Xavier Trepat highlights the first approach to measurement of forces exerted by cells

Dan Mishmar recounts the first studies that used mitochondrial DNA (mtDNA) to trace the origin of humanity to Africa and that connected mtDNA mutations with a human disease.

Hong Zhang highlights the emerging importance of lipid transfer proteins in autophagosome biogenesis.

Marianne Farnebo describes how the application of microscopy techniques has provided valuable information on repeats RNAs.

Cohesin is reported to form DNA loops in interphase chromatin by a mechanism of DNA loop extrusion.

To accommodate daily recurring environmental changes, animals show cyclic variations in behaviour and physiology, which include prominent behavioural states such as sleep–wake cycles but also a host of less conspicuous oscillations in neurological, metabolic, endocrine, cardiovascular and immune functions. Circadian rhythmicity is created endogenously by genetically encoded molecular clocks, whose components cooperate to generate cyclic changes in their own abundance and activity, with a periodicity of about a day. Throughout the body, such molecular clocks convey temporal control to the function of organs and tissues by regulating pertinent downstream programmes. Synchrony between the different circadian oscillators and resonance with the solar day is largely enabled by a neural pacemaker, which is directly responsive to certain environmental cues and able to transmit internal time-of-day representations to the entire body. In this Review, we discuss aspects of the circadian clock in Drosophila melanogaster and mammals, including the components of these molecular oscillators, the function and mechanisms of action of central and peripheral clocks, their synchronization and their relevance to human health.

The Integrator complex fine-tunes mRNA levels in response to stress by attenuating productive transcription elongation

Exciting new discoveries have transformed the view of the lysosome from a static organelle dedicated to the disposal and recycling of cellular waste to a highly dynamic structure that mediates the adaptation of cell metabolism to environmental cues. Lysosome-mediated signalling pathways and transcription programmes are able to sense the status of cellular metabolism and control the switch between anabolism and catabolism by regulating lysosomal biogenesis and autophagy. The lysosome also extensively communicates with other cellular structures by exchanging content and information and by establishing membrane contact sites. It is now clear that lysosome positioning is a dynamically regulated process and a crucial determinant of lysosomal function. Finally, growing evidence indicates that the role of lysosomal dysfunction in human diseases goes beyond rare inherited diseases, such as lysosomal storage disorders, to include common neurodegenerative and metabolic diseases, as well as cancer. Together, these discoveries highlight the lysosome as a regulatory hub for cellular and organismal homeostasis, and an attractive therapeutic target for a broad variety of disease conditions.

Biological information can be shared between cells via extracellular vesicles. However, how cargo carried by extracellular vesicles elicits biological responses remains unresolved. Deciphering the molecular mechanisms that govern packaging and targeted delivery of extracellular vesicle cargo will be required to establish extracellular vesicles as important signalling entities. Stahl and Raposo discuss the emerging paradigm of cell–cell signalling via extracellular vesicles, highlighting key questions that need to be answered to firmly establish extracellular vesicles as important signalling entities.

Epigenetic regulatory enzymes are generally considered innovative targets for cancer therapy and several histone methyltransferase inhibitors are currently being evaluated in phase I and phase II clinical trials. In this commentary, we discuss the need for better functional understanding of histone methyltransferases and especially of their potential non-histone substrates. Rodríguez-Paredes and Lyko argue that non-histone proteins should be considered when assessing cancer drugs that target protein methylation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Early in his career, Gordon Carmichael was inspired by the contradictory conclusions of three articles.

Miguel Beato describes his Eureka moment after reading that ATP is a nuclear hydrotrope.

Ageing is the most important risk factor for the majority of human pathologies. We propose the concept that the advancement of the hallmarks of ageing is dictated by several distinct biological clocks that can be decelerated by the induction of autophagy. This ‘time dilation’ delays the time-dependent manifestation of multiple diseases. Kroemer and Lopez-Otín discuss how the induction of autophagy could slow down human ageing and thus also delay the onset of ageing-associated diseases, by decelerating biological clocks.

Arnaud Echard discusses two studies that uncovered a key role for the ESCRT machinery in cytokinesis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Celebrating the 50th anniversary of the discovery of the different RNA polymerases of eukaryotes with a collection of Reviews on transcription.

Enzyme filaments are defined as reversible, functional, linear self-assemblies of a single type of enzyme. Filamentation has recently emerged as a new mode of enzymatic regulation. In this Comment, we briefly introduce the diversity and functional consequences of enzyme filamentation. Filamentation is a relatively unknown mode of enzyme regulation, which increases functional diversity.

Force-generating motor proteins usually assemble on lipid membranes inside cells. We argue that it is important to consider this membrane as a dynamic entity that responds to cellular and metabolic demands in a manner that harnesses the force from motors to control pathogen degradation, cancer metastasis, lipid homeostasis and possibly other functions relevant to health and physiology. Roop Mallik argues for the importance of considering the impact that membrane lipids have on motors, and the dynamics of the membrane–motor interface, in studies of cytoskeletal motors.

Machine learning is a branch of artificial intelligence (AI) involving computer programs that are able to improve their own performance through experience (training). The diverse applications of new ‘deep learning’ approaches with neural networks are now expanding into the field of biology. But these applications to biological data require more scrutiny and caution to increase the standards of publishing and allow the AI revolution in biology to take off. David Jones discusses problems associated with the application of machine learning to biology and advocates for improving publishing standards in this area through a more thorough reporting on the design of the computational experiments.

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