Biology subjects

Lopez, K. M.

Publications and source records attributed to Lopez, K. M..

5 recordsLinked to original sources

bioRxiv2026

Third Trimester-Equivalent Alcohol Exposure Reduces Neurons in Males and Increases Vglut2⁺ Neurons with Reduced Intrinsic Bursting in Females in The Murine Dorsal Subiculum

Individuals with Fetal Alcohol Spectrum Disorders (FASDs) show reduced subicular volume, and preclinical studies compliment this by demonstrating that third-trimester-equivalent ethanol exposure induced apoptosis in corticolimbic regions, including the subiculum. The subiculum mediates hippocampal-cortical communication critical for long-term memory consolidation. Within the distal dorsal subiculum, a population of bursting neurons uniquely express VGLUT2 and they play a key role in memory processing. We hypothesized that third-trimester-equivalent ethanol exposure would reduce neuronal and VGLUT2+ cell density in the dorsal subiculum and reduce the excitability of bursting neurons, providing a mechanism for long-term memory impairments observed in FASD. To test this, postnatal day (P)7 mice received a subcutaneous injection of ethanol and long-term effects were assessed in adolescence (P35-62). Using transgenic mice with fluorescently labeled VGLUT2+ neurons, and immunohistochemistry we observed a significant reduction in neuronal density in males and an increase in VGLUT2+ cell density in females. Using whole-cell patch clamp electrophysiology, we observed a reduction in action potentials per burst in both sexes. Additionally, females showed reduced overall excitability, and a subset of neurons exhibited a shift to regular spiking. These findings suggest that development ethanol exposure disrupts subicular output by impairing burst firing, potentially weaking hippocampal-cortical communication and contributing to the cognitive deficits associated with FASD. HighlightsO_LIThird-trimester ethanol targets VGLUT2+ neurons in the dorsal subiculum C_LIO_LIEthanol reduced neuronal density in male dorsal subiculum C_LIO_LIEthanol increases VGLUT2+ cell density in females C_LIO_LIEthanol reduces action potential per burst in both sexes C_LIO_LIFemales show reduced excitability and loss of bursting in some cells C_LI

neuroscience↗

bioRxiv2025

Diversity and composition of microbial communities in shrimp ponds sediments: A metagenomic approach

The cultivation of Litopenaeus vannamei is of great economic importance to Ecuador, yet it faces significant challenges due to microbial diseases. This study analyzes the microbial metagenome in white shrimp culture ponds sediments, assessing the diversity and communities of both pathogenic and non-pathogenic bacteria. Sediment samples were collected from ponds in three provinces with varying salinity levels: province of Guayas (6.28 g/L), El Oro (21 g/L), and Santa Elena (48 g/L). Through sequencing the V3-V4 region of the 16S rRNA gene, diverse microbial communities were identified, significantly influenced by salinity. Results revealed that microbial communities vary among locations, highlighting the presence of pathogenic bacteria such as Proteobacteria and beneficial ones like Firmicutes. Shannon and Simpson indices indicated high diversity and evenness in Guayas, El Oro, and Santa Elena (Shannon: 5.547, 5.810, and 4.326; Simpson: 0.9953, 0.9957, and 0.982, respectively). This analysis provides crucial information for improving management and sustainability of shrimp aquaculture, offering insights into the complex microbial ecosystems in culture environments and their potential impact on shrimp health and production.

genomics↗

bioRxiv2025

Fecal microbiota transplantation mitigates cardiac remodeling and functional impairment in mice with chronic colitis

BackgroundInflammatory bowel disease (IBD) is a chronic inflammatory disorder with significant extraintestinal manifestations, including cardiovascular derangements. However, the molecular mechanisms underlying the cardiac remodeling and dysfunction remain unclear. MethodsWe investigated the effects of chronic colitis on the heart using two mouse models: DSS-induced colitis and Il10-/-spontaneous colitis. Echocardiography was employed to assess heart function and molecular characterization was performed using bulk RNA-sequencing, RT-qPCR, and western blot. ResultsBoth models exhibited significant cardiac impairment, including reduced ejection fraction and fractional shortening as well as increased collagen deposition, inflammation, and myofibril reorganization. Molecular analyses revealed upregulation of fibrosis markers (i.e. COL1A1, COL3A1, Fibronectin) and {beta}-catenin reactivation, indicating a pro-fibrotic cardiac environment. Each model yielded common upregulation of eicosanoid-associated and inflammatory genes (Cyp2e1, Map3k6, Pck1, Cfd), and model-specific alterations in pathways regulating cAMP- and cGMP-signaling, arachidonic and linoleic acid metabolism, Cushing syndrome-related genes, and immune cell responses. DSS colitis caused differential regulation of 232 cardiac genes, while Il10-/- colitis yielded 105 dysregulated genes, revealing distinct molecular pathways driving cardiac dysfunction. Importantly, therapeutic fecal microbiota transplantation (FMT) restored heart function in both models, characterized by reduced fibrosis markers and downregulated pro-inflammatory genes (Lbp and Cdkn1a in Il10-/- mice and Fos in DSS mice), while also mitigating intestinal inflammation. Post-FMT cardiac RNA-sequencing revealed significant gene expression changes, with three altered genes in DSS mice and 67 genes in Il10-/- mice. Notably, Il10-/- mice showed relatively less cardiac recovery following FMT, highlighting IL-10s cardioprotective and anti-inflammatory contribution. ConclusionsOur findings elucidate novel insights into colitis-induced cardiac remodeling and dysfunction and suggest that FMT mitigates cardiac dysfunction by attenuating systemic inflammation and correcting gut dysbiosis. This study underscores the need for further evaluation of gut-heart interactions and microbiome-based therapies to improve cardiovascular health in IBD patients. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=119 SRC="FIGDIR/small/643179v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@13d79eaorg.highwire.dtl.DTLVardef@10f28a7org.highwire.dtl.DTLVardef@35f4b0org.highwire.dtl.DTLVardef@538d7e_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2024

