Biology subjects

Silva, E. A.

Publications and source records attributed to Silva, E. A..

12 recordsLinked to original sources

bioRxiv2026

Nav1.5 expressed in TrkB+ sensory neurons mediates paclitaxel-induced mechanical pain hypersensitivity

Chemotherapy-induced neuropathic pain (CINP) is a frequent and debilitating adverse effect of anti-tumor therapies, for which current treatments are largely non-specific and offer limited efficacy. Identifying molecular mechanisms that drive CINP may enable the development of targeted therapeutic strategies. Here, we demonstrate that paclitaxel-induced mechanical pain hypersensitivity in mice occurs independently of classical Nav1.8+ nociceptors but critically depends on TrkB+ sensory neurons. Transcriptomic analysis of TrkB+ sensory neurons revealed selective expression of Scn5a, which encodes the voltage-gated sodium channel Nav1.5, a channel classically associated with cardiac excitability. Importantly, SCN5A expression was also detected in human primary sensory neurons, indicating potential translational relevance. Functional studies further showed that Scn5a knockdown, using small interfering RNA, significantly attenuates paclitaxel-induced mechanical pain hypersensitivity. Together, these findings identify TrkB+ sensory neurons as key drivers of CINP and reveal Nav1.5 as a previously unrecognized contributor to chemotherapy-induced neuropathic pain. Targeting Nav1.5 in TrkB+ sensory neurons may therefore represent a novel therapeutic strategy for the treatment of CINP.

neuroscience↗

bioRxiv2025

Statistics used by ecologists: the rise of R statistical software, GLM(M)s and Networks

About 15 years ago, statistical softwares were rarely employed to conduct statistical analyses, and biologists/ecologists used roughly 100 statistical procedures in research. This number has likely increased substantially with the development of new analytical methods and the widespread adoption of computers and softwares. In this study, I investigated the temporal variation in statistical procedures and the use of softwares used in studies on plant-ant interactions. Data were collected from 142 published papers covering a period between 1979 to 2023. Information related to statistics terminology, the softwares cited and R software packages were retrieved. Each paper had on average eight statistical procedures and there was a significant increase in procedures over the years. The R software was cited in almost 80% of studies, surpassing by far the other softwares. Classical analyses such as t-tests, correlations and chi-squares are still used in research; nonetheless, from 2012 onward a new set of analyses including GLM, GLMM and Networks have emerged and are being used as the leading analyses in studies of plant-ant interactions. This coincides with the adoption of R software by scientists in this field. The most used R packages were vegan, lme4 and bipartite, followed by several other related to linear (mixed) models. Statistics literacy is a mandatory aspect of research in plant-ant interactions. The increase in statistical procedures over the years, as well as the emergence of new tests can be considered as a natural evolution of the field with demand for robustness in methods and analyses.

ecology↗

bioRxiv2025

Thresholds of drought and terrain complexity shape biomasspatterns in South America's Caatinga

Seasonally Tropical Dry Forests (STDFs) are widespread throughout the world and store significant amounts of carbon; however, they are often overlooked in spatial assessments compared to humid tropical forests. The Caatinga, which is the largest seasonally dry tropical forest in South America, covers approximately 862,000 km{superscript 2} in northeastern Brazil and supports millions of people. Unfortunately, its carbon dynamics has not been thoroughly quantified, especially after centuries of land-use transformation and wood extraction that have significantly diminished its biomass stocks. In this study, we model the potential aboveground biomass (AGB) that Caatinga could sustain under current climatic, atmospheric, and topographic conditions. We integrated data from 301 geo-referenced plots along with high-resolution environmental predictors. The principal Component Analysis revealed two main gradients: a hydro-thermal axis dominated by precipitation, temperature, and severity of drought, and a topographic axis reflecting slope, ruggedness, and terrain position. Random Forest models, validated through both random and spatial cross-validation, explained a significant amount of variation in AGB (R{superscript 2} = 0.81, RMSE = 21 Mg ha). Our findings indicated that AGB is highly sensitive to water availability. In particular, biomass increased sharply when the maximum cumulative water deficit (MCWD) was less than -500 mm and annual rainfall exceeded approximately 1,100 mm. In contrast, elevated vapour pressure deficit (VPD) and potential evapotranspiration (PET) were associated with reduced carbon storage. Topographic heterogeneity further influenced AGB, with rugged and concave terrains supporting potential biomass levels more than twice as high as those found in flat, convex areas. Our predictive map reveals a mosaic of low-biomass cores and localized high-biomass refugia, highlighting the dual influence of hydroclimatic and topographic factors. These findings reposition Caatinga as a heterogeneous and dynamic potential carbon reservoir - historically degraded by changes in land-use but still capable of storing substantial carbon. This research offers critical insights for the restoration, conservation and mitigation efforts for climate change in tropical drylands worldwide.

