Biology subjects

Gibbons, J.

Publications and source records attributed to Gibbons, J..

8 recordsLinked to original sources

bioRxiv2026

Orexinergic Input to the Supramammillary Region Links Threat Salience to Approach Behavior and Dopamine Release

Orexin (hypocretin) neurons (OXN) broadcast arousal-related signals across the forebrain, yet how their inputs shape motivated behavior remains poorly understood. The supramammillary region (SuM), a posterior hypothalamic structure implicated in arousal, active coping and reward-seeking, receives dense orexin innervation. Here, we define how orexinergic terminals in the SuM (OXNSuM) integrate threat salience with approach motivational processes. Using viral tracing and RNAscope, we show that SuM neurons express both orexin receptor subtypes, with type 2 receptors predominating. Fiber photometry recordings from OXNSuM terminals reveal strong activation by footshock and conditioned threat cues, modest responses to salient sensory stimuli, and pronounced suppression during water consumption. Optogenetic stimulation of OXNSuM terminals reinforces instrumental responding, biases real-time place preference, and elicits rapid, stimulation-locked dopamine release in the nucleus accumbens. These findings identify an orexin-to-SuM pathway that is engaged by uncertainty and threat yet promotes approach behavior through coupling to mesolimbic dopamine, revealing a mechanism linking hypothalamic arousal signals to adaptive motivational responses. SIGNIFICANCE STATEMENTThe supramammillary region (SuM) has emerged as a critical node linking arousal, threat processing, and motivated behavior, yet the sources and functions of its modulatory inputs remain unclear. Here, we identify orexinergic projections to the SuM as a circuit mechanism that couples threat-related salience with approach behavior and nucleus accumbens dopamine signaling. We show that orexin terminals in the SuM are activated by stressful and uncertain stimuli but suppressed during consummatory behavior, and that selective activation of these terminals is positively reinforcing and drives rapid dopamine release. These findings reveal a pathway through which orexin neurons promote active coping and reward-seeking, advancing our understanding of how hypothalamic neuromodulation shapes mesolimbic function and adaptive behavioral responses.

neuroscience↗

bioRxiv2026

Nitrosomes: protein language modeling and live-cell imaging reveal condensate-like nitrogenase organization in heterocysts

Biological nitrogen fixation in some filamentous cyanobacteria occurs in heterocysts, yet the subcellular organization of nitrogenase in these cells remains poorly defined. Using fluorescence microscopy of living Anabaena sp. PCC 7120, we found that a NifH-GFP fusion forms discrete puncta restricted to mature heterocysts, whereas constitutively expressed GFP in vegetative cells and a nifB-linked GFP reporter remained diffuse. To contextualize this phenotype, we built a homology-aware cyanobacterial condensate-prioritization framework across 31,028 proteins from seven proteomes, integrating ESM-2 embeddings, 27 biophysical features, and 44 curated condensate-associated positives. Because direct positives remain limited, we present the model as a ranking resource rather than a calibrated classifier. Under a deliberately conservative nitrogenase-withheld analysis that removed nitrogenase-family labels and homologous clusters from the training data, NifH retained a median rank in the highest-scoring 4.8% of cyanobacterial proteins. catGRANULE 2.0 also assigned high scores to nitrogenase iron proteins, while having only modest rank concordance to the whole atlas. Together, these data identify heterocyst-restricted NifH-GFP puncta as evidence of sub-cellular spatial organization and provide a curated resource for prioritizing cyanobacterial condensate candidates, some of which are also important for nitrogen fixation.

molecular biology↗

bioRxiv2025

Multidrug-resistant Rhodococcus equi (MDR-RE): detection in East Asia confirms global spread

Macrolide (multidrug)-resistant Rhodococcus equi (MDR-RE) emerged in the early 2000s and has since been disseminating across equine farms in the United States. In 2016, it was found in Ireland, presumably introduced through horse imports. Here, we report its identification in Japan, together with evidence of its presence in China. A recent isolate from Ireland suggests ongoing importation events. These findings highlight the continued international spread of MDR-RE and its potential to become globally established. Currently circulating among horses, MDR-RE is likely to arise in humans over time. Active surveillance is essential to monitor and control this emerging zoonotic antimicrobial resistance threat worldwide.

microbiology↗

bioRxiv2025

Acute kidney injury disrupts cardiac remodeling via SerpinA3N

Cardiorenal syndrome type 3 (CRS-3) also known as acute reno-cardiac syndrome, refers to a condition where acute kidney injury (AKI) leads to acute cardiac dysfunction or injury. The underlying mechanisms have not been elucidated. In the current study, we examined the potential mechanisms for the development of myocardial pro-fibrotic factors and cardiac remodeling in C57BL/6J mice after AKI. The mice were subjected to bilateral pedicle clamping for 30 min followed by 24 h of reperfusion. Heart tissue was collected from control (Ctrl) and AKI mice and subjected to proteomic analysis by liquid chromatography-mass spectrometry (LC-MS) and differential mRNA expression analysis by RNA-seq. Cardiac tissue was collected to assess serine protease activity, RNA, protein and cytokine expression. The results indicate that AKI significantly upregulated SerpinA3N in the heart which was negatively correlated with serine protease (Granzyme B) activity. Further, AKI induced the development of several pro-fibrotic factors, induced mitochondrial dysfunction and increased inflammation. Finally, using H9C2 cells we demonstrated that inhibiting SerpinA3N with XAV939 increased Granzyme B activity. Thus, this study suggests that AKI leads to the development of pro-fibrotic factors in the heart and disrupts cardiac remodeling by SerpinA3N mediated inhibition of serine protease Granzyme B activity. Decreased SerpinA3N expression in the heart followed by AKI could lead to a more balanced extracellular matrix (ECM) composition in the heart with an alleviated pro-fibrotic response.

molecular biology↗

bioRxiv2023

Group B Streptococcus drives major transcriptomic changes in the colonic epithelium.

