Biology subjects

Liu, C. M.

Publications and source records attributed to Liu, C. M..

10 recordsLinked to original sources

bioRxiv2026

CD11c+ myeloid cells are the predominant CD4+CCR5+ immune population in the foreskin and are increased in men with HIV-associated penile anaerobes

Specific anaerobic species within the penile microbiome - Bacteria Associated with Seroconversion, Inflammation and Immune Cells (BASIC) - have been linked to increased HIV-1 susceptibility. These bacteria can directly disrupt epithelial integrity and are believed to increase local inflammation, resulting in an increased density of HIV-susceptible T cells in the inner foreskin. It is currently unknown whether other immune cells bearing the HIV entry receptors, CD4 and CCR5, are also elevated in individuals with a high abundance of BASIC species. Using inner foreskin tissues and penile swabs from males undergoing voluntary medical male circumcision, we performed a retrospective cross-sectional study to assess the relationship between BASIC species and the tissue density of such immune cells, including CD68+ macrophages, CD11c+ dendritic cells, and CD207+ Langerhans cells. The most abundant cells in the inner foreskin expressing the HIV co-receptors were CD11c+ dendritic cells (48.6% of CD4+/CCR5+ cells), followed by CD68+ macrophages (28.6%), CD3+ T cells (18.8%), and CD207+ Langerhans-like (8.8%) cells. The absolute abundance of BASIC species was associated with elevated tissue densities of both CD4+/CCR5+ T cells (as previously reported) and a heterogeneous population of CD3-/CD4+/CCR5+ cells of myeloid origin. In the dermis, BASIC species abundance was linked to elevated densities of cells expressing CD11c, CD68, and CD207, as well as those co-expressing CD11c and CD207; furthermore, CD11c+ and CD207+ cells were farther from the basement membrane in participants with a high abundance of BASIC species. Myeloid cells were not elevated in participants with a high abundance of control taxa. In an integrated analysis including previously published data from this same cohort, myeloid-cell densities clustered tightly together, positively correlated with BASIC species and pro-inflammatory cytokines, and had trends to negative correlations with control taxa (significant for CD207+ cell density). Overall, our findings suggest that BASIC species are associated with a broader foreskin immune phenotype marked by increased densities of HIV-susceptible myeloid and T cells, alongside epithelial disruption.

immunology↗

bioRxiv2024

Oxytocin neurons in the paraventricular and supraoptic hypothalamic nuclei bidirectionally modulate food intake

Oxytocin (OT) is a neuropeptide produced in the paraventricular (PVH) and supraoptic (SON) nuclei of the hypothalamus. Either peripheral or central administration of OT suppresses food intake through reductions in meal size. However, pharmacological approaches do not differentiate whether observed effects are mediated by OT neurons located in the PVH or in the SON. To address this, we targeted OT neuron-specific designer receptors exclusively activated by designer drugs (DREADDs) in either the PVH or SON in rats, thus allowing for evaluation of food intake following selective activation of OT neurons separately in each nucleus. Results revealed that DREADDs-mediated excitation of PVH OT neurons reduced consumption of both standard chow and a high fat high sugar diet (HFHS) via reductions in meal size. On the contrary, SON OT neuron activation had the opposite effect by increasing both standard chow and liquid sucrose consumption, with the former effect mediated by an increase in meal size. To further examine the physiological role of OT neurons in eating behavior, a viral-mediated approach was used to silence synaptic transmission of OT neurons separately in either the PVH or SON. Results from these studies revealed that PVH OT neuron silencing significantly increased consumption of HFHS by increasing meal size whereas SON OT neuron silencing reduced chow consumption by decreasing meal size. Collectively these data reveal that PVH and SON OT neurons differentially modulate food intake by either increasing or decreasing satiation signaling, respectively.

neuroscience↗

bioRxiv2024

Hippocampus oxytocin signaling promotes prosocial eating in rats

The hypothalamic neuropeptide oxytocin (OT) influences both food intake and social behavior. Given that food preference and consumption are heavily affected by social factors in mammals, it is critical to understand the extent that OTs role in regulating these two fundamental behaviors is interconnected. Here we evaluated the role of OT signaling in the dentate gyrus of the dorsal hippocampus (HPCd), a brain region recently linked with eating and social memory, on food preference and consumption in rats under conditions that vary with regards to social presence and conspecific familiarity. Results from neuropharmacological and virogenetic knockdown approaches reveal that HPCd OT signaling promotes eating in the presence of a familiar but not an unfamiliar conspecific. Additionally, HPCd OT receptor signaling is required for the social transmission of food preference. These findings collectively identify the HPCd as a novel substrate where oxytocin synergistically influences eating and social behaviors.

