Editorial: Honouring John Hardy - A true pioneer in research.

This Editorial highlights the knighthood recognition of Sir John Hardy, Professor and Chair at the University College London, for his exceptional services to human health and dementia research. We also celebrate his successful trajectory in neurochemistry and neurogenetics, and acknowledge his long-standing contributions to the Journal of Neurochemistry as an author and editor. John Hardy's research identified key mutations linked to prevalent neurodegenerative diseases in humans and contributed to our understanding of the molecular pathogenesis of Alzheimer disease. As John's career has inspired many generations of researchers in neurochemistry, we present a brief Q&A interview with him on the occasion of his most recent recognition.

Preface to an editorial controversy on α-synuclein: How good are cellular models?: This is a Preface for an Editorial controversy between Hilal A. Lashuel "Monitoring alpha-synuclein oligomerization and aggregation using bimolecular fluorescence complementation assays: What you see is not always what you get" and Tiago F. Outeiro "Alpha-synuclein oligomerization and aggregation: A model will always be a model" Read Hilal A. Lashuel's reply "Alpha-Synuclein oligomerization and aggregation: All models are useful but only if we know what they model".

In many scientific disputes, research evidence may support one side or the other of a working hypothesis, and even in case of largely coherent hypotheses, arguments may be in favor of discrepant points of view. In the case of α-synuclein pathology and specific mechanisms of disease progression, various animal and cellular models have been established to pinpoint the physiological and pathological mechanisms. In the present 'Editorial controversy', two well-reputed researchers, Hilal Lashuel and Tiago F. Outeiro, discuss-with view to findings from their own and others' groups in the context of current status of knowledge-the question of how well models on α-synuclein pathology can reflect actual pathomechanisms, and derive recommendations for future research from it that shall help advance our understanding not only of α-synuclein-related pathologies and its role in the formation of Lewy bodies in particular, but of cellular or animal models in general.

How to time the time - A preface to the special issue Circadian Rhythms in the Brain.

In this Preface to the Journal of Neurochemistry special issue "Circadian Rhythms in the Brain", we summarize recent insights into connections between circadian rhythms and societal concerns related to aging and food intake, with consequences for healthy or aberrant metabolic homeostasis. The articles in this special issue were written by leading authors who presented their research at the 2019 Congress of the European Biological Rhythm Society, and are thus reflective of a broad variety of state-of-the-art research on all levels of chronobiology, from circadian rhythm generators in various tissues (including astrocytes) and the molecular mechanisms they base on, such as GABAergic regulation or ubiquitination, to the systems and behavioral level effects of chrono-nutrition and aging. Cover Image for this issue: https://doi.org/10.1111/jnc.15058.

Preface: The energetic brain - a review from students to students.

This Review article 'The energetic brain - A review from students to students' has been written by a group of students following the 14th International Society for Neurochemistry Advanced School held in 2018. Comprehensively written by students for students, it provides both an excellent educational opportunity and a state-of-the-art insight into the field of brain energy metabolism specifically targeted to young researchers, fulfilling an important aspect of the International Society for Neurochemistry's educational mission. The current Review continues a series of similar student-authored articles that Journal of Neurochemistry has published since 2016.

Reviewer selection biases editorial decisions on manuscripts.

