The 10,000-year biocultural history of fallow deer and its implications for conservation policy.

Over the last 10,000 y, humans have manipulated fallow deer populations with varying outcomes. Persian fallow deer (Dama mesopotamica) are now endangered. European fallow deer (Dama dama) are globally widespread and are simultaneously considered wild, domestic, endangered, invasive and are even the national animal of Barbuda and Antigua. Despite their close association with people, there is no consensus regarding their natural ranges or the timing and circumstances of their human-mediated translocations and extirpations. Our mitochondrial analyses of modern and archaeological specimens revealed two distinct clades of European fallow deer present in Anatolia and the Balkans. Zooarchaeological evidence suggests these regions were their sole glacial refugia. By combining biomolecular analyses with archaeological and textual evidence, we chart the declining distribution of Persian fallow deer and demonstrate that humans repeatedly translocated European fallow deer, sourced from the most geographically distant populations. Deer taken to Neolithic Chios and Rhodes derived not from nearby Anatolia, but from the Balkans. Though fallow deer were translocated throughout the Mediterranean as part of their association with the Greco-Roman goddesses Artemis and Diana, deer taken to Roman Mallorca were not locally available Dama dama, but Dama mesopotamica. Romans also initially introduced fallow deer to Northern Europe but the species became extinct and was reintroduced in the medieval period, this time from Anatolia. European colonial powers then transported deer populations across the globe. The biocultural histories of fallow deer challenge preconceptions about the divisions between wild and domestic species and provide information that should underpin modern management strategies.

P80 natural essence spray and lozenges provide respiratory protection against Influenza A, B, and SARS-CoV-2.

Seasonally circulating viruses, such as Influenza, as well as newly emerging viruses and variants thereof, and waning immunity urge the need for safe, easy-to-use and inexpensive drugs to protect from these challenges. To prevent transmission of these viruses and subsequent excessive inflammatory reactions on mucous membranes, we tested the efficacy of the natural essence P80 as spray and in form of lozenges against respiratory infections caused by SARS-CoV-2 variants of concern (VoCs), influenza A (H3N2) and influenza B (Victoria). P80 natural essence, a Dimocarpus longan extract, shielded highly differentiated human airway epithelia from SARS-CoV-2 wildtype and Omicron variant as well as Influenza A and B infection and dampened inflammation by down-modulating pro-inflammatory cytokine and anaphylatoxin secretion. A single application of P80 natural essence spray maintained tissue integrity long-term. This also significantly reduced the release of infectious viral particles and the secretion of IP10, MCP1, RANTES and C3a, all of which mediate the migration of immune cells to the sites of infection. Even P80 lozenges dissolved in distilled water or non-neutralizing saliva efficiently prevented SARS-CoV-2 and Influenza-induced tissue destruction. Consequently, our in vitro data suggest that P80 natural essence can act as antiviral prophylactic, both in form of nasal or oral spray and in form of lozenges, independent of circulating respiratory challenges.

"It is becoming increasingly difficult to find reviewers"-myths and facts about peer review.

A frequent complaint of editors of scientific journals is that it has become increasingly difficult to find reviewers for evaluating submitted manuscripts. Such claims are, most commonly, based on anecdotal evidence. To gain more insight grounded on empirical evidence, editorial data of manuscripts submitted for publication to the Journal of Comparative Physiology A between 2014 and 2021 were analyzed. No evidence was found that more invitations were necessary over time to get manuscripts reviewed; that the reviewer's response time after invitation increased; that the number of reviewers who completed their reports, relative to the number of reviewers who had agreed to review a manuscript, decreased; and that the recommendation behavior of reviewers changed. The only significant trend observed was among reviewers who completed their reports later than agreed. The average number of days that these reviewers submitted their evaluations roughly doubled over the period analyzed. By contrast, neither the proportion of late vs. early reviews, nor the time for completing the reviews among the punctual reviewers, changed. Comparison with editorial data from other journals suggests that journals that serve a smaller community of readers and authors, and whose editors themselves contact potential reviewers, perform better in terms of reviewer recruitment and performance than journals that receive large numbers of submissions and use editorial assistants for sending invitations to potential reviewers.

Ruth Beutler: the woman behind Karl von Frisch.

