An open chat with Koji Yamanaka.

Koji Yamanaka is a Professor at the Research Institute of Environmental Medicine at Nagoya University of Japan. His research interests lie in understanding the mechanism of onset and progression of motor neuron disease as well as the role of glial cells in Alzheimer's disease neuroinflammation. Koji has been serving on the FEBS Open Bio Editorial Board since 2013. In this interview, he explains the implications of recent findings in neurobiology for amyotrophic lateral sclerosis, provides updates on the research environment in Japan and discusses how editors might use their position to positively influence academic culture.

An open chat with Josep Rizo.

Josep Rizo is a Professor of Biophysics, Biochemistry and Pharmacology at the University of Texas Southwestern Medical Center, where he is Virginia Lazenby O'Hara Chair in Biochemistry. He is particularly interested in the study of the mechanisms of neurotransmitter release and intracellular membrane fusion using structural biology, a variety of biophysical techniques and reconstitution approaches. Jose has been a part of the FEBS Open Bio Editorial Board since 2021. In this interview, he shares his insights into developments in the field of neurotransmitter release, describes his move from Spain to the United States, and discusses how sometimes you need to use both logic and scientific hunches.

An open chat with Sandro Sonnino.

Sandro Sonnino is one of the founding members of the Editorial Board of FEBS Open Bio, having joined in 2011. He is also a member of the Editorial Board of FEBS Letters and is the Editor-in-Chief of Glycoconjugate Journal. He is full professor of biochemistry in the School of Medicine at the University of Milan, where he was also formerly coordinator of the Interdisciplinary Laboratory of Advanced Technology (LITA) and Director of the Department of Medical Chemistry, Biochemistry, and Biotechnology. His research is focused on the metabolism and biochemical properties of gangliosides and glycosphingolipids, and their role in cell signaling and the nervous system. He is a guest editor of this special "In the Limelight" issue on glycosphingolipids in disease, which features multiple Reviews and an original research article related to this field. In this interview, Sandro Sonnino discusses the ongoing importance of research on glycosphingolipids and his personal career journey.

An open chat with Simon Rayner.

Simon Rayner joined the FEBS Open Bio Editorial Board in March 2022. Currently, he is Professor of Bioinformatics at Oslo University Hospital and the University of Oslo in Norway. He received a PhD in computational solid-state physics from the University of East Anglia, in 1991, and served as a Lecturer at the Dept of Physics in the University of Texas before working as a Research Fellow at the McDermott Centre for Human Growth and Development, University of Texas Southwestern Medical Centre at Dallas (UTSW). He went on to become Assistant Professor at the Depts of Biochemistry & Internal Medicine, UTSW before co-founding BioAutomation Inc. where he developed DNA & RNA synthesis technology and was involved in the Human Genome Project. Simon is a CAS scholar and has also been a Professor of Bioinformatics at the Chinese Agricultural University in Beijing. Here, he tells us about his multi-disciplinary career transitions, including experience working on three continents, and reflects on implementing open science and fair data.

Sex bias in utero alters ovarian reserve but not uterine capacity in female offspring†.

Environmental stressors to which a fetus is exposed affect a range of physiological functions in postnatal offspring. We aimed to determine the in utero effect of steroid hormones on the reproductive potential of female offspring using a porcine model. Reproductive tracts of pigs from female-biased (>65% female, n = 15), non-biased (45-54.9% female, n = 15), and male-biased litters (<35% females, n = 9) were collected at slaughter (95-115 kg). Ovaries and uterine horns were processed for H&E or immunohistochemistry. Variability of data within groups was analyzed with a Levene's test, while data were analyzed using mixed linear models in R. In the ovarian reserve, there was a significant birth weight by sex ratio interaction (P = 0.015), with low birth weight pigs from male-biased litters having higher numbers of primordial follicles with opposite trends seen in pigs from female-biased litters. Sex bias held no effect on endometrial gland development. A lower birth weight decreased the proportion of glands found in the endometrium (P = 0.045) and was more variable in both male-biased and female-biased litters (P = 0.026). The variability of primordial follicles from male-biased litters was greater than non- and female-biased litters (P = 0.014). Similarly, endometrial stromal nuclei had a greater range in male- and female-biased litters than non-biased litters (P = 0.028). A crucial finding was the greater variability in primordial follicles in the ovaries from females derived from male-biased litters and stromal cell count in the endometrium of females from male- and female-biased litters. This could be inflating the variability of reproductive success seen in females from male-biased litters.

