Vitamin-D binding protein gene polymorphisms and serum 25-hydroxyvitamin-D in a Turkish population

The rs7041 and rs4588 polymorphisms found in the GC gene, encoding vitamin D-binding protein (DBP), have distinct biochemical phenotypes. The aim of this study was to investigate vitamin D parameters with these polymorphisms, in individuals with possible vitamin D deficiency. The most common (49% of the cohort) genotype in rs7041 was GT, especially among individuals with high levels of free 25(OH)D calculated but with low levels of bioavailable 25(OH)D, and in rs4588 it was AC in particular among the individuals with low levels of bioavailable 25(OH)D. The most common phenotypes were Gc1s/2 (35.3%) and Gc1s/1s (31.4%), and Gc1f/1f was rare (5.9%). The variations in free and bioavailable 25(OH)D levels among healthy Turkish individuals may be attributed to the variations in total 25(OH)D as well as GC gene polymorphisms. The Turkish population shares a similarity for allele frequencies of rs7041 with the European population and similarity for allele frequencies of rs4588 with Gujarati Indians, and this may also be important in relation to certain ethnic populations showing associations between vitamin D and COVID-19

An appeal to the global health community for a tripartite innovation: an ‘‘Essential Diagnostics List,’’ ‘‘Health in All Policies,’’ and ‘‘See-Through 21st Century Science and Ethics"

Diagnostics spanning a wide range of new biotechnologies, including proteomics, metabolomics, and nanotechnology, are emerging as companion tests to innovative medicines. In this Opinion, we present the rationale for promulgating an ‘‘Essential Diagnostics List.’’ Additionally, we explain the ways in which adopting a vision for ‘‘Health in All Policies’’ could link essential diagnostics with robust and timely societal outcomes such as sustainable development, human rights, gender parity, and alleviation of poverty. We do so in three ways. First, we propose the need for a new, ‘‘see through’’ taxonomy for knowledge-based innovation as we transition from the material industries (e.g., textiles, plastic, cement, glass) dominant in the 20th century to the anticipated knowledge industry of the 21st century. If knowledge is the currency of the present century, then it is sensible to adopt an approach that thoroughly examines scientific knowledge, starting with the production aims, methods, quality, distribution, access, and the ends it purports to serve. Second, we explain that this knowledge trajectory focus on innovation is crucial and applicable across all sectors, including public, private, or public–private partnerships, as it underscores the fact that scientific knowledge is a co-product of technology, human values, and social systems. By making the value systems embedded in scientific design and knowledge co-production transparent, we all stand to benefit from sustainable and transparent science. Third, we appeal to the global health community to consider the necessary qualities of good governance for 21st century organizations that will embark on developing essential diagnostics. These have importance not only for science and knowledge based innovation, but also for the ways in which we can build open, healthy, and peaceful civil societies today and for future generations

İlaç ve kimyasalların spermatotoksik etkilerinin saptanmasında apoptotik modelin geliştirilmesi

