Biology subjects

Bos, R.

Publications and source records attributed to Bos, R..

11 recordsLinked to original sources

bioRxiv2026

Acetylcholine drives astrocytic JAK2-STAT3 signaling to modulate male-to-female approach behavior

Astrocytes are essential regulators of neural circuits and behavior, sensing synaptic activity and modulating plasticity through diverse intracellular mechanisms. However, the contribution of astrocyte transcription factor-based cascades, linking external stimuli to long-term transcriptional programs, is currently misunderstood. Here we show that the JAK2-STAT3 signaling plays a critical role in male-to-female social behavior. Hence, in male mice, exposure to estrus females rapidly and selectively induces STAT3 signaling in ventral hippocampal astrocytes. Surprisingly, this induction is not driven through canonical cytokine signaling but by septo-hippocampal cholinergic inputs acting through 7 nicotinic acetylcholine receptors (7nAChR). Astrocytic 7nAChR-JAK2-STAT3 signaling in turn modulates vCA1 pyramidal neuron activity and is required for context-appropriate male approach behavior. These findings reveal a previously unsuspected cellular pathway integrating neuromodulatory inputs and transcription factor-based signaling to shape male behavioral response depending on female receptivity.

neuroscience↗

bioRxiv2025

Sex-specific relationship between melanopsin-dependent light sensitivity and chronotype across the lifespan

Study objectives: Light, acting primarily via melanopsin-mediated signaling, plays a central role in synchronising circadian rhythms. Individuals vary markedly in the sensitivity of their circadian system to light. Whether these differences contribute to the interindividual variability in chronotype, a behavioural manifestation of internal circadian timing, is unclear. The aim of this study was to determine the relationship between melanopsin-dependent light sensitivity and chronotype across the general population. Methods: Participants (adults and children aged [≥] 8 years) were recruited in a science museum. Chronotype was determined using the {micro}MCTQ and the post-illumination pupillary response (PIPR) to short and long-wavelength light stimuli was used as a measure of melanopsin-dependent light sensitivity. The relationship between PIPR and chronotype and their interaction with age and sex were assessed using multiple linear regression. Results: Pupil recordings and questionnaires were available from 457 participants, including 284 adults and 173 children. In adults, the relationship between melanopsin-dependent light sensitivity and chronotype depends on sex and age: in young adult men, greater light sensitivity is linked to a significantly later chronotype, whereas it is significantly associated with an earlier chronotype in older adult women. In children, no evidence was found for a relationship between light sensitivity and chronotype. Conclusions: These findings suggest that individual variation in light sensitivity interacts with sex and age-specific differences in the circadian system and light exposure behaviour to influence circadian timing. Light exposure recommendations should be personalised to take into account these sex and age-specific effects. Statement of significanceWhile individuals differ widely in how their circadian system responds to light, to what extent these individual responses influence internal circadian timing remains unclear. By studying a large and diverse sample of children and adults, our findings reveal that the relationship between light sensitivity and chronotype, a behavioural manifestation of circadian timing, is shaped by both age and sex, offering a more comprehensive understanding of this relationship than previously recognised. Specifically, greater light sensitivity is linked to later chronotype in young men but to earlier chronotype in older women. These results reveal that the impact of light on circadian timing changes across the lifespan and will contribute to the development of personalised light exposure guidelines to promote health and well-being.

neuroscience↗

bioRxiv2025

Humpback whales harbor a highly novel and endemic gut microbiome that adapts to periods of fasting during migration

Humpback whales (Megaptera novaeangliae) are cosmopolitan in distribution and most populations migrate between foraging and breeding grounds each year1,2. As capital breeders, many humpbacks reduce foraging behavior and potentially fast for a few months of the year3. Here, we present a comparative genomic analysis of the gut microbiomes from humpbacks on two breeding grounds: Gulf of California, where feeding is common4-6, and Hawai i, where feeding is extremely rare7. The humpback whale gut microbiome shows unexpected taxonomic novelty, high endemism, and coevolutionary signal. These data also suggest an imbalance in the gut community with foraging reduction, supported by the enrichment of several aerobic metabolism genes, potentially indicative of inflammation, and pathogenesis gene sets used to colonize host tissues, modulate the immune system, and lyse tissues. Pathway reconstruction revealed gut communities shared symbiotic functions including the synthesis of essential amino acids, short chain fatty acids (SCFAs), and vitamins, as well as nitrogen salvaging mechanisms and degradation of biogeochemically relevant substrates like cellulose, chitin, and wax esters (including host chitinases). Complementary sequencing and taxonomic annotation revealed that more Clostridiaceae and Oscillospiraceae genera were in foraging whales, whereas fasting samples were enriched in Erysipelotrichaceae genera, associated with gut disease8,9. These data reveal striking changes in humpback whale gut microbiomes between their feeding and breeding grounds, raise the possibility that breeding whales are more susceptible to gut dysfunction or disease, and equally important reveal how humpback whales are likely making varying biogeochemical contributions to upper ocean communities over the course of the year.