neuroscience↗

bioRxiv2022

Synthetic glycans that control gut microbiome structure mitigate colitis in mice

Relative abundances of bacterial species in the gut microbiome have been linked to many diseases. Species of gut bacteria are ecologically differentiated by their abilities to metabolize different glycans, making glycan delivery a powerful way to alter the microbiome to promote health. We describe the properties and therapeutic potential of chemically diverse synthetic glycans (SGs). Fermentation of SGs by gut microbiome cultures resulted in compound-specific shifts in taxonomic and metabolite profiles not observed with reference glycans, including prebiotics. Model enteric pathogens grow poorly on most SGs, potentially increasing their safety for at-risk populations. SGs increased survival, reduced weight loss, and improved clinical scores in mouse models of colitis. Synthetic glycans are thus a promising modality to improve health through selective changes to the gut microbiome.

microbiology↗

bioRxiv2021

Leakiness at the human-animal interface in Southeast Asia and implications for the spread of antibiotic resistance

International efforts to curb antimicrobial resistance have focused on drug development and limiting unnecessary use. However, in areas where water, sanitation, and hygiene infrastructure is lacking, and where biosecurity in food-animal production is poor, pathogen-flow between humans and animals could exacerbate the emergence and spread of resistant pathogens. Here, we compared mobile resistance elements among Escherichia coli recovered from humans and meat in Cambodia, a country with substantial connectivity between humans and animals, unregulated antibiotic use, and poor environmental controls. We identified multiple resistance-encoding plasmids and a novel, blaCTX-M and qnrS1-encoding transposon that were widely dispersed in both humans and animals, a phenomenon rarely observed in high-income settings. Our findings indicate that plugging leaks at human-animal interfaces should be a critical part of addressing antimicrobial resistance in low and middle-income countries.

ecology↗

bioRxiv2021

Integrating Sample Similarities into Latent Class Analysis: A Tree-Structured Shrinkage Approach

SO_SCPLOWUMMARYC_SCPLOWThis paper is concerned with using multivariate binary observations to estimate the probabilities of unobserved classes with scientific meanings. We focus on the setting where additional information about sample similarities is available and represented by a rooted weighted tree. Every leaf in the given tree contains multiple samples. Shorter distances over the tree between the leaves indicate a priori higher similarity in class probability vectors. We propose a novel data integrative extension to classical latent class models (LCMs) with tree-structured shrinkage. The proposed approach enables 1) borrowing of information across leaves, 2) estimating data-driven leaf groups with distinct vectors of class probabilities, and 3) individual-level probabilistic class assignment given the observed multivariate binary measurements. We derive and implement a scalable posterior inference algorithm in a variational Bayes framework. Extensive simulations show more accurate estimation of class probabilities than alternatives that suboptimally use the additional sample similarity information. A zoonotic infectious disease application is used to illustrate the proposed approach. The paper concludes by a brief discussion on model limitations and extensions.

genomics↗

bioRxiv2020

Central oxytocin signaling inhibits food reward-motivated behaviors and VTA dopamine responses to food-predictive cues

Oxytocin potently reduces food intake and is a potential target system for obesity treatment. A better understanding of the behavioral and neurobiological mechanisms mediating oxytocins anorexigenic effects may guide more effective obesity pharmacotherapy development. The present study examined the effects of central (lateral intracerebroventricular [ICV]) administration of oxytocin in rats on motivated responding for palatable food. Various conditioning procedures were employed to measure distinct appetitive behavioral domains, including food seeking in the absence of consumption (conditioned place preference expression), impulsive responding for food (differential reinforcement of low rates of responding), effort-based appetitive decision making (high-effort palatable vs. low-effort bland food), and postingestive reward value encoding (incentive learning). Results reveal that ICV oxytocin potently reduces food-seeking behavior, impulsivity, and effort-based palatable food choice, yet does not influence encoding of postingestive reward value in the incentive learning task. To investigate a potential neurobiological mechanism mediating these behavioral outcomes, we utilized in vivo fiber photometry in ventral tegmental area (VTA) dopamine neurons to examine oxytocins effect on phasic dopamine neuron responses to sucrose-predictive Pavlovian cues. Results reveal that ICV oxytocin significantly reduced food cue-evoked dopamine neuron activity. Collectively, these data reveal that central oxytocin signaling inhibits various obesity-relevant conditioned appetitive behaviors, potentially via reductions in food cue-driven phasic dopamine neural responses in the VTA. HighlightsO_LICentral oxytocin inhibits motivated responding for palatable food reinforcement C_LIO_LICentral oxytocin does not play a role in encoding postingestive reward value C_LIO_LICentral oxytocin blunts VTA dopamine neuron activity in response to food cues C_LI

neuroscience↗

bioRxiv2020

Ghrelin signaling regulates feeding behavior, metabolism, and memory through the vagus nerve

