Biology subjects

Biran, J.

Publications and source records attributed to Biran, J..

6 recordsLinked to original sources

bioRxiv2025

Cocaine- and amphetamine-regulated transcript in perciforms I. Phylogenetic, structural and spatial conservation

Cocaine- and amphetamine-regulated transcript (Cart) is a pleiotropic neuropeptide involved in the regulation of stress and anxiety, depression, reproduction and circadian functions, yet it is mainly known for its metabolic regulation of body weight and appetite. While mammals possess a single cart gene, the genomes of birds may contain up to two carts and fish may possess up to ten cart genes. Furthermore, in some fish species the number of cart paralogues exceeds the number expected according to whole-genome duplication events in actinopterygians, suggesting a species-specific diversification of the cart system. In the current study, we identified multiple cart genes in two fish species with global importance -Nile tilapia and gilthead seabream. Bioinformatics analysis revealed seven cart genes in the tilapia genome and six cart genes in the seabream genome, all of which show high homology with carts of other vertebrates. Additionally, the predicted mature cart peptide sequences contain all the cysteines known to stabilize the tertiary peptide structure in other vertebrates. Nevertheless, protein structure modeling suggested that some carts lost part or all of the cysteine-based disulfide bridges. Quantitative-PCR analyses of all cart genes cloned in this research demonstrated that while all carts are mainly expressed in the brain, some cart genes show wider tissue distribution with significant expression in peripheral tissues including the kidney and gonads. Taken together, these findings emphasize the complexity of the piscine cart system.

physiology↗

bioRxiv2025

Cocaine- and amphetamine-regulated transcript in perciforms II. Responsiveness to energetic shortage

Cocaine and amphetamine-regulated transcript (Cart) is a neuropeptide with prominent roles in appetite regulation and maintenance of energy homeostasis. Although Cart has been widely studied in vertebrates, its multigenic nature in fish elicits questions regarding the various functions affected by specific cart peptides. This is further emphasized when considering the high variation of aquatic ecosystems fish occupy. Nile tilapia (Oreochromis niloticus) and gilthead seabream (Sparus aurata) are important aquaculture species with different natural habitats, food preferences and feeding behaviors. Herein, we utilize these two species to evaluate whether food-related cart functions are species-specific. To this end, we studied how short-term (SD) or long-term (LD) food deprivation affects the central expression of the multiple cart genes of both species. Quantitative PCR analysis of cart expression demonstrated that SD resulted in decreased midbrain expression of three tilapia carts and three seabream carts while LD decreased the midbrain expression of two tilapia carts and two seabream carts. In addition, SD increased the expression of tilapia oncart1c in the anterior brain and oncart1c and oncart1b in the posterior brain while reducing the expression of seabream sacart1c. Our analyses showed that there are cart genes in each species (cart1a and cart1b for tilapia, and cart1b for seabream) that responded to both SD and LD by reduced expression in the midbrain. In addition, both conditions reduced the expression of seabream sacart1c in the posterior brain. Taken together, our current findings suggest that the major appetite regulation in each species is mediated by species-specific carts.

physiology↗

bioRxiv2025

Disruption of the developmental factor Otp in the adult forebrain reveals its diverse physiological functions

Orthopedia (Otp) transcription factor is a critical determinant in the development of the neuroendocrine hypothalamus, and its embryonic deletion results in lethality. Although Otp expression is maintained throughout life, its physiological function in adulthood is not well understood. Here, we generated a forebrain-specific, tamoxifen-inducible, conditional knockout mouse model to investigate the roles of Otp beyond development. Conditional deletion of Otp in two-month-old mice resulted in impaired stress responses, characterized by increased depressive-like behavior and elevated stress-induced cortisol levels. It also led to various metabolic changes, including reduced thyroid hormone levels and body temperature, a higher percentage of fat mass, and diminished responsiveness to ghrelin without affecting food intake, energy expenditure, or body weight. This composite metabolic phenotype was associated with reduced hypothalamic neuropeptides TRH, CRH, AgRP, and NPY expression. Our findings highlight the role of Otp in adult physiological functions as a key neuroendocrine integrator of adaptive stress response and energy balance.

