Human behavioral ecology: II

Human behavioral ecology is an interdisciplinary field of study applying theory from evolutionary ecology to a variety of anthropological questions. In Part I of this essay,¹ which appeared in an earlier issue, I surveyed key theoretical and methodological elements of the field, and summarized representative studies and issues in the topical area of subsistence strategies. In Part II, I turn to studies of reproductive strategies, and those analyzing patterns of cooperation and competition in an ecological and adaptive framework. I conclude with a brief look at possible future developments in the field.     

Staphylococcal nuclease reviewed: A Prototypic study in contemporary enzymology. II. Solution studies of the nucleotide binding site and the effects of nucleotide binding.

Summary This is the second of a series of four articles in which the chemical, enzymological and crystallographic work on Ribonucleate (deoxyribonucleate)-3-nucleotidohydrolase EC 3.1.4.4 (staphylococcal nuclease, micrococcal nuclease) will be reviewed and correlated. This article discusses studies in solution delineating the extent of the binding site of the enzyme and identifying some of the particular amino acid residues that form this site. In addition, the effects of the very potent inhibitory combination of thymidine-3,5-diphosphate and Ca²⁺ on the conformation of the enzyme and its physical, chemical and enzymological properties will be reviewed.This article is the second of a series of four which provide a comprehensive review of the biochemistry of the staphylococcal nuclease. Part I (1) presented the details of its isolation and enzymology. Part III, in the next issue of this journal, will continue with a review of the three-dimensional structure and mechanism of enzyme action. Part IV will discuss polypeptide chain folding. Work from this laboratory has been supported by grants from the National Institute of General Medical Sciences and the Robert A. Welch Foundation to F. A. Cotton and E. E. Hazen, Jr.     

Glucose catabolism during aging and differentiation in hypocotyls ofPhaseolus mungo seedlings

Changes in activities of the glycolytic and pentose phosphate (PP) pathways in glucose catabolism in various parts of the hypocotyls obtained from 4-day-old etiolatedPhaseolus mungo seedlings were investigated by measuring the inhibition rates of respiration by iodoacetate and malonate, and the release of¹⁴CO₂ from [1-¹⁴C]- and [6-¹⁴C]glucose. The relative activity of the PP pathway in glucose catabolism was higher in the immature part (Part I) and the aged part (Part V) of the hypocotyls than in the intermediary one (Part III), while the activity of the glycolytic pathway decreased with aging. On a fresh weight basis, the enzyme activities of the glycolytic and PP pathways were higher in Part I than in Parts III and V. On a protein content basis, however, activities of the enzymes of the PP pathway increased with aging and differentiation of the hypocotyls whereas those of the glycolytic pathway decreased. Levels of nicotinamide adenine nucleotides were found to be in the following order: Part I>Part III> Part V for NAD⁺+NADH; Part I>Part V>Part III for NADP⁺+NADPH. The stimulative effect of methylene blue on decreasing the C₆/C₁ ratio was greater in Part III than in Part I, and No effect was observed in Part V. These data suggest that a decrease in the activity of the glycolytic pathway with aging and differentiation may be due to the decreasing glycolytic enzyme activities and NAD(H) content. The higher activity of the PP pathway in the immature part is attributable to larger amounts of NADP(H) and enzymes of the PP pathway. The greater contribution of the PP pathway to glucose catabolism in the aged part than in the intermediary part seems to results from a more active turnover of NADP and the relatively higher activity of the enzymes of the PP pathway than those of the glycolytic pathway.     

Uncertainty in life cycle costing for long-range infrastructure. Part I: leveling the playing field to address uncertainties

Purpose

Life cycle costing (LCC) is a state-of-the-art method to analyze investment decisions in infrastructure projects. However, uncertainties inherent in long-term planning question the credibility of LCC results. Previous research has not systematically linked sources and methods to address this uncertainty. Part I of this series develops a framework to collect and categorize different sources of uncertainty and addressing methods. This systematization is a prerequisite to further analyze the suitability of methods and levels the playing field for part II.

Methods

Past reviews have dealt with selected issues of uncertainty in LCC. However, none has systematically collected uncertainties and linked methods to address them. No comprehensive categorization has been published to date. Part I addresses these two research gaps by conducting a systematic literature review. In a rigorous four-step approach, we first scrutinized major databases. Second, we performed a practical and methodological screening to identify in total 115 relevant publications, mostly case studies. Third, we applied content analysis using MAXQDA. Fourth, we illustrated results and concluded upon the research gaps.

