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Lima, S.

Publications and source records attributed to Lima, S..

8 recordsLinked to original sources

Translational profiling uncovers a tonoplast sugar transporter essential for vascular system development and cell wall composition

The inflorescence stem of Arabidopsis thaliana is a powerful model to study vascular development and carbon allocation, yet the translational landscape underlying xylem differentiation remains poorly defined. Here, we address this gap using tissue-specific Translating Ribosome Affinity Purification sequencing (TRAP-seq) to resolve the translatomes of xylem vessels, xylem parenchyma, and interfascicular fibers. We show that the very early stage of metaxylem differentiation involves coordinated activation of primary metabolism, plastid functions, and cell wall biosynthesis, supporting the metabolic demands of secondary wall formation. Xylem parenchyma displays enrichment in hormone signaling, stress, and immune pathways, consistent with a role in integrating environmental and metabolic cues. Interfascicular fibers exhibit increased translation of ribosomal proteins and spliceosome components, pointing to high translational activity and a role for alternative splicing during late development and programmed cell death. We further identify the tonoplast sugar transporter SUGAR WILL EVENTUALLY BE EXPORTED TRANSPORTER 2 (SWEET2) as a key regulator of stem radial growth. Preferentially translated in early stage of metaxylem differentiation, SWEET2 acts as a rate-limiting component of vacuolar sugar exchange, controlling cytosolic hexose availability for secondary wall biosynthesis. By contrast, SWEET16 and SWEET17 exert more specialized, tissue-specific functions. Together, our findings establish subcellular sugar partitioning as a central determinant of vascular development and highlight the power of translatome profiling.

plant biology↗

LZTS2 Emerges as a Regulator of Craniofacial Development and Modulator of DYRK1A

BackgroundPrecise control of DYRK1A dosage is essential for embryonic development, including craniofacial morphogenesis. While LZTS2 is among the most consistently identified DYRK1A-interacting proteins, its roles in embryonic development remain incompletely understood, and its potential contribution to craniofacial development has not been examined. Xenopus laevis was used to test the role of LZTS2 in craniofacial development and its functional relationship with DYRK1A. ResultsLzts2 and Dyrk1a showed overlapping expression during craniofacial development, with both proteins present in developing facial tissues. Knockdown of Lzts2 disrupted craniofacial morphogenesis and reduced expression of the neural crest-associated genes sox9 and pax3. These phenotypes closely resembled those caused by decreasing Dyrk1a function. Sub-phenotypic reductions of Lzts2 and Dyrk1a synergized to produce craniofacial defects, while partial reduction of Lzts2 attenuated aspects of the phenotype caused by Dyrk1a overexpression. Comparative analysis of human phenotypes associated with copy number gains of LZTS2 and DYRK1A revealed striking overlap, consistent with a potential functional interaction between these genes in humans. ConclusionsThese findings identify Lzts2 as a previously unrecognized regulator of craniofacial development and support a functional interaction with Dyrk1a during embryogenesis. Modulating LZTS2 or related regulatory partners may provide a strategy to selectively tune DYRK1A-dependent developmental pathways

developmental biology↗

Control of Male Mouse Copulatory Behavior by Midbrain Dopamine Neurons

Ejaculation in male mice and humans requires intravaginal thrusting movements following penile intromission, yet the underlying neural mechanisms remain poorly understood. In this study, we used fiber photometry to record real-time activity of dopamine (DA) neurons in the ventral tegmental area (VTA) of male mice during copulation across six sexual interactions, in order to investigate how these dynamics change with experience and to examine their functional significance. Contrary to expectations, phasic VTA DA activity remained stable across sessions, showing time-locked responses to mounts, penile intromission, individual thrusts, and ejaculation, indicating experience-independent neural representations of all copulatory events. Notably, thrusting-related activity sharply declined just before ejaculation. Optogenetic inhibition of DA neurons disrupted thrusting behavior, but did not block ejaculation, suggesting DA signaling is critical for sustaining copulatory actions rather than triggering ejaculation itself. While prevailing theories frame VTA DA activity as primarily experience-dependent or centered on reward prediction, we here highlight its role in behavioral persistence during copulation. More broadly, our findings extend understanding of DA function beyond classical reward paradigms to the regulation of innate complex, goal-directed behaviors.

neuroscience↗

Distinct Type 1 Immune Networks Underlie the Severity of Restrictive Lung Disease after COVID-19

The variable etiology of persistent breathlessness after COVID-19 have confounded efforts to decipher the immunopathology of lung sequelae. Here, we analyzed hundreds of cellular and molecular features in the context of discrete pulmonary phenotypes to define the systemic immune landscape of post-COVID lung disease. Cluster analysis of lung physiology measures highlighted two phenotypes of restrictive lung disease that differed by their impaired diffusion and severity of fibrosis. Machine learning revealed marked CCR5+CD95+ CD8+ T-cell perturbations in mild-to-moderate lung disease, but attenuated T-cell responses hallmarked by elevated CXCL13 in more severe disease. Distinct sets of cells, mediators, and autoantibodies distinguished each restrictive phenotype, and differed from those of patients without significant lung involvement. These differences were reflected in divergent T-cell-based type 1 networks according to severity of lung disease. Our findings, which provide an immunological basis for active lung injury versus advanced disease after COVID-19, might offer new targets for treatment.

immunology↗

Molecular basis of unidirectional information transmission in two-component systems: lessons from the DesK-DesR thermosensor