genomics↗

bioRxiv2023

A size principle for bistability in mouse spinal motoneurons

Bistability in spinal motoneurons supports tonic spike activity in the absence of excitatory drive. Earlier work in adult preparations suggested that smaller motoneurons innervating slow antigravity muscle fibers are more likely to generate bistability for postural maintenance. However, whether large motoneurons innervating fast-fatigable muscle fibers display bistability related to postural tone is still controversial. To address this, we examined the relationship between soma size and bistability in lumbar ventrolateral -motoneurons of ChAT-GFP and Hb9-GFP mice across different developmental stages: neonatal (P2-P7), young (P7-P14) and mature (P21-P25). We found that as neuron size increases, the prevalence of bistability rises. Smaller -motoneurons lack bistability, while larger fast -motoneurons (MMP-9+/Hb9+) with a soma area [≥] 400{micro}m2 exhibit significantly higher bistability. Ionic currents associated with bistability, including the persistent Nav1.6 current, thermosensitive Trpm5 Ca2+-activated Na+ current and the slowly inactivating Kv1.2 current, also scale with cell size. Serotonin evokes full bistability in large motoneurons with partial bistable properties, but not in small motoneurons. Our study provides important insights into the neural mechanisms underlying bistability and how motoneuron size dictates this process. New and NoteworthyBistability is not a common feature of all mouse spinal motoneurons. It is absent in small, slow motoneurons but present in most large, fast motoneurons. This difference results from differential expression of ionic currents that enable bistability, which are highly expressed in large motoneurons but small or absent in small motoneurons. These results support a possible role for fast motoneurons in maintenance of tonic posture in addition to their known roles in fast movements.

neuroscience↗

bioRxiv2023

Persistent Nav1.6 current drives spinal locomotor functions through nonlinear dynamics

Persistent sodium current (INaP) in the spinal locomotor network promotes two distinct nonlinear firing patterns: a self-sustained spiking triggered by a brief excitation in bistable motoneurons and bursting oscillations in interneurons of the central pattern generator (CPG). Here, we identified the NaV channels responsible for INaP and their role in motor behaviors. We report the axonal Nav1.6 as the main molecular player for INaP in lumbar motoneurons. The motoneuronal inhibition of Nav1.6, but not of Nav1.1, impairs INaP, bistability, postural tone and locomotor performance. In interneurons of the CPG region, Nav1.6 with Nav1.1 equally mediate INaP and the inhibition of both channels is required to abolish oscillatory bursting activities and the locomotor rhythm. Overall, Nav1.6 plays a significant role both in posture and locomotion by governing INaP-dependent bistability in motoneurons and working in tandem with Nav1.1 to provide INaP-dependent rhythmogenic properties of the CPG.

neuroscience↗

bioRxiv2022

Astrocytes regulate locomotion by orchestrating neuronal rhythmicity in the spinal network via potassium clearance