Results and discussion

We identified 33 sources of uncertainty and 24 addressing methods. Sources of uncertainties were categorized according to (i) its origin, i.e., parameter, model, and scenario uncertainty and (ii) the nature of uncertainty, i.e., aleatoric or epistemic uncertainty. The methods to address uncertainties were classified into deterministic, probabilistic, possibilistic, and other methods. With regard to sources of uncertainties, lack of data and data quality was analyzed most often. Most uncertainties having been discussed were located in the use stage. With regard to methods, sensitivity analyses were applied most widely, while more complex methods such as Bayesian models were used less frequently. Data availability and the individual expertise of LCC practitioner foremost influence the selection of methods.

Conclusions

This article complements existing research by providing a thorough systematization of uncertainties in LCC. However, an unambiguous categorization of uncertainties is difficult and overlapping occurs. Such a systemizing approach is nevertheless necessary for further analyses and levels the playing field for readers not yet familiar with the topic. Part I concludes the following: First, an investigation about which methods are best suited to address a certain type of uncertainty is still outstanding. Second, an analysis of types of uncertainty that have been insufficiently addressed in previous LCC cases is still missing. Part II will focus on these research gaps.

     

Chemical and biological consequences of β-decay

Summary Radioactive decay in a labelled molecule leads to specific chemical and biological consequences which are due to local transmutation effects such as recoil, electronic excitation, build-up of charge states and change of chemical identity, as well as to internal radiolytic effects. In the present paper these effects are reviewed emphasizing the relation of the chemical alterations on a molecular level to the biological manifestation. Potential importance of this type of research for biomedical applications is pointed out. In part 1 we review the underlying physical and chemical principles and consequences of -decay of³H,¹⁴C,³²P,³³P,³⁵S and¹²⁵I for gaseous and simple condensed organic systems. Part 2 which will appear in the next issue will include the discussion of biological effects associated with -decay.     

Deciphering RNA m6A regulation in aging: Perspectives on current advances and future directions

N⁶-methyladenosine (m⁶A) is a dynamic and reversible RNA modification that has emerged as a crucial player in the life cycle of RNA, thus playing a pivotal role in various biological processes. In recent years, the potential involvement of RNA m⁶A modification in aging and age-related diseases has gained increasing attention, making it a promising target for understanding the molecular mechanisms underlying aging and developing new therapeutic strategies. This Perspective article will summarize the current advances in aging-related m⁶A regulation, highlighting the most significant findings and their implications for our understanding of cellular senescence and aging, and the potential for targeting RNA m⁶A regulation as a therapeutic strategy. We will also discuss the limitations and challenges in this field and provide insights into future research directions. By providing a comprehensive overview of the current state of the field, this Perspective article aims to facilitate further advances in our understanding of the molecular mechanisms underlying aging and to identify new therapeutic targets for aging-related diseases.     

Liver bioengineering: From the stage of liver decellularized matrix to the multiple cellular actors and bioreactor special effects

Liver bioengineering has been a field of intense research and popular excitement in the past decades. It experiences great interest since the introduction of whole liver acellular scaffolds generated by perfusion decellularization^1–3. Nevertheless, the different strategies developed so far have failed to generate hepatic tissue in vitro bioequivalent to native liver tissue. Even notable novel strategies that rely on iPSC-derived liver progenitor cells potential to self-organize in association with endothelial cells in hepatic organoids are lacking critical components of the native tissue (e.g., bile ducts, functional vascular network, hepatic microarchitecture, etc)⁴. Hence, it is vital to understand the strengths and short comes of our current strategies in this quest to re-create liver organogenesis in vitro. To shed some light into these issues, this review describes the different actors that play crucial roles in liver organogenesis and highlights the steps still missing to successfully generate whole livers and hepatic organoids in vitro for multiple applications.     

Liver bioengineering

Liver bioengineering has been a field of intense research and popular excitement in the past decades. It experiences great interest since the introduction of whole liver acellular scaffolds generated by perfusion decellularization^1–3. Nevertheless, the different strategies developed so far have failed to generate hepatic tissue in vitro bioequivalent to native liver tissue. Even notable novel strategies that rely on iPSC-derived liver progenitor cells potential to self-organize in association with endothelial cells in hepatic organoids are lacking critical components of the native tissue (e.g., bile ducts, functional vascular network, hepatic microarchitecture, etc)⁴. Hence, it is vital to understand the strengths and short comes of our current strategies in this quest to re-create liver organogenesis in vitro. To shed some light into these issues, this review describes the different actors that play crucial roles in liver organogenesis and highlights the steps still missing to successfully generate whole livers and hepatic organoids in vitro for multiple applications.     