Vagal afferent neuron (VAN) signaling sends information from the gut to the brain and is fundamental in the neural control of feeding behavior and metabolism. Recent findings reveal that VAN signaling also plays a critical role in cognitive processes, including hippocampus (HPC)-dependent memory. VANs, located in nodose ganglia, express receptors for various gut-derived endocrine signals, however, the function of these receptors with regards to feeding behavior, metabolism, and memory control is poorly understood. We hypothesized that VAN-mediated processes are influenced by ghrelin, a stomach-derived orexigenic hormone, via communication to its receptor (growth hormone secretagogue receptor [GHSR]) expressed on gut-innervating VANs. To examine this hypothesis, rats received nodose ganglia injections of an adeno-associated virus (AAV) expressing short hairpin RNAs targeting GHSR (or a control AAV) for RNA interference-mediated VAN-specific GHSR knockdown. Results reveal that VAN GHSR knockdown induced various feeding and metabolic disturbances, including increased meal frequency, impaired glucose tolerance, delayed gastric emptying, and increased body weight compared to controls. Additionally, VAN-specific GHSR knockdown impaired HPC-dependent episodic contextual memory and reduced HPC brain-derived neurotrophic factor expression, but did not affect anxiety-like behavior or levels of general activity. A functional role for endogenous VAN GHSR signaling was further confirmed by results revealing that VAN signaling is required for the hyperphagic effects of ghrelin administered at dark onset, and that gut-restricted ghrelin-induced increases in VAN firing rate require intact VAN GHSR expression. Collective results reveal that VAN GHSR signaling is required for both normal feeding and metabolic function as well as HPC-dependent memory.

neuroscience↗

bioRxiv2020

Hippocampus-lateral septum circuitry mediates memory for food location in rats

Remembering the location of a food or water source is essential for survival. Here we demonstrate that spatial memory for food location is reflected in ventral hippocampus (HPCv) neuron activity and is impaired by HPCv lesion. HPCv mediation of foraging-related memory involves downstream lateral septum (LS) signaling, as both reversible and chronic disconnection of HPCv (field CA1) to LS signaling impairs spatial memory retention for the location of either food or water reinforcement. This neural pathway selectively encodes appetitive spatial memory, as HPCv-LS disconnection does not affect aversive reinforcement-based spatial memory in an escape task using the same apparatus. The selectivity of this pathway in promoting foraging-related memory is further supported by results showing that CA1v-LS disconnection does not affect food intake, motivated operant responses for food, anxiety-like behavior, locomotor activity, or social and olfactory-based appetitive learning. Fluorescent in situ hybridization reveals that LS neurons recruited during the appetitive spatial memory task are primarily GABAergic, and multisynaptic anterograde neural pathway tracing and immediate early gene mapping identify the lateral hypothalamic area as a functional downstream target of this pathway. Collective results reveal a novel neural circuit through which the hippocampus selectively mediates memory for the location of appetitive (food or water) but not aversive (escape) reinforcement.

neuroscience↗

bioRxiv2020

Nucleus accumbens melanin-concentrating hormone signaling promotes feeding in a sex-specific manner

Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide produced in the lateral hypothalamus and zona incerta that increases food intake. The neuronal pathways and behavioral mechanisms mediating the orexigenic effects of MCH are poorly understood, as is the extent to which MCH-mediated feeding outcomes are sex-dependent. Here we investigate the hypothesis that MCH-producing neurons act in the nucleus accumbens shell (ACBsh) to promote feeding behavior and motivation for palatable food in a sex-dependent manner. We utilized ACBsh MCH receptor (MCH1R)-directed pharmacology as well as a dual virus chemogenetic approach to selectively activate MCH neurons that project to the ACBsh. Results reveal that both ACBsh MCH1R activation and activating ACBsh-projecting MCH neurons increase consumption of standard chow and palatable sucrose in male rats without affecting motivated operant responding for sucrose, general activity levels, or anxiety-like behavior. In contrast, food intake was not affected in female rats by either ACBsh MCH1R activation or ACBsh-projecting MCH neuron activation. To determine a mechanism for this sexual dimorphism, we investigated whether the orexigenic effect of ACBsh MCH1R activation is reduced by endogenous estradiol signaling. In ovariectomized female rats on a cyclic regimen of either estradiol (EB) or oil vehicle, ACBsh MCH1R activation increased feeding only in oil-treated rats, suggesting that EB attenuates the ability of ACBsh MCH signaling to promote food intake. Collective results show that that MCH ACBsh signaling promotes feeding in an estrogen- and sex-dependent manner, thus identifying novel neurobiological mechanisms through which MCH and female sex hormones interact to influence food intake.

neuroscience↗