Many journals, including the Journal of Neurochemistry, enable authors to list peer reviewers as 'preferred' or 'opposed' suggestions to the editor. At the Journal of Neurochemistry, the handling editor (HE) may follow recommendations or select non-author-suggested reviewers (non-ASRs). We investigated whether selection of author-suggested reviewers (ASRs) influenced decisions on a paper, and whether differences might be related to a reviewer's, editor's or manuscript's geographical location. In this retrospective analysis, we compared original research articles submitted to the Journal of Neurochemistry from 2013 through 2016 that were either reviewed exclusively by non-ASRs, by at least one ASR, by at least one reviewer marked by the author as 'opposed' or none. Manuscript outcome, reviewer rating of manuscript quality, rating of the reviewers' performance by the editor (R-score), time to review, and the country of the editor, reviewers and manuscript author were analyzed using non-parametric rank-based comparisons, chi-square (χ2 ) analysis, multivariate linear regression, one-way analysis of variance, and inter-rater reliability determination. Original research articles that had been reviewed by at least one ASR stood a higher chance of being accepted (525/1006 = 52%) than papers that had been reviewed by non-ASRs only (579/1800 = 32%). An article was 2.4 times more likely to be accepted than rejected by an ASR compared to a non-ASR (Pearson's χ2 (1) = 181.3, p < 0.05). At decision, the editor did not simply follow the reviewers' recommendation but had a balancing role: Rates of recommendation from reviewers for rejection were 11.2% (139/1241) with ASRs versus 29.0% (1379/4755) with non-ASRs (this is a ratio of 0.39 where 1 means no difference between rejection rates for both groups), whereas the proportion of final decisions to reject was 24.7% (248/1006) versus 45.7% (822/1800) (a ratio of 0.54, considerably closer to 1). Recommendations by non-ASRs were more favorable for manuscripts from USA/Canada and Europe than for Asia/Pacific or Other countries. ASRs judged North American manuscripts most favorably, and judged papers generally more positively (mean: 2.54 on a 1-5 scale) than did non-ASRs (mean: 3.16) reviewers, whereas time for review (13.28 vs. 13.20 days) did not differ significantly between these groups. We also found that editors preferably assigned reviewers from their own geographical region, but there was no tendency for reviewers to judge papers from their own region more favorably. Our findings strongly confirm a bias toward lower rejection rates when ASRs assess a paper, which led to the decision to abandon the option to recommend reviewers at the Journal of Neurochemistry. Open Data: Materials are available on https://osf.io/jshg7/.

The malleable brain - An educational review from students to students.

The Review "The malleable brain: plasticity of neural circuits and behavior - A review from students to students" has been written by a group of students following the International Society for Neurochemistry and Journal of Neurochemistry Flagship School. Comprehensively written by students for students, it provides both an excellent educational opportunity and a state-of-the-art insight into the field of neuronal plasticity specifically targeted to young researchers, and thus fulfills an important aspect of the ISN's educational mission. Read the highlighted article 'The malleable brain: plasticity of neural circuits and behavior - a review from students to students' on page 790.

The challenges for scientific publishing, 60 years on.

The most obvious difference in science publishing between 'then' and 'now' is the dramatic change in the communication of data and in their interpretation. The democratization of science via the Internet has brought not only benefits but also challenges to publishing including fraudulent behavior and plagiarism, data and statistics reporting standards, authorship confirmation and other issues which affect authors, readers, and publishers in different ways. The wide accessibility of data on a global scale permits acquisition and meta-analysis to mine for novel synergies, and has created a highly commercialized environment. As we illustrate here, identifying unacceptable practices leads to changes in the standards for data reporting. In the past decades, science publishing underwent dramatic changes in the communication of data and in their interpretation, in the increasing pressure and commercialization, and the democratization of science on a global scale via the Internet. This article reviews the benefits and challenges to publishing including fraudulent behavior and plagiarism, data and statistics reporting standards, authorship confirmation and other issues, with the aim to provide readers with practical examples and hands-on guidelines. As we illustrate here, identifying unacceptable practices leads to changes in the standards for data reporting. This article is part of the 60th Anniversary special issue.

Synaptopathies: synaptic dysfunction in neurological disorders - A review written by students for students, and a story of success for ISN schools.

One of the major endeavors of the International Society for Neurochemistry (ISN) is the promotion and support of young researchers, for instance at 'schools' that offer young students an opportunity to closely interact with renowned researchers as well as with each other. As a result of the 13th International Society for Neurochemistry Advanced School on 'Synapses' held in Mission Beach, Australia, prior to the Biennial Meeting of the International Society for Neurochemistry in August 2016 in Cairns, we are pleased to publish this comprehensive Review article, written from students for students. Read the highlighted article 'Synaptopathies: synaptic dysfunction in neurological disorders - A review from students to students' on page 785.

