Biology subjects

Morozov, A.

Publications and source records attributed to Morozov, A..

13 recordsLinked to original sources

bioRxiv2026

How many phage species remain undiscovered? Species sampling approaches to inform phage discovery

The emergence of antimicrobial resistant bacteria has been identified as one of the most serious public health and development threats for the near future. The use of bacteriophages (phages) is a promising solution for the sustainable control of these pathogens. Phages are natural viral predators of bacterial pathogens. However, due to the variability and adaptability of bacteria, developing effective and sustainable phage treatments requires drawing from a wide variety of different phage species. This study applies specialised mathematical and computational estimation approaches to the problem of sampling and discovering species of phages in microbiological communities. Our goal is to predict how many new phage species will be discovered in future samples based on species recorded in a phage sequence database for eight common bacterial hosts. While internal validation shows that current estimators yield low prediction errors for how many new species can be found when sampling more phages, these critically assume that the underlying mechanisms of phage sampling and database inclusion remain similar across time - an assumption put into question by our analysis for all but the host genus Mycobacterium. From this, we discuss how our results can still inform future sampling strategies - both through directly predicting the number of additional species, or by detecting changes in sampling and database inclusion. Our results have the potential to inform and optimise the hunt for and isolation of novel of phages from the the natural environment. HighlightsO_LISpecies abundance distribution of phages infecting seven of eight analysed host bacterial genera collected in phage databases changed significantly over time. C_LIO_LIMaintaining current sampling strategies for phages of host Mycobacteriut may lead to diminishing returns in the number of new phages found in additional samples. C_LIO_LIBoth non-parametric and parametric estimators of the numbers of unseen species show comparable, moderate errors when predicting a random subset from the remainder of hostspecific phage sets from the INPHARED database C_LI

genomics↗

bioRxiv2026

Affiliation in mice induced by an auditory-conditioned stimulus

Social affiliation is a vital survival strategy that promotes well-being across species. While innate threats consistently trigger affiliation, it remains unclear whether learned threats engage the same affiliative systems. Here, we report that an auditory conditioned stimulus induced affiliation in mice. In same-sex dyads, mice subjected to auditory fear conditioning increased proximity during presentation of the conditioned stimulus (CS). This CS-evoked affiliation was independent of freezing levels, required familiarity between partners, and depended on intact basolateral amygdala-to-ventral hippocampus inputs and oxytocin signaling. These findings suggest that neural pathways activated by learned and innate threats converge on shared social-affiliation circuitry.

neuroscience↗

bioRxiv2024

Sex and stress interactions in fear synchrony of mouse dyads

Socially coordinated threat responses support the survival of animal groups. Given their distinct social roles, males and females must differ in such coordination. Here, we report such differences during the synchronization of auditory-conditioned freezing in mouse dyads. To study the interaction of emotional states with social cues underlying synchronization, we modulated emotional states with prior stress or modified the social cues by pairing unfamiliar or opposite-sex mice. In same-sex dyads, males exhibited more robust synchrony than females. Stress disrupted male synchrony in a prefrontal cortex-dependent manner but enhanced it in females. Unfamiliarity moderately reduced synchrony in males but not in females. In dyads with opposite-sex partners, fear synchrony was resilient to both stress and unfamiliarity. Decomposing the synchronization process in the same-sex dyads revealed sex-specific behavioral strategies correlated with synchrony magnitude: following partners state transitions in males and retroacting synchrony-breaking actions in females. Those were altered by stress and unfamiliarity. The opposite-sex dyads exhibited no synchrony-correlated strategy. These findings reveal sex-specific adaptations of socio-emotional integration defining coordinated behavior and suggest that sex-recognition circuits confer resilience to stress and unfamiliarity in opposite-sex dyads.

neuroscience↗

bioRxiv2024

A global atlas of subsurface microbiomes reveals phylogenetic novelty, large scale biodiversity gradients, and a marine-terrestrial divide

