miRNAs have emerged as critical regulators of biologic processes and important therapeutic targets for numerous diseases. This review focusses on miR‐33 as an example, and describes the obstacles, recent advances and new approaches in the miRNA field.

miRNAs have emerged as critical regulators of biologic processes and important therapeutic targets for numerous diseases. This review focusses on miR‐33 as an example, and describes the obstacles, recent advances and new approaches in the miRNA field.

Malaria and many arboviruses such as Dengue virus, Zika virus, Chikungunya virus, and Ross River virus are persistent and detrimental to the global population. Rapid and accurate diagnosis of these infections in human populations and mosquito vectors is essential for understanding their epidemiology, for prompt treatment, and to improve and guide control and elimination strategies. Raman and infrared spectroscopy are rapid and cost-effective tools that have shown potential as diagnostic and surveillance tools for malaria and arboviruses. This systematic review presents up-to-date research conducted using RS, MIRS, and NIRS for the diagnosis of malaria parasite and arboviruses as well as for the surveillance of malaria and arbovirus vectors.

Mitophagy is an evolutionarily conserved process involving the autophagic targeting and clearance of mitochondria destined for removal. Recent insights into the complex nature of the overlapping pathways regulating mitophagy illustrate mitophagy’s essential role in maintaining the health of the mitochondrial network. In this review, we highlight recent studies that have changed the way mitophagy is understood, from initiation through lysosomal degradation. We outline the numerous mitophagic receptors and triggers, with a focus on basal and physiologically relevant cues, offering insight into why they lead to mitochondrial removal. We also explore how mitophagy maintains mitochondrial homeostasis at the organ and system levels and how a loss of mitophagy may play a role in a diverse group of diseases, including cardiovascular, metabolic, and neurodegenerative diseases. With disrupted mitophagy affecting such a wide array of physiological processes, a deeper understanding of how to modulate mitophagy could provide avenues for numerous therapies.

Biological timekeeping enables the coordination and execution of complex cellular processes such as developmental programs, day/night organismal changes, intercellular signaling, and proliferative safeguards. While these systems are often considered separately owing to a wide variety of mechanisms, time frames, and outputs, all clocks are built by calibrating or delaying the rate of biochemical reactions and processes. In this review, we explore the common themes and core design principles of cellular clocks, giving special consideration to the challenges associated with building timers from biochemical components. We also outline how evolution has coopted time to increase the reliability of a diverse range of biological systems.

Lipid metabolism plays a crucial role in viral infections. Viruses can use the host lipid machinery to support their life cycle and to impair the host immune response. The altered expression of mevalonate pathway-related genes, induced by several viruses, assures survival and spread in host tissue. In some infections, statins, HMG-CoA-reductase inhibitors, reduce cholesterol in the plasma membrane of permissive cells resulting in lower viral titers and failure to internalize the virus. Statins can also counteract viral infections through their immunomodulatory, anti-inflammatory and anti-thrombotic effects. Beyond statins, interfering with the mevalonate pathway could have an adjuvant effect in therapies aimed at mitigating endothelial dysfunction and deregulated inflammation in viral infection.

In this review we depicted the historical and current evidence highlighting how lipid homeostasis and mevalonate pathway targeting represents a valid approach to rapidly neutralize viruses, focusing our attention to their potential use as effective targets to hinder SARS-CoV-2 morbidity and mortality.

Pros and cons of statins and Mevalonate-pathway inhibitors have been also dissected.

Genome-wide association studies (GWASs) have enabled unbiased identification of genetic loci contributing to common complex diseases. Because GWAS loci often harbor many variants and genes, it remains a major challenge to move from GWASs’ statistical associations to the identification of causal variants and genes that underlie these association signals. Researchers have applied many statistical and functional fine-mapping strategies to prioritize genetic variants and genes as potential candidates. There is no gold standard in fine-mapping approaches, but consistent results across different approaches can improve confidence in the fine-mapping findings. Here, we combined text mining with a systematic review and formed a catalog of 85 studies with evidence of fine mapping for at least one autoimmune GWAS locus. Across all fine-mapping studies, we compiled 230 GWAS loci with allelic heterogeneity estimates and predictions of causal variants and trait-relevant genes. These 230 loci included 455 combinations of locus-by-disease association signals with 15 autoimmune diseases. Using these estimates, we assessed the probability of mediating disease risk associations across genes in GWAS loci and identified robust signals of causal disease biology. We predict that this comprehensive catalog of GWAS fine-mapping efforts in autoimmune disease will greatly help distill the plethora of information in the field and inform therapeutic strategies.

