the rhizosphere. Due to the importance of rhizodeposition in regulating ecosystem functioning, it is critical that future research focuses on resolving the quantitative importance of the different C and N fluxes operating in the rhizosphere and the ways in which these vary spatially and temporally.
Asthma is a common chronic respiratory disease affecting more than 300 million people worldwide. Clinical features of asthma and its immunological and molecular etiology vary significantly among ...patients. An understanding of the complexities of asthma has evolved to the point where precision medicine approaches, including microbiome analysis, are being increasingly recognized as an important part of disease management. Lung and gut microbiota play several important roles in the development, regulation, and maintenance of healthy immune responses. Dysbiosis and subsequent dysregulation of microbiota-related immunological processes affect the onset of the disease, its clinical characteristics, and responses to treatment. Bacteria and viruses are the most extensively studied microorganisms relating to asthma pathogenesis, but other microbes, including fungi and even archaea, can potently influence airway inflammation. This review focuses on recently discovered connections between lung and gut microbiota, including bacteria, fungi, viruses, and archaea, and their influence on asthma.
Dysregulation of microbiota-related immunological processes affects the onset of asthma, its clinical characteristics, and responses to treatment. Finlay et al. review connections between gut and lungs microbiota and its influence on allergic airway inflammation. This review covers not only the most well-known populations of microbes in the context of asthma—bacteria—but also discusses viruses, fungi, and archaea.
The assembly of microbial communities within the gastrointestinal tract during early life plays a critical role in immune, endocrine, metabolic, and other host developmental pathways. Environmental ...insults during this period, such as food insecurity and infections, can disrupt this optimal microbial succession, which may contribute to lifelong and intergenerational deficits in growth and development. Here, we review the human microbiome in the first 1000 days – referring to the period from conception to 2 years of age – and using a developmental model, we examine the role of early microbial succession in growth and development. We propose that an ‘undernourished’ microbiome is intergenerational, thereby perpetuating growth impairments into successive generations. We also identify and discuss the intertwining host–microbe–environment interactions occurring prenatally and during early infancy, which may impair the trajectories of healthy growth and development, and explore their potential as novel microbial targets for intervention.
Undernutrition is influenced by infections, subclinical pathogen carriage and metabolic impact of ‘dysbiotic’ commensal gut microbial communities (gut microbiota) in infants during the first 1000 days.
Delayed or immature assembly of the gut microbiota underlies severe acute malnutrition in children.
The gut microbiota affects the somatotropic axis through regulation of IGF-1 and growth hormone production, thereby affecting growth.
There is emerging knowledge of the influence of prenatal microbial communities on fetal and postnatal growth.
The gut microbiota plays an influential role in inflammation and enteropathy, which may be linked to growth faltering.
The first 1000 days provides a window of opportunity for modulating the microbiota through interventions such as diet, antibiotics, probiotics, prebiotics, or fecal microbiota transplantation to promote healthy growth and development.
Signaling Pathways in Melanogenesis D'Mello, Stacey A N; Finlay, Graeme J; Baguley, Bruce C ...
International Journal of Molecular Sciences,
07/2016, Letnik:
17, Številka:
7
Journal Article, Book Review
Recenzirano
Odprti dostop
Melanocytes are melanin-producing cells found in skin, hair follicles, eyes, inner ear, bones, heart and brain of humans. They arise from pluripotent neural crest cells and differentiate in response ...to a complex network of interacting regulatory pathways. Melanins are pigment molecules that are endogenously synthesized by melanocytes. The light absorption of melanin in skin and hair leads to photoreceptor shielding, thermoregulation, photoprotection, camouflage and display coloring. Melanins are also powerful cation chelators and may act as free radical sinks. Melanin formation is a product of complex biochemical events that starts from amino acid tyrosine and its metabolite, dopa. The types and amounts of melanin produced by melanocytes are determined genetically and are influenced by a variety of extrinsic and intrinsic factors such as hormonal changes, inflammation, age and exposure to UV light. These stimuli affect the different pathways in melanogenesis. In this review we will discuss the regulatory mechanisms involved in melanogenesis and explain how intrinsic and extrinsic factors regulate melanin production. We will also explain the regulatory roles of different proteins involved in melanogenesis.