Subsurface environments constitute one of Earths largest habitats for microbial life, yet differences between surface and subsurface microbiomes and between marine and terrestrial microbiomes remain unclear. We analyzed 478 archaeal and 1054 bacterial amplicon sequence datasets and 147 metagenomes from diverse and globally distributed surface and subsurface environments. Taxonomic analyses show that archaeal and bacterial diversity is similar in marine and terrestrial microbiomes at local to global scales. However, community composition greatly differs between marine and terrestrial microbiomes, suggesting a horizontal phylogenetic divide between sea and land that mirrors patterns in plant and animal diversity. In contrast, community composition overlapped from surface to subsurface environments indicating vertical diversity continua rather than a discrete subsurface biosphere. Diversity of terrestrial microbiomes decreases from surface to subsurface environments. Marine subsurface diversity and phylogenetic novelty rivaled (bacteria) or even exceeded (archaea) that of surface environments, suggesting that the marine subsurface holds a considerable and underestimated fraction of Earths archaeal and bacterial diversity. TeaserSubsurface ecosystems within Earths crust and seafloor harbor diverse and distinct microbiomes featuring many unknown lineages.

microbiology↗

bioRxiv2022

Sex differences in social synchronization of conditioned fear.

Socially coordinated threat responses support the survival of social groups, and the distinct social roles of males and females predict sex differences in such coordination. However, this study area remains unexplored in mice, the most commonly used laboratory species. Here, we examined two behaviors: a recently reported fear synchrony, where paired mice synchronize auditory-conditioned freezing more strongly in males, and a newly identified CS-induced affiliation, where mice increase proximity upon a conditioned stimulus. These behaviors necessitate the integration of social cues with emotional CS. To understand how sex influences that process, we manipulated social cues through partner familiarity and emotional states via prior stress. Unfamiliarity moderately reduced synchrony in male dyads but not in females. Whereas stress disrupted male synchrony and contrarily enhanced female synchrony. Unfamiliarity eliminated CS-induced affiliation in both sexes, while stress caused males to distance each other but had no effects in females. Interestingly, heterosexual dyads showed resilience in both coordinated behaviors unaffected by stress or unfamiliarity. These findings reveal sex-specific adaptations in socio-emotional integration when orchestrating socially coordinated behaviors and suggest that the sex-recognition circuits confer stress- and unfamiliarity-resilience, in particular, in heterosexual dyads.

neuroscience↗

bioRxiv2021

Effects of stochasticity on the length and behaviour of ecological transients

There is a growing recognition that ecological systems can spend extended periods of time far away from an asymptotic state, and that ecological understanding will therefore require a deeper appreciation for how long ecological transients arise. Recent work has defined classes of deterministic mechanisms that can lead to long transients. Given the ubiquity of stochasticity in ecological systems, a similar systematic treatment of transients that includes the influence of stochasticity is important. Stochasticity can of course promote the appearance of transient dynamics by preventing systems from settling permanently near their asymptotic state, but stochasticity also interacts with deterministic features to create qualitatively new dynamics. As such, stochasticity may shorten, extend, or fundamentally change a systems transient dynamics. Here, we describe a general framework that is developing for understanding the range of possible outcomes when random processes impact the dynamics of ecological systems over realistic time scales. We emphasize that we can understand the ways in which stochasticity can either extend or reduce the lifetime of transients by studying the interactions between the stochastic and deterministic processes present, and we summarize both the current state of knowledge and avenues for future advances.

ecology↗

bioRxiv2021

Automatic recognition of macaque facial expressions for detection of affective states

Internal affective states produce external manifestations such as facial expressions. In humans, the Facial Action Coding System (FACS) is widely used to objectively quantify the elemental facial action-units (AUs) that build complex facial expressions. A similar system has been developed for macaque monkeys - the Macaque Facial Action Coding System (MaqFACS); yet unlike the human counterpart, which is already partially replaced by automatic algorithms, this system still requires labor-intensive coding. Here, we developed and implemented the first prototype for automatic MaqFACS coding. We applied the approach to the analysis of behavioral and neural data recorded from freely interacting macaque monkeys. The method achieved high performance in recognition of six dominant AUs, generalizing between conspecific individuals (Macaca mulatta) and even between species (Macaca fascicularis). The study lays the foundation for fully automated detection of facial expressions in animals, which is crucial for investigating the neural substrates of social and affective states.