Group B Streptococcus (GBS) is a leading cause of infant sepsis worldwide. Colonization of the gastrointestinal tract is a critical precursor to late-onset disease in exposed newborns. Neonatal susceptibility to GBS intestinal translocation stems from intestinal immaturity; however, the mechanisms by which GBS exploits the immature host remain unclear. {beta}-hemolysin/cytolysin ({beta}H/C) is a highly conserved toxin produced by GBS capable of disrupting epithelial barriers. However, its role in the pathogenesis of late-onset GBS disease is unknown. Our aim was to determine the contribution of {beta}H/C to intestinal colonization and translocation to extraintestinal tissues. Using our established mouse model of late-onset GBS disease, we exposed animals to GBS COH-1 (WT), a {beta}H/C-deficient mutant (KO), or vehicle control (PBS) via gavage. Blood, spleen, brain, and intestines were harvested 4 days post-exposure for determination of bacterial burden and isolation of intestinal epithelial cells. RNA-sequencing was used to examine the transcriptomes of host cells followed by gene ontology enrichment and KEGG pathway analysis. A separate cohort of animals was followed longitudinally to compare colonization kinetics and mortality between WT and KO groups. We demonstrate that dissemination to extraintestinal tissues occurred only in the WT exposed animals. We observed major transcriptomic changes in the colons of colonized animals, but not in the small intestines. We noted differential expression of genes that indicated the role of {beta}H/C in altering epithelial barrier structure and immune response signaling. Overall, our results demonstrate an important role of {beta}H/C in the pathogenesis of late-onset GBS disease.

microbiology↗

bioRxiv2022

MalariaSED: a deep learning framework to decipher the regulatory contributions of noncoding variants in malaria parasites

Malaria remains one of the deadliest infectious diseases. Transcriptional regulation effects of noncoding variants in this unusual genome of malaria parasites remain elusive. We developed a sequence-based, ab initio deep learning framework, MalariaSED, for predicting chromatin profiles in malaria parasites. The MalariaSED performance was validated by published ChIP-qPCR and TF motifs results. Applying MalariaSED to [~]1.3 million variants shows that geographically differentiated noncoding variants are associated with parasite invasion and drug resistance. Further analysis reveals chromatin accessibility changes at Plasmodium falciparum rings are partly associated with artemisinin resistance. MalariaSED illuminates the potential functional roles of noncoding variants in malaria parasites.

bioinformatics↗

bioRxiv2022

International spread of emerging multidrug-resistant Rhodococcus equi

The recently characterized multidrug-resistant clone of the animal and human zoonotic pathogen Rhodococcus equi, MDR-RE 2287, has been circulating among horse farms in the United States (US) since the early 2000s. Here, we report the first documented detection of the MDR-RE 2287 clone outside the US. The finding highlights the risk of MDR-RE spreading internationally with the movement of horses.

microbiology↗

bioRxiv2019

Developmentally Regulated Genome Editing in Terminally Differentiated N2-Fixing Heterocysts of Anabaena cylindrica ATCC 29414

Some vegetative cells of Anabaena cylindrica are programed to differentiate semi-regularly spaced, single heterocysts along filaments. Since heterocysts are terminally differentiated non-dividing cells, with the sole known function for solar-powered N2-fixation, is it necessary for a heterocyst to retain the entire genome ({approx}7.1 Mbp) from its progenitor vegetative cell? By sequencing the heterocyst genome, we discovered and confirmed that at least six DNA elements ({approx}0.12 Mbp) are deleted during heterocyst development. The six-element deletions led to the restoration of five genes (nifH1, nifD, hupL, primase P4 and a hypothetical protein gene) that were interrupted in vegetative cells. The deleted elements contained 172 genes present in the genome of vegetative cells. By sequence alignments of intact nif genes (nifH, nifD and hupL) from N2-fixing cyanobacteria (multicellular and unicellular) as well as other N2-fixing bacteria (non-cyanobacteria), we found that interrupted nif genes all contain the conserved core sequences that may be required for phage DNA insertion. Here, we discuss the nif genes interruption which uniquely occurs in heterocyst-forming cyanobacteria. To our best knowledge, this is first time to sequence the genome of heterocyst, a specially differentiated oxic N2-fixing cell. This research demonstrated that (1) different genomes may occur in distinct cell types in a multicellular bacterium; and (2) genome editing is coupled to cellular differentiation and/or cellular function in a heterocyst-forming cyanobacterium.

microbiology↗