Biology subjects

Acosta, G.

Publications and source records attributed to Acosta, G..

3 recordsLinked to original sources

bioRxiv2025

Unsupervised Phenotyping Reveals Disrupted Neural Firing Characteristics in the Anterior Thalamus and Surrounding Brain Regions Following Third-Trimester Equivalent Alcohol Exposure in Mice

Acute, binge-like alcohol exposure during the third-trimester-equivalent period (TTAE) produces apoptotic neurodegeneration in brain regions critical for spatial learning and memory, including the anterior thalamic nuclei (ATN), which are necessary for contextual learning and memory. To investigate the neural mechanisms underlying spatial cognition deficits following developmental alcohol exposure, we performed high-density electrophysiological recordings in and around the ATN of behaving mice, sampling 7,490 neurons across multiple, predominantly thalamic depths. To model acute binge-like TTAE, C57BL/6J mice received two injections of 2.5 g/kg ethanol (or saline) on postnatal day (PND) 7. In young adulthood (>PND 60), mice were implanted with silicon or multi-wire electrode arrays and allowed to explore a circular arena (40 cm diameter) under dim red light with two wall-mounted LED cues that rotated pseudo-randomly. Spike timing and waveform features were extracted from each putative single unit. Across the recorded population, firing rates were generally reduced following TTAE, although responses were heterogeneous. To characterize this variability, neuronal features were embedded using uniform manifold approximation and projection (UMAP). Logistic regression classified saline- and TTAE-exposed neurons based on electrophysiological properties and UMAP coordinates, achieving 80% accuracy. Cluster-based comparisons showed weak correspondence between physiological similarity and treatment response, suggesting TTAE effects are driven primarily by anatomical location. This study presents the first large-scale in vivo electrophysiological recordings in a freely behaving mouse model of fetal alcohol spectrum disorders, revealing divergent circuit adaptations marked by hippocampal hyperexcitability and thalamic dysfunction.

neuroscience↗

bioRxiv2024

Therapeutic Tumor Macrophage Reprogramming in Breast Cancer Through a Peptide-Drug Conjugate

In triple negative breast cancer (TNBC), pro-tumoral macrophages promote metastasis and suppress the immune response. To target these cells, we engineered a previously identified CD206 (mannose receptor)-binding peptide, mUNO, to enhance its affinity and proteolytic stability. The new rationally designed peptide, MACTIDE, includes a trypsin inhibitor loop, from the Sunflower Trypsin Inhibitor-I. Binding studies to recombinant CD206 revealed a 15-fold lower KD for MACTIDE compared to parental mUNO. Additionally, mass spectrometry showed a 5-fold increase in half-life in tumor lysate for MACTIDE compared to mUNO. Homing studies in TNBC-bearing mice showed that fluorescein (FAM)-MACTIDE precisely targeted CD206+ tumor-associated macrophages (TAMs) upon intravenous, intraperitoneal and even oral administration, with no significant accumulation in liver. We coupled MACTIDE to the FDA-approved drug Verteporfin, an established photosensitizer for photodynamic therapy and inhibitor of the YAP/TAZ pathway, to generate a conjugate here referred to as MACTIDE-V. In the orthotopic 4T1 TNBC mouse model, non-irradiated MACTIDE-V-treated mice unexpectedly showed a similar anti-tumoral effect and fewer signs of toxicity as irradiated MACTIDE-V-treated mice, leading to subsequent studies on the laser-independent activity of this conjugate. In vitro studies using bone-marrow derived mouse macrophages showed that MACTIDE-V excluded YAP from the nucleus, increased the phagocytic activity and upregulated several genes associated with cytotoxic anti-tumoral macrophages. In mouse models of TNBC, MACTIDE-V slowed primary tumor growth, suppressed lung metastases, increased markers of phagocytosis and antigen presentation in TAMs and monocytes, increasing the tumor infiltration of several lymphocyte subsets. We therefore propose MACTIDE-V as a useful peptide-drug conjugate to modulate macrophage function in the context of breast tumor immunotherapy.

cancer biology↗

bioRxiv2019

First identification of trombiculid mites (Acari: Trombiculidae) on rodents captured on Chiloe Island, an endemic region of scrub typhus in southern Chile

BackgroundScrub typhus in an emerging vector-borne zoonosis, caused by Orientia spp. and transmitted by larvae of trombiculid mites, called chiggers. It mainly occurs within a certain region of the Asia-Pacific, called tsutsugamushi triangle, where rodents are known as the most relevant hosts for the trombiculid vector. The disease has recently been discovered on Chiloe Island in southern Chile. Still, the reservoir(s) and vector(s) of the scrub typhus outside Asia-Pacific are unknown. The aim of the present work was to study the prevalence of chiggers on different rodent species captured in sites identified as probably hot spots of scrub typhus on Chiloe Island in southern Chile.\n\nMethodology/Principal FindingsDuring austral summer 2018, rodents were live-trapped in six sites and examined for chigger infestation. During a total of 4,713 trap-nights, 244 rodents of seven species were captured: the most abundant was Abrothrix olivacea. All study sites were rural areas on Chiloe Island, previously identified as localities of probable human infection with scrub typhus. Chiggers were detected on all seven rodent species with a 55% prevalence rate. Chiggers showed low host specificity and varied according to site specific host abundance. We identified trombiculids of three genera. Colicus was the most abundant chigger (93%), prevalent in five of six sites, followed by Quadraseta (7%) and Paratrombicula (7%), which were in only one site. Infestation rates showed site specific differences, which were statistically different using a GLM model with binomial errors.\n\nConclusions/SignificanceThis study firstly reports the presence of different rodent-associated chigger mites in a region with endemic scrub typhus in southern Chile. Colicus and two other genera of mites were found with high infestation rates in sites previously identified as hot spots of scrub typhus, suggesting their role as vectors and reservoirs of this emerging zoonosis in South America.\n\nAuthor SummaryScrub typhus is a chigger-transmitted zoonotic infection, which is endemic in the tsutsugamushi triangle in Asia-Pacific. Recently, a first focus of scrub typhus in South America has been confirmed on Chiloe Island in southern Chile. Still, the vectors of scrub typhus in this region remain unknown. We undertook a survey to study the prevalence of chiggers on different rodent species in areas identified as probable hot spots of scrub typhus on Chiloe Island. The study showed that 55% of rodents were infested by trombiculids. Three chigger genera were identified, of which Colicus was the most abundant. Chiggers showed low host specificity, but spatial differences. This first demonstration of rodent-associated chigger mites in hot spots of scrub typhus suggests their possible role as vectors of this infection in Chile.

zoology↗