Wnt5a induces a tolerogenic phenotype of macrophages in sepsis and breast cancer patients

A well-orchestrated inflammatory reaction involves the induction of effector functions and, at a later stage, an active downregulation of this potentially harmful process. In this study we show that under proinflammatory conditions the noncanonical Wnt protein, Wnt5a, induces immunosuppressive macrophages. The suppressive phenotype induced by Wnt5a is associated with induction of IL-10 and inhibition of the classical TLR4-NF-κB signaling. Interestingly, this phenotype closely resembles that observed in reprogrammed monocytes in sepsis patients. The Wnt5a-induced feedback inhibition is active both during in vitro LPS stimulation of macrophages and in patients with sepsis caused by LPS-containing, gram-negative bacteria. Furthermore, using breast cancer patient tissue microarrays, we find a strong correlation between the expression of Wnt5a in malignant epithelial cells and the frequency of CD163(+) anti-inflammatory tumor-associated macrophages. In conclusion, our data point out Wnt5a as a potential target for an efficient therapeutic modality in severe human diseases as diverse as sepsis and malignancy.     

Timing of malolactic fermentation inoculation in Shiraz grape must and wine: influence on chemical composition

Malolactic fermentation (MLF) is an integral step in red winemaking, which in addition to deacidifying wine can also influence the composition of volatile fermentation-derived compounds with concomitant affects on wine sensory properties. Long-established winemaking protocols for MLF induction generally involve inoculation of bacteria starter cultures post alcoholic fermentation, however, more recently there has been a trend to introduce bacteria earlier in the fermentation process. For the first time, this study shows the impact of bacterial inoculation on wine quality parameters that define red wine, including wine colour and phenolics, and volatile fermentation-derived compounds. This study investigates the effects of inoculating Shiraz grape must with malolactic bacteria at various stages of alcoholic fermentation [beginning of alcoholic fermentation (co-inoculation, with yeast), mid-alcoholic fermentation, at pressing and post alcoholic fermentation] on the kinetics of MLF and wine chemical composition. Co-inoculation greatly reduced the overall fermentation time by up to 6 weeks, the rate of alcoholic fermentation was not affected by the presence of bacteria and the fermentation-derived wine volatiles profile was distinct from wines produced where bacteria were inoculated late or post alcoholic fermentation. An overall slight decrease in wine colour density observed following MLF was not influenced by the MLF inoculation regime. However, there were differences in anthocyanin and pigmented polymer composition, with co-inoculation exhibiting the most distinct profile. Differences in yeast and bacteria metabolism at various stages in fermentation are proposed as the drivers for differences in volatile chemical composition. This study demonstrates, with an in-depth analysis, that co-inoculation of yeast and bacteria in wine fermentation results in shorter total vinification time and produces sound wines, thus providing the opportunity to stabilise wines more rapidly than traditional inoculation regimes permit and thereby reducing potential for microbial spoilage.     

The additional value of TGFβ1 and IL-7 to predict the course of prostate cancer progression

Background

Given the fact that prostate cancer incidence will increase in the coming years, new prognostic biomarkers are needed with regard to the biological aggressiveness of the prostate cancer diagnosed. Since cytokines have been associated with the biology of cancer and its prognosis, we determined whether transforming growth factor beta 1 (TGFβ1), interleukin-7 (IL-7) receptor and IL-7 levels add additional prognostic information with regard to prostate cancer-specific survival.

Materials and methods

Retrospective survival analysis of forty-four prostate cancer patients, that underwent radical prostatectomy, was performed (1989–2001). Age, Gleason score and pre-treatment PSA levels were collected. IL-7, IL-7 receptor and TGFβ1 levels in prostate cancer tissue were determined by quantitative real-time RT-PCR and their additional prognostic value analyzed with regard to prostate cancer survival. Hazard ratios and their confidence intervals were estimated, and Akaike’s information criterion was calculated for model comparison.

Results

The predictive ability of a model for prostate cancer survival more than doubled when TGFβ1 and IL-7 were added to a model containing only the Gleason score and pre-treatment PSA (AIC: 18.1 and AIC: 6.5, respectively).

Conclusion

IL-7 and TGFβ1 are promising markers to indicate those at risk for poor prostate cancer survival. This additional information may be of interest with regard to the biological aggressiveness of the diagnosed prostate cancer, especially for those patients screened for prostate cancer and their considered therapy.     

Expression of a C3 plant Rubisco SSU gene in regenerated C4 Flaveria plants

We report the successful transformation, via Agrobacterium tumefaciens infection, and regeneration of two species of the genus Flaveria: F. brownii and F. palmeri. We document the expression of a C₃ plant gene, an abundantly expressed ribulose 1,5-bisphosphate carboxylase/oxygenase small subunit gene isolated from petunia, in these C₄ plants. The organ-specific expression of this petunia gene in Flaveria brownii is qualitatively identical to its endogenous pattern of expression.     

Elaboration of an electroporation protocol for Bacillus cereus ATCC 14579

An electro-transformation procedure was established for Bacillus cereus ATCC 14579. Using early growth-stage culture and high electric field, the ectroporation efficiency was up to 2 x 10(9) cfu microg(-1) ml(-1) with pC194 plasmid DNA. The procedure was tested with three other plasmids, of various sizes, replication mechanisms and selection markers, and the transformation efficiencies ranged between 2 x 10(6) and 1 x 10(8) cfu microg(-1) ml(-)(1). The effects of two wall-weakening agents on electroporation rates were also evaluated. The transformation rate that was reached with our procedure is 10(3) times higher than that previously obtained with members of the Bacillus genus with similar plasmids, and 10(6) times superior than that achieved with available protocols for B. cereus. The proposed method is quick, simple, efficient with small rolling circle plasmids and large theta replicating plasmids with low copy number per cell, and suitable for many genetic manipulations that are not possible without high-efficiency transformation protocols.     

Age matters in the prevalence and clinical significance of ultra‐high‐risk for psychosis symptoms and criteria in the general population: Findings from the BEAR and BEARS‐kid studies

Early detection of psychosis is an important topic in psychiatry. Yet, there is limited information on the prevalence and clinical significance of high‐risk symptoms in children and adolescents as compared to adults. We examined ultra‐high‐risk (UHR) symptoms and criteria in a sample of individuals aged 8‐40 years from the general population of Canton Bern, Switzerland, enrolled from June 2011 to May 2014. The current presence of attenuated psychotic symptoms (APS) and brief intermittent psychotic symptoms (BLIPS) and the fulfillment of onset/worsening and frequency requirements for these symptoms in UHR criteria were assessed using the Structured Interview for Psychosis Risk Syndromes. Additionally, perceptive and non‐perceptive APS were differentiated. Psychosocial functioning and current non‐psychotic DSM‐IV axis I disorders were also surveyed. Well‐trained psychologists performed assessments. Altogether, 9.9% of subjects reported APS and none BLIPS, and 1.3% met all the UHR requirements for APS. APS were related to more current axis I disorders and impaired psychosocial functioning, indicating some clinical significance. A strong age effect was detected around age 16: compared to older individuals, 8‐15‐year olds reported more perceptive APS, that is, unusual perceptual experiences and attenuated hallucinations. Perceptive APS were generally less related to functional impairment, regardless of age. Conversely, non‐perceptive APS were related to low functioning, although this relationship was weaker in those below age 16. Future studies should address the differential effects of perceptive and non‐perceptive APS, and their interaction with age, also in terms of conversion to psychosis.     

Helianthus maximiliani and species fine‐scale spatial pattern affect diversity interactions in reconstructed tallgrass prairies

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