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Biology subjects

Carvalho, C.

Publications and source records attributed to Carvalho, C..

9 recordsLinked to original sources

Continuous monitoring of plant transpiration dynamics with a leaf-mounted sensor across environmental conditions

O_LITranspiration plays a central role in plant water relations and strongly influences plant growth. Continuous monitoring is essential for understanding responses to environmental conditions and improving water management in both natural and agricultural systems. Gas-exchange techniques such as infrared gas analysers (IRGAs) and porometers are widely used but are challenging for long-term or large-scale monitoring. On the other hand, the FylloClip is a low-cost, leaf-mounted capacitance sensor developed previously to monitor transpiration by detecting condensation of water vapour near the leaf surface. Here, we evaluated the potential of the FylloClip for monitoring transpiration dynamics and assessed environmental conditions that may affect its performance. C_LIO_LIThe FylloClip was tested under growth chamber, greenhouse, and tropical field conditions. We evaluated how its capacitance measurements respond to rainfall, temperature and humidity, and compared FylloClip measurements with transpiration measured with an IRGA. C_LIO_LIThere was a strong correlation (r = 0.85) between FylloClip and IRGA data. Both systems captured similar diurnal transpiration patterns, with transpiration declining simultaneously under water deficit. Rainfall and very high relative humidity produced FylloClip signals that could be misinterpreted as high transpiration, although transpiration is negligible under these conditions. C_LIO_LIOur results revealed that FylloClips capture temporal patterns of transpiration with high accuracy and resolution, providing a reliable tool for long-term, large-scale monitoring of transpiration dynamics in ecophysiological studies and precision agriculture. C_LI

Plant Biology↗

A telomere-to-telomere map of somatic mutation burden and functional impact in cancer

Oncogenesis involves widespread genetic and epigenetic alterations, yet the full spectrum of somatic variation genome-wide remains unresolved. We generated a near-telomere-to-telomere (T2T) diploid assembly of a donor paired with deep short- and long-read sequencing of their melanoma. This revealed that 16% of somatic variants occur in sequences absent from GRCh38, with satellite repeats acting as hotspots for UV-induced damage due to sequence-intrinsic mutability and inefficient repair. Centromere kinetochore domains emerged as focal sites of structural, genetic, and epigenetic variation, leading to remodeling of centromere kinetochore binding domains during tumor evolution. Single-molecule telomere reconstructions uncovered cycles of attrition, deletion, and telomerase-mediated extension that shape cancer telomeres. Finally, diploid chromatin maps exposed that copy number alterations and epimutations, rather than point mutations, predominate in rewiring cancer regulatory programs. These findings define the full landscape of a cancers somatic variation and their functional impact, establishing a blueprint for T2T studies of mosaicism.

genomics↗

Lipid droplet dysmetabolism affects cell homeostasis in an in vitro model of Alzheimer disease

Lipid droplets (LD) are dynamic organelles involved in neutral lipid storage, energy homeostasis, and can prevent lipotoxicity and oxidative distress. LD dysmetabolism has been considered a pathological hallmark in neurodegenerative disorders, including Alzheimers disease (AD). In this study, we investigated the alterations in LD metabolism and their impact on mitochondria-associated membranes (MAM) in an in vitro model of AD, namely the mouse neuroblastoma cell (N2A) line overexpressing the amyloid precursor protein with the familial Swedish mutation (APPswe). In APPswe cells, we found depletion of LD associated with an accumulation of free fatty acids that can be related with the observed LD degradation by chaperone-mediated autophagy. In these cells we also found decreased levels of seipin, which might contribute to triacylglycerol accumulation. These lipid alterations are associated with increased levels of ROS and lipid peroxidation in APPswe cells. The pharmacological modulation of DGAT1, that mediates triacylglycerol synthesis, normalized LD size and improved ER-mitochondria contacts and mitochondrial function in APPswe cells. In summary, these observations suggest the involvement of altered LD metabolism in AD pathophysiology, which impact on MAM and mitochondria function leading to cell dyshomeostasis. Our findings also support the idea that LD are relevant therapeutic targets in AD. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/658644v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@de3fc6org.highwire.dtl.DTLVardef@12d1f2forg.highwire.dtl.DTLVardef@15a5185org.highwire.dtl.DTLVardef@9e1655_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

The Sleep-Mood Connection: Temperament Modulates Neuroinflammation, Clock Genes, and Dopaminergic Receptors Expression in Rats