The Journal of Comparative Physiology A was founded in 1924 as the Zeitschrift für vergleichende Physiologie by Karl von Frisch and Alfred Kühn. Given the marginalization of women in science at that time, it is remarkable that the first article in the Journal was authored by a female scientist, Ruth Beutler. Throughout her scientific career, she was affiliated with the Zoological Institute of the University of Munich, which, under the leadership of von Frisch, evolved into a world-class academic institution. Despite chronic health problems, Beutler was one of the first women who succeeded in obtaining the Habilitation as qualification for appointment to a professorial position. She was also one of the first scientists who applied methods from physiological chemistry to the study of zoological phenomena. Yet, for many years she was employed as a technician only, and she was never appointed to an Ordinarius (tenured full professorship) position. Her most important contributions to comparative physiology outside her own area of research were her support for, and protection of, Karl von Frisch, particularly during the Nazi era when he, as a 'quarter-Jew,' faced imminent threat of forced retirement; and after World War II, when her efforts as interim Ordinarius were instrumental in re-building the bombed-out Zoological Institute to persuade Karl von Frisch to return to Munich. It was also one of her observations that prompted him to revisit, and revise, his earlier (incorrect) model of how honeybees communicate, through their dances, the direction and distances of food sources from the hive.

Centennial issue.

The Journal of Comparative Physiology A, also known as JCPA, was founded by Karl von Frisch and Alfred Kühn in 1924, then under its German title Zeitschrift für vergleichende Physiologie. During the 100 years of its history, it became the leading international journal in comparative physiology and its daughter discipline, neuroethology. As such, it had a major impact on the development of these disciplines. In celebration of this achievement and the nearly 10,000 articles that appeared during the last 100 years, this Centennial Issue is published. Its authors reflect on the history of JCPA and the early pioneers, including women scientists, of comparative physiology; share the impact that the Journal had on their careers; discuss the benefit of the enormous taxonomic diversity of model systems used in studies published in JCPA; contrast this philosophy with the strategy of a limited number of standard biomedical model systems; review popular and trending research topics covered in JCPA; and, by interrogating the past, take a peek into the future of neuroethology.

The effect of extracellular potassium concentration on the oscillation frequency of the pacemaker nucleus in the weakly electric fish Apteronotus leptorhynchus.

The weakly electric brown ghost knifefish (Apteronotus leptorhynchus) exhibits a pronounced sexual dimorphism in its electric behavior-males discharge at higher frequencies than females, with little overlap between the sexes. The frequency of these electric organ discharges is controlled by the frequency of the synchronized oscillations of the medullary pacemaker nucleus. Previous studies have suggested that sex-specific differences in the morphology and gene expression pattern of the astrocytic syncytium that envelopes the pacemaking neural network cause differences in its capacity to buffer the extracellular concentration of K+. This change in the K+ buffering capacity affects the K+ equilibrium potential of the neurons constituting the neural network, which in turn modulates the frequency of the pacemaker nucleus. In the present study, we have tested a critical element of this hypothesis by examining whether, and how, changes in the extracellular K+ concentration influence the frequency of the pacemaker nucleus oscillations. By using an in vitro preparation of the pacemaker nucleus, the results of this investigation demonstrate that exposure of this nucleus to acutely increased/decreased concentrations of K+ in the perfusate (while maintaining osmolarity) leads to concentration-dependent increases/decreases in the frequency of the synchronized oscillations generated by the pacemaker nucleus.

"Resistance leads to self-destruction": how an (a)political strategy helped Karl von Frisch succeed during the Nazi era.

Karl von Frisch, one of the leading zoologists of the twentieth century and co-founder of the Journal of Comparative Physiology A, has been frequently portrayed as an opponent of the Nazi regime because he, as a 'quarter-Jew,' faced the threat of forced retirement from his position as a professor at the University of Munich during the Third Reich. However, doubts about an active opposition role have surfaced in recent years. A litmus test for assessing the validity of this notion is provided by our discovery that four of the six core members of the anti-Nazi resistance group 'White Rose'-Sophie Scholl, Hans Scholl, Christoph Probst, and Alexander Schmorell-were his students. When they were arrested, sentenced to death, and executed, he seemed to ignore this historic event, both during and after World War II-in line with his belief that resistance leads to self-destruction, and research can flourish only by ignoring what happens around oneself. On the other hand, this seemingly apolitical attitude did not prevent him from making use of politics when it served his interests. Such actions included his (pseudo-)scientific justification of forced sterilization of people suffering from hereditary disorders during the Third Reich and his praise of the Nazi government's efforts to "keep races pure." As unsettling as these and some other political views and actions of Karl von Frisch are, they enabled him to carry out several critical pieces of his research agenda during the Third Reich, which three decades later earned him a Nobel Prize.