The impact of fraudulent and irreproducible data to the translational research crisis - solutions and implementation.

One of the aims of basic neuroscience research is ultimately the development of therapeutics to cure diseases. Funders granting money to research institutions increasingly express interest into how their financial resources are used and look for successful translation in clinical practice. Disappointingly, many findings that started out promising in basic research projects and phase I trials did not live up to the promise of therapeutic efficacy in later phase II or III trials. An inordinately high amount of time and money is thus spent on research that does not always have the required human impact. Potential reasons for these problems are numerous. Although research misconduct occurs and contributes to this shortcoming, it is not the only important factor. Frequently, basic science results turn out to be irreproducible. Irreproducibility, outside of malfeasance, is multifactorial and can include poor experimental design, conduct, statistical analysis, reporting standards, and conceptual flaws. Further confounding problems include an insufficient transferability of animal to human physiology, as well as intersubject group variability, for example, sexual dimorphisms. While the causes of poor data reproducibility are therefore numerous, equally there are many groups that can contribute to improvements in how basic science is reported. Here, we will review how the Journal of Neurochemistry can contribute to increasing the value of preclinical and translational research. Despite a vast amount of very promising basic research findings, these failed to successfully translate into the clinical practice so far. The reasons for this 'data reproducibility crisis' are numerous, for example, rooting in insufficient experimental design, conceptual flaws, incorrect statistical planning and evaluation, incomplete model system that do not adequately reproduce the human physiology, and further reasons discussed in this Review with the aim to present practical solutions that can be implemented by researchers, journals editors, and reviewers. We will also explain measures the Journal of Neurochemistry have implemented to overcome these issues and weaknesses in preclinical research. These includes adherence to the ARRIVE ( www.nc3rs.org) guidelines, NINDS standards (doi: 10.1038/nature11556), and The Transparency and Openness Promotion Guidelines (TOP) Committee guidelines (https://cos.io/top/#TOP). This article is part of the 60th Anniversary special issue.

199 years of Parkinson disease - what have we learned and what is the path to the future?

In 1817, 199 years ago, James Parkinson described for the first time in 'An Essay on the Shaking Palsy' the symptoms of the disease that was later named Parkinson Disease. The current special issue of the Journal of Neurochemistry is dedicated to the discoveries and advances that have been made since, leading to a better understanding of this neurodegenerative disease and of potential treatment options. Reputed researchers cover various aspects from neuroanatomical basics; genetic and molecular risk factors such as LRRK2; the available cell and animal models that mimic crucial features of the pathophysiology; to clinical aspects and treatments, including deep brain stimulation. This article is part of a special issue on Parkinson disease.

Reflections on 60 years of publication of the Journal of Neurochemistry.

This review reflects on the origins, development, publishing trends, and scientific directions of the Journal of Neurochemistry over its 60 year lifespan as seen by key contributors to the Journal's production. The Journal first appeared in May 1956 with just two issues published in that inaugural year. By 1963, it appeared monthly and, by 2002, 24 hard copy issues were published yearly. In 2014, the Journal became online only. For much of its time, the Journal was managed through two separate editorial offices each with their respective Chief Editor (the 'Western' and 'Eastern' hemispheres). The Journal was restructured to operate through a single editorial office and Editor-in-Chief from 2013. Scientifically, the Journal progressed through distinct scientific eras with the first two decades generally centered around developments in methodology followed by a period when publications delved deeper into underlying mechanisms. By the late 1980s, the Journal had entered the age of genetics and beyond, with an increasing focus on neurodegenerative diseases. Reviews have played a regular part in the success of J Neurochem with focused special and virtual issues being a highlight of recent years. Today, 60 years and onwards, J Neurochem continues to be a leading source of top-quality, original and review articles in neuroscience. We look forward to its continued success at the forefront of neurochemistry in the decades to come. This article celebrates 60 years of publication of Journal of Neurochemistry including personal reminiscences from some of the Chief Editors, past and present, as well as input from some of the key contributors to the Journal over this period. We highlight the scientific, technological, and publishing developments along the way, with reference to key papers published in the Journal. The support of the Journal toward the aims and objectives of the International Society for Neurochemistry (ISN) is also emphasized. This article is part of the 60th Anniversary special issue.

