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Pereira, N.

Publications and source records attributed to Pereira, N..

5 recordsLinked to original sources

Cold acclimation reprograms hepatic lipid composition toward n-3 HUFAs to uncouple adipose-derived lipid flux from steatosis

While cold exposure drives lipid flux from adipose tissue to the liver, this enhanced inter-organ crosstalk does not result in sustained hepatic steatosis during prolonged acclimation, indicating that factors beyond lipid flux shape metabolic outcome. To interrogate this adaptation, we performed integrated lipidomic and metabolic profiling across tissues and circulating lipoproteins over the course of cold acclimation. We showed that cold acclimation induces systemic reprogramming of lipid quality in mice, characterized by enrichment of n-3 highly unsaturated fatty acids (HUFAs) as a consequence of upregulation of fatty acid desaturases (FADS1 and 2) in the liver and white adipose tissue, thus increasing hepatic n-3/n-6 ratio. Cold-induced increase in n-3 HUFAs cause the suppression of SCD1-mediated desaturation, thus yielding a depletion of monounsaturated fatty acids (MUFAs) in the liver, along with the suppression of lipogenic markers. Notably, this high-HUFA/low-MUFA lipid signature is present in both hepatic free fatty acid and triglyceride pools, indicating that lipid remodeling occurs upstream of triglyceride synthesis. Lipidomic analysis revealed that the remodeled triglycerides are incorporated into very-low-density and intermediate density lipoproteins (VLDL and IDL), thereby propagating hepatic lipid reprogramming to the circulation. Thus, by selectively increasing endogenous n-3 HUFA availability, cold adaptation suppresses hepatic DNL and MUFA-driven triglyceride assembly, buffering lipid accumulation despite sustained fatty acid influx and reshaping systemic lipid distribution with potential cardiometabolic impact.

biochemistry↗

Non-invasive and unbiased assessment of thermogenesis in mice through thermal gradient ring

Accurately assessing whole-body heat production requires reliable thermometry methods. In mice, common approaches include rectal temperature (RT) measurement, infrared (IR) thermography, and implanted probes. However, factors such as stress, handling, surgery, and variability limit their applicability for evaluating thermogenesis. The Thermal Gradient Ring (TGR), widely used in neuropathic pain and ion channel studies, consists of a circular structure with twelve temperature zones and an integrated IR camera for real-time behavior monitoring. This system allows precise analysis of preferred temperature (PT), heat tolerance, locomotion, and zone occupancy over time, thereby offering a behavioral perspective beyond traditional thermometric methods, which provides only temperature data. In this study, we evaluated TGR as a non-invasive tool for detecting thermogenic changes. Since mice with higher thermogenesis prefer cooler zones, while those with reduced thermogenesis seek warmth, TGR provides a sensitive readout of metabolic behavior. Using models with both enhanced and impaired thermogenesis, we demonstrated TGRs ability to detect thermogenic status under different conditions. These findings suggest that TGR is a valuable tool for metabolic research, offering a reliable alternative for assessing thermogenesis in mice.

physiology↗

A PI3Kδ-Foxo1-FasL signaling amplification loop rewires CD4+ T helper cell signaling, differentiation and epigenetic remodeling

While inputs regulating CD4+ T helper cell (Th) differentiation are well-defined, the integration of downstream signaling with transcriptional and epigenetic programs that define Th-lineage identity remain unresolved. PI3K signaling is a critical regulator of T cell function; activating mutations affecting PI3K{delta} result in an immunodeficiency with multiple T cell defects. Using mice expressing activated-PI3K{delta}, we found aberrant expression of proinflammatory Th1-signature genes under Th2-inducing conditions, both in vivo and in vitro. This dysregulation was driven by a robust PI3K{delta}-IL-2-Foxo1 signaling loop, fueling Foxo1-inactivation, loss of Th2-lineage restriction, altered chromatin accessibility and global impairment of CTCF-DNA interactions. Surprisingly, ablation of Fasl, a Foxo1-repressed gene, restored normal Th2 differentiation, TCR signaling and CTCF expression. BioID revealed Fas interactions with TCR- signaling components, which were supported by Fas-mediated potentiation of TCR signaling. Our results highlight Fas-FasL signaling as a critical intermediate in phenotypes driven by activated-PI3K{delta}, thereby linking two key pathways of immune dysregulation.

