A trial at the Grove Research Station in southern Tasmania examined methods of protection against black spot and the effect of these treatments on russeting of Red Fuji apples. An untreated control ...was compared with sprays of cupric hydroxide (wettable powder and dry flowable forms, 2.5 g per L) and copper oxychloride (4.0 g per L), and with dithianon (wettable powder 5 g per L, or suspension concentrate 5.0 or 7.5 g per L). All sprays were applied at greentip, and dithianon was also applied at 10-day intervals for 5 sprays (spring program). Copper treatments were followed, or not, by a spring program of thiram, and all treatments were with or without a following summer program of thiram. Control of black spot (95 percent fruit with no spot) was not achieved with copper sprays at greentip alone, although control was better than on the unsprayed treatment. All dithianon programs, and cupric hydroxide sprays followed by thiram, controlled black spot. No difference was found between formulations for either cupric hydroxide or dithianon. Copper oxychloride increased the incidence of severe russet to above 50 percent compared with the unsprayed control (28.5 percent). All other treatments were satisfactory, with similar incidence of russet to the control treatment, and could be used in commercial practices.
Red Delicious apple trees at Spreyton in northwest Tasmania were thinned with ethephon using an air-shear-electrostatic sprayer (low volume: 100 or 200 L per ha with or without electrostatics) or a ...commercial air-blast sprayer (high volume: 2000 or 4000 L per ha). Treatments were applied at 2 and 10 days after full bloom. Also included were an unsprayed control and a hand-thinned treatment (15-20 days after full bloom). Carbaryl plus Thiram was also applied 3 times (20, 32 and 40 days after full bloom) using the same spray treatments. All dosage rates were equilibrated to apply the same amount of active ingredient per ha. The spay treatments thinned fruit more than the controls when compared for fruit number and all size variables measured except percentage of fruit 80 mm or greater. There were significant differences for fruit number between the hand-thinned, 4000 L per ha high volume and 200 L per ha air-shear treatments, and all the remaining treatments. This applied to both total numbers of fruit set or numbers of fruit hand-thinned at 80-90 days after full bloom. This late hand-thinned had the effect of evening up the fruit size but the control still had significantly smaller fruit than all the other treatments due to the larger number of fruit carried through to hand-thinning.
In high-grade serous ovarian carcinoma (HGSC), deleterious mutations in DNA repair gene
are established drivers of defective homologous recombination and are emerging biomarkers of PARP inhibitor ...(PARPi) sensitivity.
promoter methylation (me
) is detected at similar frequencies to mutations, yet its effects on PARPi responses remain unresolved.In this study, three HGSC patient-derived xenograft (PDX) models with methylation at most or all examined CpG sites in the
promoter show responses to PARPi. Both complete and heterogeneous methylation patterns were associated with
gene silencing and homologous recombination deficiency (HRD). PDX models lost me
following treatment with PARPi rucaparib or niraparib, where a single unmethylated copy of
was sufficient to drive PARPi resistance. Genomic copy number profiling of one of the PDX models using SNP arrays revealed that this resistance was acquired independently in two genetically distinct lineages.In a cohort of 12 patients with
-methylated HGSC, various patterns of me
were associated with genomic "scarring," indicative of HRD history, but exhibited no clear correlations with clinical outcome. Differences in methylation stability under treatment pressure were also observed between patients, where one HGSC was found to maintain me
after six lines of therapy (four platinum-based), whereas another HGSC sample was found to have heterozygous me
and elevated
gene expression (relative to homozygous me
controls) after only neoadjuvant chemotherapy.As me
loss in a single gene copy was sufficient to cause PARPi resistance in PDX, methylation zygosity should be carefully assessed in previously treated patients when considering PARPi therapy. SIGNIFICANCE: Homozygous
methylation is a positive predictive biomarker for sensitivity to PARP inhibitors, whereas a single unmethylated gene copy is sufficient to confer resistance.