SO_SCPLOWUMMARYC_SCPLOWNeuronal rhythmogenesis in the spinal cord is correlated with variations in extracellular K+ levels ([K+]e). Astrocytes play important role in[K+]e homeostasis and compute neuronal information. Yet it is unclear how neuronal oscillations are regulated by astrocytic K+ homeostasis. Here we identify the astrocytic inward-rectifying K+ channel Kir4.1 (a.k.a. Kcnj10) as a key molecular player for neuronal rhythmicity in the spinal central pattern generator (CPG). By combining two-photon calcium imaging with electrophysiology, immunohistochemistry and genetic tools, we report that astrocytes display Ca2+ transients before and during oscillations of neighbouring neurons. Inhibition of astrocytic Ca2+ transients with BAPTA decreases the barium-sensitive Kir4.1 current responsible of K+ clearance. Finally, we show in mice that Kir4.1 knockdown in astrocytes progressively prevents neuronal oscillations and alters the locomotor pattern resulting in lower motor performances in challenging tasks. These data identify astroglial Kir4.1 channels as key regulators of neuronal rhythmogenesis in the CPG driving locomotion. SO_SCPLOWIGNIFICANCEC_SCPLOWO_SCPCAP C_SCPCAPO_SCPLOWSTATEMENTC_SCPLOWDespite decades of research, the cellular mechanisms responsible of the synchronized rhythmic oscillations driving locomotion remain elusive. To gain insight into the function of the spinal locomotor network, numerous studies have characterized diverse classes of locomotor-related neurons to determine their role in generating rhythmic movements during locomotion. In contrast, studies investigating non-neuronal components of the spinal cord are sparse. Our study represents a significant breakthrough by identifying astrocytic K+ uptake as a key regulator of neuronal rhythmicity synchronization and locomotor pattern at the cellular, microcircuit and system levels. These data provide mechanistic insights into the neuroglial dialogue at play during rhythmogenesis and point to a novel astroglial target for restoring normal neuronal network excitability in brain disorders and neurodegenerative diseases.

neuroscience↗

bioRxiv2022

Immunogenicity of an Ad26-based SARS-CoV-2 Omicron Vaccine in Naïve Mice and SARS-CoV-2 Spike Pre-immune Hamsters

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant sparked concern due to its fast spread and the unprecedented number of mutations in the spike protein that enables it to partially evade spike-based COVID-19 vaccine-induced humoral immunity. In anticipation of a potential need for an Omicron spike-based vaccine, we generated an Ad26 vector encoding an Omicron (BA.1) spike protein (Ad26.COV2.S.529). Ad26.COV2.S.529 encodes for a prefusion stabilized spike protein, similar to the current COVID-19 vaccine Ad26.COV2.S encoding the Wuhan-Hu-1 spike protein. We verified that spike expression by Ad26.COV2.S.529 was comparable to Ad26.COV2.S. Immunogenicity of Ad26.COV2.S.529 was then evaluated in naive mice and SARS-CoV-2 Wuhan-Hu-1 spike pre-immunized hamsters. In naive mice, Ad26.COV2.S.529 elicited robust neutralizing antibodies against SARS-CoV-2 Omicron (BA.1) but not to SARS-CoV-2 Delta (B.1.617.2), while the opposite was observed for Ad26.COV2.S. In pre-immune hamsters, Ad26.COV2.S.529 vaccination resulted in robust increases in neutralizing antibody titers against both SARS-CoV-2 Omicron (BA.1) and Delta (B.1.617.2), while Ad26.COV2.S vaccination only increased neutralizing antibody titers against the Delta variant. Our data imply that Ad26.COV2.S.529 can both expand and boost a Wuhan-Hu-1 spike-primed humoral immune response to protect against distant SARS-CoV-2 variants.

immunology↗

bioRxiv2021

Ad26.COV2.S elicited neutralizing activity against Delta and other SARS-CoV-2 variants of concern

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and recently emerging variants with substitutions in the Spike protein have led to growing concerns over increased transmissibility and decreased vaccine coverage due to immune evasion. Here, sera from recipients of a single dose of our Ad26.COV2.S COVID-19 vaccine were tested for neutralizing activity against several SARS-CoV-2 variants of concern. All tested variants demonstrated susceptibility to Ad26.COV2.S-induced serum neutralization albeit mainly reduced as compared to the B.1 strain. Most pronounced reduction was observed for the B.1.351 (Beta; 3.6-fold) and P.1 (Gamma; 3.4-fold) variants that contain similar mutations in the receptor-binding domain (RBD) while only a 1.6-fold reduction was observed for the widely spreading B.1.617.2 (Delta) variant.

immunology↗

bioRxiv2021

Altered action potential waveform and shorter axonal initial segment in hiPSC-derived motor neurons with mutations in VRK1

