Sperm induce a secondary increase in ATP levels in mouse eggs that is independent of Ca2+ oscillations

Egg activation at fertilization in mouse eggs is caused by a series of cytosolic Ca2+ oscillations that are associated with an increase in ATP concentrations driven by increased mitochondrial activity. We have investigated the role of Ca2+ oscillations in these changes in ATP at fertilization by measuring the dynamics of ATP and Ca2+ in mouse eggs. An initial ATP increase started with the first Ca2+ transient at fertilization and then a secondary increase in ATP occurred about 1 hour later and this preceded a small and temporary increase in the frequency of Ca2+ oscillations. Other stimuli that caused Ca2+ oscillations such as PLCz1 or thimerosal, caused smaller or slower changes in ATP that failed to show the distinct secondary rise. Sperm induced Ca2+ oscillations in the egg also triggered changes in fluorescence of NADH which followed the pattern of Ca2+ spikes in a similar pattern to oscillations triggered by PLCz1 or thimerosal. When eggs were loaded with low concentrations of the Ca2+ chelator BAPTA, sperm triggered one small Ca2+ increase, but there were still extra phases of ATP increase that were similar to control fertilized eggs. Singular Ca2+ increases caused by thapsigargin were much less effective in elevating ATP levels. Together these data suggest that the secondary ATP increase at fertilization in mouse eggs is not caused by increases in cytosolic Ca2+. The fertilizing sperm may stimulate ATP production in eggs via both Ca2+ and by another mechanism that is independent of PLCz1 or Ca2+ oscillations

European Society of Cardiology: Cardiovascular Disease Statistics 2019

Aims The 2019 report from the European Society of Cardiology (ESC) Atlas provides a contemporary analysis of cardiovascular disease (CVD) statistics across 56 member countries, with particular emphasis on international inequalities in disease burden and healthcare delivery together with estimates of progress towards meeting 2025 World Health Organization (WHO) non-communicable disease targets. Methods and results In this report, contemporary CVD statistics are presented for member countries of the ESC. The statistics are drawn from the ESC Atlas which is a repository of CVD data from a variety of sources including the WHO, the Institute for Health Metrics and Evaluation, and the World Bank. The Atlas also includes novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery obtained by annual survey of the national societies of ESC member countries. Across ESC member countries, the prevalence of obesity (body mass index ≥30 kg/m2) and diabetes has increased two- to three-fold during the last 30 years making the WHO 2025 target to halt rises in these risk factors unlikely to be achieved. More encouraging have been variable declines in hypertension, smoking, and alcohol consumption but on current trends only the reduction in smoking from 28% to 21% during the last 20 years appears sufficient for the WHO target to be achieved. The median age-standardized prevalence of major risk factors was higher in middle-income compared with high-income ESC member countries for hypertension {23.8% [interquartile range (IQR) 22.5–23.1%] vs. 15.7% (IQR 14.5–21.1%)}, diabetes [7.7% (IQR 7.1–10.1%) vs. 5.6% (IQR 4.8–7.0%)], and among males smoking [43.8% (IQR 37.4–48.0%) vs. 26.0% (IQR 20.9–31.7%)] although among females smoking was less common in middle-income countries [8.7% (IQR 3.0–10.8) vs. 16.7% (IQR 13.9–19.7%)]. There were associated inequalities in disease burden with disability-adjusted life years per 100 000 people due to CVD over three times as high in middle-income [7160 (IQR 5655–8115)] compared with high-income [2235 (IQR 1896–3602)] countries. Cardiovascular disease mortality was also higher in middle-income countries where it accounted for a greater proportion of potential years of life lost compared with high-income countries in both females (43% vs. 28%) and males (39% vs. 28%). Despite the inequalities in disease burden across ESC member countries, survey data from the National Cardiac Societies of the ESC showed that middle-income member countries remain severely under-resourced compared with high-income countries in terms of cardiological person-power and technological infrastructure. Under-resourcing in middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, device implantation and cardiac surgical procedures. Conclusion A seemingly inexorable rise in the prevalence of obesity and diabetes currently provides the greatest challenge to achieving further reductions in CVD burden across ESC member countries. Additional challenges are provided by inequalities in disease burden that now require intensification of policy initiatives in order to reduce population risk and prioritize cardiovascular healthcare delivery, particularly in the middle-income countries of the ESC where need is greatest

Borrowability, inheritance, and semantic change in the Indo-European and Caucasian vocabulary for hunting, farming, and technology

