Biology subjects

Smith, W.

Publications and source records attributed to Smith, W..

At least 19 recordsLinked to original sources

bioRxiv2026

A Neurotensin Brake on Exploratory Drive under Persistent Threat

Avoidance behavior is an adaptive response that delays exploration to promote survival. Avoidance is enhanced by psychological stress and is a hallmark of many neuropsychiatric disorders. Neural circuits that control avoidance by integrating stressful stimuli and modulating exploratory behavior remain underexplored. Elucidating the functional dynamics of this highly conserved phenomenon and the underlying neural mechanism of avoidance is an important open-ended question, with relevance to understanding both innate behaviors and neuropsychiatric disorders. Using predator odor as an innate, chronic stressor to increase avoidance behaviors in mice, we identified a neural population in the lateral septum (LS) that integrates threat information and modulates latency to explore. Calcium recordings in freely exploring mice combined with activity-based transcriptomics revealed that predator-responsive LS neurons are GABAergic and express neurotensin (LSNT). Further, single nuclei RNA-seq analysis revealed that among predator-responsive neurons, NT-enriched inhibitory clusters are predominant. Chronic activation of LSNT neurons induces avoidance behaviors in the absence of predator odor, while synaptic silencing of this population abrogates predator-enhanced avoidance. Using transgenic mouse models to indelibly tag predator-responsive neurons, we defined the downstream circuit that connects the encoding of predator odor information to the lateral hypothalamus. Projection-specific activation of LSNT[->]LHA neurons recapitulate stress-induced avoidance behaviors in mice. Finally, we showed that deletion of neurotensin from LS neurons prevented the effects of predator odor on exploration. Together, these findings offer a genetically-and projection-defined, top-down circuit linking the limbic neurotensinergic system to chronic psychological stress and avoidance behaviors in mice.

neuroscience↗

bioRxiv2026

Proximity labeling at H3K9me3 reveals VRK-1 regulate global chromatin distribution in C. elegans

Heterochromatin marked by histone H3 lysine 9 di- or trimethylation (H3K9me2/3) underpins transcriptional silencing and nuclear organization, yet its full complement of associated proteins remains incompletely defined. Here, we apply ChromID proximity labelling with the mouse HP1{beta} chromodomains to map the H3K9me3-proximal proteome in Caenorhabditis elegans, recovering known heterochromatin factors alongside previously uncharacterized candidates. We pursued one such candidate, the vaccinia-related kinase VRK-1, because of its established but poorly understood links to chromatin organization. Intriguingly, VRK-1 dynamically relocates from a broad nuclear distribution to the nuclear periphery upon azide or heat stress. Following these stresses, bulk chromatin exhibits similarly increased peripheral enrichment and apparent compaction, as assessed by radial fluorescence profiles. Although VRK-1 is not necessary for stress-induced chromatin reorganization, decompaction and repositioning of chromatin away from the nuclear envelope during recovery requires VRK-1. VRK-1 depletion leads to persistent perinuclear chromatin retention and compromises post-stress survival. Furthermore, loss of VRK-1 catalytic activity results in over-retention of chromatin at the nuclear periphery under normal growth conditions; this phenotype can be reversed by depletion of a key VRK-1 substrate at the nuclear envelope BAF-1. Our findings identify VRK-1 as a key regulator that controls the interaction of chromatin with the nuclear lamina through regulation of BAF-1.