Biz kimyasalların toksikolojik sınıflandırılmalarında genotoksisite eşiği ve repro-toksisite eşiğinin insan hücrelerinde saptanarak belirtilmeleri gereğine inanıyoruz.Geliştirmeye çalıştığımız model önce kimyasalların farelerin spermatogenezinden sorumlu jerminal hücrelerinde apoptototik ölüme sebep oldukları konsentrasyonları saptamaktı. Bu modelin pratik zorlukları ile karşılaştık. İnsanın kimyasal maddelere duyarlılıklarını fareleri kullanarak saptamak gene bir ekstrapolasyonu gerektirecekti. İnsan fare değildi. Model olarak dönor kanlarının lökositlerinde söz konusu kimyasalların insan hücrelerinde apoptosisi (programlı hücre ölümünü) başlattıkları konsentrasyonları tesbit etmeye yöneldik. Apoptotik ölümü kriter olarak alışımızın nedeni DNA hasarını gideremeyen hücrelerin kimyasalları artık tolere edemedikleri ve ölüme gittikleri sınırları bize göstrebilecekleri içindi. Apoptotik ölüm ve nekrotik ölümü aynı anda görebilecek Annexin-V & Propidyum-iyodür yöntemini seçtik. Böylelikle insan hücreleri için sadece aoptototik hücre ölümünü başlattıkları sınırları değil hücrelerin nekrotik ölüm sınırlarınıda saptama olanağı elde edebilecektik. Örnek olarak seçtğimiz DES'in (sentetik-östrojen) insan hücreleri için nekrotik olduğu sınırları ve de Ftalosiyaninler adlı kimyasalların sadece apoptosisi uyardığı dozları saptadık. Modelimiz tekrarlanabilir sonuçlar veriyordu ve gerçekten toksisitesi çok düşük ve de repro-toksisitesi olmayan bir tarım ilacı olan 2,4,5-T ile çalıştığımız dozlarda apoptosis veya nekroz ihmal edilebilir düzeylerde düşükken, reprotokisitesi bilinen ve toksik olan bir tarım-ilacının (2,4 DB) da bizim test sistemimizle apoptosis ve nekrozu başlattığını gördük.Elde ettiğimiz orjinal bulgular şunlardı. 1. İnsan hücreleri ile kimyasalların toksisite eşiklerini saptamada basit, ucuz, hızlı ve objektif bir imkanın olduğu gösterilmiştir. 2. Hücre kültürü insan hücreleri ile de olsa laboratuar hücreleridir ve artık metabolizmaları çok değişmiştir. Bu çalışmada doğrudan dönor kanlarından alınacak 0.2 ml kanla bu çalışmanın yapılabileceği gösterilmiştir. 3. Aynı çalışmada aynı maddenin hangi eşik değerlerde apoptoza hangi eşik değerlerde nekroza sebep olabileceğini bulmak mümkündür. 4. Bu çalışma biyokimyasal toksikoloji alanında yeni bir vizyonu getirmektedir. 5. Ayrıcada geliştirilen bu model ileride anti-karsinojenik maddelerin sitotoksisitesi içinde kullanılabilir. We assume that ın the toxicologic classification of chemicals, the genotoxicity and reprotoxicity thresholds must be indicated on the basis of values determined in human cells. In the model developed by us we first aimed to determine the concentrations of chemicals causing apoptosis in the germinal cells responsible for spermatogenesis of rats. The determination of sensitivity of human cells against chemicals by experiments conducted on rats would recuire additional extrapolation since the respose of a human being would be different than that of a rat. As a model, we directed our studies to determine the concentrations of chemicals concerned in the leucocytes of donor bloods which would start the apoptosois in human cells. We have chosen the apoptotic death as a criteria in this study because we would be able to see the limits of concentration at which the cells failing to repair the DNA damage would no longer tolerate the chemicals and would die. We have chosen the Annexin-V & Propidium Iodide Method which would enable us to observe both the apoptosis and necrotic death. We have determined the limits of concentration of DES (synthetic oestrogen) chosen as a sample in this study which would be necrotic for human cells and also the doses of chemicals named Phthalocyanines which would induce only apoptosis. 2,4,5-T (herbicide) known to have a very low toxicity and exhibiting no reprotoxicity, was at negligibly low levels of apoptosis inducing. But another herbicide, 2,4 DB known to be toxic and have reprotoxicity started apoptosis and necrosis in the system we employed. The original findings we obtained are as follows: 1. Model is a simple, inexpensive, rapid and objective method in determining the toxicity thresholds of chemicals for human cells. 2.. Such studies could be carried out using a 0.2 ml donor blood. 3. It will be responsible to determine the threshold values of a chemical causing apoptosis and necrosis, in the same study. 4. This study has brought a new vision to the field of biochemical toxicology. 5. With the same model, it will be possible to show the cytotoxicities of anti-carcinogenic substances

İlaç ve kimyasalların spermatotoksik etkilerinin saptanmasında apoptotik modelin geliştirilmesi