Cellular signaling systems transmit information over long distances using allosteric transitions and/or post-translational modifications. In two-component systems the sensor histidine kinase and response regulator are wired through phosphoryl-transfer reactions, using either a uni- or bi-directional transmission mode, allowing to build rich regulatory networks. Using the thermosensor DesK-DesR two-component system from Bacillus subtilis and combining crystal structures, QM/MM calculations and integrative kinetic modeling, we uncover that: i) longer or shorter distances between the phosphoryl-acceptor and -donor residues can shift the phosphoryl-transfer equilibrium; ii) the phosphorylation-dependent dimerization of the regulator acts as a sequestering mechanism by preventing the interaction with the histidine kinase; and iii) the kinases intrinsic conformational equilibrium makes the phosphotransferase state unlikely in the absence of histidine phosphorylation, minimizing backwards transmission. These mechanisms allow the system to control the direction of signal transmission in a very efficient way, showcasing the key role that structure-encoded allostery plays in signaling proteins to store and transmit information.

biophysics↗

Immunization with SARS-CoV-2 nucleocapsid protein triggers a pulmonary immune response in rats

The SARS-CoV-2 pandemic have been affecting millions of people worldwide, since the beginning of 2020. COVID-19 can cause a wide range of clinical symptoms, which varies from asymptomatic presentation to severe respiratory insufficiency, exacerbation of immune response, disseminated microthrombosis and multiple organ failure, which may lead to dead. Due to the rapid spread of SARS-CoV-2, the development of vaccines to minimize COVID-19 severity in the world population is imperious. One of the employed techniques to produce vaccines against emerging viruses is the synthesis of recombinant proteins, which can be used as immunizing agents. Based on the exposed, the aim of the present study was to verify the systemic and immunological effects of IM administration of recombinant Nucleocapsid protein (NP), derived from SARS-CoV-2 and produced by this research group, in 2 different strains of rats (Rattus norvegicus); Wistar and Lewis. For this purpose, experimental animals received 4 injections of NP, once a week, and were submitted to biochemical and histological analysis. Our results showed that NP inoculations were safe for the animals, which presented no clinical symptoms of worrying side effects, nor laboratorial alterations in the main biochemical and histological parameters, suggesting the absence of toxicity induced by NP. Moreover, NP injections successfully triggered the production of specific anti-SARS-CoV-2 IgG antibodies by both Wistar and Lewis rats, showing the sensitization to have been well sufficient for the immunization of these strains of rats. Additionally, we observed the local lung activation of the Bronchus-Associated Lymphoid Tissue (BALT) of rats in the NP groups, suggesting that NP elicits specific lung immune response. Although pre-clinical and clinical studies are still required, our data support the recombinant NP produced by this research group as a potential immunizing agent for massive vaccination, and may represent advantages upon other recombinant proteins, since it seems to induce specific pulmonary protection.

immunology↗

Additive and non-additive epigenetic signatures of hybridisation between fish species with different mating systems

Hybridisation is a major source of evolutionary innovation. However, several prezygotic and postzygotic factors influence its likelihood and evolutionary outcomes. Differences in mating systems can have a major effect on the extent and direction of hybridisation and introgression. In plants, epigenetic mechanisms help to stabilize hybrid genomes and contribute to reproductive isolation, but the relationship between genetic and epigenetic changes in animal hybrids is unclear. We analysed the extent of a unique case of natural hybridisation between two genetically distant mangrove killifish species with different mating systems, Kryptolebias hermaphroditus (self-fertilising) and K. ocellatus (outcrossing), and the methylation patterns of their hybrids. Hybridisation rate between the species ranged between 14% and 26%. Although co-existing parental species displayed highly distinct genetic (microsatellites and SNPs) and methylation patterns (37,000 differentially methylated cytosines), our results indicate that F1 hybrids are viable and able to backcross with parental species. Hybrids had predominantly intermediate methylation patterns (88.5% of the sites) suggesting additive effects, as expected from hybridisation between genetically distant species. Differentially methylated cytosines between hybrids and both parental species (5,800) suggest that introgressive hybridisation may play a role in generating novel genetic and epigenetic variation which could lead to species diversification. We also found a small percentage of non-additive epigenetic effects which might act as an evolutionary bet-hedging strategy and increase fitness under environmental change.

evolutionary biology↗

Temporal refuges differ between anthropogenic and natural top down pressures in a subordinate carnivore

Apex predators structure communities through consumptive and non-consumptive pathways. In the carnivore guild, this can result in a within-guild cascade through the suppression of mesocarnivores. As the top-down influences of apex predators wane due to human-driven declines, landscape level anthropogenic pressures are rising. Human impacts can be analogous to apex predators in that humans can drive increased mortality in both prey species and carnivores, and impact communities through indirect fear effects and food subsidies. Here, we evaluate whether anthropogenic top-down pressures can structure communities in a similar manner as apex predators in shaping the interactions of mesocarnivores. Specifically, we expect anthropogenic forces to induce comparable effects as occurrence of apex predators in driving spatiotemporal partitioning between two mesocarnivores. Using multiple camera-trap surveys, we compared the temporal response of a small carnivore, the raccoon (Procyon lotor), to the larger coyote (Canis latrans) at four sites across Michigan that represented opposing gradients of pressure from humans and apex predators. Contrary to our expectations, we found that raccoons shifted their activity pattern in response to coyotes at sites with higher anthropogenic pressures and exhibited no temporal response at sites with apex predators. Temporal shifts were characterized by raccoons being more diurnal in areas of high coyote activity. We conclude that despite superficial similarities, anthropogenic forces do not replace the function of native apex predators in structuring the mesocarnivore guild. As such, an intact and functioning native predator guild remains necessary to preserve spatiotemporal community structure, in natural and disturbed systems alike.

ecology↗