cell biology↗

bioRxiv2026

Efficacy of glucocorticoid modulator PT150 as a weight loss strategy

Obesity affects millions of people worldwide and has serious complications such as cardiovascular disease and diabetes. Current treatments for obesity target proteins such as the receptors for glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP) and/or glucagon (GCG). These interventions have revolutionized the treatment of obesity and represent first-line pharmacotherapeutic strategies. One major weakness to these strategies is that once drug treatment stops, most patients are unable to maintain the new body weight setpoint, often gaining weight back rapidly. Thus, the identification of new therapies that focus on the ability to maintain homeostatic setpoint are necessary. The glucocorticoid receptor (GR) has been implicated in several pathways including reward-seeking, inflammation, stress and energy balance. Here, we investigated the effects of 30 days treatment with PT150 (40 mg/kg), a novel GR antagonist, alone and in combination with semaglutide (30 nmol/kg) on food intake, glucose homeostasis, body weight and setpoint maintenance using a C57Bl/6 diet-induced obesity (DIO) mouse model. We monitored food intake and body weight throughout treatment and after drug washout for 20 days to evaluate defended body weight maintenance (body weight setpoint). Our results indicate that treatment with PT150 alone does not significantly alter body weight but in combination with semaglutide it shows the most promising effects in body weight reduction and homeostatic setpoint maintenance. Together, these data suggest that PT150, a GR modulator, may be effective as a homeostatic setpoint modulator when combined with semaglutide.

physiology↗

bioRxiv2025

Screening of a kinase library in human Huntington disease iPSC derived striatal precursor neurons reveals a neuroprotective effect of PKC alpha and PKC beta1 inhibition

The loss of striatal medium spiny neurons is a hallmark of Huntingtons disease (HD). To identify potential disease-modifying treatments, we previously developed a human neuronal model by immortalizing and differentiating HD patient-derived iPSCs into highly homogeneous striatal precursor neurons (ISPNs). Using a 96-well screening platform, and two rounds of re-screening, we tested a kinase inhibitor library and identified 5 compounds that protected HD ISPNs from mutant huntingtin (mHTT)-induced toxicity. Among these, we prioritized the PKC-/{beta}1 inhibitor GO6976, which rescued HD ISPNs from mHTT toxicity in a dose-dependent manner. Further, we found increased phosphorylation of PKC- and PKC-{beta}1 in HD cells and tissues, while their overexpression was toxic to HD ISPNs. Knockdown of PKC-/{beta}1 protected the neurons, and both isoforms interacted and colocalized with HTT. These results suggest that PKC-/{beta}1 plays a role in HD neurodegeneration, and that inhibiting their activity may offer a potential therapeutic approach for HD. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=194 SRC="FIGDIR/small/677178v2_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@256d6org.highwire.dtl.DTLVardef@1931e7borg.highwire.dtl.DTLVardef@1b6598borg.highwire.dtl.DTLVardef@b0bbb5_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIHD patient-derived iPSC-based striatal precursor neurons (ISPNs) were used to screen and identify neuroprotective compounds. C_LIO_LIThe PKC-/{beta}1 inhibitor GO6976 rescues HD ISPNs from mutant huntingtin (HTT)-induced toxicity. C_LIO_LIThe phosphorylation of PKC-/{beta}1 is elevated in HD cell and tissues, and PKC-/{beta}1 interact with both wild-type and mutant huntingtin. C_LIO_LIOverexpression of PKC-/{beta}1 is toxic to HD ISPNs, while its knockdown protects the neurons. C_LI

neuroscience↗

bioRxiv2025

The dorsal/ventral subdivision of the hindbrain predates the tunicate/vertebrate split

While the CNSs of the chordate sister clades Tunicata and Vertebrata have unmistakable homology, the extent of their conservation is still being uncovered. We report that the hindbrain of the tunicate Ciona, like those of vertebrates, has functionally-distinct dorsal and ventral domains. The Ciona dorsal hindbrain functions as a relay and processing center for peripheral sensory neurons, while in vertebrates the dorsal hindbrain forms the cerebellum. Despite the different fates of dorsal hindbrains in Ciona versus vertebrates, we present evidence from analysis of gene expression, developmental mechanisms, and neural circuit architecture that they share a common origin. While it is generally agreed that the cerebellum evolved in vertebrates, our findings indicate that a dorsally-positioned precursor to the cerebellum has much deeper roots.

evolutionary biology↗

bioRxiv2025

In-situ calibration of passive samplers for monitoring host-associated fecal markers in an urban river