Connectivity of the neuronal network for contextual fear memory is disrupted in a mouse model of third-trimester binge-like ethanol exposure

BackgroundIn rodents, third-trimester equivalent alcohol exposure (TTAE) produces significant deficits in hippocampal-dependent memory processes such as contextual fear conditioning (CFC). The present study sought to characterize changes in both behavior and Fos+ neurons following CFC in ethanol (EtOH)-treated versus saline-treated mice using TRAP2:Ai14 mice that permanently label Fos+ neurons following a tamoxifen injection. We hypothesized that TTAE would produce long-lasting disruptions to the networks engaged following CFC with a particular emphasis on the limbic memory system. MethodsOn postnatal day 7, mice received either two injections of saline or 2.5 g/kg EtOH spaced 2 hours apart. The mice were left undisturbed until they reached adulthood, at which point they underwent CFC. After context exposure on day 2, mice received a tamoxifen injection. Brain tissue was harvested. Slides were automatically imaged using a Zeiss AxioScanner. Manual counts on a priori regions of interest were conducted. Automated counts were performed on the whole brain using the QUINT 2D stitching pipeline. Last, novel network analyses were applied to identify future regions of interest. ResultsTTAE reduced context recall on day 2 of CFC. Fos+ neural density increased in the CA1 and CA3. Fos+ counts were reduced in the anteroventral (AV) and anterodorsal thalamus. The limbic memory system showed significant hyperconnectivity in male TTAE mice and the AV shifted affinity towards hippocampal subregions. Last, novel regions such as a subparafascicular area and basomedial amygdalar nucleus were implicated as important mediators. DiscussionThese results suggest that CFC is mediated by the limbic memory system and is disrupted following TTAE. Given the increase in CA1 and CA3 activity, a potential hypothesis is that TTAE causes disruptions to memory encoding following day 1 conditioning. Future studies will aim to determine whether this disruption specifically affects the encoding or retrieval of fear memories.

neuroscience↗

bioRxiv2022

Hippo pathway-mediated YAP1/TAZ inhibition is essential for proper pancreatic endocrine specification and differentiation

The Hippo pathway plays a central role in tissue development and homeostasis. However, the function of Hippo in pancreatic endocrine development remains obscure. Here, we examined the roles of Hippo pathway mediated YAP1/TAZ inhibition in the development stages of endocrine specification and differentiation. While YAP1 protein was localized to the nuclei in bipotent progenitor cells, Ngn3 expressing endocrine progenitors completely lost YAP1. Using genetic mouse models, we found that this inactivation of YAP1 requires both intact Hippo pathway and NGN3 protein. Deleting the Lats1 and 2 kinases (Lats1&2) in endocrine progenitor cells of developing mouse pancreas with Ngn3-Cre blocked endocrine progenitor cell differentiation and specification, resulting in reduced islets size and disorganized pancreas at birth. Loss of Lats1&2 in NGN3 expressing cells activated YAP1/TAZ transcriptional activity and recruited macrophages to the developing pancreas. These defects were rescued by deletion of YAP1/TAZ genes, suggesting that tight regulation of YAP1/TAZ by Hippo signaling is crucial for pancreatic endocrine specification. In contrast, deletion of Lats1&2 using beta-cell specific MIP1CreER resulted in a phenotypically normal pancreas, indicating that Lasts1&2 are dispensable for pancreatic beta-cell function. Our results demonstrate that YAP1/TAZ inhibition in the pancreatic endocrine compartment is not a passive consequence of endocrine specification. Rather, Hippo pathway-mediated YAP1/TAZ inhibition in endocrine progenitors is a prerequisite for endocrine specification and differentiation.

developmental biology↗