ecology↗

bioRxiv2025

Sensory neurons shape macrophage identity via TGF-β signalling

Macrophages play integral roles in maintaining homeostasis and function in their tissues of residence. In the skin, prenatally seeded and highly specialized macrophages physically interact with sensory nerves and contribute to their regeneration after injury. However, mechanisms underlying the development and maintenance of this potentially lifelong commitment of macrophages to nociceptors remain largely elusive. Here, we found that infiltrating myeloid progenitor cells approached the sprouting axons of sensory nerves and gradually adopted a nerve-associated macrophage-like profile. This change in identity was steered and maintained by the immediate microenvironment, in particular TGF-{beta}, which was locally activated by the physical interaction with nerves and integrin-mediated cleavage. Following injury, TGF-{beta} driven specification of macrophages essentially supported nerve regeneration. Overall, we identified TGF-{beta} as a central mediator governing local imprinting and long-term specialization of macrophages in the skin, providing insights into the bidirectional communication between macrophages and sensory nerves.

immunology↗

bioRxiv2024

Fabaceae and Cerrado savanna: Two descriptors of Brazilian extrafloral nectary plants

Extrafloral nectaries (EFNs) have been described in almost 4000 plant species, but there are several gaps in our knowledge of their occurrence and distribution. Here, we investigated the geographical distribution and richness of EFN-plants in Brazilian biomes (Cerrado, Atlantic Forest, Caatinga, Amazon, Pantanal, and Pampa). Data were extracted from 170 papers, and our analysis included only EFN-plants that interacted with ants. A total of 224 EFN-plant species in 115 genera and 48 families were registered in five biomes: Cerrado, Atlantic Forest, Caatinga, Pampa, and the Amazon. The Cerrado was evaluated in 64% of all publications, had the highest richness (90 species) and the most exclusive flora compared to the other biomes. In addition, the most studied species belonged to the Cerrado flora (e.g., Caryocar brasiliense). Fabaceae was the most speciose family, with 76 species, being dominant in all biomes and greatly surpassing other families. Only Fabaceae and Euphorbiaceae were found in all biomes, and in general, each biome had its own flora, as only 18 (of 224) plants were found in more than one biome. In a network analysis, Qualea grandilflora and Plathymenia reticulata were relatively more important than other species, as they connected biomes and increased the cohesion of the community. Our study shows that our understanding of EFN-plants is limited because the Fabaceae and Cerrado were overrepresented. A detailed record of species occurrence and distribution could be a valuable tool for studying the biodiversity of EFN-plants and their potential mutualistic interactions.

ecology↗

bioRxiv2023

Harnessing EGLN1 Gene Editing to Amplify HIF-1α and Enhance Human Angiogenic Response

Therapeutic angiogenesis has been the focus of hundreds of clinical trials but approval for human treatment remains elusive. Current strategies often rely on the upregulation of a single proangiogenic factor, which fails to recapitulate the complex response needed in hypoxic tissues. Hypoxic oxygen tensions dramatically decrease the activity of hypoxia inducible factor prolyl hydroxylase 2 (PHD2), the primary oxygen sensing portion of the hypoxia inducible factor 1 alpha (HIF-1) proangiogenic master regulatory pathway. Repressing PHD2 activity increases intracellular levels of HIF-1 and impacts the expression of hundreds of downstream genes directly associated with angiogenesis, cell survival, and tissue homeostasis. This study explores activating the HIF-1 pathway through SpCas9 knockout of the PHD2 encoding gene EGLN1 as an innovative in situ therapeutic angiogenesis strategy for chronic vascular diseases. Our findings demonstrate that even low editing rates of EGLN1 lead to a strong proangiogenic response regarding proangiogenic gene transcription, protein production, and protein secretion. In addition, we show that secreted factors of EGLN1 edited cell cultures may enhance human endothelial cell neovascularization activity in the context of proliferation and motility. Altogether, this study reveals that EGLN1 gene editing shows promise as a potential therapeutic angiogenesis strategy.

