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Unmanned aerial vehicles are poised to take off as popular tools for scientific research.

Liver transplantation has progressed from an experimental procedure to routine operation since the first human liver transplantation in 1963. This Timeline article revisits the important milestones in the development of liver transplantation, discussing how the procedure has evolved over time and what challenges are still to overcome.

Maintaining steroid-free remission in children with idiopathic nephrotic syndrome is an important goal of therapy. A new trial provides evidence that mycophenolate mofetil can be added to the list of effective steroid-sparing agents. The majority of participants relapsed, however, highlighting an unmet need for more effective treatment modalities.

A recent study reports that the global prevalence of paediatric obesity increased to >5% between 1975 and 2016. This increase occurred even as the prevalence of paediatric underweight decreased slightly but remained >8%. These average prevalence changes blur the remarkable regional variations in how prevalence has changed. There is a pressing need to address both underweight and obesity worldwide.

Studies published in 2016 provide insights that bring us closer to achieving the goal of personalized therapy for primary glomerular diseases. Moreover, promising renal outcome data with new classes of glucose-lowering agents — SGLT2 inhibitors and GLP-1 agonists — offer new hope for patients with diabetic nephropathy.

The goal of management for both type 1 and type 2 diabetes is the maintenance of blood glucose levels within healthy normoglycaemic ranges. However, safely achieving this goal using current therapeutic approaches has proved challenging. Here, Langer and colleagues review the developing role of nanotechnology in diabetes management, from diagnosis and disease monitoring to therapeutics.

Planctomycetes are bacteria that lack peptidoglycan in their cell walls and possess membrane-bound intracellular compartments, some of which may be analogous to the nucleus and the mitochondria of eukaryotes. Here, Fuerst and Sagulenko summarize recent progress in planctomycete cell biology and its implications for our understanding of the origin of eukaryotes.

Brain metastasis is an important complication associated with a number of common primary cancers, including lung and breast cancers, and melanoma, and has major effects on patient morbidity and mortality. This Review discusses the advances in our understanding of the molecular biology of brain metastases, and how this knowledge has influenced the imaging, surgical, radiological and pharmaceutical approaches involved in the management of brain metastasis.

In this Review, Weiser and colleagues outline a number of parameters for evaluating the quality of surgical care and explore some systems-based interventions that aim to improve teamwork, communication, and the evaluation of safety and outcomes, with particular focus on urological procedures.

MHC class II molecules are important factors that contribute to the susceptibility of an individual to autoimmune disease. Jones and colleagues look for clues to their involvement in disease by analysing crystal structures of peptide–MHC-class II complexes.

Biomaterials can be used as a scaffold for regenerative stem cells to regrow the urinary bladder after resection for cancer treatment. Such engineered tissues show promise in urologic tissue regeneration, but are faced with a number of challenges. In this Review, the authors discuss these challenges and the potential of various cell sources for use in bladder regeneration.

In this Viewpoint article, we asked four scientists working to target important, but so-called 'undruggable', proteins in cancer for their opinions on the most crucial advances, as well as the challenges and what the future holds for this important area of cancer research.

In this Review, Vaegler and colleagues provide an overview of the use of stem cell therapy for voiding dysfunction and ED. Stem cell sources and isolation techniques are considered, and the authors discuss major clinical studies, as well as preclinical animal studies, that illustrate potential mechanisms of action for this therapeutic approach.

The pathological underpinnings of Alzheimer disease (AD) are now known to begin up to two decades before manifestation of clinical disease, and intervention during preclinical AD stages is increasingly recognized as key to therapeutic success. Here, Eric Reiman and colleagues discuss strategies to study changes in the brain and bodily fluids that precede clinical AD, focusing in particular on genetic at-risk individuals, who might be suitable candidates for secondary prevention trials.