Ingeborg Beling and the time memory in honeybees: almost one hundred years of research.

Bees are known for their ability to forage with high efficiency. One of their strategies to avoid unproductive foraging is to be at the food source at the right time of the day. Approximately one hundred years ago, researchers discovered that honeybees have a remarkable time memory, which they use for optimizing foraging. Ingeborg Beling was the first to examine this time memory experimentally. In her doctoral thesis, completed under the mentorship of Karl von Frisch in 1929, she systematically examined the capability of honeybees to remember specific times of the day at which they had been trained to appear at a feeding station. Beling was a pioneer in chronobiology, as she described the basic characteristics of the circadian clock on which the honeybee's time memory is based. Unfortunately, after a few years of extremely productive research, she ended her scientific career, probably due to family reasons or political pressure to reduce the number of women in the workforce. Here, we present a biographical sketch of Ingeborg Beling and review her research on the time memory of honeybees. Furthermore, we discuss the significance of her work, considering what is known about time memory today - nearly 100 years after she conducted her experiments.

One hundred years of excellence: the top one hundred authors of the Journal of Comparative Physiology A.

The Journal of Comparative Physiology A is the premier peer-reviewed scientific journal in comparative physiology, in particular sensory physiology, neurophysiology, and neuroethology. Founded in 1924 by Karl von Frisch and Alfred Kühn, it celebrates its 100th anniversary in 2024. During these 100 years, many of the landmark achievements in these disciplines were published in this journal. To commemorate these accomplishments, we have compiled a list of the Top 100 Authors over these 100 years, representing approximately 1% of all its authors. To select these individuals, three performance criteria were applied: number of publications, total number of citations attracted by these articles, and mean citation rate of the papers published by each author. The resulting list of the Top 100 Authors provides a fascinating insight into the history of the disciplines covered by the Journal of Comparative Physiology A and into the academic careers of many of their leading representatives.

GlyPerA™ effectively shields airway epithelia from SARS-CoV-2 infection and inflammatory events.

New SARS-CoV-2 variants of concern (VOCs) and waning immunity illustrate that quick and easy-to-use agents are needed to prevent infection. To protect from viral transmission and subsequent inflammatory reactions, we applied GlyperA™, a novel antimicrobial formulation that can be used as mouth gargling solution or as nasal spray, to highly differentiated human airway epithelia prior infection with Omicron VOCs BA.1 and BA.2. This formulation fully protected polarized human epithelium cultured in air-liquid interphase (ALI) from SARS-CoV-2-mediated tissue destruction and infection upon single application up to two days post infection. Moreover, inflammatory reactions induced by the Omicron VOCs were significantly lowered in tissue equivalents either pre-treated with the GlyperA™ solution, or even when added simultaneously. Thus, the GlyperA™ formulation significantly shielded epithelial integrity, successfully blocked infection with Omicron and release of viral particles, and decreased intracellular complement C3 activation within human airway epithelial cell cultures. Crucially, our in vitro data imply that GlyperA™ may be a simple tool to prevent from SARS-CoV-2 infection independent on the circulating variant via both, mouth and nose.

Computational modeling predicts regulation of central pattern generator oscillations by size and density of the underlying heterogenous network.

Central pattern generators are characterized by a heterogeneous cellular composition, with different cell types playing distinct roles in the production and transmission of rhythmic signals. However, little is known about the functional implications of individual variation in the relative distributions of cells and their connectivity patterns. Here, we addressed this question through a combination of morphological data analysis and computational modeling, using the pacemaker nucleus of the weakly electric fish Apteronotus leptorhynchus as case study. A neural network comprised of 60-110 interconnected pacemaker cells and 15-30 relay cells conveying its output to electromotoneurons in the spinal cord, this nucleus continuously generates neural signals at frequencies of up to 1 kHz with high temporal precision. We systematically explored the impact of network size and density on oscillation frequencies and their variation within and across cells. To accurately determine effect sizes, we minimized the likelihood of complex dynamics using a simplified setup precluding differential delays. To identify natural constraints, parameter ranges were extended beyond experimentally recorded numbers of cells and connections. Simulations revealed that pacemaker cells have higher frequencies and lower within-population variability than relay cells. Within-cell precision and between-cells frequency synchronization increased with the number of pacemaker cells and of connections of either type, and decreased with relay cell count in both populations. Network-level frequency-synchronized oscillations occurred in roughly half of simulations, with maximized likelihood and firing precision within biologically observed parameter ranges. These findings suggest the structure of the biological pacemaker nucleus is optimized for generating synchronized sustained oscillations.

