Inositols: From established knowledge to novel approaches

Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects

The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10−12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10−14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10−103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10−49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10−93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10−23 and OR = 3.39, P = 5.2 × 10−82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20–37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk

The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10-12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10-14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10-103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10-49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10-93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10-23 and OR = 3.39, P = 5.2 × 10-82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk

The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10-12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10-14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10-103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10-49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10-93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10-23 and OR = 3.39, P = 5.2 × 10-82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk

Teaching cell division to secondary school students: an investigation of difficulties experienced by Turkish teachers

This study examines the difficulties biology teachers face when teaching cell division in the secondary schools of the central part of the Erzurum province in Turkey. During this research, a questionnaire was distributed to a total of 36 secondary school biology teachers

Turkish Laicism in Indonesia's Newspapers (1920-1940) and Its Influence on Indonesian Secularists and Muslims Thoughts

The Republic of Turkey was established in 1923 after the Treaty of Sevres and Lausanne were ratified by the Turkish nationalists led by Mustafa Kamal. This establishment has marked the beginning of a new era in the political, social, economic, and cultural lives of Turks. The main concern for Turkish statesmen was laicism. The policy has a significant effect on the global world, especially for the Dutch Indies. The purpose of this article is to provide a critical analysis of the roles of Indonesian-language newspapers in informing Dutch Indies citizens about Turkey's secularization process and how newspapers served as the primary medium for disseminating information about Turkey. Through newspapers, Muslims from Nusantara (the archipelago) expressed their views on the Turks' secularisation efforts. This study employed a historical method using contemporary Indonesian-language newspapers from the National Library of the Republic of Indonesia. The news of Turkey's secularisation had a significant impact on the thoughts of Indonesian secularists and Muslims in laying the nation's foundation in the 1940s

Effects Of Filtration Process And Storage Time On The Chemical Changes And Sensory Properties Of Olive Oil Extracted From Turkish Uslu Cultivar

Upper Mesopotamia is a part of Turkish territory is the homeland of the olive tree with a wide range genetic resource. This is the first report on chemical composition and oxidative stability of olive oil extracted from Uslu cultivar grown locally in a small amount. In this research, a Turkish olive cultivar named as “Uslu” locally grown in Akhisar was used for production of monocultivar extra virgin olive oil by using Mobile Olive Oil Processing Unit”. Olive oil samples were bottled before and after filtration and stored up to 24 months. Some chemical properties such as free fatty acid content, peroxide value, moisture content, UV absorbance value, minor and major components (fatty acid composition, tocopherols, total phenol compounds and phenolic composition), were determined during storage for 24 months. Chemical parameters such as free fatty acid, peroxide value except UV absorption values of both filtered and unfiltered “Uslu” olive oil samples were in agreement with the trade standards of International Olive Council (IOC). Color values of EVOO changed from green to yellow while UV absorbance values altered during storage. Very low free fatty acidy (0.2%) values which are unusual for commercial olive oils in Turkey were obtained for filtered and unfiltered samples. A slight increase was seen for unfiltered sample at the end of storage. Filtration had no detectable effect on fatty acid profile. Filtered sample had higher total phenols (407.64 +/- 4.051 ppm) and alpha-tocopherol (237 and 123.31 ppm) contents than unfiltered ones and their contents decreased approximately 50% at the end of storage. Luteolin was the most abundant phenolic compound and its concentration decreased from 268.65 +/- 5.428 to 93.57 +/- 0.541 ppm during storage. It seemed effect of filtration was more obvious on total phenolic contents. This study was good practice for producing premium extra virgin olive oil by using Mobile Olive Oil Processing Unit. The results obtained in this study showed that Uslu olive oils has a unique chemical composition and a good oxidative stability with high tocopherols and phenolics contents that are uncommon in most of the commercial olive oils.Wo