Harnessing the Wild Relatives and Landraces for Fe and Zn Biofortification in Wheat through Genetic Interventions—A Review

Micronutrient deficiencies, particularly iron (Fe) and zinc (Zn), in human diets are affecting over three billion people globally, especially in developing nations where diet is cereal-based. Wheat is one of several important cereal crops that provide food calories to nearly one-third of the population of the world. However, the bioavailability of Zn and Fe in wheat is inherently low, especially under Zn deficient soils. Although various fortification approaches are available, biofortification, i.e., development of mineral-enriched cultivars, is an efficient and sustainable approach to alleviate malnutrition. There is enormous variability in Fe and Zn in wheat germplasm, especially in wild relatives, but this is not utilized to the full extent. Grain Fe and Zn are quantitatively inherited, but high-heritability and genetic correlation at multiple locations indicate the high stability of Fe and Zn in wheat. In the last decade, pre-breeding activities have explored the potential of wild relatives to develop Fe and Zn rich wheat varieties. Furthermore, recent advances in molecular biology have improved the understanding of the uptake, storage, and bioavailability of Fe and Zn. Various transportation proteins encoding genes like YSL 2, IRT 1, OsNAS 3, VIT 1, and VIT 2 have been identified for Fe and Zn uptake, transfer, and accumulation at different developing stages. Hence, the availability of major genomic regions for Fe and Zn content and genome editing technologies are likely to result in high-yielding Fe and Zn biofortified wheat varieties. This review covers the importance of wheat wild relatives for Fe and Zn biofortification, progress in genomics-assisted breeding, and transgenic breeding for improving Fe and Zn content in wheat.

Steady agronomic and genetic interventions are essential for sustaining productivity in intensive rice cropping

Intensive systems with two or three rice (Oryza sativa L.) crops per year account for about 50% of the harvested area for irrigated rice in Asia. Any reduction in productivity or sustainability of these systems has serious implications for global food security. Rice yield trends in the world’s longest-running long-term continuous cropping experiment (LTCCE) were evaluated to investigate consequences of intensive cropping and to draw lessons for sustaining production in Asia. Annual production was sustained at a steady level over the 50-y period in the LTCCE through continuous adjustment of management practices and regular cultivar replacement. Within each of the three annual cropping seasons (dry, early wet, and late wet), yield decline was observed during the first phase, from 1968 to 1990. Agronomic improvements in 1991 to 1995 helped to reverse this yield decline, but yield increases did not continue thereafter from 1996 to 2017. Regular genetic and agronomic improvements were sufficient to maintain yields at steady levels in dry and early wet seasons despite a reduction in the yield potential due to changing climate. Yield declines resumed in the late wet season. Slower growth in genetic gain after the first 20 y was associated with slower breeding cycle advancement as indicated by pedigree depth. Our findings demonstrate that through adjustment of management practices and regular cultivar replacement, it is possible to sustain a high level of annual production in irrigated systems under a changing climate. However, the system was unable to achieve further increases in yield required to keep pace with the growing global rice demand.

The science of transhumanism: Are we nearly there?

Transhumanism looks to utilise science and technology to move humans beyond the limitations of their natural form. Recent scientific advances have, for the first time, presented plausible genetic interventions for the directed evolution of humans. In separate developments, electromechanical innovations, including miniaturisation of components and improvements in bio-compatible materials, have seen breakthroughs in brain-machine interfaces (BMIs) that potentiate a cybernetic dimension, in which mechanical devices would be under the direct control of the mind. This article offers insight into the most important of these recent advances, with particular emphasis on genome editing and therapeutic uses of BMIs in which the same technology might be employed for enhancement.

Sirtuin 3 (SIRT3) Pathways in Age-Related Cardiovascular and Neurodegenerative Diseases

Age-associated cardiovascular and neurodegenerative diseases lead to high morbidity and mortality around the world. Sirtuins are vital enzymes for metabolic adaptation and provide protective effects against a wide spectrum of pathologies. Among sirtuins, mitochondrial sirtuin 3 (SIRT3) is an essential player in preserving the habitual metabolic profile. SIRT3 activity declines as a result of aging-induced changes in cellular metabolism, leading to increased susceptibility to endothelial dysfunction, hypertension, heart failure and neurodegenerative diseases. Stimulating SIRT3 activity via lifestyle, pharmacological or genetic interventions could protect against a plethora of pathologies and could improve health and lifespan. Thus, understanding how SIRT3 operates and how its protective effects could be amplified, will aid in treating age-associated diseases and ultimately, in enhancing the quality of life in elders.

Genetic interventions, inequalities and the role of the state

A central issue in the ethical public debate on genetic enhancement concerns the inequalities in skills, opportunities and welfare that might be created and established between rich and poor. Many argue that if only the wealthy can have access to enhancements, then existing unjust inequalities will be consolidated and new ones will emerge in the future. Therefore, they argue, state has a role to play against the exacerbating of existing inequalities and the emergence of future ones and determine a genetic policy that will regulate a fair distribution of genetic means under specific principles of justice. This article has two main sections. In the first and shorter section, I examine a case where access to enhancement would be unlimited for everyone. In the second and longer section, I examine the principles that a state should adopt in order to treat the unjust inequalities that could result from limited access to enhancement. Finally, I outline part of my own approach to a just genetic state policy.