The intricacies of the structure and function of eosinophils are emerging within the context of eosinophilic diseases, in particular vasculitis. In this Review, the authors describe what is known about the biology of eosinophils and their potential to cause tissue and organ damage, with a focus on the role of these cells in eosinophilic granulomatosis with polyangiitis.

Accurate diagnosis and staging of NAFLD is of utmost prognostic importance. The gold standard for diagnosis is histological examination, but growing interest exists in novel noninvasive methods to evaluate NAFLD. This Review describes the advantages and limitations of noninvasive methods for the diagnosis and quantification of steatosis, diagnosis of NASH and staging of hepatic fibrosis in NAFLD.

Minimal change disease and idiopathic focal segmental glomerulosclerosis are often described as separate disease entities. Here, the authors propose that they are in fact different manifestations of the same disease process and review the evidence that led to this hypothesis.

Several studies have demonstrated that reactivation of telomerase in the presence of short telomeres is one of the most common features of human cancers. This Review focuses on the alterations of the telomerase complex that are associated with cancers of the endocrine system, particularly the possible diagnostic, prognostic and therapeutic applications of telomerase.

Although breast density is a powerful factor for predicting the risk of developing breast cancer, unfortunately current methods of measuring mammographic density are not entirely satisfactory. This Review analyzes the different factors affecting breast density and how to consider them so that the accuracy of individual risk assessments can be improved.

In this Review, Myers and McAninch discuss the presentation, assessment and treatment of posterior urethral disruption injuries. Their discussion focuses on the potential benefits of primary urethral realignment, and on the technique and outcomes of posterior urethroplasty.

Thiazide diuretics lower blood pressure and cardiovascular risk but can cause severe hyponatraemia. Researchers now demonstrate that thiazide-induced hyponatraemia is associated with a genetic variant in a distal nephron prostaglandin transporter. They propose that reduced prostaglandin reabsorption through this transporter facilitates activation of the prostaglandin EP4 receptor to increase water reabsorption.

In recent years microbial ecology has experienced a renaissance. In this Essay, a group of leading microbial ecologists argue that the key to realizing the full potential of this renaissance lies in theory.

Children with vesicoureteral reflux (VUR), who are already at high risk of renal injury, are at particular risk for bladder and bowel dysfunction (BBD). In this Review, Elder and Diaz describe the association between BBD and VUR, the evaluation for BBD, and its management in children with VUR.

What constitutes a drug target? Imming and colleagues consider this question, and by classifying known drug substances on the basis of the discussed principles, provide an estimation of the total number of current drug targets.

Fibrosis is a common but often debilitating pathological process involved in diseases of different tissues. Here, Macdonald and colleagues describe the common features and pathophysiological processes that lead to fibrosis of different organs, and present a 'fibrosis toolbox': a collection of small molecules that can be used to further dissect the pathogenesis of tissue fibrosis.

Human papillomavirus (HPV)-screening technologies and HPV vaccination are revolutionizing the management of cancers related to this virus, in particular, cervical neoplasms. At present, however, the effectiveness of these modalities is not optimal, owing to the limited scope of HPV-vaccination and cervical screening programmes. In this Perspectives, an international panel of experts describes for the first time a new campaign, termed 'HPV-FASTER', which aims to broaden the use of HPV vaccination coupled with HPV testing to women aged up to 30 years, and in some settings up to 50 years, with the aim of accelerating the reduction in the incidence of HPV infections and cervical cancer. The authors describe the evidence supporting this approach and details on how it might be implemented, discuss the opportunities—particularly in low-resource settings—and challenges associated with the strategy, and highlight key research gaps that need to be addressed in future studies.

This Review outlines the molecular basis of nongenomic mechanisms of thyroid hormone action. Davis and colleagues also discuss the possible physiological or pathophysiological consequences of these actions, as well as the interactions between nongenomic and genomic effects of thyroid hormone.