Cover images of the Journal of Comparative Physiology A and the stories behind them.

The cover images of the 2023 issues of the Journal of Comparative Physiology A, as well as its logo image, are presented at full size and high resolution, together with the stories behind them. These images are testament to the artistic quality of the scientific illustrations published in the Journal of Comparative Physiology A.

Supervised learning algorithm for analysis of communication signals in the weakly electric fish Apteronotus leptorhynchus.

Signal analysis plays a preeminent role in neuroethological research. Traditionally, signal identification has been based on pre-defined signal (sub-)types, thus being subject to the investigator's bias. To address this deficiency, we have developed a supervised learning algorithm for the detection of subtypes of chirps-frequency/amplitude modulations of the electric organ discharge that are generated predominantly during electric interactions of individuals of the weakly electric fish Apteronotus leptorhynchus. This machine learning paradigm can learn, from a 'ground truth' data set, a function that assigns proper outputs (here: time instances of chirps and associated chirp types) to inputs (here: time-series frequency and amplitude data). By employing this artificial intelligence approach, we have validated previous classifications of chirps into different types and shown that further differentiation into subtypes is possible. This demonstration of its superiority compared to traditional methods might serve as proof-of-principle of the suitability of the supervised machine learning paradigm for a broad range of signals to be analyzed in neuroethology.

Neuroethology of auditory systems: contributions in memory of Albert S. Feng.

Albert (Al) S. Feng (1944 - 1921) was a pioneer in the area of neuroethology of auditory systems. This special issue of the Journal of Comparative Physiology A commemorates his life and work by presenting 15 articles written by friends, students, and colleagues, many of whom have become leading experts themselves in this field. Their contributions not only provide a comprehensive overview of bioacoustics in amphibians and mammals (including bats), but also are intended to inspire a new generation of scientists to advance our understanding of brain mechanisms of acoustic perception.

The effect of urethane and MS-222 anesthesia on the electric organ discharge of the weakly electric fish Apteronotus leptorhynchus.

Urethane and MS-222 are agents widely employed for general anesthesia, yet, besides inducing a state of unconsciousness, little is known about their neurophysiological effects. To investigate these effects, we developed an in vivo assay using the electric organ discharge (EOD) of the weakly electric fish Apteronotus leptorhynchus as a proxy for the neural output of the pacemaker nucleus. The oscillatory neural activity of this brainstem nucleus drives the fish's EOD in a one-to-one fashion. Anesthesia induced by urethane or MS-222 resulted in pronounced decreases of the EOD frequency, which lasted for up to 3 h. In addition, each of the two agents caused a manifold increase in the generation of transient modulations of the EOD known as chirps. The reduction in EOD frequency can be explained by the modulatory effect of urethane on neurotransmission, and by the blocking of voltage-gated sodium channels by MS-222, both within the circuitry controlling the neural oscillations of the pacemaker nucleus. The present study demonstrates a marked effect of urethane and MS-222 on neural activity within the central nervous system and on the associated animal's behavior. This calls for caution when conducting neurophysiological experiments under general anesthesia and interpreting their results.

Contact chemoreception, magnetic maps, thermoregulation by a superorganism, and, thanks to Einstein, an all-time record: the Editors' and Readers' Choice Awards 2023.

During the 99 years of its history, the Journal of Comparative Physiology A has published many of the most influential papers in comparative physiology and related disciplines. To celebrate this achievement of the journal's authors, annual Editors' Choice Awards and Readers' Choice Awards are presented. The winners of the 2023 Editors' Choice Awards are 'Contact chemoreception in multi­modal sensing of prey by Octopus' by Buresch et al. (J Comp Physiol A 208:435-442, 2022) in the Original Paper category; and 'Magnetic maps in animal navigation' by Lohmann et al. (J Comp Physiol A 208:41-67, 2022) in the Review/Review-History Article category. The winners of the 2023 Readers' Choice Awards are 'Coping with the cold and fighting the heat: thermal homeostasis of a superorganism, the honeybee colony' by Stabentheiner et al. (J Comp Physiol A 207:337-351; 2021) in the Original Paper category; and 'Einstein, von Frisch and the honeybee: a historical letter comes to light' by Dyer et al. (J Comp Physiol A 207:449-456, 2021) in the Review/Review-History category.