neuroscience↗

bioRxiv2019

Disinhibition-assisted LTP in the prefrontal-amygdala pathway via suppression of somatostatin-expressing interneurons

Natural brain adaptations often involve changes in synaptic strength. The artificial manipulations can help investigate the role of synaptic strength in a specific brain circuit not only in various physiological phenomena like correlated neuronal firing and oscillations but also in behaviors. High and low-frequency stimulation at presynaptic sites has been used widely to induce long-term potentiation (LTP) and depression (LTD), respectively. This approach is effective in many brain areas, but not in the basolateral amygdala (BLA), because the robust local GABAergic tone inside the BLA restricts synaptic plasticity. Here, we identified the subclass of GABAergic neurons that gate LTP in the BLA afferents from the dorsomedial prefrontal cortex (dmPFC). Chemogenetic suppression of somatostatin-positive interneurons (Sst-INs) enabled the ex vivo LTP by high-frequency stimulation of the afferent, but the suppression of parvalbumin-positive interneurons (PV-INs) did not. Moreover, optogenetic suppression of Sst-INs with Arch also enabled LTP of the dmPFC-BLA synapses both ex vivo and in vivo. These findings reveal that Sst-INs but not PV-INs gate LTP in the dmPFC-BLA pathway and provide a method for artificial synaptic facilitation in BLA.

neuroscience↗

bioRxiv2019

Shared neural codes for eye-gaze and valence

The eye-gaze of others is a prominent social cue in primates and crucial for communication1-7, and atypical processing occurs in several conditions as autism-spectrum-disorder (ASD)1,9-14. The neural mechanisms that underlie eye-gaze remain vague, and it is still debated if these computations developed in dedicated neural circuits or shared with non-social elements. In many species, eye-gaze signals a threat and elicits anxiety, yet can also serve as a predictor for the outcome of the encounter: negative or positive2,4,8. Here, we hypothesized and find that neural codes overlap between eye-gaze and valence. Monkeys participated in a modified version of the human-intruder-test8,15 that includes direct and averted eye-gaze and interleaved with blocks of aversive and appetitive conditioning16,17. We find that single-neurons in the amygdala encode gaze18, whereas neurons in the anterior-cingulate-cortex encode the social context19,20 but not gaze. We identify a shared amygdala circuitry where neural responses to averted and direct gaze parallel the responses to appetitive and aversive value, correspondingly. Importantly, we distinguish two shared coding mechanisms: a shared-intensity scheme that is used for gaze and the unconditioned-stimulus, and a shared-activity scheme that is used for gaze and the conditioned-stimulus. The shared-intensity points to overlap in circuitry, whereas the shared-activity requires also correlated activity. Our results demonstrate that eye-gaze is coded as a signal of valence, yet also as the expected value of the interaction. The findings may suggest new insights into the mechanisms that underlie the malfunction of eye-gaze in ASD and the comorbidity with impaired social skills and anxiety.

neuroscience↗

bioRxiv2018

Observing fear enables plasticity of the dmPFC-BLA pathway during subsequent learning of inhibitory avoidance

Observing fear in others is a form of social distress. In mice, it leads to the formation of silent synapses in the prefrontal-amygdala pathway and enhances inhibitory avoidance learning at a later time. Here, we report that observing fear enabled ex vivo LTP. The unsilencing of silent synapses was the prevailing mechanism and the plasticity was occluded by inhibitory avoidance training. In free moving mice with OF experience, the inhibitory avoidance training transiently facilitated local field potentials evoked in BLA by stimulating the prefrontal afferents. The facilitation persisted during the first 4 hours after IA training, which is the time when IA memories consolidate. Thus, the OF-generated silent synapses enable plasticity that may enhance consolidation of IA memories.