Biz kimyasalların toksikolojik sınıflandırılmalarında genotoksisite eşiği ve repro-toksisite eşiğinin insan hücrelerinde saptanarak belirtilmeleri gereğine inanıyoruz.Geliştirmeye çalıştığımız model önce kimyasalların farelerin spermatogenezinden sorumlu jerminal hücrelerinde apoptototik ölüme sebep oldukları konsentrasyonları saptamaktı. Bu modelin pratik zorlukları ile karşılaştık. İnsanın kimyasal maddelere duyarlılıklarını fareleri kullanarak saptamak gene bir ekstrapolasyonu gerektirecekti. İnsan fare değildi. Model olarak dönor kanlarının lökositlerinde söz konusu kimyasalların insan hücrelerinde apoptosisi (programlı hücre ölümünü) başlattıkları konsentrasyonları tesbit etmeye yöneldik. Apoptotik ölümü kriter olarak alışımızın nedeni DNA hasarını gideremeyen hücrelerin kimyasalları artık tolere edemedikleri ve ölüme gittikleri sınırları bize göstrebilecekleri içindi. Apoptotik ölüm ve nekrotik ölümü aynı anda görebilecek Annexin-V & Propidyum-iyodür yöntemini seçtik. Böylelikle insan hücreleri için sadece aoptototik hücre ölümünü başlattıkları sınırları değil hücrelerin nekrotik ölüm sınırlarınıda saptama olanağı elde edebilecektik.Örnek olarak seçtğimiz DES'in (sentetik-östrojen) insan hücreleri için nekrotik olduğu sınırları ve de Ftalosiyaninler adlı kimyasalların sadece apoptosisi uyardığı dozları saptadık. Modelimiz tekrarlanabilir sonuçlar veriyordu ve gerçekten toksisitesi çok düşük ve de repro-toksisitesi olmayan bir tarım ilacı olan 2,4,5-T ile çalıştığımız dozlarda apoptosis veya nekroz ihmal edilebilir düzeylerde düşükken, reprotokisitesi bilinen ve toksik olan bir tarım-ilacının (2,4 DB) da bizim test sistemimizle apoptosis ve nekrozu başlattığını gördük.Elde ettiğimiz orjinal bulgular şunlardı.1.İnsan hücreleri ile kimyasalların toksisite eşiklerini saptamada basit, ucuz, hızlı ve objektif bir imkanın olduğu gösterilmiştir.2.Hücre kültürü insan hücreleri ile de olsa laboratuar hücreleridir ve artık metabolizmaları çok değişmiştir. Bu çalışmada doğrudan dönor kanlarından alınacak 0.2 ml kanla bu çalışmanın yapılabileceği gösterilmiştir.3.Aynı çalışmada aynı maddenin hangi eşik değerlerde apoptoza hangi eşik değerlerde nekroza sebep olabileceğini bulmak mümkündür.4.Bu çalışma biyokimyasal toksikoloji alanında yeni bir vizyonu getirmektedir.5.Ayrıcada geliştirilen bu model ileride anti-karsinojenik maddelerin sitotoksisitesi içinde kullanılabilir.We assume that ın the toxicologic classification of chemicals, the genotoxicity and reprotoxicity thresholds must be indicated on the basis of values determined in human cells. In the model developed by us we first aimed to determine the concentrations of chemicals causing apoptosis in the germinal cells responsible for spermatogenesis of rats. The determination of sensitivity of human cells against chemicals by experiments conducted on rats would recuire additional extrapolation since the respose of a human being would be different than that of a rat. As a model, we directed our studies to determine the concentrations of chemicals concerned in the leucocytes of donor bloods which would start the apoptosois in human cells. We have chosen the apoptotic death as a criteria in this study because we would be able to see the limits of concentration at which the cells failing to repair the DNA damage would no longer tolerate the chemicals and would die. We have chosen the Annexin-V & Propidium Iodide Method which would enable us to observe both the apoptosis and necrotic death. We have determined the limits of concentration of DES (synthetic oestrogen) chosen as a sample in this study which would be necrotic for human cells and also the doses of chemicals named Phthalocyanines which would induce only apoptosis. 2,4,5-T (herbicide) known to have a very low toxicity and exhibiting no reprotoxicity, was at negligibly low levels of apoptosis inducing. But another herbicide, 2,4 DB known to be toxic and have reprotoxicity started apoptosis and necrosis in the system we employed. The original findings we obtained are as follows:1. Model is a simple, inexpensive, rapid and objective method in determining the toxicity thresholds of chemicals for human cells.2.. Such studies could be carried out using a 0.2 ml donor blood.3. It will be responsible to determine the threshold values of a chemical causing apoptosis and necrosis, in the same study.4. This study has brought a new vision to the field of biochemical toxicology.5. With the same model, it will be possible to show the cytotoxicities of anti-carcinogenic substances

Digging deeper into precision/personalized medicine: cracking the sugar code, the third alphabet of life, and sociomateriality of the cell