Almost half the cells and 1% of the unique genes found in our bodies are human, the rest are from microbes, predominantly bacteria, archaea, fungi, and viruses. These microorganisms collectively form ...the human microbiota, with most colonizing the gut. Recent technological advances, open access data libraries, and application of high‐throughput sequencing have allowed these microbes to be identified and their contribution to neurological health to be examined. Emerging evidence links perturbations in the gut microbiota to neurological disease, including disease risk, activity, and progression. This review provides an overview of the recent advances in microbiome research in relation to neuro(auto)immune and neurodegenerative conditions affecting humans, such as multiple sclerosis, neuromyelitis optica spectrum disorders, Parkinson disease, Alzheimer disease, Huntington disease, and amyotrophic lateral sclerosis. Study design and terminology used in this rapidly evolving, highly multidisciplinary field are summarized to empower and engage the neurology community in this “newly discovered organ.” Ann Neurol 2017;81:369–382
Thermokarst lakes formed across vast regions of Siberia and Alaska during the last deglaciation and are thought to be a net source of atmospheric methane and carbon dioxide during the Holocene epoch. ...However, the same thermokarst lakes can also sequester carbon, and it remains uncertain whether carbon uptake by thermokarst lakes can offset their greenhouse gas emissions. Here we use field observations of Siberian permafrost exposures, radiocarbon dating and spatial analyses to quantify Holocene carbon stocks and fluxes in lake sediments overlying thawed Pleistocene-aged permafrost. We find that carbon accumulation in deep thermokarst-lake sediments since the last deglaciation is about 1.6 times larger than the mass of Pleistocene-aged permafrost carbon released as greenhouse gases when the lakes first formed. Although methane and carbon dioxide emissions following thaw lead to immediate radiative warming, carbon uptake in peat-rich sediments occurs over millennial timescales. We assess thermokarst-lake carbon feedbacks to climate with an atmospheric perturbation model and find that thermokarst basins switched from a net radiative warming to a net cooling climate effect about 5,000 years ago. High rates of Holocene carbon accumulation in 20 lake sediments (47 ± 10 grams of carbon per square metre per year; mean ± standard error) were driven by thermokarst erosion and deposition of terrestrial organic matter, by nutrient release from thawing permafrost that stimulated lake productivity and by slow decomposition in cold, anoxic lake bottoms. When lakes eventually drained, permafrost formation rapidly sequestered sediment carbon. Our estimate of about 160 petagrams of Holocene organic carbon in deep lake basins of Siberia and Alaska increases the circumpolar peat carbon pool estimate for permafrost regions by over 50 per cent (ref. 6). The carbon in perennially frozen drained lake sediments may become vulnerable to mineralization as permafrost disappears, potentially negating the climate stabilization provided by thermokarst lakes during the late Holocene.
We present a new climatological model of the ionospheric current system, determined from magnetic measurements taken by the Challenging Minisatellite Payload (CHAMP) and Swarm satellites. The model ...describes the horizontal currents in the ionosphere, below the satellites, and the field‐aligned (Birkeland) currents that connect the ionosphere with the magnetosphere. The model provides ionospheric current values at any location as continuous functions of solar wind speed, interplanetary magnetic field, dipole tilt angle, and the F10.7 index of solar flux. Geometric distortions due to variations in the Earth's main magnetic field are taken into account, thus allowing for precise comparisons between the two hemispheres. The model is the first of its kind to describe the full 3‐D electric currents and not only the field‐aligned or the equivalent horizontal current. We use this capability to demonstrate a key difference between seasons: During winter, the total horizontal current is almost entirely confined to the auroral oval, for all interplanetary magnetic field orientations, where it connects upward and downward Birkeland currents. During more sunlit conditions, the horizontal current extends beyond the auroral oval and is a sum of currents connecting Birkeland currents and currents that circulate in the ionosphere. The westward electrojet is the only large‐scale current structure that is persistent across seasons. Comparison with average convection maps suggests that it is comprised largely of Hall currents, which connect to Birkeland currents in the winter but not in summer.
Key Points
We present a new global model of the full ionospheric current system based on magnetic field measurements from LEO by Swarm and CHAMP
The horizontal current is confined to the auroral oval in the winter, and it connects Birkeland currents
Compared to other parts of the ionospheric current system, the westward electrojet shows little seasonal variation
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