bioengineering↗

bioRxiv2022

Complement receptor C5aR1 signaling in sensory neuron-associated macrophages drives neuropathic pain

Neuroimmune interactions across the pain pathway play a predominant role in the development of neuropathic pain. Previous reports demonstrated that complement driven effector systems including the C5a/C5aR1 axis contribute to these neuro-immune mechanisms. However, the cellular and molecular mechanisms underlying C5a/C5aR1 signaling-mediated neuropathic pain development remain ill-identified. Here we show that neuropathic pain following peripheral nerve injury was attenuated in C5aR1-deficient male and female mice as well as in wild type mice treated with a selective allosteric C5aR1 antagonist. Using two complementary cell-specific C5aR1 knockout mouse strains, we identified C5a/C5aR1 driven-activation of sensory neuron-associated macrophages (sNAMs) located in the sensory ganglia as the key site of peripheral nerve injury-induced neuropathic pain, whereas activation of macrophages of the local of peripheral nerve injury was not involved. Mechanistically, we uncovered IL-1b the main mediator of pain hypersensitivity in response to C5aR1 signaling in sNAMs. Our findings highlight a crucial role of C5a/C5aR1 axis activation in sNAMs for the development of neuropathic pain and identify this pathway as a promising novel target for neuropathic pain therapy.

pharmacology and toxicology↗

bioRxiv2022

Sensory neuron-associated macrophages proliferate in the sensory ganglia after peripheral nerve injury in a CX3CR1 signaling dependent manner

Resident macrophages are distributed across all tissues and are highly heterogeneous as a consequence of adaptation to different tissue-specific environments. The resident macrophages of the sensory ganglia (sensory neuron-associated macrophages, sNAMs) are in close contact with the cell body of primary sensory neurons and might play physiological and pathophysiological roles. After peripheral nerve injury, there is an increase in the population of macrophages in the sensory ganglia which have been involved in different conditions, especially in neuropathic pain development and nerve regeneration. However, it is still under debate whether macrophages accumulation in the sensor ganglia after peripheral nerve injury is due to the local proliferation of resident macrophages or as a result of blood monocytes infiltration. Here, we confirmed that the number of macrophages increased in the DRGs after spared nerve injury (SNI) model in mice. By using different approaches, we found that the increase in the number of macrophages in the DRGs after SNI is mainly in consequence of the proliferation of resident CX3CR1+ macrophages but not due to infiltration of CCR2+ blood monocytes. These proliferating macrophages are the source of the production of pro-inflammatory cytokines such as TNF and IL-1b. In addition, we found that CX3CR1 signaling is involved in the sNAMs proliferation after peripheral nerve injury. In summary, these results indicated that peripheral nerve injury leads to sNAMs proliferation in the sensory ganglia in a CX3CR1-dependent manner. In conclusion, sNAMs proliferation could be modulated to change pathophysiological conditions such as chronic neuropathic pain and/or nerve regeneration.

immunology↗

bioRxiv2020

Evaluation of Alginate-Based Bioinks for 3D Bioprinting, Mesenchymal Stromal Cell Osteogenesis, and Application for Patient-Specific Bone Grafts

To realize the promise of 3D bioprinting, it is imperative to develop bioinks that possess the biological and rheological characteristics needed for the printing of cell-laden tissue grafts. Alginate is widely used as a bioink because its rheological properties can be modified through pre-crosslinking or the addition of thickening agents to increase printing resolution. However, modification of alginates physicochemical characteristics using common crosslinking agents can affect its cytocompatibility. Therefore, we evaluated the printability, physicochemical properties, and osteogenic potential of four common alginate bioinks: alginate-CaCl2 (alg-CaCl2), alginate-CaSO4 (alg-CaSO4), alginate-gelatin (alg-gel) and alginate-nanocellulose (alg-ncel) for the 3D bioprinting of patient-specific osteogenic grafts. While all bioinks possessed similar viscosity, printing fidelity was lower in the pre-crosslinked bioinks. When used to print geometrically defined constructs, alg-CaSO4 and alg-ncel exhibited higher mechanical properties and lower mesh size than those printed with alg-CaCl2 or alg-gel. The physical properties of these constructs affected the biological performance of encapsulated bone marrow-derived mesenchymal stromal cells (MSCs). Cell-laden constructs printed using alg-CaSO4 and alg-ncel exhibited greater cell apoptosis and contained fewer living cells 7 days post-printing. In addition, effective cell-matrix interactions were only observed in alg-CaCl2 printed constructs. When cultured in osteogenic media, MSCs in alg-CaCl2 constructs exhibited increased osteogenic differentiation compared to the other three bioinks. This bioink was then used to 3D print anatomically accurate cell-laden scaphoid bones that were capable of partial mineralization after 14 days of in vitro culture. These results highlight the importance of bioink properties to modulate cell behavior and the biofabrication of clinically relevant bone tissues.

