A growing body of literature links events associated with the progression and severity of immunity and inflammatory disease with the composition of the tissue extracellular matrix as defined by the ...matrisome. One protein in the matrisome that is common to many inflammatory diseases is the large proteoglycan versican, whose varied function is achieved through multiple isoforms and post-translational modifications of glycosaminoglycan structures. In cancer, increased levels of versican are associated with immune cell phenotype, disease prognosis and failure to respond to treatment. Whether these associations between versican expression and tumour immunity are the result of a direct role in the pathogenesis of tumours is not clear. In this review, we have focused on the role of versican in the immune response as it relates to tumour progression, with the aim of determining whether our current understanding of the immunobiology of versican warrants further study as a cancer immunotherapy target.
•Definable and unique web structures were identified in the premature biofilms.•The structural backbone of biofilms was built by particles less than 30μm.•Insoluble precipitates of bicarbonate were ...discovered in the dried biomass.•Weaker shear forces at the entrance of labyrinth channel caused more clogging.•Flushing was more effective when the biomass contained lower level of carbohydrate.
Emitter clogging is very common in reclaimed water drip irrigation schemes. The clogging biomass appears due to bio-fouling of the emitters’ flow paths. The fouling biomass is a composite of microbial secretions and suspended particles both of which originate from the reclaimed water. This study investigates the process of bio-fouling in three types of pressure compensated (PC) emitters applying reclaimed water in South Australia. An experimental drip irrigation (DI) system containing subsurface type emitters was built and operated under a specific thermal range (16–24°C). A constant load of suspended solid in the reclaimed water was maintained throughout the experiment. Four ranges of organic particles (up to 300μm) were applied as the suspended load. The study identified series of definable web structures in the matrix of premature biofilms. The majority of the particles that contributed in building the interior of the biofilm were smaller than 30μm. The protein–carbohydrate ratio (>1) in the exo-polymeric substance (EPS) was recommended as a tool to predict the best period for flushing. Weaker hydrodynamic forces were observed in the low flow emitters (<2L/h) which were also very sensitive to clogging. On the contrary, emitters with higher flow rate experienced much stronger shear forces in the system and showed better anti-clogging performances throughout the experiment.
A consumer study was performed in four EU countries to further clarify the acceptability of meat with boar taint. In Denmark, France, Italy and Poland, a total of 476 female consumers evaluated 8 ...meat patties from boars with varying levels of skatole (0.10–0.40μg/g fat tissue) and androstenone (0.47–2.00 μg/g fat tissue), in a pair-wise comparison with patties from castrates. Boar meat patties were always less preferred than the castrate meat patties, regardless of the level of androstenone and skatole. Acceptability of the boar meat patties decreased with increasing skatole level. In samples with low skatole levels, higher levels of androstenone also reduced acceptability among androstenone sensitive consumers. No clear threshold levels for androstenone and skatole could be identified. Maps presenting the reduction in preference due to increasing levels of skatole and androstenone, and corrected for the general acceptance of the meat product were developed, taking into account androstenone sensitivity. Further work is needed, covering the whole range of androstenone and skatole levels found in entire male pigs and for a wider set of meat products.
•Consumer and expert panel evaluations were closely correlated with skatole.•At low skatole level, preference for boar meat patties decreased with increasing androstenone level.•Effect of androstenone level was only significant for androstenone sensitive consumers.•A map presenting the reduction in preference depending on the level of androstenone and skatole was developed.•No clear threshold/rejection level for skatole or androstenone could be determined.
Molecular studies have revealed that many putative 'species' are actually complexes of multiple morphologically conservative, but genetically divergent 'cryptic species'. In extreme cases processes ...such as non-adaptive diversification (speciation without divergent selection) could mask the existence of ancient lineages as divergent as ecologically and morphologically diverse radiations recognised as genera or even families in related groups. The identification of such ancient, but cryptic, lineages has important ramifications for conservation, biogeography and evolutionary biology. Herein, we use an integrated multilocus genetic dataset (allozymes, mtDNA and nuclear DNA) to test whether disjunct populations of the widespread nominal Australian gecko species Crenadactylus ocellatus include distinct evolutionary lineages (species), and to examine the timing of diversification among these populations.