This review provides a complete account of the on‐surface spin‐state switching behavior of films of spin‐crossover (SCO) complexes of molecular to multilayer thickness. SCO‐based molecular and thin‐film device architectures fabricated employing vacuum sublimation are also described.

Recently, hitherto elusive acid‐ and base‐free main group carbonyl analogues (R₂E=O) derived from group 13 to 15 elements have been isolated in crystalline form. Their unperturbed nature elicits exciting new chemistry, spanning the vista from classical organic carbonyl‐type reactions to transition metal‐like oxide ion transfer chemistry.

This Review critically discusses recent breakthroughs and future challenges in research on polyoxovanadate energy materials. The use of polyoxovanadates in batteries, redox‐flow batteries, light‐driven catalysis, and electrocatalysis is described together with an outlook on emerging themes and areas of future application.

Recent advances in the delivery of nucleic acid‐based therapeutics and in the development of model systems, as well as safety considerations and regulatory requirements for synthetic oligonucleotide chemistries are discussed in this review on oligonucleotide‐based therapeutics.

Recent advances in the delivery of nucleic acid‐based therapeutics and in the development of model systems, as well as safety considerations and regulatory requirements for synthetic oligonucleotide chemistries are discussed in this review on oligonucleotide‐based therapeutics.

This review by A. Lewis and L. Kats summarizes the recent advances in our understanding of "differentiation therapy". The authors share new developments into non‐genetic heterogeneity, and propose a conceptual framework for therapies that aim to alter cell fate decisions in cancer.

This review by A. Lewis and L. Kats summarizes the recent advances in our understanding of "differentiation therapy". The authors share new developments into non‐genetic heterogeneity, and propose a conceptual framework for therapies that aim to alter cell fate decisions in cancer.

Community-directed distributors (CDDs), sometimes known as community health workers (CHWs), have proved to be critical in the delivery of medicines and other tools for the control of neglected tropical diseases (NTDs), prevention of malaria, and other beneficial health interventions. The distributors are the unsung heroes and heroines without whom the health of hundreds of thousands of communities in rural Africa would be worse than it is today. In this paper, we document more than 2 decades (1997–2019) of the contributions of 146,000 communities and 4.8 million CDDs of medicines for NTDs, unpaid or minimally compensated, some have provided 18 years of uninterrupted service. We report on the burden of work and their perspectives of the challenges involved in mass drug administration (MDA) across 27 countries in sub-Saharan Africa. We suggest that they have not been adequately recognised and that harnessing such community human resources could contribute to improving health system’s responses to the ongoing Coronavirus Disease 2019 (COVID-19) crisis. We recommend policy measures for a wider application of existing networks of CDDs by countries’ health systems to consolidate and accelerate the achievements made as well as for the attainment of the goals set forth in the newly developed World Health Organization (WHO) NTD Roadmap.

Chikungunya and Zika are 2 mosquito-borne viral diseases that can cause both acute symptoms and long-term, debilitating complications in infected individuals. Chikungunya is best known as a cause of persistent arthritis in otherwise recovered patients and Zika as a cause of cognitive, motor, and sensory anomalies in newborn children. Both diseases emerged in the Americas within the last decade and have since spread rapidly throughout the region. Despite their widespread transmission there and throughout much of the world, chikungunya and Zika remain neglected diseases. One of the most significant obstacles to address their spread is a lack of data involving their burden. We searched the published literature and surveillance reports to collect information about the incidence, mortality, and morbidity associated with each of these diseases to estimate their regional and global burden during the last decade. Our estimates confirm that chikungunya and Zika caused substantial burden throughout this time frame and place them among the most problematic mosquito-borne viral diseases worldwide. We found that the largest proportion of global burden linked to each disease between 2010 and 2019 occurred in the Americas, although this observation is likely due to limited reporting in other regions.

Background

Schistosomiasis is a parasitic disease caused by trematode worms of the genus Schistosoma and belongs to the neglected tropical diseases. The disease has been reported in 78 countries, with around 290.8 million people in need of treatment in 2018. Schistosomiasis is predominantly considered a rural disease with a subsequent focus of research and control activities in rural settings. Over the past decades, occurrence and even expansion of schistosomiasis foci in peri-urban and urban settings have increasingly been observed. Rural–urban migration in low- and middle-income countries and subsequent rapid and unplanned urbanization are thought to explain these observations. Fifty-five percent (55%) of the world population is already estimated to live in urban areas, with a projected increase to 68% by 2050. In light of rapid urbanization and the efforts to control morbidity and ultimately achieve elimination of schistosomiasis, it is important to deepen our understanding of the occurrence, prevalence, and transmission of schistosomiasis in urban and peri-urban settings. A systematic literature review looking at urban and peri-urban schistosomiasis was therefore carried out as a first step to address the research and mapping gap.

