β-Glucosidases are enzymes with high importance for many industrial processes, catalyzing the last and limiting step of the conversion of lignocellulosic material into fermentable sugars for biofuel production. However, β-glucosidases are inhibited by high concentrations of the product (glucose), which limits the biofuel production on an industrial scale. For this reason, the structural mechanisms of tolerance to product inhibition have been the target of several studies. In this study, we performed in silico experiments, such as molecular dynamics (MD) simulations, free energy landscape (FEL) estimate, Poisson–Boltzmann surface area (PBSA), and grid inhomogeneous solvation theory (GIST) seeking a better understanding of the glucose tolerance and inhibition mechanisms of a representative GH1 β-glucosidase and a GH3 one. Our results suggest that the hydrophobic residues Y180, W350, and F349, as well the polar one D238 act in a mechanism for glucose releasing, herein called “slingshot mechanism”, dependent also on an allosteric channel (AC). In addition, water activity modulation and the protein loop motions suggest that GH1 β-Glucosidases present an active site more adapted to glucose withdrawal than GH3, in consonance with the GH1s lower product inhibition. The results presented here provide directions on the understanding of the molecular mechanisms governing inhibition and tolerance to the product in β-glucosidases and can be useful for the rational design of optimized enzymes for industrial interests.

This brief communication presents the deployment of open-source large language models (LLMs) on the Santos Dumont Brazilian Supercomputer to support the Laborat´orio Nacional de Computa¸c˜ao Cient´ıfica (LNCC) academic community. The solution, named Carcar´a, leverages key optimizations such as dynamic quantization techniques to enable an accessible, scalable, and cost-effective implementation. As a result, a single-instance stateof- the-art independent model was deployed on a single node equipped with 4 × NVIDIA H100 GPUs. The quantized models fit entirely within the node’s VRAM, enabling horizontal scaling without the need for inter-node synchronization. In this way, we could provide access to these models to the entire LNCC academic community using only four computational nodes, demonstrating the efficiency and scalability of this approach. Crucially, our approach ensures data sovereignty, allowing LNCC researchers and postgraduate students to utilize AI for sensitive research topics with full control over their data, free from the privacy risks associated with proprietary solutions. This initiative strengthens national scientific autonomy while providing secure and efficient AI tools for academic and research advancements. The code to deploy this solution is openly available, and we encourage other institutions to adapt it and support their own communities. Discussions with the Brazilian Ministry of Science, Technology and Innovation are underway to expand this strategic solution to other research centers and universities in Brazil.

Upon subsequent blood meals Aedes aegypti can transmit pathogens like dengue, Zika, and chikungunya. The hematophagic behavior does not start right after transition from pupae to adult mosquito, and it is deeply influenced by the metabolic balance after emergence, which regulates the biochemical and molecular changes necessary to seek the vertebrate host. The reproductive success, biting rate, number of eggs laid, and adult longevity are also affected by the metabolic balance. The study of the Insulin/insulin-like growth factor-1 signaling (IIS), is an important source of information that may aid in the development of vector control strategies. The protein tyrosine phosphatases (PTPs) family regulates the IIS, however, they are poorly explored in invertebrates. In the present work, we explore the PTP Leukocyte Common Antigen-Related (LAR) in the mosquito Ae. aegypti (AeLAR), silencing it after emergence to demonstrate that this enzyme also modulates the mosquito IIS pathway. We found that AeLAR knockdown induced glycogen accumulation, even on a restricted diet. The consequence of this accumulation was associated with increased tolerance to starvation and reduced locomotor activity. We also observed changes in the expression of clock genes, host-seeking behavior, blood feeding, and in the number of eggs laid. These results show the importance of AeLAR in insect metabolism and physiology. Disrupting mosquito metabolism during the onset of the adult stage, as demonstrated here, can be used as an additional resource to existing control methods before the mosquitoes become infected