Passive sampling in aquatic environments has shown promise as a time- and cost-efficient method with improved sensitivity for detecting microbial pollution in dynamic and variable conditions. However, quantitative descriptions of its field performance have been scarce, impeding its broader application in environmental settings. The performance of two membrane-based passive samplers (Torpedo and MSTFlow) in quantifying human (Carjivirus, Pepper Mild Mottle Virus [PMMoV], Tomato Brown Rugose Fruit Virus [ToBRFV]) and avian (Helicobacter spp. GFD marker) fecal pollution markers in an urban riverine environment over a 72-h deployment was evaluated using a first-order kinetic model to characterize their microbial adsorption characteristics. Results were compared with those from parallel composite and time-weighted auto-sampling. Accumulation in passive samplers exhibited an initial lag phase (0 to 8 h for viruses) and reached equilibrium within 16 h of initial deployment, except for GFD. Sampling rates were highest for PMMoV (6.29 and 5.11 mL/h) for MSTFlow and Torpedo samplers respectively, followed by Carjivirus (4.63 and 3.63 mL/h), ToBRFV (2.17 and 1.22 mL/h) and GFD (0.68 mL/h in Torpedo sampler). At equilibrium, both sampler configurations accumulated more than 22-170 times the amount of target gene copies in each mL of grab water samples depending on sampler and virus. These findings highlight passive sampling as a promising, sensitive, cost-effective, and low-maintenance alternative for continuous microbial water quality monitoring in aquatic environments. Overall, this study advances the understanding of passive sampling kinetics and supports broader adoption of passive samplers for tracking fecal pollution in environmental waters.

microbiology↗

bioRxiv2025

Integrating affinity chromatography in the platform process for Adenovirus purification

Adenoviral vectors (AdVs) are gaining prominence in cancer therapy and vaccine development, posing the need for a modern AdV manufacturing platform. Current AdV purification by ion-exchange chromatography indeed struggles to achieve the products yield and purity of processes that employ affinity technologies. Addressing these challenges, this study presents the first affinity-based process that delivers high product yield and clearance of host cell proteins and DNA (HCPs and hcDNA) in two chromatography steps. The affinity capture utilizes resins functionalized with peptide ligands that target AdV hexon proteins (AEFFIWNA and TNDGPDYSSPLTGSG), and provide high capacity (>5{middle dot}1010 vp per mL of resin) and yield under mild elution conditions ([~]50% at pH 8.0). Peptide-functionalized adsorbents prepared using different matrices (polymethylmethacrylate vs. agarose) were initially tested to compare the purification performance. AEFFIWNA-SulfoLink resin was selected for its yield of cell- transducing AdVs ([~]50%) and removal of HCPs and hcDNA (144-fold and 56-fold). Similarly, TNDGPDYSSPLTGSG-Toyopearl(R) resin afforded [~]50% yield and >50-fold reduction of con- taminants. Additional gains in product purity were achieved by optimizing the washing step, which removed free hexon proteins and additional HCPs. All peptide-functionalized resins maintained their purification performance for ten cycles upon regeneration at pH [~]2.0. The purification process was assembled to include clarification, affinity capture in bind-and-elute mode using AEFFIWNA-SulfoLink resin, and polishing in flow-through mode using mixed- mode resins. The optimized process provided a yield [~]50% of cell-infecting units (IFU) and a product titer [~]107 IFU/mL, along with residual HCP and hcDNA levels ([~]10 ng/mL and 44 ng per dose, respectively) that meet clinical requirements.

bioengineering↗

bioRxiv2025

Green cities and the risk for vector-borne disease transmission for humans and animals: a scoping review