Schistosomiasis is an infectious parasitic disease and one of the 20 diseases considered by the World Health Organization as a neglected tropical disease. It is typically associated with poor environmental and sanitary conditions, primarily affecting rural communities. However, with the currently observed rapid urbanization and predicted two-thirds of the world population living in urban areas by 2050, concerns are raised about a spread of schistosomiasis to urban and peri-urban areas. At the same time, there seems to be little knowledge of the extent of schistososomiasis in urban areas. In light of the efforts to control morbidity and ultimately achieve elimination of schistosomiasis as well as reaching Sustainable Development Goals 3 “achieve health for all” and 11 “make human settlements inclusive, safe, resilient, and sustainable,” this systematic literature review was conducted to address the existing research and mapping gaps and to contribute to the understanding of the burden of schistosomiasis in areas that have not, as yet, been the focus of control efforts and mass drug administration programs. The review suggests that rapid and unorganized urbanization and resulting poor living conditions in urban and peri-urban areas may lead to new disease foci and thereby increase the overall disease burden. Research and policy implications are discussed.

Abbreviations: NCDs: non-communicable disease, IBD: inflammatory bowel disease, IL: interleukin, T2D: type 2 diabetes, SCFAs: short-chain fatty acids, HDAC: histone deacetylases, GPCR: G-protein coupled receptors, 5-HT: 5-hydroxytryptamine receptor signaling, DCs: dendritic cells, IECs: intestinal epithelial cells, T-reg: T regulatory cell, NF-κB: nuclear factor κB, TNF-α: tumor necrosis factor alpha, Th: T helper cell, CNS: central nervous system, ECs: enterochromaffin cells, NSAIDs: non-steroidal anti-inflammatory drugs, AhR: aryl hydrocarbon receptor, IDO: indoleamine 2,3-dioxygenase, QUIN: quinolinic acid, PC: phosphatidylcholine, TMA: trimethylamine, TMAO: trimethylamine N-oxide, CVD: cardiovascular disease, NASH: nonalcoholic steatohepatitis, BAs: bile acids, FXR: farnesoid X receptor, CDCA: chenodeoxycholic acid, DCA: deoxycholic acid, LCA: lithocholic acid, UDCA: ursodeoxycholic acid, CB: cannabinoid receptor, COBRA: constraint-based reconstruction and analysis

Abbreviations: NCDs: non-communicable disease, IBD: inflammatory bowel disease, IL: interleukin, T2D: type 2 diabetes, SCFAs: short-chain fatty acids, HDAC: histone deacetylases, GPCR: G-protein coupled receptors, 5-HT: 5-hydroxytryptamine receptor signaling, DCs: dendritic cells, IECs: intestinal epithelial cells, T-reg: T regulatory cell, NF-κB: nuclear factor κB, TNF-α: tumor necrosis factor alpha, Th: T helper cell, CNS: central nervous system, ECs: enterochromaffin cells, NSAIDs: non-steroidal anti-inflammatory drugs, AhR: aryl hydrocarbon receptor, IDO: indoleamine 2,3-dioxygenase, QUIN: quinolinic acid, PC: phosphatidylcholine, TMA: trimethylamine, TMAO: trimethylamine N-oxide, CVD: cardiovascular disease, NASH: nonalcoholic steatohepatitis, BAs: bile acids, FXR: farnesoid X receptor, CDCA: chenodeoxycholic acid, DCA: deoxycholic acid, LCA: lithocholic acid, UDCA: ursodeoxycholic acid, CB: cannabinoid receptor, COBRA: constraint-based reconstruction and analysis

Which C−H bond? The iridium‐catalysed C−H borylation reaction is a powerful method for the preparation of aromatic organoboronate esters. Sterically regulated regioselectivity dominates carbocyclic aromatic C−H borylation. In contrast, heterocyclic aromatics display a much greater influence from electronic effects. In this review, examples of heterocyclic C−H borylation are surveyed, and the origins of heterocyclic C−H borylation regioselectivities discussed.