We recently described new pathogenic variants in VRK1, in patients affected with distal Hereditary Motor Neuropathy associated with upper motor neurons signs. Specifically, we provided evidences that hiPSC-derived Motor Neurons (hiPSC-MN) from these patients display Cajal bodies (CBs) disassembly and defects in neurite outgrowth and branching. We here focused on the Axonal Initial Segment (AIS) and the related firing properties of hiPSC-MNs from these patients. We found that the patients Action Potential (AP) was smaller in amplitude, larger in duration, and displayed a more depolarized threshold while the firing patterns were not altered. These alterations were accompanied by a decrease in the AIS length measured in patients hiPSC-MNs. These data indicate that mutations in VRK1 impact the AP waveform and the AIS organization in MNs and may ultimately lead to the related motor neuron disease. HighlightsO_LIhiPSC-MNs are functional and sustain firing patterns, typical of spinal MNs C_LIO_LIhiPSC-MNs from patients with VRK1 mutations have altered Action Potential C_LIO_LIAxonal Initial Segment is shorter in hiPSC-MNs from patients with mutated VRK1 C_LIO_LIhiPSC-MNs are a useful platform to study Motor Inherited Peripheral Neuropathies C_LI eTOC BlurbIn human spinal Motor Neurons derived from induced Pluripotent Stem Cells from patients with VRK1 -related distal Hereditary Motor Neuropathy, Bos, Rihan et al. show that the mutations in VRK1 affect the electrical properties of these neurons: they display defects in the initiation of the Action Potential due to a shortening of the Axonal Initial Segment.

neuroscience↗

bioRxiv2020

Ad26-vector based COVID-19 vaccine encoding a prefusion stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses

Development of effective preventative interventions against SARS-CoV-2, the etiologic agent of COVID-19 is urgently needed. The viral surface spike (S) protein of SARS-CoV-2 is a key target for prophylactic measures as it is critical for the viral replication cycle and the primary target of neutralizing antibodies. We evaluated design elements previously shown for other coronavirus S protein-based vaccines to be successful, e.g. prefusion-stabilizing substitutions and heterologous signal peptides, for selection of a S-based SARS-CoV-2 vaccine candidate. In vitro characterization demonstrated that the introduction of stabilizing substitutions (i.e., furin cleavage site mutations and two consecutive prolines in the hinge region of S1) increased the ratio of neutralizing versus non-neutralizing antibody binding, suggestive for a prefusion conformation of the S protein. Furthermore, the wild type signal peptide was best suited for the correct cleavage needed for a natively-folded protein. These observations translated into superior immunogenicity in mice where the Ad26 vector encoding for a membrane-bound stabilized S protein with a wild type signal peptide elicited potent neutralizing humoral immunity and cellular immunity that was polarized towards Th1 IFN-{gamma}. This optimized Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in a phase I clinical trial (ClinicalTrials.gov Identifier: NCT04436276).

immunology↗

bioRxiv2019

EVALUATION OF OSTEOINDUCTIVITY OF DIFFERENT CALCIUM PHOSPHATE AND PTMC-CALCIUM PHOSPHATE COMPOSITE BIOMATERIALS IN A SHEEP MODEL

Osteoinduction refers to de novo bone formation induced by biomaterials in places where physiologically no bone tissue is formed. Biomaterials with osteoinductive capacities have been shown to fill bone defects of critical sizes with ubiquitous new bone formation. Therefore, osteoinduction has been regarded as an important characteristic for biomaterials aiming at bone regeneration. In our study, we tested osteoinductive capacities of different calcium phosphate bioceramic particles, calcium phosphate scaffolds, and porous poly(trimethylene carbonate)(PTMC)-calcium phosphate composite scaffolds in a sheep model. Biphasic calcium phosphate (BCP) particles of 45-150 m and 150-500 m, microporous {beta}-tricalcium phosphate ({beta}-TCP) particles of 45-150 m, non-microporous {beta}-TCP particles of 45-150 m and 150-500 m, and porous {beta}-TCP scaffolds were implanted in sheep long dorsal muscle for three and nine months. Likewise, porous composite scaffolds, in which BCP particles, microporous {beta}-TCP particles and {beta}-TCP particles, all of 45-150 m, had been incorporated into PTMC matrices, were implanted in sheep long dorsal muscle for three and nine months. Porous PTMC scaffolds were implanted as controls. Abundant new bone formation was induced by BCP particles of both size ranges, the {beta}-TCP scaffold was also able to induce new bone formation at both three and nine months follow up, while no new bone formation was induced by the other biomaterials. Implantation of the abovementioned biomaterials led to uneventful degradation of the PTMC matrices and the incorporated calcium phosphate particles, and provoked no obvious tissue reaction. Future studies are needed to determine the optimal composition of composite biomaterials based on PTMC and calcium phosphate to produce osteoinductive composites.

bioengineering↗