Vocabulary for subsistence and technology may vary a great deal in their degree of borrowability, depending on time, place, inherent subsistence and technology, and the situation of the borrowing. In cross-linguistic typological studies of borrowability, these words tend to group somewhere from middle to high in borrowability, depending on lexical concept (Haspelmath & Tadmor, 2009). We have compiled a set of 100 lexical concepts of importance to hunting, farming, and technology from a perspective of high age and presumed high stability from a cultural perspective. These concepts include, e.g., bovine cattle (BULL, OX, COW), animals of traction (HORSE, DONKEY), important metals (GOLD, IRON, COPPER), important crops (GRAIN, WHEAT), important game (HARE, DEER), essential technological innovations (WHEEL, WAGON). We have compiled a complete data set of lexemes from Indo-European, Caucasian (Kartvelian, Nakh-Dagestanian, Northwest Caucasian), as well as adjacent Uralic and Turkic languages, in all around 300 languages. In particular the Caucasian data is rich and new, based on fieldwork of poorly documented languages. The lexemes have been coded for etymology as well as for borrowing, lexical derivation and semantic change, and are amassed in a lexical cognacy database (Carling, 2017). Preliminary studies on the material indicate, first, that there is a high degree of inherited words for both farming and technology, which are paralleled and independent in both Indo-European and Caucasian families. Interestingly enough, we also find a great deal of vocabulary in the families that apparently have their roots in joint, very ancient migration words. Also, we notice that some words are similar between the families in the way they are derived (e.g., Proto-Kartvelian *borbal ‘wheel’, from *bor- ‘rotation’). An interesting parallel between Indo-European and Caucasian is that semantic change of culture words within etymologies follow almost identical principles, indicating a high cultural component in semantic change. Finally, we notice that borrowability may be high in certain areas and in certain languages, also targeting concepts of very high age, such as farming words. Much of this borrowing is relatively late (e.g., in Caucasian from Persian, Arabic, or Turkic), indicating that cultural impact may have played an important role in changing the vocabulary also for concept for which there must have been an inherent vocabulary. The presentation will look at particular concepts and lexemes, both inherited words, possible ancient loans, migration words, as well as later, obvious borrowings. Further, we will look at statistics on borrowability in general, and type and direction of semantic change of culture concepts of the data. Carling, G. (2017). DiACL - Diachronic Atlas of Comparative Linguistics Online (Publication no. https://diacl.ht.lu.se/). from Lund University https://diacl.ht.lu.se/ Haspelmath, M., & Tadmor, U. (2009). Loanwords in the world's languages: a comparative handbook (M. Haspelmath & U. Tadmor Eds.). Berlin: Mouton de Gruyter

Azerbaijani adaptation of the WHO-5 wellbeing index: investigating its relationship with psychological distress, resilience, and life satisfaction

Abstract Background The WHO-5 Wellbeing Index is a widely used tool for assessing psychological well-being. Despite its global application, its adaptation and validation for the Azerbaijani population had not been previously explored. This study aims to fill this gap by adapting the WHO-5 Wellbeing Index for Azerbaijani adults and examining its relationship with psychological distress, resilience, and life satisfaction. Methods A sample of 875 Azerbaijani adults aged 18 to 89 (mean age = 29.13, SD = 10.98) participated in this study. The adaptation process included confirmatory factor analysis to test the original 5-item structure of the index in the Azerbaijani context. Additionally, item response theory analysis was employed to evaluate the discriminative values of the items. Reliability was assessed through various methods, including Cronbach’s alpha, McDonald’s omega, and Guttmann’s lambda. Results Confirmatory factor analysis supported the original 5-item structure of the WHO-5 Wellbeing Index for the Azerbaijani sample, demonstrating alignment with the index’s original version. All items showed acceptable discriminative values in item response theory analysis. The index also exhibited sufficient reliability, as evidenced by Cronbach’s alpha, McDonald’s omega, and Guttmann’s lambda. Correlation and network analyses indicated significant associations of the WHO-5 Wellbeing Index with psychological distress, resilience, and life satisfaction. Specifically, the index was negatively correlated with depression, anxiety, and stress, and positively correlated with resilience and life satisfaction. Conclusion The findings suggest that the WHO-5 Wellbeing Index is a valid and reliable tool for assessing psychological well-being in the Azerbaijani population. Its significant associations with psychological distress, resilience, and life satisfaction further affirm its utility in this cultural context

The causality of borrowing : Lexical loans in Eurasian languages

All languages borrow words from other languages. Some languages are more prone to borrowing, while others borrow less, and different domains of the vocabulary are unequally susceptible to borrowing. Languages typically borrow words when a new concept is introduced, but languages may also borrow a new word for an already existing concept. Linguists describe two causalities for borrowing: need, i.e., the internal pressure of borrowing a new term for a concept in the language, and prestige, i.e., the external pressure of borrowing a term from a more prestigious language. We investigate lexical loans in a dataset of 104 concepts in 115 Eurasian languages from 7 families occupying a coherent contact area of the Eurasian landmass, of which Indo-European languages from various periods constitute a majority. We use a cognacy-coded dataset, which identifies loan events including a source and a target language. To avoid loans for newly introduced concepts in languages, we use a list of lexical concepts that have been in use at least since the Chalcolithic (4000–3000 BCE). We observe that the rates of borrowing are highly variable among concepts, lexical domains, languages, language families, and time periods. We compare our results to those of a global sample and observe that our rates are generally lower, but that the rates between the samples are significantly correlated. To test the causality of borrowing, we use two different ranks. Firstly, to test need, we use a cultural ranking of concepts by their mobility (of nature items) or their labour intensity and “distance-from-hearth” (of culture items). Secondly, to test prestige, we use a power ranking of languages by their socio-cultural status. We conclude that the borrowability of concepts increases with increasing mobility (nature), and with increased labour intensity and “distance-from-hearth” (culture). We also conclude that language prestige is not correlated with borrowability in general (all languages borrow, independently of prestige), but prestige predicts the directionality of borrowing, from a more prestigious language to a less prestigious one. The process is not constant over time, with a larger inequality during the ancient and modern periods, but this result may depend on the status of the data (non-prestigious languages often remain unattested). In conclusion, we observe that need and prestige compete as causes of lexical borrowing