BackgroundGreening cities is a nature-based strategy for sustainable urban development that integrates natural elements like plants or water bodies, to mitigate climate change impacts and enhance human well-being. However, urban green infrastructures (UGIs) can influence the distribution of disease vectors, potentially affecting vector-borne diseases (VBDs). UGIs may provide new suitable environments for urban vectors, while also creating opportunities to mitigate VBD risks through predation, competition, and dilution effects. This article examined the relationships between UGIs, vectors, and associated pathogens, impacting both human and animal health, highlighting knowledge gaps and identifying research priorities to support VBD risk mitigation measures and to guide smart urban planning and design. MethodsA systematic literature search was conducted following PRISMA guidelines in three databases (Pubmed, Scopus, Web of Science). Selected articles involved (i) any aspect of a urban vector system, (ii) in UGIs, and (iii) statistical analysis of the effects of UGIs on VBD risk. Methods employed to characterize UGIs and VBDs were described and the identified impacts were summarized by vector group. ResultsAmong the 98 articles reviewed, most addressed mosquito-pathogen systems (66), tick-pathogen systems (29), and few other vector-borne pathogen systems (3), with studies often confined to a single city or several cities within the same country and focused on one vector group. Urban vegetation generally appeared to heighten the risk of tick-borne diseases. In contrast, the influence of UGIs on the risk of mosquito-borne diseases varied depending on the vector system and on the environmental and climatic context. The diversity of indicators used to assess UGIs and VBD risks may affect the observed impact on VBD risk. ConclusionGiven the increasing popularity of urban greening, it is crucial to investigate its potential implications for public health, and thereby urban planning decisions. However, the lack of standardized protocols complicates the accurate assessment of the effects of UGIs on the risk for VBD emergence and transmission and consequently, on potential mitigation measures.

ecology↗

bioRxiv2025

Surveillance of Japanese Encephalitis Virus in Piggery Effluent and Environmental Samples: A Complementary Tool for Outbreak Detection

Japanese encephalitis virus (JEV) is an emerging public health and biosecurity concern in Australia, with recent human cases and detections in mosquitoes and pigs across multiple states highlight the risk to susceptible human and animal populations. While traditional surveillance methods such as mosquito trapping, sentinel chicken programs and direct testing of pig specimens remain essential, monitoring effluent offers a valuable complementary approach for detecting infections within animal populations. This study presents the first evidence of JEV in Australian piggery effluents/environmental waters, demonstrating the feasibility of effluent and environmental water surveillance for JEV monitoring. Effluent/environmental samples from multiple piggery sites were analyzed using real-time reverse transcription polymerase chain reaction (RT-PCR), revealing the presence of JEV genetic fragments in solid and liquid fractions of effluents at three farms, with corresponding veterinary cases in some herds. Viral RNA was detected more frequently in solid fraction of effluent samples, aligning with previous findings on the partitioning behaviour of mosquito-borne viruses. The detection of JEV in the borrow pit (i.e., a man-made excavation that holds water) water sample highlights potential transmission pathways via mosquito vectors. These findings demonstrate the value of effluent monitoring as an additional tool for JEV surveillance in piggery settings, supporting potential early warning systems and mitigation strategies. Integrating effluent-based monitoring with traditional surveillance approaches could improve livestock industry related disease detection, risk assessments, and response efforts for human and animal health in endemic and emerging regions. Wastewater/effluent surveillance may have important applications for the management of a wide range of emerging animal diseases. IMPORTANCEThis study presents the first evidence of Japanese encephalitis virus (JEV) detection in Australian piggery effluents, establishing effluent surveillance as a valuable complementary tool for monitoring viral pathogens in animal populations. Our findings support the integration of effluent monitoring with traditional surveillance systems to improve early warning capabilities, enhance biosecurity, and mitigate risks to both animal and human health.

molecular biology↗

bioRxiv2025

An evolutionarily conserved microRNA, miR-185, regulates key pathways that may contribute to implantation failure.