Application of three-dimensional molecular hydrophobicity potential to the analysis of spatial organization of membrane domains in proteins: I. Hydrophobic properties of transmembrane segments of Na+, K+-ATPase

A new computer-aided molecular modeling approach based on the concept of three-dimensional (3D) molecular hydrophobicity potential has been developed to calculate the spatial organization of intramembrane domains in proteins. The method has been tested by calculating the arrangement of membrane-spanning segments in the photoreaction center ofRhodopseudomonas viridis and comparing the results obtained with those derived from the X-ray data. We have applied this computational procedure to the analysis of interhelical packing in membrane moiety of Na⁺, K⁺-ATPase. The work consists of three parts. In Part I, 3D distributions of electrostatic and molecular hydrophobicity potentials on the surfaces of transmembrane helical peptides were computed and visualized. The hydrophobic and electrostatic properties of helices are discussed from the point of view of their possible arrangement within the protein molecule. Interlocation of helical segments connected with short extramembrane loops found by means of optimization of their hydrophobic/hydrophilic contacts is considered in Part II. The most probable 3D model of packing of helical peptides in the membrane domain of Na⁺, K⁺-ATPase is discussed in the final part of the work.     

Application of three-dimensional molecular hydrophobicity potential to the analysis of spatial organization of membrane domains in proteins: I. Hydrophobic properties of transmembrane segments of Na+, K+-ATPase

A new computer-aided molecular modeling approach based on the concept of three-dimensional (3D) molecular hydrophobicity potential has been developed to calculate the spatial organization of intramembrane domains in proteins. The method has been tested by calculating the arrangement of membrane-spanning segments in the photoreaction center ofRhodopseudomonas viridis and comparing the results obtained with those derived from the X-ray data. We have applied this computational procedure to the analysis of interhelical packing in membrane moiety of Na⁺, K⁺-ATPase. The work consists of three parts. In Part I, 3D distributions of electrostatic and molecular hydrophobicity potentials on the surfaces of transmembrane helical peptides were computed and visualized. The hydrophobic and electrostatic properties of helices are discussed from the point of view of their possible arrangement within the protein molecule. Interlocation of helical segments connected with short extramembrane loops found by means of optimization of their hydrophobic/hydrophilic contacts is considered in Part II. The most probable 3D model of packing of helical peptides in the membrane domain of Na⁺, K⁺-ATPase is discussed in the final part of the work.     

The Molecular Basis of Voltage-gated Ca2+ Channel Diversity: Is It Time for T?

The existence of diversity in the voltage activated Ca²⁺ channel populations of vertebrate cells has been long recognized. More recently, the molecular cloning of a considerable number of Ca²⁺ channel subunits from cDNA libraries has indicated that the range of possible Ca²⁺ channel phenotypes a cell can express may be even greater than was previously appreciated. A challenge of recent years has been to resolve how the properties of recombinant channels correspond with their counterparts experimentally characterized in native cells. In this short review I will outline the properties of both native and recombinant Ca²⁺ channels, and will then describe the current agreements and controversies concerning their relationships to each other. Received: 14 July 1997/Revised: 4 November 1997     

Student-oriented learning: an inquiry-based developmental biology lecture course

In this junior-level undergraduate course, developmental life cycles exhibited by various organisms are reviewed, with special attention--where relevant--to the human embryo. Morphological features and processes are described and recent insights into the molecular biology of gene expression are discussed. Ways are studied in which model systems, including marine invertebrates, amphibia, fruit flies and other laboratory species are employed to elucidate general principles which apply to fertilization, cleavage, gastrulation and organogenesis. Special attention is given to insights into those topics which will soon be researched with data from the Human Genome Project. The learning experience is divided into three parts: Part I is a in which the Socratic (inquiry) method is employed by the instructor (GMM) to organize a review of classical developmental phenomena; Part II represents an in which students study the details related to the surveys included in Part I as they have been reported in research journals; Part III focuses on a class project--the preparation of a spiral bound on a topic of relevance to human developmental biology (e.g.,Textbook of Embryonal Stem Cells). Student response to the use of the Socratic method increases as the course progresses and represents the most successful aspect of the course.     

Long COVID and its Management

The pandemic of COVID-19 is the biggest public health crisis in 21^st Century. Besides the acute symptoms after infection, patients and society are also being challenged by the long-term health complications associated with COVID-19, commonly known as long COVID. While health professionals work hard to find proper treatments, large amount of knowledge has been accumulated in recent years. In order to deal with long COVID efficiently, it is important for people to keep up with current progresses and take proactive actions on long COVID. For this purpose, this review will first introduce the general background of long COVID, and then discuss its risk factors, diagnostic indicators and management strategies. This review will serve as a useful resource for people to understand and prepare for long COVID that will be with us in the foreseeable future.     