Enoch Bell use of funds for Aleppo College in the 20th century

Ankara : İhsan Doğramacı Bilkent Üniversitesi İktisadi, İdari ve Sosyal Bilimler Fakültesi, Tarih Bölümü, 2018.This work is a student project of the Department of History, Faculty of Economics, Administrative and Social Sciences, İhsan Doğramacı Bilkent University.The History of Turkey course (HIST200) is a requirement for all Bilkent undergraduates. It is designed to encourage students to work in groups on projects concerning any topic of their choice that relates to the history of Turkey. It is designed as an interactive course with an emphasis on research and the objective of investigating events, chronologically short historical periods, as well as historic representations. Students from all departments prepare and present final projects for examination by a committee, with 10 projects chosen to receive awards.Includes bibliographical references (page 13).by Burcu Feyzullahoğlu

Development of recombinant PLC-zeta protein as a therapeutic intervention for the clinical treatment of Oocyte Activation Failure

The sperm-specific phospholipase C zeta (PLCζ) protein is widely considered as the predominant physiological stimulus for initiating the Ca2+ release responsible for oocyte activation during mammalian fertilization. The increasing number of genetic and clinical reports that directly link PLCζ defects and/or deficiencies with oocyte activation failure (OAF) necessitates the use of a powerful therapeutic intervention to overcome such cases of male factor infertility. Currently, in vitro fertilization (IVF) clinics treat OAF cases after intracytoplasmic sperm injection (ICSI) with Ca2+ ionophores. Despite their successful use, such chemical agents are unable to trigger the physiological pattern of Ca2+ oscillations. Moreover, the safety of these ionophores is not yet fully established. We have previously demonstrated that recombinant PLCζ protein can be successfully used to rescue failed oocyte activation, resulting in efficient blastocyst formation. Herein, we produced a maltose binding protein (MBP)-tagged recombinant human PLCζ protein capable of inducing Ca2+ oscillations in mouse oocytes similar to those observed at fertilization. Circular dichroism (CD) experiments revealed a stable, well-folded protein with a high helical content. Moreover, the recombinant protein could retain its enzymatic properties for at least up to 90 days after storage at −80 °C. Finally, a chick embryo model was employed and revealed that exposure of fertilized chicken eggs to MBP-PLCζ did not alter the embryonic viability when compared to the control, giving a first indication of its safety. Our data support the potential use of the MBP-PLCζ recombinant protein as an effective therapeutic tool but further studies are required prior to its use in a clinical setting

Development of Recombinant PLC-Zeta Protein as a Therapeutic Intervention for the Clinical Treatment of Oocyte Activation Failure

The sperm-specific phospholipase C zeta (PLCζ) protein is widely considered as the predominant physiological stimulus for initiating the Ca2+ release responsible for oocyte activation during mammalian fertilization. The increasing number of genetic and clinical reports that directly link PLCζ defects and/or deficiencies with oocyte activation failure (OAF) necessitates the use of a powerful therapeutic intervention to overcome such cases of male factor infertility. Currently, in vitro fertilization (IVF) clinics treat OAF cases after intracytoplasmic sperm injection (ICSI) with Ca2+ ionophores. Despite their successful use, such chemical agents are unable to trigger the physiological pattern of Ca2+ oscillations. Moreover, the safety of these ionophores is not yet fully established. We have previously demonstrated that recombinant PLCζ protein can be successfully used to rescue failed oocyte activation, resulting in efficient blastocyst formation. Herein, we produced a maltose binding protein (MBP)-tagged recombinant human PLCζ protein capable of inducing Ca2+ oscillations in mouse oocytes similar to those observed at fertilization. Circular dichroism (CD) experiments revealed a stable, well-folded protein with a high helical content. Moreover, the recombinant protein could retain its enzymatic properties for at least up to 90 days after storage at −80 °C. Finally, a chick embryo model was employed and revealed that exposure of fertilized chicken eggs to MBP-PLCζ did not alter the embryonic viability when compared to the control, giving a first indication of its safety. Our data support the potential use of the MBP-PLCζ recombinant protein as an effective therapeutic tool but further studies are required prior to its use in a clinical setting.This study was performed according to the guidelines of the Qatar University ethical committee. All procedures were ethically approved by the Qatar University Institutional Animal Care and Use Committee (QU-IACUC) (IACUC REFERENCE number: QU-IACUC 007/2021-REN1)