Polyelectrolytes such as DNA or heparin are long linear or branched macromolecules onto which charges are appended. The counterions neutralizing these charges can dissociate in water and this will largely determine the interaction of such polyelectrolytes with biomolecules, particularly with proteins. This Review discusses studies on the interaction of proteins with polyelectrolytes and how this knowledge can be used for medical applications.

Materials that respond to endogenous stimuli are being leveraged to enhance spatiotemporal control in a range of biomedical applications from drug delivery to diagnostic tools. The design of materials that undergo morphological or chemical changes in response to specific biological cues or pathologies will be an important area of research for improving efficacies of existing therapies and imaging agents, while also being promising for developing personalized theranostic systems. Internal stimuli-responsive systems can be engineered across length scales from nanometers to macroscopic and can respond to endogenous signals such as enzymes, pH, glucose, ATP, hypoxia, redox signals, and nucleic acids by incorporating synthetic bio-inspired moieties or natural building blocks. This Review will summarize response mechanisms and fabrication strategies used in internal stimuli-responsive materials with a focus on drug delivery and imaging for a broad range of pathologies, including cancer, diabetes, vascular disorders, inflammation, and microbial infections. We will also discuss observed challenges, future research directions, and clinical translation aspects of these responsive materials.

In the last decade, our understanding of lysosomal storage diseases immensely improved. The current article comprehensively reviews recent advances in lysosomal storage diseases research and therapy development.

In the last decade, our understanding of lysosomal storage diseases immensely improved. The current article comprehensively reviews recent advances in lysosomal storage diseases research and therapy development.

Biocatalysis has developed into a mature technology for chemical and pharmaceutical synthesis as well as other areas where high selectivity and mild reaction conditions are required. This Review highlights recent achievements with a special focus on industrialized applications including the introduction of key performance indicators (KPIs) to judge the efficiency of enzymes.

Chromosome structure and dynamics are essential for life, as the way that our genomes are spatially organized within cells is crucial for gene expression, differentiation, and genome transfer to daughter cells. There is a wide variety of methods available to study chromosomes, ranging from live-cell studies to single-molecule biophysics, which we briefly review. While these technologies have yielded a wealth of data, such studies still leave a significant gap between top-down experiments on live cells and bottom-up in vitro single-molecule studies of DNA–protein interactions. Here, we introduce “genome-in-a-box” (GenBox) as an alternative in vitro approach to build and study chromosomes, which bridges this gap. The concept is to assemble a chromosome from the bottom up by taking deproteinated genome-sized DNA isolated from live cells and subsequently add purified DNA-organizing elements, followed by encapsulation in cell-sized containers using microfluidics. Grounded in the rationale of synthetic cell research, the approach would enable to experimentally study emergent effects at the global genome level that arise from the collective action of local DNA-structuring elements. We review the various DNA-structuring elements present in nature, from nucleoid-associated proteins and SMC complexes to phase separation and macromolecular crowders. Finally, we discuss how GenBox can contribute to several open questions on chromosome structure and dynamics.

Mitochondria, so much more than just being energy factories, also have the capacity to synthesize macromolecules including phospholipids, particularly cardiolipin (CL) and phosphatidylethanolamine (PE). Phospholipids are vital constituents of mitochondrial membranes, impacting the plethora of functions performed by this organelle. Hence, the orchestrated movement of phospholipids to and from the mitochondrion is essential for cellular integrity. In this review, we capture recent advances in the field of mitochondrial phospholipid biosynthesis and trafficking, highlighting the significance of interorganellar communication, intramitochondrial contact sites, and lipid transfer proteins in maintaining membrane homeostasis. We then discuss the physiological functions of CL and PE, specifically how they associate with protein complexes in mitochondrial membranes to support bioenergetics and maintain mitochondrial architecture.

Bacterial pathogens have evolved a repertoire of diverse effector proteins that are secreted or injected into the host cell cytosol, reprogramming the host cell into a more favorable environment. Many of these pathogens possess nuclear-targeted effector proteins (nucleomodulins) that modulate host cell gene expression without altering the cellular genomic sequence. By utilizing nucleomodulins obtained through evolution, pathogens can manipulate host cell gene regulation and alter host immune response to infection. Here, we provide a comprehensive review discussing a diverse array of nucleomodulins that target and modulate the host genome through interference with chromatin dynamics, histone modifications, regulation of transcription, interference of the cell cycle, and regulation of cell signaling pathways for immune response. This unique targeting of host cell gene regulation through bacterial nucleomodulins is an emerging theme and likely the tip of an iceberg regarding host–pathogen interactions at the level of the host command center.