A Learned Society's Perspective on Publishing.

Scientific journals that are owned by a learned society, like the Journal of Neurochemistry (JNC), which is owned by the International Society for Neurochemistry (ISN), benefit the scientific community in that a large proportion of the income is returned to support the scientific mission of the Society. The income generated by the JNC enables the ISN to organize conferences as a platform for members and non-members alike to share their research, supporting researchers particularly in developing countries by travel grants and other funds, and promoting education in student schools. These direct benefits and initiatives for ISN members and non-members distinguish a society journal from pure commerce. However, the world of scholarly publishing is changing rapidly. Open access models have challenged the business model of traditional journal subscription and hence provided free access to publicly funded scientific research. In these models, the manuscript authors pay a publication cost after peer review and acceptance of the manuscript. Over the last decade, numerous new open access journals have been launched and traditional subscription journals have started to offer open access (hybrid journals). However, open access journals follow the general scheme that, of all participating parties, the publisher receives the highest financial benefit. The income is generated by researchers whose positions and research are mostly financed by taxpayers' or funders' money, and by reviewers and editors, who frequently are not reimbursed. Last but not least, the authors pay for the publication of their work after a rigorous and sometimes painful review process. JNC itself has an open access option, at a significantly reduced cost for Society members as an additional benefit. This article provides first-hand insights from two former Editors-in-Chief, Kunihiko Suzuki and Leslie Iversen, about the history of JNC's ownership and about the difficulties and battles fought along the way to its current success and reputation. Scientific journals that are owned by a learned society, like the Journal of Neurochemistry (JNC) which is owned by the International Society for Neurochemistry (ISN), benefit the scientific community in that a large proportion of the income is returned to support the scientific mission of the Society. The income generated by the JNC enables the ISN to organize conferences as a platform for members and non-members alike to share their research, supporting researchers particularly in developing countries by travel grants and other funds, and to promote education in student schools. These direct benefits and initiatives for ISN members and non-members distinguish a society journal from pure commerce. However, the world of scholarly publishing is changing rapidly. Open access models have challenged the business model of traditional journal subscription and hence provide free access to publicly funded scientific research. In these models, the manuscript authors pay a publication cost after peer review and acceptance of the manuscript. Over the last decade, numerous new open access journals have been launched and traditional subscription journals have started to offer open access (hybrid journals). However, open access journals pertain to the general scheme that, of all participating parties, the publisher receives the highest financial benefit. The income is generated by researchers whose positions and research are mostly financed by tax payers' or funders' money, reviewers and editors, who frequently are not reimbursed. Last but not least, the authors pay for the publication of their work after a rigorous and sometimes painful review process. JNC itself has an open access option, at a significantly reduced cost for Society members as an additional benefit. This article provides first-hand insights from a long-standing Editor-in-Chief, Kunihiko Suzuki, about the history of JNC's ownership and about difficulties and battles fought on the way to its current success and reputation today. This article is part of the 60th Anniversary special issue.

Submitting a manuscript for peer review--integrity, integrity, integrity.

Publication of a flawed manuscript has significant consequences for the progress of science. When this proves to be intentional, science is brought into disrepute and this puts even more pressure on the shrinking resources that society is prepared to invest in research. All scientific journals, including the Journal of Neurochemistry, have witnessed a marked increase in the number of corrections and retractions of published articles over the last 10 years, and uncovered a depressingly large number of fabrications among submitted manuscripts. The increase in number of 'spoiled' manuscripts reflects not only the improved methods that journals employ to detect plagiarism in its many forms but also suggests a measurable change in the behavior of authors. The increased policing of submissions by reviewers, editors, and publishers expends time and money. The sanctions imposed by journal editors on authors found guilty of malpractice are transparent and severe.