neuroscience↗

bioRxiv2022

Taxonomy of introns, their evolution, and the role of minor introns in stress response

Despite the high conservation of minor introns across eukaryotic supergroups, specific lineages have completely lost minor intron splicing, which has raised questions about their evolution and purpose. Addressing these questions requires identification of the introns that are affected by minor spliceosome inhibition. To this end, we applied principles of Linnaean taxonomy combined with position-weight matrices to produce five intron classes: minor, minor-like, hybrid, major-like and major. We classified introns across the genomes of 263 species of six eukaryotic supergroups, which can be viewed at the Minor Intron Database (MIDB). Transcriptomic analysis revealed that [~]40% of the minor introns are responsive to minor spliceosome inhibition, while an additional 5% of the minor-like and hybrid introns are also affected. We propose that minor-like introns represent an intermediate in the conversion of minor to major introns and uncover the importance of a guanine at the -1 position of the 5 splice site in facilitating this shift in spliceosome dependence. Finally, we find that minor introns are aberrantly spliced in fish and plants upon cold stress, thereby providing a potential explanation for their high degree of conservation in these lineages.

molecular biology↗

bioRxiv2021

Oxytocin Signaling Regulates the Homeostatic Response to Cold Stress in Poikilothermic Vertebrates

When exposed to low temperature, homeothermic vertebrates maintain internal body temperature by activating thermogenesis and by altered metabolism, synchronized by neuroendocrine responses. Although such physiological responses also occur in poikilothermic vertebrates, the prevailing notion is that their reactions are passive. Here, we explored molecular hypothalamic and physiological responses to cold stress in the tropical poikilotherm Nile tilapia (Oreochromis niloticus). We show that cold exposed tilapia exhibit complex homeostatic responses, including increased hypothalamic oxytocin, plasma glucose and cortisol concomitant with reduced plasma lactate and metabolic rate. Pharmacological or genetic blockage of oxytocin signaling further affected metabolic rate in two cold-exposed poikilothermic models. This indicates that oxytocin, a known thermoregulator in homeotherms, actively regulates temperature-related homeostasis in poikilotherms. Overall, our findings show that the brain of poikilotherms actively responds to cold temperature by regulating metabolic physiology. Moreover, we identify oxytocin signaling as an adaptive and evolutionarily conserved metabolic regulator of temperature-related homeostasis.

physiology↗

bioRxiv2020

Splice-specific deficiency of the PTSD-associated gene PAC1 leads to a paradoxical age-dependent stress behavior

The pituitary adenylate cyclase-activating polypeptide receptor (PAC1, also known as ADCYAP1R1) is associated with post-traumatic stress disorder and modulation of stress response in general. Alternative splicing of PAC1 results in multiple gene products, which differ in their mode of signalling and tissue distribution. However, the roles of distinct splice variants in the regulation of stress behavior is poorly understood. Alternative splicing of a short exon, which is known as the "hop cassette", occurs during brain development and in response to stressful challenges. To examine the function of this variant, we generated a splice-specific zebrafish mutant lacking the hop cassette, which we designated hopless. We show that hopless mutant larvae display increased anxiety-like behavior, including reduced dark exploration and impaired habituation to dark exposure. Conversely, adult hopless mutants displayed superior ability to rebound from an acute stressor, as they exhibited reduced anxiety- like responses to an ensuing novelty stress. We propose that the developmental loss of a specific PAC1 splice variant mimics prolonged mild stress exposure, which in the long term, predisposes the organisms stress response towards a resilient phenotype. Our study presents a unique genetic model demonstrating how early-life state of anxiety paradoxically correlates with reduced stress susceptibility in adulthood.

animal behavior and cognition↗