Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder characterized by focal lymphocytic infiltration of the exocrine glands causing dry eyes and dry mouth. Similar glandular features ...can also occur as a late complication in patients with other rheumatic disorders, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and scleroderma (‘secondary’ Sjögren's syndrome).1
Anti-Ro and/or anti-La (ENA) antibodies are found in approximately 70% of pSS patients, generally with ANA positivity. Hypergammaglobulinaemia is also common. Systemic features also occur in some patients with pSS. A positive rheumatoid factor (RF) is often seen and so if patients present with arthritis, dryness and a positive RF a diagnosis of pSS should be considered as a possible alternative to RA. Anti-CCP antibodies are more specific for RA.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Colonialism has disrupted Indigenous socioecological systems around the globe, including those supported by intentional landscape burning. Because most disruptions happened centuries ago, our ...understanding of Indigenous fire management is largely inferential and open to debate. Here, we investigate the ecological consequences of the loss of traditional Aboriginal fire management on fire-exposed savannas on the Arnhem Plateau, northern Australia, using the fire-sensitive conifer Callitris intratropica as a bio-indicator. We contrast Kakadu National Park, where traditional Aboriginal fire management was severely disrupted during the early twentieth century following Aboriginal relocation to surrounding settlements, and an adjacent Aboriginal estate where traditional Aboriginal fire management endures. Since 2006, traditional Aboriginal fire management at this site has been overlaid by a program of broad-scale institutionalized burning in the early dry season, designed to reduce greenhouse emissions. Using remote sensing, field survey, and dendrochronology, we show that on the Aboriginal estate, C. intratropica populations depend on the creation of a shifting patch mosaic of long unburned areas necessary for the recruitment of C. intratropica. However, the imposition of broad-scale fire management is disrupting this population patch dynamic. In Kakadu, there have been extreme declines of C. intratropica associated with widespread fires since the mid twentieth century and consequent proliferation of grass fuels. Fire management in Kakadu since 2007, designed to increase the size and abundance of patches of unburned vegetation, has not been able to reverse the population collapse of C. intratropica. Our study demonstrates that colonial processes including relocation of Indigenous people and institutional fire management can have deleterious consequences that are nearly irreversible because of hysteresis in C. intratropica population dynamics.
Motivated by the urgent need to understand how water stress-induced embolism limits the survival and recovery of plants during drought, the linkage between water-stress tolerance and xylem cavitation ...resistance was examined in one of the world's most drought resistant conifer genera, Callitris. Four species were subjected to drought treatments of -5, -8 and -10 MPa for a period of 3-4 wk, after which plants were rewatered. Transpiration, basal growth and leaf water potential were monitored during and after drought. Lethal water potential was correlated with the tension producing a 50% loss of stem hydraulic conductivity. The most resilient species suffered minimal embolism and recovered gas exchange within days of rewatering from -10 MPa, while the most sensitive species suffered major embolism and recovered very slowly. The rate of repair of water transport in the latter case was equal to the rate of basal area growth, indicating xylem reiteration as the primary means of hydraulic repair. The survival of, and recovery from, water stress in Callitris are accurately predicted by the physiology of the stem water-transport system. As the only apparent means of xylem repair after embolism, basal area growth is a critical part of this equation.
Dense SNP genotypes are often combined with complex trait phenotypes to map causal variants, study genetic architecture and provide genomic predictions for individuals with genotypes but no ...phenotype. A single method of analysis that jointly fits all genotypes in a Bayesian mixture model (BayesR) has been shown to competitively address all 3 purposes simultaneously. However, BayesR and other similar methods ignore prior biological knowledge and assume all genotypes are equally likely to affect the trait. While this assumption is reasonable for SNP array genotypes, it is less sensible if genotypes are whole-genome sequence variants which should include causal variants.