An open chat with Alexander Wlodawer.

Alexander Wlodawer has been a member of the FEBS Open Bio Editorial Board since the journal's launch in 2011. Currently, he is Senior Investigator at the Center for Structural Biology, National Cancer Institute in Frederick, Maryland, USA. He received his Ph.D. from the University of California, Los Angeles in 1974, completed postdoctoral training at Stanford University and has also worked at the National Bureau of Standards, the ABL-Basic Research Program at the NCI-FCRDC and the University of Cambridge, UK. He is Doctor Honoris Causa of the Technical University of Lodz, Poland. Alexander Wlodawer is also a recipient of the 2006 NCI Mentor of Merit Award, was awarded the Heyrovsky Honorary Medal by the Czech Academy of Sciences in 2008, was elected Foreign Member of the Polish Academy of Sciences in 2005, and has been member of the Editorial Board of The FEBS Journal since 2007. He is currently Editor-in-Chief of the journal Current Research in Structural Biology. In this compelling interview, he shares with us his experiences on solving the structures of IL-4 and retroviral proteases, advice on how to deal with being scooped, and his thoughts on open data sharing and AlphaFold.

Outlook of women in science: an interview with our authors.

Diversity in research teams ties alternative perspectives into research projects, and this can fast-forward scientific progress. Concerted efforts have been aimed at encouraging and supporting women to pursue a career in science, yet a gender disparity can still be observed at senior positions, with fewer women in leadership roles. To get insight into how the current landscape for women in science is perceived by different career stages, we interviewed female authors of Molecular Oncology from diverse career stages and disciplines about their inspiration, challenges they have faced as scientists as well as their thoughts on how gender diversity can be further enhanced.

Safeguarding cancer research funding by European charities amidst the COVID-19 pandemic.

The COVID-19 outbreak has affected cancer research and cancer care. European cancer charities need to reconsider strategies for safeguarding income and supporting cancer researchers, in times when sustaining cancer research funding is more crucial than ever.

Long non-coding RNAs in development and disease: conservation to mechanisms.

Our genomes contain the blueprint of what makes us human and many indications as to why we develop disease. Until the last 10 years, most studies had focussed on protein-coding genes, more specifically DNA sequences coding for proteins. However, this represents less than 5% of our genomes. The other 95% is referred to as the 'dark matter' of our genomes, our understanding of which is extremely limited. Part of this 'dark matter' includes regions that give rise to RNAs that do not code for proteins. A subset of these non-coding RNAs are long non-coding RNAs (lncRNAs), which in particular are beginning to be dissected and their importance to human health revealed. To improve our understanding and treatment of disease it is vital that we understand the molecular and cellular function of lncRNAs, and how their misregulation can contribute to disease. It is not yet clear what proportion of lncRNAs is actually functional; conservation during evolution is being used to understand the biological importance of lncRNA. Here, we present key themes within the field of lncRNAs, emphasising the importance of their roles in both the nucleus and the cytoplasm of cells, as well as patterns in their modes of action. We discuss their potential functions in development and disease using examples where we have the greatest understanding. Finally, we emphasise why lncRNAs can serve as biomarkers and discuss their emerging potential for therapy. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

C9orf72 expansion disrupts ATM-mediated chromosomal break repair.

Hexanucleotide repeat expansions represent the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, though the mechanisms by which such expansions cause neurodegeneration are poorly understood. We report elevated levels of DNA-RNA hybrids (R-loops) and double strand breaks in rat neurons, human cells and C9orf72 ALS patient spinal cord tissues. Accumulation of endogenous DNA damage is concomitant with defective ATM-mediated DNA repair signaling and accumulation of protein-linked DNA breaks. We reveal that defective ATM-mediated DNA repair is a consequence of P62 accumulation, which impairs H2A ubiquitylation and perturbs ATM signaling. Virus-mediated expression of C9orf72-related RNA and dipeptide repeats in the mouse central nervous system increases double strand breaks and ATM defects and triggers neurodegeneration. These findings identify R-loops, double strand breaks and defective ATM-mediated repair as pathological consequences of C9orf72 expansions and suggest that C9orf72-linked neurodegeneration is driven at least partly by genomic instability.