Recurrent implantation failure (RIF) is defined after three or more good quality embryo transfers following in vitro fertilisation without a successful pregnancy outcome. Many factors contribute to RIF however, the endometrial contribution remains unclear. Previous work by our group has identified a micro-RNA (miRNA) miR-185-5p as conserved across placental mammal irrespective of implantation strategies. We tested the hypothesis that miR-185-5p and the pathways it regulates, may be disrupted in the endometria of women with RIF. A human endometrial epithelial cells line (Ishikawa cells) was transfected with mimics or inhibitors for miR-185-5p for 24 (for implantation assay) or 48 hr (for proteomic analysis) along with non-targeting controls. There was a significant different in percentage attachment of BeWoW spheroids to cells transfected with miR-185-5p mimic compared to inhibitor (P<0.05). Transfection of epithelial cells with miR-185-5p altered expression of 1450 (mimic alone) and 509 (inhibitor alone) proteins respective of which, 146 were modified by both. Comparison of predicted targets of miR-185-5p, proteins modified by this study, and key endometrial genes from the literature determined genes and proteins associated with CNP family were further investigated in biopsies from individuals with (n=10) and without RIF (n=9) with CSNK1D expression significantly lower (p<0.05) in individuals with RIF. Collectively these data demonstrate that miR-185-5p modifies pathways that are important for successful implantation in humans.

cell biology↗

bioRxiv2024

Deep homologies in chordate caudal central nervous systems

Invertebrate chordates, such as the tunicate Ciona, can offer insight into the evolution of the chordate phylum. Anatomical features that are shared between invertebrate chordates and vertebrates may be taken as evidence of their presence in a common chordate ancestor. The central nervous systems of Ciona larvae and vertebrates share a similar anatomy despite the Ciona CNS having [~]180 neurons. However, the depth of conservation between the Ciona CNS and those in vertebrates is not resolved. The Ciona caudal CNS, while appearing spinal cord-like, has hitherto been thought to lack motor neurons, bringing into question its homology with the vertebrate spinal cord. We show here that the Ciona larval caudal CNS does, in fact, have functional motor neurons along its length, pointing to the presence of a spinal cord-like structure at the base of the chordates. We extend our analysis of shared CNS anatomy further to explore the Ciona "motor ganglion", which has been proposed to be a homolog of the vertebrate hindbrain, spinal cord, or both. We find that a cluster of neurons in the dorsal motor ganglion shares anatomical location, developmental pathway, neural circuit architecture, and gene expression with the vertebrate cerebellum. However, functionally, the Ciona cluster appears to have more in common with vertebrate cerebellum-like structures, insofar as it receives and processes direct sensory input. These findings are consistent with earlier speculation that the cerebellum evolved from a cerebellum-like structure, and suggest that the latter structure was present in the dorsal hindbrain of a common chordate ancestor.

neuroscience↗

bioRxiv2023

Highly pathogenic avian influenza causes mass mortality in Sandwich tern (Thalasseus sandvicensis) breeding colonies across northwestern Europe

AO_SCPLOWBSTRACTC_SCPLOWIn 2022, highly pathogenic avian influenza (HPAI) A(H5N1) virus clade 2.3.4.4b became enzootic and caused mass mortality in Sandwich terns and other seabird species across northwestern Europe. We present data on characteristics of the spread of the virus between breeding colonies and the number of dead adult Sandwich terns recorded at breeding sites throughout northwestern Europe. Within two months after the first mortalities were reported, in total 20,531 adult Sandwich terns were found dead, which is >17% of the total northwestern European breeding population. Losses are likely higher, as we expect that many victims were not found (mortality rate might be up to 74% of the breeding population). Inside the colonies almost all chicks died. After the peak of the outbreak, in a colony established by late breeders, 25.7% of adults showed immunity against HPAI subtype H5. Removal of carcasses helped in reducing the spread of the disease and consequently total mortality. More research on the sources and modes of transmission, incubation times, effective containment and immunity is urgently needed to combat this major threat for colonial seabirds.

ecology↗

bioRxiv2023

An single oscillating proto-hypothalamic neuron gates taxis behavior in the primitive chordate Ciona

