Rewriting Human History and Empowering Indigenous Communities with Genome Editing Tools.

Appropriate empirical-based evidence and detailed theoretical considerations should be used for evolutionary explanations of phenotypic variation observed in the field of human population genetics (especially Indigenous populations). Investigators within the population genetics community frequently overlook the importance of these criteria when associating observed phenotypic variation with evolutionary explanations. A functional investigation of population-specific variation using cutting-edge genome editing tools has the potential to empower the population genetics community by holding "just-so" evolutionary explanations accountable. Here, we detail currently available precision genome editing tools and methods, with a particular emphasis on base editing, that can be applied to functionally investigate population-specific point mutations. We use the recent identification of thrifty mutations in the CREBRF gene as an example of the current dire need for an alliance between the fields of population genetics and genome editing

Computer simulations explain mutation-induced effects on the DNA editing by adenine base editors.

Adenine base editors, which were developed by engineering a transfer RNA adenosine deaminase enzyme (TadA) into a DNA editing enzyme (TadA*), enable precise modification of A:T to G⋮C base pairs. Here, we use molecular dynamics simulations to uncover the structural and functional roles played by the initial mutations in the onset of the DNA editing activity by TadA*. Atomistic insights reveal that early mutations lead to intricate conformational changes in the structure of TadA*. In particular, the first mutation, Asp108Asn, induces an enhancement in the binding affinity of TadA to DNA. In silico and in vivo reversion analyses verify the importance of this single mutation in imparting functional promiscuity to TadA* and demonstrate that TadA* performs DNA base editing as a monomer rather than a dimer

Selective Cytotoxicity of Rhodium Metalloinsertors in Mismatch Repair-Deficient Cells

Mismatches in DNA occur naturally during replication and as a result of endogenous DNA damaging agents, but the mismatch repair (MMR) pathway acts to correct mismatches before subsequent rounds of replication. Rhodium metalloinsertors bind to DNA mismatches with high affinity and specificity and represent a promising strategy to target mismatches in cells. Here we examine the biological fate of rhodium metalloinsertors bearing dipyridylamine ancillary ligands in cells deficient in MMR versus those that are MMR-proficient. These complexes are shown to exhibit accelerated cellular uptake which permits the observation of various cellular responses, including disruption of the cell cycle, monitored by flow cytometry assays, and induction of necrosis, monitored by dye exclusion and caspase inhibition assays, that occur preferentially in the MMR-deficient cell line. These cellular responses provide insight into the mechanisms underlying the selective activity of this novel class of targeted anticancer agents

American Football Strategy and Tactics

The difficulty in visualization of the game of football has made it problematic to create a football strategy and hard to coordinate it with others as coaching is not modernized. The majority of people do not realize that football is a complex strategic and tactical game. An augmentation of this process, using mixed reality and mobility to improve the experience will show football in a new light to allow for new collaborations and various new plays that will take the game to a whole new level. There is no current solution for the average football coach. Coaches watch a game and work on their game strategy with whiteboards or tablets, but it can be hard to visualize the game of war happening behind the scenes between the teams of coaches and coordinators on both teams beyond the individual players

The economic dimension of space

Purpose: The main purpose of this study is to identify and analyze the impact of economic space diversity on economic development processes. Design/Methodology/Approach: The paper uses the method of literature studies. The data underwent quantitative analysis with the use of descriptive and parametric (r-Pearson correlation index) statistics. The study analysed the structure, dynamics and intensity indices, as well as the r-Pearson correlation index. Findings: The paper identifies the features of space (i.e. limitation, resistance and diversification). Space can influence development processes by influencing sales revenues and production costs of enterprises. Space is created by places of varied value for people, therefore the economy develops unevenly in space. Practical Implications: The results of the research can be used by decision-makers to shape public aid instruments. The results of the conducted research indicate that in the next programming period there will be a further reduction in the maximum intensity of regional investment aid for Polish regions, which creates the need to seek new development impulses. Originality/Value: The paper shows the simultaneous existence of two processes, i.e. narrowing of the development gap between Polish and EU regions and deepening of regional development disparities in Poland. There is no consensus in the literature on the existence and nature of a link between public aid and economic development processes. This study shows that other factors had a stronger impact on the pace of regional development in Poland than the maximum regional aid intensity.peer-reviewe

Wpływ działań promocyjnych na zachowania zakupowe młodych konsumentów na rynku żywności

The main objective of this paper was to assess the impact of promotional measures on the buying process of young consumers on selected food products markets. The empirical part was prepared based on surveys, which were conducted in 2016 and involved a group of 486 students using the purposive sampling method. As a result of the conducted surveys, it was determined that the individual types of promotional measures had a different impact on food buyers in terms of their food-buying decisions. The differences, however, were not signifiant. The most important role, in relation to all the studied product groups, was played by price discounts, followed by special offers at the place of sale and recommendations by family and friends.Celem głównym pracy była ocena wpływu działań promocyjnych na kształtowanie się procesu zakupowego młodych konsumentów na rynku wybranych produktów żywnościowych. Część empiryczną opracowano na podstawie badań sondażowych, które zostały przeprowadzone w 2016 roku na grupie 486 studentów przy wykorzystaniu metody doboru celowego. W wyniku przeprowadzonych badań wykazano, że poszczególne rodzaje działań promocyjnych miały dla badanych młodych nabywców żywności zróżnicowane znaczenie w procesie podejmowania decyzji o zakupie żywności, choć różnice te nie były duże. Najistotniejszą rolę w odniesieniu do wszystkich badanych grup produktów miały rabaty cenowe, a w dalszej kolejności promocje handlowe w miejscu sprzedaży, a także rekomendacje rodziny i znajomyc