We introduce a new method (BayesRC) based on BayesR that incorporates prior biological information in the analysis by defining classes of variants likely to be enriched for causal mutations. The information can be derived from a range of sources, including variant annotation, candidate gene lists and known causal variants. This information is then incorporated objectively in the analysis based on evidence of enrichment in the data. We demonstrate the increased power of BayesRC compared to BayesR using real dairy cattle genotypes with simulated phenotypes. The genotypes were imputed whole-genome sequence variants in coding regions combined with dense SNP markers. BayesRC increased the power to detect causal variants and increased the accuracy of genomic prediction. The relative improvement for genomic prediction was most apparent in validation populations that were not closely related to the reference population. We also applied BayesRC to real milk production phenotypes in dairy cattle using independent biological priors from gene expression analyses. Although current biological knowledge of which genes and variants affect milk production is still very incomplete, our results suggest that the new BayesRC method was equal to or more powerful than BayesR for detecting candidate causal variants and for genomic prediction of milk traits.
BayesRC provides a novel and flexible approach to simultaneously improving the accuracy of QTL discovery and genomic prediction by taking advantage of prior biological knowledge. Approaches such as BayesRC will become increasing useful as biological knowledge accumulates regarding functional regions of the genome for a range of traits and species.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The hyphal tips of Neurospora crassa have prevacuolar compartments (PVCs) of unusual size and shape. They appear to function as late endosomes/multivesicular bodies. PVCs are highly variable in size ...(1-3 microns) and exhibit rapid changes in structure. When visualized with tagged integral membrane proteins of the vacuole the PVCs appear as ring or horseshoe-shaped structures. Some soluble molecules that fill the lumen of mature spherical vacuoles do not appear in the lumen of the PVC but are seen in the ring or horseshoe-shaped structures. By using super-resolution microscopy I have achieved a better understanding of the structure of the PVCs. The PVC appears to form a pouch with an open end. The walls of the pouch are composed of small vesicles or tubules, approximately 250 nm in diameter. The shape of the PVC can change in a few seconds, caused by the apparent movement of the vesicles/tubules. In approximately 85% of the PVCs dynein and dynactin were observed as poorly defined lumps inside the pouch-shaped PVCs. Within the PVCs they were not attached to microtubules nor did they appear to be in direct contact with the vesicles and tubules that formed the PVCs. In the future, the structure and relatively large size of the Neurospora PVC may allow us to visualize protein-sorting events that occur in the formation of vacuoles.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Immunosuppression regimens used in solid organ transplant have evolved significantly over the past 70 years in the United States. Early immunosuppression and targets for allograft success were ...measured by incidence and severity of allograft rejection and 1‐year patient survival. The limited number of agents, infancy of human leukocyte antigen (HLA) matching techniques and lack of understanding of immunoreactivity limited the early development of effective regimens. The 1980s and 1990s saw incredible advancements in these areas, with acute rejection rates halving in a short span of time. However, the constant struggle to achieve the optimal balance between under‐ and overimmunosuppression is weaved throughout the history of transplant immunosuppression. The aim of this paper is to discuss the different eras of immunosuppression and highlight the important milestones that were achieved while also discussing this in the context of rational agent selection and regimen design. This discussion sets the stage for how we can achieve optimal long‐term outcomes during the next era of immunosuppression, which will move from universal protocols to patient‐specific optimization.
In temperate and boreal ecosystems, seasonal cycles of growth and dormancy allow perennial plants to adapt to winter conditions. We show, in hybrid aspen trees, that photoperiodic regulation of ...dormancy is mechanistically distinct from autumnal growth cessation. Dormancy sets in when symplastic intercellular communication through plasmodesmata is blocked by a process dependent on the phytohormone abscisic acid. The communication blockage prevents growth-promoting signals from accessing the meristem. Thus, precocious growth is disallowed during dormancy. The dormant period, which supports robust survival of the aspen tree in winter, is due to loss of access to growth-promoting signals.