Ciona larvae display a number of behaviors, including negative phototaxis. In negative phototaxis, the larvae first perform short spontaneous rhythmic casting swims. As larvae cast in a light field, their photoreceptors are directionally shaded by an associated pigment cell, providing a phototactic cue. This then evokes an extended negative taxis swim. We report here that the larval forebrain of Ciona has a previously uncharacterized single slow-oscillating inhibitory neuron (neuron cor-assBVIN78) that projects to the midbrain, where it targets key interneurons of the phototaxis circuit known as the photoreceptor relay neurons. The anatomical location, gene expression and oscillation of cor-assBVIN78 suggest homology to oscillating neurons of the vertebrate hypothalamus. Ablation of cor-assBVIN78 results in larvae showing extended phototaxis-like swims, but which occur in the absence of phototactic cues. These results indicate that cor-assBVIN78 has a gating activity on phototaxis by projecting temporally-oscillating inhibition to the photoreceptor relay neurons. However, in intact larvae the frequency of cor-assBVIN78 oscillation does not match that of the rhythmic spontaneous swims, indicating that the troughs in oscillations do not themselves initiate swims, but rather that cor-assBVIN78 may modulate the phototaxis circuit by filtering out low level inputs while restricting them temporally to the troughs in inhibition.

neuroscience↗

bioRxiv2023

A whole nervous system atlas of glutamate receptors reveals distinct receptor roles in sensorimotor circuits

A goal of connectomics is to reveal the links between neural circuits and behavior. Larvae of the primitive chordate Ciona are well-suited to make contributions in this area. The small size of the Ciona larval nervous system ([~]180 neurons) has facilitated the full characterization of a connectome. In addition, the larvae display a range of behaviors that are readily quantified in both normal and manipulated larvae. Moreover, the small number of neurons allows for a neuron-by-neuron characterization of attributes such as neurotransmitter use. We present here a nervous system-wide atlas of glutamate receptor expression. Included in the atlas are both ionotropic receptors (AMPA, NMDA, and Kainate), and metabotropic receptors. The expression of these receptors is presented in the context of known circuits driving behaviors such as phototaxis, mechanosensation, and looming shadow response. The expression of AMPA and NMDA receptors, in particular, helps to resolve the apparently paradoxical coproduction of GABA and glutamate by some photoreceptors. We find that the targets of these photoreceptors, midbrain relay neurons, primarily express NMDA receptors in the absence of AMPA receptors. This is in agreement with previous results indicating that GABA is the primary neurotransmitter from the photoreceptors evoking a behavioral response (swimming) through a disinhibition mechanism. We hypothesize that NMDA receptors have a modulatory effect in the relay neurons. Other findings reported here are more unexpected. For example, the targets of glutamatergic epidermal sensory neurons (ESNs) do not express any of the ionotropic receptors, yet the ESNs themselves express metabotropic receptors. Thus, we speculate that their production of glutamate may be for communication with neighboring ESNs, rather than to their interneuron targets.

neuroscience↗

bioRxiv2022

DBERlibR: Automated Data Analysis for Discipline-Based Education Research

Discipline-Based Education Research (DBER) scientists repeatedly analyze assessment data to ensure question items reliability and examine the efficacy of a new educational intervention. Analyzing assessment data comprises multiple steps and statistical techniques that consume much of researchers time and are error-prone. While education research continues to grow across many disciplines of science, technology, engineering, and mathematics (STEM), the DBER community lacks tools to streamline education research data analysis. DBERlibR--an R package to streamline and automate DBER data processing and analysis--fills this gap. The package reads user-provided assessment data, cleans them, merges multiple datasets (as necessary), checks assumption(s) for specific statistical techniques (as necessary), applies various statistical tests (e.g., one-way analysis of covariance, one-way repeated-measures analysis of variance), and presents and interprets the results all at once. By providing the most frequently used analytic techniques, this package will contribute to DBER by facilitating the creation and widespread use of evidence-based knowledge and practices. The outputs contain a sample interpretation of the results for users convenience. User inputs are minimal; they only need to prepare the data files as instructed and type a function in RStudio to conduct a specific data analysis.