Pollutants corrupt resilience pathways of aging in the nematode C. elegans

Delaying aging while prolonging health and lifespan is a major goal in aging research. While many resources have been allocated to find positive interventions with promising results, negative interventions such as pollution and their accelerating effect on age-related degeneration and disease have been mostly neglected. Here, we used the short-lived model organism C. elegans to analyze whether two candidate pollutants interfere with positive interventions by corrupting general aging pathways. We took advantage of the immense data sets describing the age-related remodeling of the proteome including increased protein insolubilities to complement our analysis. We show that the emergent pollutant silica nanoparticles (NP) and the classic xenobiotic inorganic mercury reduce lifespan and cause a premature protein aggregation phenotype. Silica NPs rescaled the longevity effect of genetic interventions targeting the IGF-1/insulin-like signaling pathway. Comparative mass spectrometry revealed that increased insolubility of proteins with important functions in proteostasis is a shared phenotype of intrinsic- and pollution-induced aging supporting the hypothesis that proteostasis is a central resilience pathway controlling lifespan and aging. The presented data demonstrate that pollutants corrupt intrinsic aging pathways, which results in premature aging phenotypes. Reducing pollution is therefore an important step to increase healthy aging and prolong life expectancies on a population level in humans and animals.

Pravne, socijalne i etičke implikacije editovanja humanog genoma primenom tehnologije CRISPR/Cas9

Discovery of CRISPR/Cas9 technology produced a revolution in human medicine, because of the availability, efficiency and low cost, which has raised a number of questions. Given that by applying CRISPR/Cas9 technology we can program our future children and extend their life expectancy, question is whether we should allow it. The point of the paper is to determine the limits of legal admissibility and ethical justification of this procedure, considering contemporary legal theoretical views, ethical values and social significance. Using normative, comparative and sociological method the authors analyze the impact of biotechnology development, in the context of genetic interventions, on redefining the regulatory framework. Critical consideration in the context of legal standardization of human genetic interventions and meeting the interests of all participants, has been identified as a core subject of research, which will be considered in accordance with a holistic approach to the realization of human rights.

Apoptosis and Efferocytosis in Inflammatory Diseases

BACKGROUND: Millions of cells in multicellular organisms regenerate every day to replace aged and died cells. Effective cell clearance (efferocytosis) is critical for tissue homeostasis, as the human body recycles its cellular components. We summarize what is known about the mechanisms of efferocytosis and how it impacts the physiology of the organism, effects on inflammation and the adaptive immune response, as well as the consequences of defects in this critical homeostatic mechanism in this review.CONTENT: Cell death is the process by which the human body replaces aged or damaged cells with new ones. It can be triggered by genetically encoded machinery or regulated cell death, or by specific pharmacologic or genetic interventions, resulting in accidental cell death. Dying cells release signals that entice phagocytes to engulf them in a process known as efferocytosis. Efferocytosis is a multistep process involving the release of “find me” and “eat me” signals and destruction of death cells by phagocytes. Different types of cell death including apoptosis and necroptosis can express pro- or anti-inflammatory signals via macrophage activity modulation.SUMMARY: Failed or ineffective efferocytosis can result in disruption of tissue homeostasis, which can contribute to the development of chronic inflammatory diseases such as atherosclerosis, obesity, diabetes, and heart failure. Therefore, any therapeutic strategy that enhances efferocytosis will have a beneficial effect on the treatment of these metabolic disorders.KEYWORDS: apoptosis, necroptosis, phagocytosis, efferocytosis, macrophage.

GRP78 Overexpression Triggers PINK1-IP3R-Mediated Neuroprotective Mitophagy

An experimental model of spinal root avulsion (RA) is useful to study causal molecular programs that drive retrograde neurodegeneration after neuron-target disconnection. This neurodegenerative process shares common characteristics with neuronal disease-related processes such as the presence of endoplasmic reticulum (ER) stress and autophagy flux blockage. We previously found that the overexpression of GRP78 promoted motoneuronal neuroprotection after RA. After that, we aimed to unravel the underlying mechanism by carrying out a comparative unbiased proteomic analysis and pharmacological and genetic interventions. Unexpectedly, mitochondrial factors turned out to be most altered when GRP78 was overexpressed, and the abundance of engulfed mitochondria, a hallmark of mitophagy, was also observed by electronic microscopy in RA-injured motoneurons after GRP78 overexpression. In addition, GRP78 overexpression increased LC3-mitochondria tagging, promoted PINK1 translocation, mitophagy induction, and recovered mitochondrial function in ER-stressed cells. Lastly, we found that GRP78-promoted pro-survival mitophagy was mediated by PINK1 and IP3R in our in vitro model of motoneuronal death. This data indicates a novel relationship between the GRP78 chaperone and mitophagy, opening novel therapeutical options for drug design to achieve neuroprotection.

SOCIOSCIENTIFIC ISSUES AND PRE-SERVICE SCIENCE TEACHERS’ BIOETHICAL VALUES

Considering the recent rapid developments in science and technology, it is quite important for individuals to be able to make decisions about their own future and their children's future for the society in which they live and to know how to establish a balance of risk and decision. For this reason, teacher training programs should be planned to internalize pre-service teachers' awareness of responsibility. Regarding this point, the development of pre-service science teachers' bioethical values was examined on a class level basis using survey research. Research sample consisted total of 286 pre-service teachers of Science Teacher Training Program. Bioethical Values Questionnaire was applied to determine pre-service teachers’ bioethical values. As a result of analyses, it was determined that pre-service teachers’ bioethical values increased according to their class levels they attended. It was stated that pre-service science teachers’ bioethical values related to sub-dimensions of “Benefits of Biotechnology Applications”, “Science and Ethics”, “Reproductive Technologies and Cloning” and “Control of Genetic Interventions” were increased based on participants’ class levels. In addition, the results of the study revealed that pre-service teachers also had some concerns about the benefits of biotechnology applications. Keywords: bioethics level, science teaching, pre-service science teachers, socio-scientific issues