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Biology subjects

Maldonado, C. A.

Publications and source records attributed to Maldonado, C. A..

3 recordsLinked to original sources

Connectome-driven neural inventory of a complete visual system

Vision provides animals with detailed information about their surroundings, conveying diverse features such as color, form, and movement across the visual scene. Computing these parallel spatial features requires a large and diverse network of neurons, such that in animals as distant as flies and humans, visual regions comprise half the brains volume. These visual brain regions often reveal remarkable structure-function relationships, with neurons organized along spatial maps with shapes that directly relate to their roles in visual processing. To unravel the stunning diversity of a complex visual system, a careful mapping of the neural architecture matched to tools for targeted exploration of that circuitry is essential. Here, we report a new connectome of the right optic lobe from a male Drosophila central nervous system FIB-SEM volume and a comprehensive inventory of the flys visual neurons. We developed a computational framework to quantify the anatomy of visual neurons, establishing a basis for interpreting how their shapes relate to spatial vision. By integrating this analysis with connectivity information, neurotransmitter identity, and expert curation, we classified the [~]53,000 neurons into 727 types, about half of which are systematically described and named for the first time. Finally, we share an extensive collection of split-GAL4 lines matched to our neuron type catalog. Together, this comprehensive set of tools and data unlock new possibilities for systematic investigations of vision in Drosophila, a foundation for a deeper understanding of sensory processing.

neuroscience↗

Structural basis for broad anti-phage immunity by DISARM

In the evolutionary arms race against phage, bacteria have assembled a diverse arsenal of antiviral immune strategies. While the recently discovered DISARM (Defense Island System Associated with Restriction-Modification) systems can provide protection against a wide range of phage, the molecular mechanisms that underpin broad antiviral targeting but avoiding autoimmunity remain enigmatic. Here, we report cryo-EM structures of the core DISARM complex, DrmAB, both alone and in complex with an unmethylated phage DNA mimetic. These structures reveal that DrmAB core complex is autoinhibited by a trigger loop (TL) within DrmA and binding to DNA substrates containing a 5 overhang dislodges the TL, initiating a long-range structural rearrangement for DrmAB activation. Together with structure-guided in vivo studies, our work provides insights into the mechanism of phage DNA recognition and specific activation of this widespread antiviral defense system.

biochemistry↗

Neonatal endotoxin stimulation was associated with long- term innate immune markers and an anti-allergic response in bronchiolar epithelium in spite of allergen challenge

Asthma is a heterogeneous disease underlying different medical processes, being the allergic asthma, with an early-onset in childhood, the most common type. In this phenotype, the continuous exposure to allergens produces a Th2-driven airway remodeling process that leads to symptoms and pathophysiological changes in asthma. Strategies as the avoidance of aeroallergen exposure in early life have been tested to prevent asthma, without a clear success. Alongside, several mouse models of aeroallergen challenge have dissected potential homeostatic responses by which environmental microbial stimulation reduces the subsequent allergic inflammation in the offspring. This suggests the onset of underlying preventive mechanisms in the beginning of asthma that have not been fully recognized. In this study, we aimed to evaluate if neonatal LPS-induced stimulus in epithelial host defenses could contribute to the prevent asthma in adult Balb/c mice. For this purpose, we studied the response of bronchiolar club cells (CC) that are situated in the crossroads of the host defense and allergic inflammation, and express specific pro and antiallergic proteins. LPS stimulus in the neonatal life intensified the production of TLR-4, TNF, and natural anti-allergic products (CCSP and SPD), changes that contributed to prevent asthma triggering in adulthood. At epithelial level, CC skipped the mucous metaplasia, declining the overproduction of mucin via the EGFR pathway and the mice expressed normal breathing patterns in front of OVA challenge. Furthermore, the overexpression of TSLP, an epithelial pro-Th2 cytokine was blunted and normal TSLP and IL-4 levels were found in bronchoalveolar lavage (BAL). Complementing this shift, we also detected lower eosinophilia in BAL while an increase in phagocytes as well as in regulatory cells (CD4+CD25+FOXP3+ and CD4+IL-10+) was seen, whit an elevation in IL-12 and TNF secretion. Summarizing, our study pointed to stable asthma-preventive effects promoted by neonatal LPS-stimulation; the main finding was the increase of several anti-Th2 specific proteins at epithelial level, together with an important diminution of pro-Th2 TSLP, conditions that promoted changes in the local immune response with Treg. We thus evidenced several anti-allergic dynamic mechanisms overlying in the epithelium that could be favored in an adequate epidemiological environment

cell biology↗