scientific communication and education↗

bioRxiv2022

Transcellular chaperone signaling is an intercellular stress-response distinct from the HSF-1 mediated HSR

Organismal proteostasis is maintained by intercellular signaling processes including cell nonautonomous stress responses such as transcellular chaperone signaling (TCS). When TCS is activated upon tissue-specific knockdown of hsp-90 in the C. elegans intestine, heat-inducible hsp-70 is induced in muscle cells at the permissive temperature resulting in increased heat stress resistance and lifespan extension. However, our understanding of the molecular mechanism and signaling factors mediating transcellular activation of hsp-70 expression from one tissue to another is still in its infancy. Here we conducted a combinatorial approach using transcriptome RNA-Seq profiling and a forward genetic mutagenesis screen to elucidate how stress-signaling from the intestine to the muscle is regulated. We find that the TCS-mediated "gut-to-muscle" induction of hsp-70 expression is suppressed by HSF-1 and instead relies on transcellular-X-cross-tissue (txt) genes. We identify a key role for the PDZ-domain guanylate cyclase txt-1 and the homeobox transcription factor ceh-58 as signaling hubs in the stress receiving muscle cells to initiate hsp-70 expression and facilitate TCS-mediated heat stress resistance and lifespan extension. Our results provide a new view on cell-nonautonomous regulation of "inter-tissue" stress responses in an organism that highlight a key role for the gut. Our data suggest that the HSF-1-mediated HSR is switched off upon TCS activation, in favor of an intercellular stress-signaling-route to safeguard survival.

genetics↗

bioRxiv2021

Automatic Detection and Neurotransmitter Prediction of Synapses in Electron Microscopy

This paper presents a deep-learning based workflow to detect synapses and predict their neurotransmitter type in the primitive chordate Ciona intestinalis (Ciona) EM images. Identifying synapses from electron microscopy (EM) images to build a full map of connections between neurons is a labor-intensive process and requires significant domain expertise. Automation of synapse detection and classification would hasten the generation and analysis of connectomes. Furthermore, inferences concerning neuron type and function from synapse features are in many cases difficult to make. Finding the connection between synapse structure and function is an important step in fully understanding a connectome. Activation maps derived from the convolutional neural network provide insights on important features of synapses based on cell type and function. The main contribution of this work is in the differentiation of synapses by neurotransmitter type through the structural information in their EM images. This enables prediction of neurotransmitter types for neurons in Ciona which were previously unknown. The prediction model with code is available on Github.

neuroscience↗

bioRxiv2021

An ancestral burst of regulatory and protein innovation drives divergent implantation in eutherian mammals.

Summary paragraphThe origin of live birth in mammals [~]148 million years ago was a dramatic shift in reproductive strategy, yet the molecular changes that established mammal viviparity are largely unknown. Although progesterone receptor signalling predates the origin of mammals andis highly conserved in, and critical for, successful mammal pregnancy, it alone cannot explain the origin and subsequent diversity of implantation strategies throughout the placental mammal radiation. MiRNAs are known to be flexible and dynamic regulators with a well established role in the pathophysiology of mammal placenta. We propose that a dynamic core microRNA (miRNA) network originated early in placental mammal evolution, responds to conserved mammal pregnancy cues (e.g. progesterone), and facilitates species-specific responses. Here we identify 13 miRNAs that arose at the origin of placental mammals and were subsequently retained in all descendent lineages. The expression of these 13 miRNAs in response to early pregnancy molecules is regulated in a species-specific manner in endometrial epithelia of species with extremes of implantation strategies. Furthermore, these 13 miRNAs preferentially target 84 proteins under positive selective pressure on ancestral eutherian. Discovery of this core "live-birth" toolkit and specifically adapted proteins helps explain the origin and evolution of the placenta in mammals.

evolutionary biology↗