There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

/pdf/free-radicals-in-the-physiological-control-of-cell-function-g3w3iyr0ph.pdf

Free Radicals in the Physiological Control of Cell Function

Research on fluorescent semiconductor nanocrystals (also known as quantum dots or qdots) has evolved over the past two decades from electronic materials science to biological applications. We review current approaches to the synthesis, solubilization, and functionalization of qdots and their applications to cell and animal biology. Recent examples of their experimental use include the observation of diffusion of individual glycine receptors in living neurons and the identification of lymph nodes in live animals by near-infrared emission during surgery. The new generations of qdots have farreaching potential for the study of intracellular processes at the single-molecule level, high-resolution cellular imaging, long-term in vivo observation of cell trafficking, tumor targeting, and diagnostics.

/pdf/quantum-dots-for-live-cells-in-vivo-imaging-and-diagnostics-3y9ayecoh8.pdf

Quantum Dots for Live Cells, in Vivo Imaging, and Diagnostics

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.

For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.

Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

/pdf/guidelines-for-the-use-and-interpretation-of-assays-for-ijf2t30pbq.pdf

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Suicide substrates for specific target enzymes

In vitro analysis of metabolic pathways is becoming a powerful method for gaining a deeper understanding of nature’s core biochemical transformations. Through the astounding advances in biotechnology, the purification of the enzymatic components of a given metabolic pathway is becoming a tractable problem; such in vitro studies permit scientists to capture the fine details of the mechanisms, kinetics, and identities of organic products of enzymatic reactions. In this review, we describe eleven metabolic pathways that have been the subject of recently reported in vitro reconstitution studies. In addition, we have selected and analyzed a subset of four case studies within these eleven examples that exemplify the remarkable organic chemistry that occurs within biological systems. These examples serves as tangible reminders that nature’s biochemical routes obey the fundamental principles of organic chemistry, as their chemical mechanisms are reminiscent of those occurring in conventional synthetic organic routes. The illustrations of biosynthetic chemistry presented in this review might inspire the development of biomimetic chemistries involving abiotic chemical techniques. 1 	Introduction 2 	Bacterial Metabolites 2.1 	Fatty Acids 2.2 	Farnesene 2.3 	O-Polysaccharides 3 	Plant Metabolites 3.1 	Dhurrin 3.2 	Camalexin 4 	Polyketides and Nonribosomal Peptides 4.1 	Aromatic Polyketides 4.1.1 	Actinorhodin-Derived Polyketides 4.1.2 	Enterocin 4.2 	Fungal Polyketides 4.2.1 	Norsolorinic Acid 4.2.2 	Dihydromonacolin L 4.3 	Assembly Line Polyketides and Nonribosomal Peptides 4.3.1 	6-Deoxyerythronolide B 4.3.2 	Asperlicin 5 	Discussion of Chemical Insights 5.1 	Allylic Carbocation Chemistry Drives Farnesene Synthesis 5.2 	Multifunctional Oxidation Chemistry of Cytochrome P450 Enzymes 5.3 	A Remarkable Favorskiiase Enzyme Within Enterocin Biosynthesis 5.4 	Diels–Alder Chemistry Appears in Biology 6 	Concluding Remarks

In vitro Reconstitution of Metabolic Pathways: Insights into Nature′s Chemical Logic

How Nature Morphs Reptide Scaffolds into Antibiotics

Acetylenic enzyme inactivators, inactivation of gamma-cystathionase, in vitro and in vivo, by propargylglycin, highly spezific enzyme inhibitors, inhibition of plasma amine oxidase

Opportunities for self-determined online professional development (OPD) are emerging, but their potential for increasing adult learners’ agency is not yet fully realised. Faced with the problem of successfully designing a self-determined comprehensive evidence-based online numeracy resource for educators who are often time poor and do not engage with online learning unless they are intrinsically motivated, we engaged in design research to conceptualise the Birth to Level 10 Numeracy Guide for educators and families. The Birth to Level 10 Numeracy Guide fosters educators’ and adult learners’ numeracy capability across numeracy focus areas from birth to level 10 (16-year-olds). This extensive OPD resource incorporates consistent design elements, double-looped learning, nonlinear learning, self-reflection, and metacognition activities to foster educators’ pedagogical content knowledge (PCK) through experiential learning. With a section dedicated to families, the resource provides suggestions and advice to parents and carers on everyday, authentic activities to develop children and young people’s numeracy understandings at home and in the local community. As education systems continue to grapple with the disruption brought about by the COVID-19 pandemic, the Birth to Level 10 Numeracy Guide is a timely, freely accessed, viable, and scalable option for providing low-cost OPD.

/pdf/unleashing-adult-learners-numeracy-agency-through-self-e1612c47.pdf

Christopher T. Walsh

Papers

Suicide substrates for specific target enzymes

In vitro Reconstitution of Metabolic Pathways: Insights into Nature′s Chemical Logic

How Nature Morphs Reptide Scaffolds into Antibiotics

Acetylenic enzyme inactivators, inactivation of gamma-cystathionase, in vitro and in vivo, by propargylglycin, highly spezific enzyme inhibitors, inhibition of plasma amine oxidase

Unleashing Adult Learners’ Numeracy Agency Through Self-Determined Online Professional Development