In this review, we examine the current state of nuclear architecture in infectious diseases with an emphasis on chromosomal reorganization. Nuclear architecture plays an important role in regulation of transcription for several pathogens, as well as inflammatory responses in their host. Recent advances in technologies such as Hi-C have allowed in-depth studies of chromosomal reorganization during infectious disease development and provided insights into transcription mechanisms and pathogenicity. In addition, it has been demonstrated that pathogens can also affect/utilize the hosts nuclear architecture. These areas are heavily understudied in pathogens, and we hope this review will provide a comprehensive review on the current state of nuclear architecture in infectious diseases and provide an additional avenue for eradication efforts.

A matter of concentration: The latest ground‐breaking advances and strategies of using concentrated electrolyte for aqueous batteries, are discussed. Emphasis is placed on aqueous batteries for lithium and post‐lithium chemistries, with improved energy density, resulting from the unique properties of salt‐concentrated electrolytes.

This review describes the conserved pathways for mitochondrial degradation via selective autophagy across species, and how multiple mitophagy pathways cooperate to modulate mitochondrial fitness and number in normal or disease physiology.

Liquid–liquid phase separation (LLPS) compartmentalizes and concentrates biomacromolecules into distinct condensates. Liquid-like condensates can transition into gel and solid states, which are essential for fulfilling their different functions. LLPS plays important roles in multiple steps of autophagy, mediating the assembly of autophagosome formation sites, acting as an unconventional modulator of TORC1-mediated autophagy regulation, and triaging protein cargos for degradation. Gel-like, but not solid, protein condensates can trigger formation of surrounding autophagosomal membranes. Stress and pathological conditions cause aberrant phase separation and transition of condensates, which can evade surveillance by the autophagy machinery. Understanding the mechanisms underlying phase separation and transition will provide potential therapeutic targets for protein aggregation diseases.

This Review provides an overview of the field of organic–inorganic nanocomposites with a focus on materials that exhibit a significant degree of electronic coupling across the hybrid interface. The characteristic properties of these nanocomposites pave the way to potential optoelectronic applications in devices which exploit singlet fission, triplet energy harvesting, photon upconversion or hot charge carrier transfer.

Topochemical modifications at the reducing end of nanocellulose are a new trend in cellulose materials research. The chemistry is aldehyde‐specific and exploits the inherent directionality of the chains in the cellulose I crystal bearing aldehyde groups exclusively on one end. This Review discusses challenges related to end‐specific modifications and highlights the opportunities for nanocellulose materials.

Small cell lung cancer (SCLC) is highly metastatic, but rare resections of SCLC tumors and metastases have hampered our understanding of SCLC progression. This review offers a comprehensive overview of recent advances on models and mechanisms of SCLC metastasis.

Background

The possibility that onchocerciasis may cause epilepsy has been suggested for a long time, but thus far, an etiological link has not been universally accepted. The objective of this review is to critically appraise the relationship between Onchocerca volvulus and epilepsy and subsequently apply the Bradford Hill criteria to further evaluate the likelihood of a causal association.

There is growing epidemiological evidence that an infection with Onchocerca volvulus (the parasite causing onchocerciasis or river blindness) can trigger epilepsy, including nodding and Nakalanga syndromes. We studied the association between onchocerciasis and epilepsy using previously proposed criteria for causality and found strong arguments in favor of a causal relationship. The risk for children to develop epilepsy seems to be determined by the O. volvulus microfilarial load. However, the mechanism by which the O. volvulus parasite is able to trigger seizures remains to be elucidated. This form of epilepsy, called onchocerciasis-associated epilepsy (OAE), is an important public health problem in onchocerciasis-endemic regions with nonexistent or suboptimal onchocerciasis elimination programs. OAE is often characterized by sudden seizure onset in previously healthy children, between 3 to 18 years, without any other obvious cause of epilepsy. On the basis of the findings presented in this paper, it appears that onchocerciasis control may be able to prevent OAE. This further highlights the importance to eliminate onchocerciasis, particularly in areas with a high burden of epilepsy.