Measurements of 21 cm Epoch of Reionization (EoR) structure are subject to systematics originating from both the analysis and the observation conditions. Using 2013 data from the Murchison Widefield ...Array (MWA), we show the importance of mitigating both sources of contamination. A direct comparison between results from Beardsley et al. and our updated analysis demonstrates new precision techniques, lowering analysis systematics by a factor of 2.8 in power. We then further lower systematics by excising observations contaminated by ultra-faint RFI, reducing by an additional factor of 3.8 in power for the zenith pointing. With this enhanced analysis precision and newly developed RFI mitigation, we calculate a noise-dominated upper limit on the EoR structure of Δ2 ≤ 3.9 × 103 mK2 at k = 0.20 h Mpc−1 and z = 7 using 21 hr of data, improving previous MWA limits by almost an order of magnitude.
AIMS: The relationship of Atlantic salmon gastrointestinal (GI) tract bacteria to environmental factors, in particular water temperature within a commercial mariculture system, was investigated. ...METHODS AND RESULTS: Salmon GI tract bacterial communities commercially farmed in south‐eastern Tasmania were analysed, over a 13‐month period across a standard commercial production farm cycle, using 454 16S rRNA‐based pyrosequencing. Faecal bacterial communities were highly dynamic but largely similar between randomly selected fish. In postsmolt, the faecal bacteria population was dominated by Gram‐positive fermentative bacteria; however, by midsummer, members of the family Vibrionaceae predominated. As fish progressed towards harvest, a range of different bacterial genera became more prominent corresponding to a decline in Vibrionaceae. The sampled fish were fed two different commercial diet series with slightly different protein, lipid and digestible energy level; however, the effect of these differences was minimal. CONCLUSIONS: The overall data demonstrated dynamic hind gut communities in salmon that were related to season and fish growth phases but were less influenced by differences in commercial diets used routinely within the farm system studied. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides understanding of farmed salmon GI bacterial communities and describes the relative impact of diet, environmental and farm factors.
A new technology called genomic selection is revolutionizing dairy cattle breeding. Genomic selection refers to selection decisions based on genomic breeding values (GEBV). The GEBV are calculated as ...the sum of the effects of dense genetic markers, or haplotypes of these markers, across the entire genome, thereby potentially capturing all the quantitative trait loci (QTL) that contribute to variation in a trait. The QTL effects, inferred from either haplotypes or individual single nucleotide polymorphism markers, are first estimated in a large reference population with phenotypic information. In subsequent generations, only marker information is required to calculate GEBV. The reliability of GEBV predicted in this way has already been evaluated in experiments in the United States, New Zealand, Australia, and the Netherlands. These experiments used reference populations of between 650 and 4,500 progeny-tested Holstein-Friesian bulls, genotyped for approximately 50,000 genome-wide markers. Reliabilities of GEBV for young bulls without progeny test results in the reference population were between 20 and 67%. The reliability achieved depended on the heritability of the trait evaluated, the number of bulls in the reference population, the statistical method used to estimate the single nucleotide polymorphism effects in the reference population, and the method used to calculate the reliability. A common finding in 3 countries (United States, New Zealand, and Australia) was that a straightforward BLUP method for estimating the marker effects gave reliabilities of GEBV almost as high as more complex methods. The BLUP method is attractive because the only prior information required is the additive genetic variance of the trait. All countries included a polygenic effect (parent average breeding value) in their GEBV calculation. This inclusion is recommended to capture any genetic variance not associated with the markers, and to put some selection pressure on low-frequency QTL that may not be captured by the markers. The reliabilities of GEBV achieved were significantly greater than the reliability of parental average breeding values, the current criteria for selection of bull calves to enter progeny test teams. The increase in reliability is sufficiently high that at least 2 dairy breeding companies are already marketing bull teams for commercial use based on their GEBV only, at 2 yr of age. This strategy should at least double the rate of genetic gain in the dairy industry. Many challenges with genomic selection and its implementation remain, including increasing the accuracy of GEBV, integrating genomic information into national and international genetic evaluations, and managing long-term genetic gain.
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