immunology↗

Body size-dependent effects on the distribution patterns of phoretic mites of the multi-symbiont Rhynchophorus ferrugineus (Olivier, 1790) host

Phoretic mites have been found attached to different body parts of the red palm weevil (RPW), Rhynchophorus ferrugineus (Olivier, 1790), to disperse. However, the question of how the patterns of attachment sites are formed remains intriguing. Here, we conducted the first study of RPW-associated phoretic mites in Portugal, particularly in the districts of Viana do Castelo, Braga, Porto and Aveiro in Northern Portugal (macrohabitat), and investigated the patterns of mite distribution on six body parts of RPW (microhabitat). At the macrohabitat level, we detected seven phoretic mite taxa actively using the RPW host in each of the four studied districts, all documented for the first time in association with this invasive exotic species in Portugal. However, their relative abundance (species evenness) varied between districts, as did species diversity. All examined weevils carried mites, and the prevalence of the different taxa did not differ between districts or sex of weevils. Measured by mean abundance and degree of aggregation, Centrouropoda sp. proved to be the common dominant taxon, while Acarus sp. And C. rhynchoporus were considered common subordinate taxa and Uroovobella sp., Mesostigmata, N. extremica and Dendrolaelaps sp. sparse taxa. At the microhabitat level, all taxa were present in all body parts of the RPW; the highest abundance was in a region encompassing the inner surface of the elytra and the membranous hind wings (subelytral space). Analysis of niche overlap revealed that the distribution patterns of phoretic mite taxa on the RPW were not randomly structured. In the subelytral space, interspecific coexistence of mites increased as a function of body size difference with the dominant Centrouropoda sp. We conclude that the distribution patterns of RPW-associated phoretic mites show body size-dependent effects that resulted in the dominant taxon displacing similar size taxa and accepting taxa with which it has the greatest size difference as co-habitants.

ecology↗

TsTX-kappa beta (Ts8), a neurotoxin from the venom of the scorpion Tityus serrulatus: antimicrobial and hemolytic activity.

Increase of infections caused by microorganisms resistant to conventional antibiotics is a health problem in Brazil and worldwide. The search for new molecules capable of inhibiting the growth of pathogens is a challenge for researchers, who find in venoms a rich source of biomolecules, including antimicrobial peptides (AMPs). The Brazilian scorpion, Tityus serrulatus, is one of the species that cause serious accidents; its venom is rich in neurotoxins that have been well characterized, highlighting their activities on channels (especially sodium and potassium). In this study we identifified and characterized one AMPs in T. serrulatus venom. After milking, the venom was fractioned by high performance liquid chromatography and the fractions were tested by liquid growth inhibition assay, the minimum inhibitory concentration (MIC) against Escherichia coli, Micrococcus luteus, Candida albicans and Aspergillus niger. The fraction identified with antimicrobial activity was analyzed by electrophoresis and mass spectrometry and this AMP (with molecular mass 6.882 kDa) has a similar amino acid sequence to TsTX-{kappa} beta, a neurotoxin that acts on ion channels. The TsTX-{kappa} beta in this study was identified by de novo sequencing. This peptide showed activity against all microorganisms tested. At high concentrations, this peptide, showed hemolytic activity against human erythrocytes. This is a new function described for this peptide, the identification of antimicrobial activity in a neurotoxin already known. Key ContributionMultifunction: antimicrobial and hemolytic activity associated to TsTX-{kappa} beta, a neurotoxin that acts on potassium channels.

microbiology↗