Abbreviations: 3-MA: 3-methyladenine (autophagy inhibitor); AKT/protein kinase B: AKT serine/threonine kinase; ATG: autophagy related; ATPase: adenosine triphosphatase; BMM: bone marrow macrophage; CGAS: cyclic GMP-AMP synthase; CHO: Chinese hamster ovary/cell line; CoV: coronaviruses; COVID-19: Coronavirus disease 2019; DMV: double-membrane vesicle; EAV: equine arteritis virus; EDEM1: ER degradation enhancing alpha-mannosidase like protein 1; ER: endoplasmic reticulum; ERAD: ER-associated degradation; GFP: green fluorescent protein; HCoV: human coronavirus; HIV: human immunodeficiency virus; HSV: herpes simplex virus; IBV: infectious bronchitis virus; IFN: interferon; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCoV: mouse coronavirus; MERS-CoV: Middle East respiratory syndrome coronavirus; MHV: mouse hepatitis virus; NBR1: NBR1 autophagy cargo receptor; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2 (autophagy receptor that directs cargo to phagophores); nsp: non-structural protein; OS9: OS9 endoplasmic reticulum lectin; PEDV: porcine epidemic diarrhea virus; PtdIns3K: class III phosphatidylinositol 3-kinase; PLP: papain-like protease; pMEF: primary mouse embryonic fibroblasts; SARS-CoV: severe acute respiratory syndrome coronavirus; SKP2: S-phase kinase associated protein 2; SQSTM1: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; ULK1: unc-51 like autophagy activating kinase 1; Vps: vacuolar protein sorting

Abbreviations: 3-MA: 3-methyladenine (autophagy inhibitor); AKT/protein kinase B: AKT serine/threonine kinase; ATG: autophagy related; ATPase: adenosine triphosphatase; BMM: bone marrow macrophage; CGAS: cyclic GMP-AMP synthase; CHO: Chinese hamster ovary/cell line; CoV: coronaviruses; COVID-19: Coronavirus disease 2019; DMV: double-membrane vesicle; EAV: equine arteritis virus; EDEM1: ER degradation enhancing alpha-mannosidase like protein 1; ER: endoplasmic reticulum; ERAD: ER-associated degradation; GFP: green fluorescent protein; HCoV: human coronavirus; HIV: human immunodeficiency virus; HSV: herpes simplex virus; IBV: infectious bronchitis virus; IFN: interferon; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCoV: mouse coronavirus; MERS-CoV: Middle East respiratory syndrome coronavirus; MHV: mouse hepatitis virus; NBR1: NBR1 autophagy cargo receptor; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2 (autophagy receptor that directs cargo to phagophores); nsp: non-structural protein; OS9: OS9 endoplasmic reticulum lectin; PEDV: porcine epidemic diarrhea virus; PtdIns3K: class III phosphatidylinositol 3-kinase; PLP: papain-like protease; pMEF: primary mouse embryonic fibroblasts; SARS-CoV: severe acute respiratory syndrome coronavirus; SKP2: S-phase kinase associated protein 2; SQSTM1: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; ULK1: unc-51 like autophagy activating kinase 1; Vps: vacuolar protein sorting

The maintenance of axons for the lifetime of an organism requires an axonal cytoskeleton that is robust but also flexible to adapt to mechanical challenges and to support plastic changes of axon morphology. Furthermore, cytoskeletal organization has to adapt to axons of dramatically different dimensions, and to their compartment-specific requirements in the axon initial segment, in the axon shaft, at synapses or in growth cones. To understand how the cytoskeleton caters to these different demands, this review summarizes five decades of electron microscopic studies. It focuses on the organization of microtubules and neurofilaments in axon shafts in both vertebrate and invertebrate neurons, as well as the axon initial segments of vertebrate motor- and interneurons. Findings from these ultrastructural studies are being interpreted here on the basis of our contemporary molecular understanding. They strongly suggest that axon architecture in animals as diverse as arthropods and vertebrates is dependent on loosely cross-linked bundles of microtubules running all along axons, with only minor roles played by neurofilaments.

Tissue damage triggers a rapid and robust inflammatory response in order to clear and repair a wound. Remarkably, many of the cell biology features that underlie the ability of leukocytes to home in to sites of injury and to fight infection—most of which are topics of intensive current research—were originally observed in various weird and wonderful translucent organisms over a century ago by Elie Metchnikoff, the “father of innate immunity,” who is credited with discovering phagocytes in 1882. In this review, we use Metchnikoff’s seminal lectures as a starting point to discuss the tremendous variety of cell biology features that underpin the function of these multitasking immune cells. Some of these are shared by other cell types (including aspects of motility, membrane trafficking, cell division, and death), but others are more unique features of innate immune cells, enabling them to fulfill their specialized functions, such as encapsulation of invading pathogens, cell–cell fusion in response to foreign bodies, and their self-sacrifice as occurs during NETosis.