Substrate Specificity for Human Histidine Methyltransferase SETD3

Histidine methyltransferase SETD3 plays an important role in human biology and diseases. Previously, we showed that SETD3 catalyzes N3-methylation of histidine 73 in β-actin (Kwiatkowski et al., 2018). Here we report integrated synthetic, biocatalytic, biostructural and computational analyses on human SETD3-catalyzed methylation of β-actin peptides possessing histidine and its structurally and chemically diverse mimics. Our enzyme assays supported by biostructural analyses demonstrate that SETD3 has a broader substrate scope beyond histidine, including N-nucleophiles on the aromatic and aliphatic side chains. Quantum mechanical/molecular mechanical (QM/MM) molecular dynamics and free-energy simulations provide insight into binding geometries and the free energy barrier for the enzymatic methyl transfer to histidine mimics, further supporting experimental data that histidine is the superior SETD3 substrate over its analogs. This work demonstrates that human SETD3 has a potential to catalyze efficient methylation of several histidine mimics, overall providing mechanistic, biocatalytic and functional insight into β-actin histidine methylation by SETD3.

The Role of Methyl Donors of the Methionine Cycle in Gastrointestinal Infection and Inflammation

Vitamin deficiency is well known to contribute to disease development in both humans and other animals. Nonetheless, truly understanding the role of vitamins in human biology requires more than identifying their deficiencies. Discerning the mechanisms by which vitamins participate in health is necessary to assess risk factors, diagnostics, and treatment options for deficiency in a clinical setting. For researchers, the absence of a vitamin may be used as a tool to understand the importance of the metabolic pathways in which it participates. This review aims to explore the current understanding of the complex relationship between the methyl donating vitamins folate and cobalamin (B12), the universal methyl donor S-adenosyl-L-methionine (SAM), and inflammatory processes in human disease. First, it outlines the process of single-carbon metabolism in the generation of first methionine and subsequently SAM. Following this, established relationships between folate, B12, and SAM in varying bodily tissues are discussed, with special attention given to their effects on gut inflammation.

Introduction

The introductory chapter sets forth the book’s central argument that the struggle over inequality has been the underlying force driving the unfolding of all human history. This struggle underlies the other presumed primary drivers of history such as technological advances, demographics, group conflict, war, religion, or great men. Three key supporting claims are briefly explored. First, the ultimate driving force for inequality is found in human biology, the fact that the decisive competition that counts for sexually reproducing animal species is success in mating and thereby sending one’s unique set of genes into future generations. Second, because of sexual selection and because humans are social beings, inequality underlies all politics. Third, although physical violence always remains the trump card in creating, maintaining, or increasing inequality, ideology has always been, day to day, the most important inequality-sustaining political weapon. How the book will unfold is then set forth.

Shame

Reliance on mutual aid is a distinctive characteristic of human biology. Consequently, a central adaptive problem for our ancestors was the potential or actual spread of reputationally damaging information about the self – information that would decrease the inclination of other group members to render assistance. The emotion of shame appears to be the solution engineered by natural selection to defend against this threat. The existing evidence suggests that shame is a neurocomputational program that orchestrates various elements of the cognitive architecture in the service of (i) deterring the individual from making choices wherein the personal benefits are exceeded by the prospective costs of being devalued by others, (ii) preventing negative information about the self from reaching others, and (iii) minimizing the adverse effects of social devaluation when it occurs. The flow of costs (e.g., punishment) and benefits (e.g., income, aid during times of hardship) in human societies is regulated to an important extent by this interlinked psychology of social evaluation and shame (as well as other social emotions). For example, the intensity of shame that laypeople express at the prospect of committing each of various offenses closely matches the intensity of the actual offense-specific punishments called for by criminal laws, including modern laws and ancient laws that are millennia old. Because shame, like pain, causes personal suffering and sometimes leads to hostile behavior, shame has been termed a “maladaptive” and “ugly” emotion. However, an evolutionary psychological analysis suggests that the shame system is elegantly designed to deter injurious choices and make the best of a bad situation.

Analisis Soal Computer Based Test untuk Tes Potensi Akademik dan Biologi Manusia

Education providers, one of which is a private university in Bandung, conducts entrance exams for student participants through a computer-based test system. In the entrance examination, which is carried out is a test of academic potential and human biology. Every question that belongs to both the TPA and human biology questions is stored in the university's computer-based test system. The saved questions can be used at any time, during the entrance examination period. The stored questions need to be analyzed and reviewed, with the aim that the questions can be used properly and can maintain the quality of the questions given to each examinee. In this study, an analysis of the level of difficulty and effectiveness of the distractor will be carried out. This analysis is carried out using data from 2018 to 2020 stored in the system.

“What the One Thing Shows Me in the Case of Two Things”: Comparison as Essential to a Proper Academic Study of Religion

Comparison is a fundamental operation in the milieu of the remarkable abilities of human beings to transcend themselves in acts of perception and the accumulation of knowledge. Comparison is holding together things that are at once the same and different. The very possibility of the copresence of same and different, of is and is not, is a gift of human biology and evolution. Humans compare because it is our distinctive nature to do so. Academics have the added responsibility of being self-aware, self-reflective, and articulate when comparing. This article develops a rich theory of comparison in conjunction with detailed reflections on late nineteenth century encounters of European-Australians and Aborigines in Central Australia. The intent is to advance our understanding of comparison and also to articulate in the practical terms of method what is involved in comparison, arguing most generally that comparison is of the fabric of any proper study of religion.

OMAMO: orthology-based model organism selection

The conservation of pathways and genes across species has allowed scientists to use non-human model organisms to gain a deeper understanding of human biology. However, the use of traditional model systems such as mice, rats, and zebrafish is costly, time-consuming and increasingly raises ethical concerns, which highlights the need to search for less complex model organisms. Existing tools only focus on the few well-studied model systems, most of which are higher animals. To address these issues, we have developed Orthologous Matrix and Model Organisms, a software and a website that provide the user with the best simple organism for research into a biological process of interest based on orthologous relationships between the human and the species. The outputs provided by the database were supported by a systematic literature review.