Effect of Nettle (Urtica dioca L.) density on fiber yield and quality in a natural ecosystem under East Mediterranean conditions

Nettle (Urtica dioica L.), a new industrial crop, has been cultivated since the 12th century for its fibers. This study was conducted to specify the optimal density of plants in order to move from wild harvest to nettle cultivation. For the present study, sampling was performed in 21 different fields throughout Greece, during October 2018. The effect of nine different plant densities on several agronomic (plants height, leaf area and dry matter) and fiber quality (straw length, fiber percentage, yield, extension at break, strength, length, diameter) characteristics was determined. The higher fiber yield occurred at the lower density (4 plants m2), while the higher fiber diameter observed at the highest density (12 plants m2). Comparisons were performed at the 5% level of significance (p ≤ 0.05). According to our results, there have been negative correlations between plant density and certain agronomic and quality characteristics such as plant height and fiber length, hence the optimal density is about seven plants per m2

'Thrown Out Into the World': Transition to Post Schooling for Autistic Young People

Autistic Young People in Australia experience poorer employment outcomes upon transition out of school than their non-disabled peers. This can lead to significant disadvantages in terms of financial, social, physical and mental well being as they may not be able to experience the benefits of work. the transition from school to post-school has been identified as a period where Autistic young people do not receive adequate support and, regrettably, understanding how to improve support remains a gap in the research literature. The introduction of the National Disability Insurance Scheme (NDIS) changed the funding landscape for Autistic young people in terms of the supports they may be eligible to receive, leaving potential gaps in support at a critical time in an Autistic Young Person's life. This research was co-produced and adopted a qualitative methodology and aimed to understand the perspectives and experiences of key stakeholders (Autistic Young People, Parent/Carers, Educators and Disability Employment Service Providers) around the transition of Autistic young people from school to post-school education and employment options. Reflective Thematic Analysis was adopted to analyse transcribed interview data from 39 participants across the four stakeholder groups. Key Findings indicated the uniqueness of young autistic peoples' experiences and their desire to prove themselves as well as the importance of harnessing autistic strengths and interests and the need for early, collaborative transition planning. It calls attention to gaps in transition, including delayed planning, limited and inconsistent supports, siloed approaches to transition planning, strain on families and the impact of ongoing stigma and discrimination toward neurodivergent people. Recommendations are posed to optimise post school transition. This study contributes new knowledge to the evidence base surrounding the transition of Autistic Young People out of school. It highlights recommendations for research, policy, education, and practice to improve outcomes for Autistic Young People

ESR2 Drives Mesenchymal-to-Epithelial Transition in Triple-Negative Breast Cancer and Tumorigenesis In Vivo

Estrogen receptors (ERs) have pivotal roles in the development and progression of triple-negative breast cancer (TNBC). Interactions among cancer cells and tumor microenvironment are orchestrated by the extracellular matrix that is rapidly emerging as prominent contributor of fundamental processes of breast cancer progression. Early studies have correlated ER beta expression in tumor sites with a more aggressive clinical outcome, however ER beta exact role in the progression of TNBC remains to be elucidated. Herein, we introduce the functional role of ER beta suppression following isolation of monoclonal cell populations of MDA-MB-231 breast cancer cells transfected with shRNA against human ESR2 that permanently resulted in 90% reduction of ER beta mRNA and protein levels. Further, we demonstrate that clone selection results in strongly reduced levels of the aggressive functional properties of MDA-MB-231 cells, by transforming their morphological characteristics, eliminating the mesenchymal-like traits of triple-negative breast cancer cells. Monoclonal populations of shER beta MDA-MB-231 cells undergo universal matrix reorganization and pass on a mesenchymal-to-epithelial transition state. These striking changes are encompassed by the total prevention of tumorigenesis in vivo following ER beta maximum suppression and isolation of monoclonal cell populations in TNBC cells. We propose that these novel findings highlight the promising role of ER beta targeting in future pharmaceutical approaches for managing the metastatic dynamics of TNBC breast cancer

Designer Xanthone An Inhibitor Scaffold for MDR-Involved Human Glutathione Transferase Isoenzyme A1-1

Glutathione transferases (GSTs) are cell detoxifiers involved in multiple drug resistance (MDR), hampering the effectiveness of certain anticancer drugs. To our knowledge, this is the first report on well-defined synthetic xanthones as GST inhibitors. Screening 18 xanthones revealed three derivatives bearing a bromomethyl and a methyl group (7) or two bromomethyl groups (8) or an aldehyde group (17), with high inhibition potency (>85%), manifested by low IC50 values (7: 1.59 ± 0.25 μM, 8: 5.30 ± 0.30 μM, and 17: 8.56 ± 0.14 μM) and a competitive modality of inhibition versus CDNB (Ki(7) = 0.76 ± 0.18 and Ki(17) = 1.69 ± 0.08 μM). Of them, derivative 17 readily inhibited hGSTA1-1 in colon cancer cell lysate (IC50 = 10.54 ± 2.41 μM). Furthermore, all three derivatives were cytotoxic to Caco-2 intact cells, with 17 being the least cytotoxic (LC50 = 151.3 ± 16.3 μM). The xanthone scaffold may be regarded as a pharmacophore for hGSTA1-1 and the three derivatives, especially 17, as potent precursors for the synthesis of new inhibitors and conjugate prodrugs for human GSTs

Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms

Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL, but the contribution of inherited factors is poorly characterized. Using a three-stage genome-wide association study of 3,437 MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance in JAK2V617F-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 × 10−10) and rs2201862 (MECOM; meta-analysis P=1.96 × 10−9). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when including JAK2V617F-positive cases. rs9376092 has a stronger effect in JAK2V617F-negative cases with CALR and/or MPL mutations (Breslow–Day P=4.5 × 10−7), whereas in JAK2V617F-positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic χ2 P=7.3 × 10−7). Reduced MYB expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in MYB expression to disease phenotype

Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet

Glucocorticoid hormones are critical to respond and adapt to stress. Genetic variations in the glucocorticoid receptor (GR) gene alter hypothalamic-pituitary-adrenal (HPA) axis activity and associate with hypertension and susceptibility to metabolic disease. Here we test the hypothesis that reduced GR density alters blood pressure and glucose and lipid homeostasis and limits adaption to obesogenic diet. Heterozygous GR βgeo/+ mice were generated from embryonic stem (ES) cells with a gene trap integration of a β-galactosidase-neomycin phosphotransferase (βgeo) cassette into the GR gene creating a transcriptionally inactive GR fusion protein. Although GRβgeo/+ mice have 50% less functional GR, they have normal lipid and glucose homeostasis due to compensatory HPA axis activation but are hypertensive due to activation of the renin-angiotensin- aldosterone system (RAAS). When challenged with a high-fat diet, weight gain, adiposity, and glucose intolerance were similarly increased in control and GRβgeo/+ mice, suggesting preserved control of intermediary metabolism and energy balance. However, whereas a high-fat diet caused HPA activation and increased blood pressure in control mice, these adaptions were attenuated or abolished in GRβgeo/+ mice. Thus, reduced GR density balanced by HPA activation leaves glucocorticoid functions unaffected but mineralocorticoid functions increased, causing hypertension. Importantly, reduced GR limits HPA and blood pressure adaptions to obesogenic diet

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum