Assessment of genotype x environment interaction on yield and yield components of durum wheat genotypes by multivariate analyses

Wheat breeders have to determine the new cultivars and lines responsive to the environmental changes for grain yield and yield components. Therefore, this study was conducted to evaluate 25 durum wheat (Triticum turgidum spp. durum) genotypes including 12 registered cultivars and 13 advanced breeding lines for their stability grown in three different locations (Tokat-Kazova, Diyarbakir and Sivas-Ulas) of Turkey for two growing seasons (2005-2006 and 2006-2007), and to select genotypes having desirable traits to be used in future durum wheat breeding program. Field trials were conducted in a randomized complete block design with three replications at each location. Days to heading, plant height, number of spikes per square meter, number of kernels per spike, spike weight, 1000 kernel weight and grain yield of the genotypes were evaluated in each location. The regression coefficient (bi) of Finlay and Wilkinson (1963) and mean square of deviation from regression (S2d) of Eberhart and Russell (1966) were used as the stability parameters. The results of combined analysis of variance showed a strong influence of the locations on plant height, number of spikes per square meter, number of kernels per spike,  spike weight, 1000 kernel weight and grain yield. Genotypic effects were mainly observed for spike length and test weight. Year had strong impact only on the days to heading. Ecological conditions of Diyarbakir among locations offer the better opportunity for production of durum wheat. Line 5 and cultivar Gidara were both stable in yield ability and also appeared the stable group based on the cluster analysis. In the first principal component days to heading, number of spikes per square meter and spike length  were the most important traits contributing to variation that obtained about 44.3%. There was a positive relationship between grain yield and number of spikes per square meter together test weight, whereas days to heading and spike length were negatively correlated to grain yield. The results of this study also imply that Line-5 and cultivar Gidara among genotypes were the most stable cultivars and can be used as breeding materials. The days to heading, number of spikes per square meter and spike length could be adequate to introduce the differences among genotypes.Key words: Durum wheat, stability, principal component analysis, cluster analysis

The serum steroid signature of PCOS hints at the involvement of novel pathways for excess androgen biosynthesis.

CONTEXT Polycystic ovary syndrome (PCOS) is defined by androgen excess and ovarian dysfunction in the absence of a specific physiological diagnosis. The best clinical marker of androgen excess is hirsutism, while the best biochemical parameter is still a matter of debate. Current consensus guidelines recommend, among other hormones, serum free testosterone as an important serum parameter to measure androgen excess. Recently, however, novel active androgens and androgen metabolic pathways have been discovered. OBJECTIVE To assess the contribution of novel androgens and related steroid biosynthetic pathways to the serum steroid pool in PCOS women in comparison to healthy controls. DESIGN This is a case control study, wherein PCOS was diagnosed according to the AE-PCOS 2009 criteria. Serum steroid profiling was performed by liquid chromatography high-resolution mass spectrometry. SETTING Yeditepe University and associated clinics in Istanbul, Turkey, together with Bern University Hospital Inselspital, Bern, Switzerland. PARTICIPANTS 42 PCOS women and 42 matched, healthy control women. MAIN OUTCOME MEASURES Assessment of 34 steroids compartmentalized in four androgen related pathways: the classic androgen pathway, the backdoor pathway, the C11-oxy backdoor pathway, and the C11-oxy (11β-hydroxyandrostenedione) pathway. RESULTS Metabolites of all four pathways were identified in healthy and PCOS women. Highest concentrations were found for progesterone in controls and androstenedione in PCOS. Lowest levels were found for 11-ketotestosterone in controls compared to PCOS, and for 20α-hydroxyprogesterone in PCOS compared to controls. PCOS also had higher serum testosterone levels compared to the controls. PCOS women had overall higher levels of steroid metabolites of all four androgen pathways compared to healthy controls. CONCLUSIONS Novel alternative pathways contribute to the androgen production in healthy and PCOS women. Hyperandrogenism in PCOS is characterized by an overall increase of serum androgens in the classic, backdoor and C11-oxy pathways. While monogenetic disorders of steroid biosynthesis can be recognized by a specific pattern in the steroid profile, no diagnostic pattern or classifier was found in the serum for PCOS

Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group)

Background/aim: Perioperative FLOT regimen is a standard of care in locally advanced operable gastric and GEJ adenocarcinoma. We aimed to determine the efficacy, prognostic factors of perioperative FLOT chemotherapy in real-life gastric and GEJ tumors. Materials and methods: The data of patients who were treated with perioperative FLOT chemotherapy were retrospectively analyzed from 34 different oncology centers in Turkey. Baseline clinical and demographic characteristics, pretreatment laboratory values, histological and molecular characteristics were recorded. Results: A total of 441 patients were included in the study. The median of age our study population was 60 years. The majority of patients with radiological staging were cT3-4N(+) (89.9%, n = 338). After median 13.5 months (IQR: 8.5–20.5) follow-up, the median overall survival was NR (95% CI, NR to NR), and median disease free survival was 22.9 (95% CI, 18.6 to 27.3) months. The estimated overall survival at 24 months was 62%. Complete pathological response (pCR) and near pCR was achieved in 23.8% of all patients. Patients with lower NLR or PLR have significantly longer median OS (p = 0.007 and p = 0.033, respectively), and patients with lower NLR have significantly longer median DFS (p = 0.039), but PLR level did not affect DFS (p = 0.062). The OS and DFS of patients with better ECOG performance scores and those who could receive FLOT as adjuvant chemotherapy instead of other regimens were found to be better. NLR was found to be independent prognostic factor for OS in the multivariant analysis. At least one adverse event reported in 57.6% of the patients and grade 3–4 toxicity was seen in 23.6% patients. Conclusion: Real-life perioperative FLOT regimen in operable gastric and GEJ tumors showed similar oncologic outcomes compared to clinical trials. Better performance status, receiving adjuvant chemotherapy as same regimen, low grade and low NLR and PLR improved outcomes in real-life. However, in multivariate analysis, only NLR affected OS. © TÜBİTAK

Integrating Human-Centred Design Approach into Sustainable-Oriented 3D Printing Systems

Modern 3D printing systems have become pervasive and widely used both in professional and in informal contexts, including sustainable-oriented ones. However, the risk to create very effective but non-sustainable solutions is very high since 3D printing systems could potentially increase the environmental emergencies and the unsustainable growth. In the transition process toward sustainable ways of production and consumption, the so-called human factor still plays an important role in the achievement of sustainable-oriented actions; it drives the adoption of proper lifestyles that directly and indirectly influence the ways through which such technologies are used. Therefore, future Sustainable 3D Printing Systems should integrate the humans in the systems’ development. This study presents two important results: (a) it presents a set of interdisciplinary ‘Sustainable 3D Printing Systems’, which compose a promising sustainable-oriented scenario useful to support the transition processes toward sustainable designs and productions, and (b) it proposes a new strategy for the integration of human-centred aspects into Sustainable 3D Printing Systems, by combining insights from human-centred design approach

Matched pairs of human prostate stromal cells display differential tropic effects on LNCaP prostate cancer cells

Prostate stromal cells may play binary roles in the process of prostate cancer development. As the first to be encountered by infiltrating prostate cancer cells, prostate stromal cells form the first defense line against prostate cancer progression and metastasis. However, interaction between prostate cancer and stromal cells may facilitate the formation of a tumor microenvironment favoring cancer cell growth and survival. To establish an experimental system for studying the interaction between cancer and stromal cells, we isolated three matched pairs of normal and cancer-associated human prostate stromal clones. In this report, we describe the morphologic and behavioral characteristics of these cells and their effect on LNCaP prostate cancer cells in co-culture. Unlike LNCaP prostate cancer cells, the isolated prostate stromal clones are large fibroblast-like cells with a slow proliferation rate. Growth and survival of these clones are not affected by androgens. The stromal cells display high resistance to serum starvation, while cancer-associated stromal clones have differentiated survival ability. In co-culture experiments, the stromal cells protected some LNCaP prostate cancer cells from death by serum starvation, and cancer-associated stromal clones showed more protection. This work thus established a panel of valuable human prostate stromal cell lines, which could be used in co-culture to study the interaction between prostate cancer and prostate stromal cells

Complete Phenotypic Recovery of an Alzheimer's Disease Model by a Quinone-Tryptophan Hybrid Aggregation Inhibitor

The rational design of amyloid oligomer inhibitors is yet an unmet drug development need. Previous studies have identified the role of tryptophan in amyloid recognition, association and inhibition. Furthermore, tryptophan was ranked as the residue with highest amyloidogenic propensity. Other studies have demonstrated that quinones, specifically anthraquinones, can serve as aggregation inhibitors probably due to the dipole interaction of the quinonic ring with aromatic recognition sites within the amyloidogenic proteins. Here, using in vitro, in vivo and in silico tools we describe the synthesis and functional characterization of a rationally designed inhibitor of the Alzheimer's disease-associated β-amyloid. This compound, 1,4-naphthoquinon-2-yl-L-tryptophan (NQTrp), combines the recognition capacities of both quinone and tryptophan moieties and completely inhibited Aβ oligomerization and fibrillization, as well as the cytotoxic effect of Aβ oligomers towards cultured neuronal cell line. Furthermore, when fed to transgenic Alzheimer's disease Drosophila model it prolonged their life span and completely abolished their defective locomotion. Analysis of the brains of these flies showed a significant reduction in oligomeric species of Aβ while immuno-staining of the 3rd instar larval brains showed a significant reduction in Aβ accumulation. Computational studies, as well as NMR and CD spectroscopy provide mechanistic insight into the activity of the compound which is most likely mediated by clamping of the aromatic recognition interface in the central segment of Aβ. Our results demonstrate that interfering with the aromatic core of amyloidogenic peptides is a promising approach for inhibiting various pathogenic species associated with amyloidogenic diseases. The compound NQTrp can serve as a lead for developing a new class of disease modifying drugs for Alzheimer's disease

Pore timing:the evolutionary origins of the nucleus and nuclear pore complex

The name “eukaryote” is derived from Greek, meaning “true kernel”, and describes the domain of organisms whose cells have a nucleus. The nucleus is thus the defining feature of eukaryotes and distinguishes them from prokaryotes (Archaea and Bacteria), whose cells lack nuclei. Despite this, we discuss the intriguing possibility that organisms on the path from the first eukaryotic common ancestor to the last common ancestor of all eukaryotes did not possess a nucleus at all—at least not in a form we would recognize today—and that the nucleus in fact arrived relatively late in the evolution of eukaryotes. The clues to this alternative evolutionary path lie, most of all, in recent discoveries concerning the structure of the nuclear pore complex. We discuss the evidence for such a possibility and how this impacts our views of eukaryote origins and how eukaryotes have diversified subsequent to their last common ancestor

Microbial diversity and biogeochemical cycling in soda lakes

Soda lakes contain high concentrations of sodium carbonates resulting in a stable elevated pH, which provide a unique habitat to a rich diversity of haloalkaliphilic bacteria and archaea. Both cultivation-dependent and -independent methods have aided the identification of key processes and genes in the microbially mediated carbon, nitrogen, and sulfur biogeochemical cycles in soda lakes. In order to survive in this extreme environment, haloalkaliphiles have developed various bioenergetic and structural adaptations to maintain pH homeostasis and intracellular osmotic pressure. The cultivation of a handful of strains has led to the isolation of a number of extremozymes, which allow the cell to perform enzymatic reactions at these extreme conditions. These enzymes potentially contribute to biotechnological applications. In addition, microbial species active in the sulfur cycle can be used for sulfur remediation purposes. Future research should combine both innovative culture methods and state-of-the-art ‘meta-omic’ techniques to gain a comprehensive understanding of the microbes that flourish in these extreme environments and the processes they mediate. Coupling the biogeochemical C, N, and S cycles and identifying where each process takes place on a spatial and temporal scale could unravel the interspecies relationships and thereby reveal more about the ecosystem dynamics of these enigmatic extreme environments

Impact of systemic inflammatory markers in patients with ALK-positive non-small cell lung cancer treated with crizotinib

Objectives: To evaluate the prognostic utility of inflammation-based prognostic scores in patients with ALK-positive metastatic or non-resectable non-small-cell lung cancer (NSCLC) treated with crizotinib. Patients and Methods: A total of 82 patients with ALK-positive metastatic or non-resectable NSCLC who received ALK TKI crizotinib were included. Pre-treatment modified Glasgow prognostic score (mGPS), prognostic nutritional index (PNI), and systemic immune-inflammation index (SII) were calculated. Multivariable logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment mGPS, PNI, and SII on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Results: The ORR was 77.2%, while 1-year OS and PFS rates were 95.0% and 93.5%, respectively. The univariate analysis revealed significantly higher 1-year PFS (89.4 vs. 64.4%, p=0.043) and OS (92.0 vs. 83.3%, p=0.01) rates in patients with low (<934.7) vs. high (?934.7) SII scores. Multivariate analysis revealed that PNI ?0.09 was a significant determinant of poorer 1-year OS rates (hazard ratio [HR]: 2.46, 95% confidence interval [CI] 0.88–4.85, p=0.035). No significant difference was observed in survival rates according to gender, age, smoking status, prior lines of therapy, or mGPS scores, while higher mGPS scores (odds ratio [OR]: 0.1, 95%CI 0.16–1.04; p=0.009) and higher PNI scores (OR: 0.16, 95% CI 0.02–0.55; p=0.035) were associated with poorer ORR. Conclusion: Our findings indicate the prognostic significance of PNI and SII in terms of survival outcome and the impact of mGPS and PNI on treatment response in patients with ALK-positive NSCLC treated with crizotinib. © 2022 Sociedade Portuguesa de Pneumologi