We identify at least 10 deeply divergent lineages within the single recognised species Crenadactylus ocellatus, including a radiation of five endemic to the Kimberley region of north-west Australia, and at least four known from areas of less than 100 km2. Lineages restricted to geographically isolated ranges and semi-arid areas across central and western Australia are estimated to have began to diversify in the late Oligocene/early Miocence (~20-30 mya), concurrent with, or even pre-dating, radiations of many iconic, broadly sympatric and much more species-rich Australian vertebrate families (e.g. venomous snakes, dragon lizards and kangaroos).
Instead of a single species, Crenadactylus is a surprisingly speciose and ancient vertebrate radiation. Based on their deep divergence and no evidence of recent gene flow, we recognise each of the 10 main lineages as candidate species. Molecular dating indicates that the genus includes some of the oldest vertebrate lineages confounded within a single species yet identified by molecular assessments of diversity. Highly divergent allopatric lineages are restricted to putative refugia across arid and semi-arid Australia, and provide important evidence towards understanding the history and spread of the Australian arid zone, suggesting at a minimum that semi-arid conditions were present by the early Miocene, and that severe aridity was widespread by the mid to late Miocene. In addition to documenting a remarkable instance of underestimation of vertebrate species diversity in a developed country, these results suggest that increasing integration of molecular dating techniques into cryptic species delimitation will reveal further instances where taxonomic conservatism has led to profound underestimation of not only species numbers, but also highly significant phylogenetic diversity and evolutionary history.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Predation and/or parasitism often limits the evolution of conspicuous male traits and female preferences because conspicuous traits can attract predators or parasites and it is costly for females to ...associate with males that attract predators or parasites. As a result, males and females in high-risk populations are expected to evolve safer mating behaviors compared to individuals from low-risk populations. We tested this antagonistic selection hypothesis in the field cricket Gryllus lineaticeps. Males produce chirped songs, and both female crickets and the eavesdropping parasitoid fly Ormia ochracea prefer faster chirp rates. The flies attack the field crickets late in the breeding season and parasitized crickets die. We used a common garden rearing design to test for evolved differences in songs and preferences between high- and low-risk populations. In contrast to predictions of the antagonistic selection hypothesis, males from high-risk populations produced faster (riskier) chirp rates and females preferred faster chirps. We suggest that late-season parasitism selects for increased investment in reproductive traits to maximize reproduction before the advent of parasitoid activity ("late-season parasitism hypothesis"), which would at least explain riskier female preferences and potentially riskier male songs in the high-risk populations. Prédation and parasitism may thus have diverse and unexpected effects on the evolution of reproductive behavior, depending upon the temporal pattern of predator- or parasite-induced mortality.
This study aims to determine the rate of and risk factors for total knee arthroplasty (TKA) after operative management of tibial plateau fractures (TPFs) in older adults.
This is a retrospective ...cohort study of 182 displaced TPFs in 180 patients aged ≥ 60 years, over a 12-year period with a minimum follow-up of one year. The mean age was 70.7 years (SD 7.7; 60 to 89), and 139/180 patients (77.2%) were female. Radiological assessment consisted of fracture classification; pre-existing knee osteoarthritis (OA); reduction quality; loss of reduction; and post-traumatic OA. Fracture depression was measured on CT, and the volume of defect estimated as half an oblate spheroid. Operative management, complications, reoperations, and mortality were recorded.
Nearly half of the fractures were Schatzker II AO B3.1 fractures (n = 85; 47%). Radiological knee OA was present at fracture in 59/182 TPFs (32.6%). Primary management was fixation in 174 (95.6%) and acute TKA in eight (4.4%). A total of 13 patients underwent late TKA (7.5%), most often within two years. By five years, 21/182 12% (95% confidence interval (CI) 6.0 to 16.7) had required TKA. Larger volume defects of greater depth on CT (median 15.9 mm vs 9.4 mm; p < 0.001) were significantly associated with TKA requirement. CT-measured joint depression of > 12.8 mm was associated with TKA requirement (area under the curve (AUC) 0.766; p = 0.001). Severe joint depression of > 15.5 mm (hazard ratio (HR) 6.15 (95% CI 2.60 to 14.55); p < 0.001) and pre-existing knee OA (HR 2.70 (95% CI 1.14 to 6.37); p = 0.024) were independently associated with TKA requirement. Where patients with severe joint depression of > 15.5 mm were managed with fixation, 11/25 ultimately required TKA.
Overall, 12% of patients aged ≥ 60 years underwent TKA within five years of TPF. Severe joint depression and pre-existing knee arthritis were independent risk factors for both post-traumatic OA and TKA. These features should be investigated as potential indications for acute TKA in older adults with TPFs.
Astrophysical shocks are commonly revealed by the non-thermal emission of energetic electrons accelerated in situ1–3. Strong shocks are expected to accelerate particles to very high energies4–6; ...however, they require a source of particles with velocities fast enough to permit multiple shock crossings. While the resulting diffusive shock acceleration4 process can account for observations, the kinetic physics regulating the continuous injection of non-thermal particles is not well understood. Indeed, this injection problem is particularly acute for electrons, which rely on high-frequency plasma fluctuations to raise them above the thermal pool7,8. Here we show, using laboratory laser-produced shock experiments, that, in the presence of a strong magnetic field, significant electron pre-heating is achieved. We demonstrate that the key mechanism in producing these energetic electrons is through the generation of lower-hybrid turbulence via shock-reflected ions. Our experimental results are analogous to many astrophysical systems, including the interaction of a comet with the solar wind9, a setting where electron acceleration via lower-hybrid waves is possible.
Lactate formation in highly proliferative tumors such as malignant gliomas is associated with poor survival and contributes to the suppression of local immunity. Here, we report that diclofenac used ...at nontoxic concentrations significantly decreased lactate production in murine glioma cells and inhibited the expression of lactate dehydrogenase‐A in vitro. Lactate reduction was accompanied by a dose‐dependent inhibition of cell growth and a cell cycle arrest at the G2/M checkpoint. In the presence of diclofenac, murine bone marrow‐derived dendritic cells (DCs) showed enhanced IL‐12, but decreased IL‐10 secretion on Toll‐like receptor stimulation with R848 that correlated with reduced lactate levels in the glioma cell coculture and a blockade of signal transducers and activators of transcription 3 phosphorylation. In vivo, diclofenac treatment diminished intratumoral lactate levels and resulted in a significant delay of glioma growth. Ex vivo analyses revealed that tumor‐infiltrating DCs regained their capacity to produce IL‐12 on R848 stimulation. Moreover, diclofenac reduced the number of tumor‐infiltrating regulatory T cells and impaired the upregulation of the Treg activation marker CD25. Nevertheless, a single intratumoral injection of R848 combined with diclofenac failed to induce an additional survival advantage in glioma‐bearing mice. Further analyses illustrated that the presence of diclofenac during T‐cell activation compromised INF‐γ production and T‐cell proliferation, indicating that immunotherapeutic approaches have to be carefully timed when combined with diclofenac. In summary, diclofenac appears as an attractive agent for targeting lactate production and counteracting local immune suppression in malignant gliomas.
What's new?
Elevated lactate production is associated with poor survival and immune escape in malignant glioma. In this study, the nonsteroidal anti‐inflammatory drug diclofenac was found to decrease lactate production in murine glioma cells and to inhibit the expression of the lactate‐encoding gene lactate dehydrogenase‐A (LDH‐A) in vitro. While diclofenac exerts a direct inhibitory effect on T‐cells, preventing its co‐administration with active immunotherapies, it may be an attractive agent for counteracting local immune suppression in malignant glioma.
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