neuroscience↗

bioRxiv2018

Oscillating bacterial expression states generate herd immunity to viral infection

Hypermutable loci are widespread in bacteria as mechanisms for rapid generation of phenotypic diversity, enabling individual populations to survive fluctuating, often antagonistic, selection pressures. As observed for adaptive immunity, hypermutation may facilitate survival of multiple, spatially-separated bacterial populations. We developed an oscillating prey assay to examine bacteriophage (phage) spread through populations of Haemophilus influenzae whose phage receptor gene, lic2A, is switched ON and OFF by mutations in a hypermutable tetranucleotide repeat tract. Phage extinction was frequently observed when the proportion of phage-resistant sub-populations exceeded 34%. In silico modelling indicated that phage extinction was interdependent on phage loss during transfer between populations and the frequency of resistant populations. In a fixed-area oscillating prey assay, heterogeneity in phage resistance was observed to generate vast differences in phage densities across multiple bacterial populations resulting in protective quarantining of some populations from phage attack. We conclude that phase-variable hypermutable loci produce bacterial herd immunity with resistant intermediary-populations acting as a barricade to reduce the viral load faced by phage-sensitive sub-populations. This paradigm of meta-population protection is applicable to evolution of hypermutable loci in multiple bacteria-phage and host-pathogen interactions.\n\nImportanceHerd immunity is a survival strategy wherein populations are protected against invading pathogens by resistant individuals within the population acting as a barrier to spread of the infectious agent. Although, this concept is normally only applied to higher eukaryotes, prokaryotic organisms also face invasion by infectious agents, such as bacterial viruses, bacteriophage (phage). Here we use novel experimental approaches and mathematical modelling, to show that bacteria exhibit a form of herd immunity through stochastically generated resistant variants acting as barricades to phage predation of sensitive cells. With hypermutable loci found in many prokaryotic systems, this phenomenon may be widely applicable to phage-bacteria interactions and could even impact phage-driven evolution in bacteria.

microbiology↗

bioRxiv2017

Impaired social contacts with familiar anesthetized conspecific in CA3-restricted BDNF knockout mice

Familiarity is the vital characteristic conveyed by social cues to determine behaviors towards conspecific. Here we characterize social contacts to familiar vs unfamiliar male conspecific, anesthetized to eliminate inter-male aggression. During initial 10 min (phase-1), subjects contacted demonstrators vigorously regardless of familiarity. During subsequent 80 min (phase-2), however, they contacted more with familiar than unfamiliar conspecifics. Then, this test was applied on highly aggressive mice with hippocampal CA3-restricted BDNF knockout (KO), in which aggression may mask other behaviors. KO showed less preference to contacting familiar conspecific than wild type (WT) during phase-2 but no differences during phase-1. Among non-social behaviors, eating duration was shorter in the presence of familiar than unfamiliar conspecific in WT, but same in KO. Additionally, KO exhibited reduced pain sensitization. Altogether, these findings suggest that KO has deficits in circuits that process social cues from familiar conspecifics and pain and, possibly, underlie empathy-like behaviors.

animal behavior and cognition↗

bioRxiv2017

Overexpression of Channelrhodopsin 2 interferes with the GABAb receptor-mediated depression of GABA release from the somatostatin-containing interneurons of the prefrontal cortex

Region and cell-type restricted expression of light activated ion channels is the indispensable tool to study properties of synapses in specific circuits and to monitor synaptic alterations by various stimuli including neuromodulators and behaviors, both ex vivo and in vivo. These analyses require the light-activated proteins or viral vectors for their delivery that do not interfere with the phenomenon under study. Here, we report a case of such interference in which the high-level expression of Channelrhodopsin-2 (ChR2) introduced in the somatostatin-positive GABAergic neurons (SOM-INs) of the dorsomedial prefrontal cortex (dmPFC) by an adeno-associated virus vector (AAV) weakens the presynaptic GABAb receptor-mediated suppression of GABA release.

neuroscience↗