Precision/personalized medicine is a hot topic in health care. Often presented with the motto "the right drug, for the right patient, at the right dose, and the right time," precision medicine is a theory for rational therapeutics as well as practice to individualize health interventions (e.g., drugs, food, vaccines, medical devices, and exercise programs) using biomarkers. Yet, an alien visitor to planet Earth reading the contemporary textbooks on diagnostics might think precision medicine requires only two biomolecules omnipresent in the literature: nucleic acids (e.g., DNA) and proteins, known as the first and second alphabet of biology, respectively. However, the precision/personalized medicine community has tended to underappreciate the third alphabet of life, the "sugar code" (i.e., the information stored in glycans, glycoproteins, and glycolipids). This article brings together experts in precision/personalized medicine science, pharmacoglycomics, emerging technology governance, cultural studies, contemporary art, and responsible innovation to critically comment on the sociomateriality of the three alphabets of life together. First, the current transformation of targeted therapies with personalized glycomedicine and glycan biomarkers is examined. Next, we discuss the reasons as to why unraveling of the sugar code might have lagged behind the DNA and protein codes. While social scientists have historically noted the importance of constructivism (e.g., how people interpret technology and build their values, hopes, and expectations into emerging technologies), life scientists relied on the material properties of technologies in explaining why some innovations emerge rapidly and are more popular than others. The concept of sociomateriality integrates these two explanations by highlighting the inherent entanglement of the social and the material contributions to knowledge and what is presented to us as reality from everyday laboratory life. Hence, we present a hypothesis based on a sociomaterial conceptual lens: because materiality and synthesis of glycans are not directly driven by a template, and thus more complex and open ended than sequencing of a finite length genome, social construction of expectations from unraveling of the sugar code versus the DNA code might have evolved differently, as being future-uncertain versus future-proof, respectively, thus potentially explaining the "sugar lag" in precision/personalized medicine diagnostics over the past decades. We conclude by introducing systems scientists, physicians, and biotechnology industry to the concept, practice, and value of responsible innovation, while glycomedicine and other emerging biomarker technologies (e.g., metagenomics and pharmacomicrobiomics) transition to applications in health care, ecology, pharmaceutical/diagnostic industries, agriculture, food, and bioengineering, among others

Translating Biotechnology To Knowledge-Based Innovation, Peace, And Development? Deploy A Science Peace Corps-An Open Letter To World Leaders

Scholarship knows no geographical boundaries. This science diplomacy and biotechnology journalism article introduces an original concept and policy petition to innovate the global translational science, a Science Peace Corps. Service at the new Corps could entail volunteer work for a minimum of 6 weeks, and up to a maximum of 2 years, for translational research in any region of the world to build capacity manifestly for development and peace, instead of the narrow bench-to-bedside model of life science translation. Topics for translational research are envisioned to include all fields of life sciences and medicine, as long as they are linked to potential or concrete endpoints in development, foreign policy, conflict management, post-crisis capacity building, and/or peace scholarship domains. As a new instrument in the global science and technology governance toolbox, a Science Peace Corps could work effectively, for example, towards elucidating the emerging concept of "one health"-encompassing human, environmental, plant, microbial, ecosystem, and planet health-thus serving as an innovative crosscutting pillar of 21st century integrative biology. An interdisciplinary program of this caliber for development would link 21st century life sciences to foreign policy and peace, in ways that can benefit many nations despite their ideological differences. We note that a Science Peace Corps is timely. The Intergovernmental Panel on Climate Change (IPCC) of the United Nations released the Fifth Assessment Report on March 31, 2014. Worrisomely, the report underscores that no person or nation will remain untouched by the climate change, highlighting the shared pressing life sciences challenges for global society. To this end, we recall that President John F. Kennedy advocated for volunteer work that has enduring, transgenerational, and global impacts. This culminated in establishment of the Peace Corps in 1961. Earlier, President Abraham Lincoln aptly observed, "nearly all men can stand adversity, but if you want to test a man's character, give him power." We therefore petition President Barack Obama, other world leaders, and international development agencies in positions of power around the globe, to consider deploying a Science Peace Corps to cultivate the essential (and presently missing) ties among life sciences, foreign policy, development, and peace agendas. A Science Peace Corps requires support by a credible and independent intergovernmental organization or development agency for funding, and arbitration in the course of volunteer work when the global versus local (glocal) value-based priorities and human rights intersect in synergy or conflict. In all, Science Peace Corps is an invitation to a new pathway for competence in 21st century science that is locally productive and globally competitive. It can open up scientific institutions to broader considerations and broader inputs, and thus cultivate vital translational science in a world sorely in need of solidarity and sustainable responses to the challenges of 21st century science and society.Wo