The pathophysiology of IBD is complex. A number of genetic association studies and findings from research consortia have identified a large number of IBD susceptibility genes. Here, the authors describe available evidence on the genetics of IBD, and how this data can be used to inform our understanding of the disease itself, including insights into the functional consequences and how they provide novel therapeutic targets or disease biomarkers.

Immunosuppressive treatment of patients with idiopathic membranous nephropathy is controversial because of the toxicity of the therapy and the variable natural course of the disease. In this Review, the authors discuss the 2012 Kidney Disease: Improving Global Outcomes guideline for the treatment of patients with idiopathic membranous nephropathy and highlight the remaining areas of uncertainty.

Lesion activity detected on MRI scans has become an accepted surrogate for disease activity in relapsing–remitting multiple sclerosis (MS). Barkhof and colleagues provide key recommendations for efficient use of MRI in clinical trials for relapse-onset MS, including practical issues related to acquisition, analysis and reporting of MRI data, approaches to optimization of trial design, and safety considerations.

Men of African origin are disproportionately affected by prostate cancer; in this Review, McGinley and colleagues discuss the disparities in treatment, the cancer-survivorship experience, and quality-of-life outcomes, as well as aspects that might contribute to these differences including socioeconomic, cultural, and genetic factors.

Over the past few decades, considerable progress has been made in understanding the mechanisms underlying the relapsing–remitting stage of multiple sclerosis (MS), but the disease processes that drive progressive MS remain largely unresolved. In this Review, Lassmann and colleagues explore the current state of knowledge on the pathophysiology of progressive MS, and present a pathogenetic concept for this phase of the disease that involves oxidative stress and mitochondrial injury.

Modern cancer treatment is a complex process that requires the cooperation of individuals with a range of specialties and backgrounds. In this Perspective, a multidisciplinary team of authors propose a conceptual model to improve patient-centered cancer care. This model describes the roles of the active caregivers (for example, physicians), basic supportive caregivers (for example, psychologists) and community support (for example, advocacy groups) in providing the full continuum of the cancer treatment experience.

The large-scale study of protein expression and protein function by using molecular technologies—proteomics—has become increasingly attractive, because the proteome reflects the intrinsic genetic program of the cell and the impact of its immediate environment. This Review describes conventional proteomic technologies currently being used and their limitations, and demonstrates their clinical applicability, with specific reference to published data of relevance to the gastroenterology field.

Aptamers are oligonucleotide sequences that are capable of recognizing target proteins with an affinity and specificity rivalling that of antibodies. In this article, Keefe and colleagues discuss the development, properties and therapeutic potential of aptamers, highlighting those currently in the clinic.

Combining cytotoxic drugs with radiation is aimed at improving survival without compromising quality of life. While the current trend in treating epithelial tumors favors concurrent chemoradiation, future regimens should exploit spatial cooperation and temporal modulation mechanisms to optimize the balance between treatment risks and benefits. The authors of this review propose that effective exploration of novel strategies will require a rigorous scientific and mechanistic framework to best identify and test exploitable mechanisms of drug-radiation interaction.

Time well spent.

Lipopolysaccharide (LPS) from Gram-negative bacteria is a potent activator of the innate immune response. Clare Bryant and colleagues discuss recent exciting data that have revealed the structural basis of the recognition of LPS by the Toll-like receptor 4–MD2 complex.

Important advances in Parkinson disease (PD) in 2015 included a revision of its clinical diagnostic criteria and a proposal for research criteria defining prodromal PD. Research published in the past year has also continued to expand our understanding of the roles of Lewy pathology and α-synuclein in the pathobiology of PD.

Making discoveries is the most important part of being a scientist, and also the most fun. This article provides practical advice to young scientists on choosing a research topic, on designing, performing and interpreting experiments and on maintaining their sanity in the process.

Membrane nanotubes are thin extensions of the plasma membrane that connect cells transiently and might facilitate intercellular communication. Recent studies have revealed considerable heterogeneity in their structure, formation, mode of cargo transport and functional properties, depending on the cell types involved.