The effect of eugenol anesthesia on the electric organ discharge of the weakly electric fish Apteronotus leptorhynchus.

Eugenol, the major active ingredient of clove oil, is widely used for anesthesia in fish. Yet virtually nothing is known about its effects on CNS functions, and thus about potential interference with neurophysiological experimentation. To address this issue, we employed a neuro-behavioral assay recently developed for testing of water-soluble anesthetic agents. The unique feature of this in-vivo tool is that it utilizes a readily accessible behavior, the electric organ discharge (EOD), as a proxy of the neural activity generated by a brainstem oscillator, the pacemaker nucleus, in the weakly electric fish Apteronotus leptorhynchus. A deep state of anesthesia, as assessed by the cessation of locomotor activity, was induced within less than 3 min at concentrations of 30-60 µL/L eugenol. This change in locomotor activity was paralleled by a dose-dependent, pronounced decrease in EOD frequency. After removal of the fish from the anesthetic solution, the frequency returned to baseline levels within 30 min. Eugenol also led to a significant increase in the rate of 'chirps,' specific amplitude/frequency modulations of the EOD, during the 30 min after the fish's exposure to the anesthetic. At 60 µL/L, eugenol induced a collapse of the EOD amplitude after about 3.5 min in half of the fish tested. The results of our study indicate strong effects of eugenol on CNS functions. We hypothesize that these effects are mediated by the established pharmacological activity of eugenol to block the generation of action potentials and to reduce the excitability of neurons; as well as to potentiate GABAA-receptor responses.

The Neurosphere Simulator: An educational online tool for modeling neural stem cell behavior and tissue growth.

Until very recently, distance education, including digital science labs, served a rather small portion of postsecondary students in the United States and many other countries. This situation has, however, dramatically changed in 2020 in the wake of the COVID-19 pandemic, which forced colleges to rapidly transit from face-to-face instructions to online classes. Here, we report the development of an interactive simulator that is freely available on the web (http://neurosphere.cos.northeastern.edu/) for teaching lab classes in developmental biology. This simulator is based on cellular automata models of neural-stem-cell-driven tissue growth in the neurosphere assay. By modifying model parameters, users can explore the role in tissue growth of several developmental mechanisms, such as regulation of mitosis or apoptotic cell death by contact inhibition. Besides providing an instantaneous animation of the simulated development of neurospheres, the Neurosphere Simulator tool offers also the possibility to download data for detailed analysis. The simulator function is complemented by a tutorial that introduces students to computational modeling of developmental processes.

The Journal of Comparative Physiology A: rooted in great tradition, committed to innovation and discovery.

The current volume of the Journal of Comparative Physiology A marks a transition in editorship. This event provides the opportunity to reflect on the 98 years of the history of the Journal; on the impact of its legacy on the evolution of neuroethology and the comparative branches of sensory physiology and neurobiology; and on future changes in editorial organization and content.

Suggested reviewers: friends or foes?

Peer review, a core element of the editorial processing of manuscripts submitted for publication in scientific journals, is widely criticized as being flawed. One major criticism is that many journals allow or request authors to suggest reviewers, and that these 'preferred reviewers' assess papers more favorably than do reviewers not suggested by the authors. To test this hypothesis, a retrospective analysis was conducted of 162 manuscripts submitted to the Journal of Comparative Physiology A between 2015 and 2021. Out of these manuscripts, 83 were finally rejected and 79 were finally accepted for publication. In neither group could a statistically significant difference be detected in the rating of manuscripts between reviewers suggested by the authors and reviewers not suggested by the authors. Similarly, pairwise comparison of the same manuscripts assessed by one reviewer suggested by the authors and one reviewer not suggested by the authors did not reveal any significant difference in the median recommendation scores between these two reviewer types. Thus, author-suggested reviewers are not necessarily, as commonly assumed, less neutral than reviewers not suggested by the authors, especially if their qualification and impartiality is vetted by the editor before they are selected for peer review.