Recent advances in the discovery and development of glyoxalase I inhibitors

Glyoxalase I (GLO1) is a homodimeric Zn²⁺-metalloenzyme that catalyses the transformation of methylglyoxal (MG) to d-lacate through the intermediate S-d-lactoylglutathione. Growing evidence indicates that GLO1 has been identified as a potential target for the treatment cancer and other diseases. Various inhibitors of GLO1 have been discovered or developed over the past several decades including natural or natural product-based inhibitors, GSH-based inhibitors, non-GSH-based inhibitors, etc. The aim of this review is to summarize recent achievements of concerning discovery, design strategies, as well as pharmacological aspects of GLO1 inhibitors with the target of promoting their development toward clinical application.     

131I Radioiodine therapy in Graves’ disease: Us et coutumes,controversies and guidelines

For almost 80 years ¹³¹I radioiodine (RAI) therapy has proven to be an efficient and well-tolerated therapeutic option in patients with Graves’ disease (GD). Along with anti-thyroid drugs (ATD) and thyroidectomy, RAI is one the three major therapeutic tools for this autoimmune disease. The objective of this article is to review how RAI treatment is usually conducted in clinical routine and to discuss the main controversies surrounding this treatment in the light of recent national or international guidelines. This will be an opportunity to discuss the indications and contraindications for this treatment, its advantages and limits, and more generally its practical organization by a specialized team.     

The sarcoplasmic reticulum Ca2+-ATPase

Summary This review summarizes studies on the structural organization of Ca²⁺-ATPase in the sarcoplasmic reticulum membrane in relation to the function of the transport protein. Recent advances in this field have been made by a combination of protein-chemical, ultrastructural, and physicochemical techniques on membraneous and detergent solubilized ATPase. A particular feature of the ATPase (Part I) is the presence of a hydrophilic head, facing the cytoplasm, and a tail inserted in the membrane. In agreement with this view the protein is moderately hydrophobic, compared to many other integral membrane proteins, and the number of traverses of the 115 000 Dalton peptide chain through the lipid may be limited to 3–4.There is increasing evidence (Part II) that the ATPase is self-associated in the membrane in oligomeric form. This appears to be a common feature of many transport proteins. Each ATPase peptide seems to be able to perform the whole catalytic cycle of ATP hydrolysis and Ca²⁺ transport. Protein-protein interactions seem to have a modulatory effect on enzyme activity and to stabilize the enzyme against inactivation.Phospholipids (Part III) are not essential for the expression of enzyme activity which only requires the presence of flexible hydrocarbon chains that can be provided e.g. by polyoxyethylene glycol detergents. Perturbation of the lipid bilayer by the insertion of membrane protein leads to some immobilization of the lipid hydrocarbon chains, but not to the extent envisaged by the annulus hypothesis. Strong immobilization, whenever it occurs, may arise from steric hindrance due to protein-protein contacts. Recent studies suggest that breaks in Arrhenius plots of enzyme activity primarily reflect intrinsic properties of the protein rather than changes in the character of lipid motion as a function of temperature.     

Studies on the phosphate potentials of soils

Summary When a sample of Upper Greensand soil was shaken in dilute solutions of calcium chloride containing orthophosphate, microbial activity was sufficiently stimulated to alter the measured value of Schofield's phosphate potential. The effect was more rapid and more marked for air-dried than for field-moist soils. However, the effect on the potential^SP was not significant during the first 2 to 4 hours of shaking a moist sample, and probably not significant during the first 1/2 to 1 hour of shaking an air-dried sample.It was also shown that the changes in the phosphate potential^SP during the first few hours of shaking an untreated field sample are not due to microbial interference. These changes appear to result from the co-existence, in field soils, of micro-volumes of soil of potential^SP higher and lower than the mean for the soil (Part I, and Part III, in preparation).     

Staphylococcal nuclease reviewed: A prototypic study in contemporary enzymology. I isolation; physical and enzymatic properties

Summary This is the first of a series of four articles in which the chemical, enzymological, and crystallographic work on Ribonucleate (deoxyribonucleate)-3-nucleotidohydrolase, EC 3.1.4.7, (Staphylococcal nuclease, Micrococcal nuclease) will be reviewed and correlated. This article discusses the purification of the enzyme and its general physical and enzymological properties. Subsequent articles will deal with specific studies of the nucleotide binding site, crystallographic studies of a nuclease-inhibitor complex, use of the nuclease as a model for protein folding and possible mechanisms for the action of the enzyme.This article is the first in a series of four parts. Part II will discuss chemical and physical studies related specifically to the nucleotide binding site. Part III will review the crystallographic studies as well as presenting a rational mechanism for the nuclease's mode of action. Part IV will deal with the use of the enzyme as a model for protein folding. Parts II–IV will appear in subsequent issues. The work from this laboratory has been supported by grants from the National Institute of General Medical Sciences, N. I. H. and the Robert A. Welch Foundation io F. A. COTTON and from the Welch Foundation to E. E. HAZEN, Jr.