We considered whether US Blacks experience early health deterioration, as measured across biological indicators of repeated exposure and adaptation to stressors.
Using National Health and Nutrition ...Examination Survey data, we examined allostatic load scores for adults aged 18-64 years. We estimated probability of a high score by age, race, gender, and poverty status and Blacks' odds of having a high score relative to Whites' odds.
Blacks had higher scores than did Whites and had a greater probability of a high score at all ages, particularly at 35-64 years. Racial differences were not explained by poverty. Poor and nonpoor Black women had the highest and second highest probability of high allostatic load scores, respectively, and the highest excess scores compared with their male or White counterparts.
We found evidence that racial inequalities in health exist across a range of biological systems among adults and are not explained by racial differences in poverty. The weathering effects of living in a race-conscious society may be greatest among those Blacks most likely to engage in high-effort coping.
Aims
To evaluate the effects of 12 weeks of treatment with a whey/guar preload on gastric emptying, postprandial glycaemia and glycated haemoglobin (HbA1c) levels in people with type 2 diabetes ...(T2DM).
Materials and methods
A total of 79 people with T2DM, managed on diet or metformin (HbA1c 49 ± 0.7 mmol/mol 6.6 ± 0.1%), were randomized, in single‐blind fashion, to receive 150 mL flavoured preloads, containing either 17 g whey protein plus 5 g guar (n = 37) or flavoured placebo (n = 42), 15 minutes before two meals, each day for 12 weeks. Blood glucose and gastric emptying (breath test) were measured before and after a mashed potato meal at baseline (without preload), and after the preload at the beginning (week 1) and end (week 12) of treatment. HbA1c levels, energy intake, weight and body composition were also evaluated.
Results
Gastric emptying was slower (P < 0.01) and postprandial blood glucose levels lower (P < 0.05) with the whey/guar preload compared to placebo preload, and the magnitude of reduction in glycaemia was related to the rate of gastric emptying at both week 1 (r = −0.54, P < 0.001) and week 12 (r = −0.54, P < 0.0001). At the end of treatment, there was a 1 mmol/mol 0.1% reduction in HbA1c in the whey/guar group compared to the placebo group (49 ± 1.0 mmol/mol 6.6 ± 0.05% vs. 50 ± 0.8 mmol/mol 6.7 ± 0.05%; P < 0.05). There were no differences in energy intake, body weight, or lean or fat mass between the groups.
Conclusions
In patients with well‐controlled T2DM, 12 weeks' treatment with a low‐dose whey/guar preload, taken twice daily before meals, had sustained effects of slowing gastric emptying and reducing postprandial blood glucose, which were associated with a modest reduction in HbA1c, without causing weight gain.
Macrophages are central orchestrators of the tissue response to injury, with distinct macrophage activation states playing key roles in fibrosis progression and resolution. Identifying key macrophage ...populations found in human fibrotic tissues could lead to new treatments for fibrosis. Here, we used human liver and lung single-cell RNA sequencing datasets to identify a subset of
macrophages that express
,
,
, and
. In both human and murine hepatic and pulmonary fibrosis, these macrophages were enriched at the outside edges of scarring and adjacent to activated mesenchymal cells. Neutrophils expressing MMP9, which participates in the activation of TGF-β1, and the type 3 cytokines GM-CSF and IL-17A coclustered with these macrophages. In vitro, GM-CSF, IL-17A, and TGF-β1 drive the differentiation of human monocytes into macrophages expressing scar-associated markers. Such differentiated cells could degrade collagen IV but not collagen I and promote TGF-β1-induced collagen I deposition by activated mesenchymal cells. In murine models blocking GM-CSF, IL-17A or TGF-β1 reduced scar-associated macrophage expansion and hepatic or pulmonary fibrosis. Our work identifies a highly specific macrophage population to which we assign a profibrotic role across species and tissues. It further provides a strategy for unbiased discovery, triage, and preclinical validation of therapeutic targets based on this fibrogenic macrophage population.
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