Deferiprone for the treatment of Friedreich's ataxia.

Friedreich's ataxia (FRDA) is a neurological disease related to a deficiency of the protein frataxin involved in iron-sulfur (Fe-S) cluster biogenesis. This leads to an increased cellular iron uptake accumulating in mitochondria, and a subsequently disturbed iron homeostasis. The detailed mechanism of iron regulation of frataxin expression is yet unknown. Deferiprone, an iron chelator that may cross the blood-brain barrier, was shown to shuttle iron between subcellular compartments. It could also transfer iron from iron-overloaded cells to extracellular apotransferrin and pre-erythroid cells for heme synthesis. Here, clinical studies on Deferiprone are reviewed in the context of alternative agents such as desferoxamine, with specific regard to its mechanistic and clinical implications.

Exercise-induced Nogo-A influences rodent motor learning in a time-dependent manner.

The adult, mature central nervous system (CNS) has limited plasticity. Physical exercising can counteract this limitation by inducing plasticity and fostering processes such as learning, memory consolidation and formation. Little is known about the molecular factors that govern these mechanisms, and how they are connected with exercise. In this study, we used immunohistochemical and behavioral analyses to investigate how running wheel exercise affects expression of the neuronal plasticity-inhibiting protein Nogo-A in the rat cortex, and how it influences motor learning in vivo. Following one week of exercise, rats exhibited a decrease in Nogo-A levels, selectively in motor cortex layer 2/3, but not in layer 5. Nogo-A protein levels returned to baseline after two weeks of running wheel exercise. In a skilled motor task (forelimb-reaching), administration of Nogo-A function-blocking antibodies over the course of the first training week led to improved motor learning. By contrast, Nogo-A antibody application over two weeks of training resulted in impaired learning. Our findings imply a bimodal, time-dependent function of Nogo-A in exercise-induced neuronal plasticity: While an activity-induced suppression of the plasticity-inhibiting protein Nogo-A appears initially beneficial for enhanced motor learning, presumably by allowing greater plasticity in establishing novel synaptic connections, this process is not sustained throughout continued exercise. Instead, upregulation of Nogo-A over the course of the second week of running wheel exercise in rats implies that Nogo-A is required for consolidation of acquired motor skills during the delayed memory consolidation process, possibly by inhibiting ongoing neuronal morphological reorganization to stabilize established synaptic pathways. Our findings suggest that Nogo-A downregulation allows leaning to occur, i.e. opens a 'learning window', while its later upregulation stabilizes the learnt engrams. These findings underline the importance of appropriately timing of application of Nogo-A antibodies in future clinical trials that aim to foster memory performance while avoiding adverse effects.

Properties of low-frequency head-related transfer functions in the barn owl (Tyto alba).

The barn owl (Tyto alba) possesses several specializations regarding auditory processing. The most conspicuous features are the directionally sensitive facial ruff and the asymmetrically arranged ears. The frequency-specific influence of these features on sound has consequences for sound localization that might differ between low and high frequencies. Whereas the high-frequency range (>3 kHz) is well investigated, less is known about the characteristics of head-related transfer functions for frequencies below 3 kHz. In the present study, we compared 1/3 octaveband-filtered transfer functions of barn owls with center frequencies ranging from 0.5 to 9 kHz. The range of interaural time differences was 600 micros at frequencies above 4 kHz, decreased to 505 micros at 3 kHz and increased again to about 615 micros at lower frequencies. The ranges for very low (0.5-1 kHz) and high frequencies (5-9 kHz) were not statistically different. Interaural level differences and monaural gains increased monotonically with increasing frequency. No systematic influence of the body temperature on the measured localization cues was observed. These data have implications for the mechanism underlying sound localization and we suggest that the barn owl's ears work as pressure receivers both in the high- and low-frequency ranges.