bioengineering↗

bioRxiv2020

Clues on an intraspecific communication system in early plant establishment: The seed-seedling transition from the point of view of a crosstalk between information theory and gene expression

How much interactivity is there in a seed-seedling transition system? The answer for this question can reveal a key aspect for early plant establishment. Thus, we hypothesize that information entropy is correlated with early plant development because it is directly related to interactions between seed-seed, seed-seedling, and seedling-seedling. To test this hypothesis, we perform an overlapping of classical physiological measurements (embryo protrusion), gene expression in germination sensu stricto, water dynamics in germinating seeds and information theory. For a biological model, we used Solanum lycocarpum A. St.{square}Hil. seeds. This is a Neotropical species with high intra-specific variability in the seed sample. Our finds demonstrate that the dynamic and transient seed-seedling transition system is influenced by the number of individuals (seed or seedling) in the sample, especially at a same physiological stage. In addition, we also discuss that: (i) information entropy enables the quantification of system disturbance relative to individuals in the same physiological stage (seed-seed or seedling-seedling), which may be determinant for embryo growth during germination. (ii) there is possible intraspecific communication in seed-seedling transition systems formed by germinating seeds with the potential to alter the pattern of embryonic development of the sample. In view of this, we suggest the use of information entropy as a tool for studies of biological systems to clarify the phenomenon of mutual stimulation in the germination process.

plant biology↗

bioRxiv2019

Open-source 3D printed air-jet for generating monodispersed alginate microhydrogels

Open-source designs represent an attractive and new tool for research as it provides both affordable and accessible options to the lab environment. In particular, with the advent of new and cheap additive manufacturing technologies, the open-source design of lab hardware enables others to perform research that would be difficult otherwise. This manuscript describes an air-jet system designed to be open-source and simple to produce with 3D printing. The fully 3D printed air-jet was designed for the generation of hydrogel microbeads of a controllable size. Alginate microbeads were used as a working model, given that it has many promising research applications due to their injectability and highly reproducible properties. A fit definitive design of experiments was performed to determine critical factors affecting diameter, index of dispersity, and circularity of microbeads from this air-jet design. By regulating alginate concentration, air pressure, pump speed, and needle diameter could achieve control over microbeads size from 200-800 {micro}m with low variance. Furthermore, we also demonstrate the potential probiotic research applications of the open-source air-jet through the encapsulation of bacteria in alginate microbeads with controllable degradation. The results of this study exhibit an open-source platform for making microscale biomaterials with controllable properties that can be achieved through budget 3D printers.

bioengineering↗

bioRxiv2019

Where do our graduates go? A toolkit for retrospective and ongoing career outcomes data collection for biomedical PhD students and postdoctoral scholars

Universities are at long last undertaking efforts to collect and disseminate information about student career outcomes, after decades of calls to action. Organizations such as Rescuing Biomedical Research and Future of Research brought this issue to the forefront of graduate education, and the second Future of Biomedical Graduate and Postdoctoral Training conference (FOBGAPT2) featured the collection of career outcomes data in its final recommendations, published in this journal (Hitchcock et al., 2017). More recently, 26 institutions assembled as the Coalition for Next Generation Life Science, committing to ongoing collection and dissemination of career data for both graduate and postdoc alumni. A few individual institutions have shared snapshots of the data in peer-reviewed publications (Mathur et al., 2018; Silva, des Jarlais, Lindstaedt, Rotman, Watkins, 2016) and on websites. As more and more institutions take up this call to action, they will now be looking for tools, protocols, and best practices for ongoing career outcomes data collection, management, and dissemination. Here, we describe UCSF's experiences in conducting a retrospective study, and in institutionalizing a methodology for annual data collection and dissemination. We describe and share all tools we have developed, and we provide calculations of the time and resources required to accomplish both retrospective studies and annual updates. We also include broader recommendations for implementation at your own institutions, increasing the feasibility of this endeavor.

scientific communication and education↗