Temperament may influence mood disorder risk under sleep disturbances. Using high- and low-exploratory rats as a temperament model, we examined the effects of paradoxical sleep deprivation (PSD) on mood behaviors, neuroinflammation, oxidative stress, clock genes, and dopamine receptor expression. Eighty male Wistar rats were screened for exploratory activity, while 20 were classified as high (HE) and 21 as low (LE) exploratory based on open-field performance. HE and LE rats were subjected to PSD or remained undisturbed (controls). Behavioral assessments included impulsivity, risk-taking, anhedonia, and forced swim test (FST) performance. Neurobiological analyses measured hippocampal lipid peroxidation, pro-inflammatory markers (IL-6, TLR4), gene expression of Clock, Tph2, Tdo2, and protein expression of D1, and D2, which regulate, respectively, circadian rhythms, serotonin synthesis, tryptophan metabolism, and dopaminergic signaling--key pathways implicated in mood disorders. HE rats showed increased impulsivity, risk-taking, and exploratory behaviors, resembling mania, while LE rats exhibited avoidance. PSD intensified these traits, heightening risk-taking in HE rats and inducing depressive-like behaviors in LE rats, including anhedonia and FST immobility linked to reduced Tph2 expression. Both groups had post-PSD working memory deficits. Neurobiologically, HE+PSD rats showed increased lipid peroxidation, neuroinflammation (IL-6, TLR4), and upregulation of Clock and DRD1 genes, while LE+PSD rats had elevated hippocampal Tdo2 expression. Temperament shapes PSD-induced behavioral and neurobiological effects. HE rats showed mania-like traits, while LE rats exhibited depressive behaviors. PSD impaired working memory in both. Oxidative stress, inflammation, and gene expression changes highlight distinct vulnerabilities and potential therapeutic targets for mood disorders.

animal behavior and cognition↗

Mast cells are not essential for pubertal mammary gland branching.

Mast cells are long-lived, tissue-resident immune cells of the myeloid lineage with cardinal functions in allergy and atopic disease. They are now increasingly recognized also for protective roles e.g. against infections and venoms. Other functions originally assigned to mast cells in development and physiology, however, have been refuted, and for yet others, their true contribution remains uncertain. Mast cells have been implicated in promoting ductal branching in the pubertal mammary gland, the organ that produces and secretes milk in mammals, but these findings are based on mouse models that are not mast cell-specific. In this study, we therefore re-addressed the impact of mast cells on mammary gland branching using several complementary genetic models, including a new transgenic line. We report that neither constitutive deficiency of mast cells, nor their conditional ablation induced at puberty affected mammary gland branching. Our results thus dispute that mast cells promote this process in mice, at least in a unique and non-redundant manner. This study adds to a growing body of work clarifying the biological roles of mast cells, and further expands the toolbox available to the field of mast cell research.

developmental biology↗

Dynein directs prophase centrosome migration to control the stem cell division axis in the developing C. elegans epidermis

The microtubule motor dynein is critical for the assembly and positioning of mitotic spindles. In C. elegans, these dynein functions have been extensively studied in the early embryo but remain poorly explored in other developmental contexts. Here we use a hypomorphic dynein mutant to investigate the motors contribution to asymmetric stem cell-like divisions in the larval epidermis. Live imaging of seam cell divisions that precede formation of the seam syncytium shows that mutant cells properly assemble but frequently mis-orient their spindle. Mis-oriented divisions misplace daughter cells from the seam cell row, generate anucleate compartments due to aberrant cytokinesis, and disrupt asymmetric cell fate inheritance. Consequently, the seam becomes disorganized and populated with extra cells that have lost seam identity, leading to fatal epidermal rupture. We show that dynein orients the spindle through the cortical GOA-1Gi-LIN-5NuMA pathway, which directs the migration of prophase centrosomes along the anterior-posterior axis. Spindle mis-orientation in the dynein mutant can be rescued by stretching cells, implying that dynein-dependent cortical cues and elongated cell shape jointly ensure correct asymmetric division of epithelial stem cells.

cell biology↗

Mast cell-mediated inflammation relies on insulin-regulated aminopeptidase controlling cytokine export from the Golgi

Upon activation, mast cells rapidly release preformed inflammatory mediators from large cytoplasmic granules via regulated exocytosis. This acute degranulation is followed by a late activation phase involving synthesis and secretion of cytokines, growth factors and other inflammatory molecules via the constitutive pathway that remains ill-defined. Here we describe a role for an insulin-responsive vesicle-like endosomal compartment, marked by insulin-regulated aminopeptidase (IRAP), in the secretion of TNF-- and IL-6 in mast cells and macrophages. IRAP-deficient mice are protected from TNF--dependent kidney injury and inflammatory arthritis. In the absence of IRAP, TNF- fails to be efficiently exported from the Golgi. Subsequently, reduced co-localization of VAMP3+ endosomes with Stx4 was observed, while VAMP8-dependent exocytosis of secretory granules was facilitated. Chemical targeting of IRAP+ endosomes reduced pro-inflammatory cytokine secretion thereby highlighting this compartment as a promising target for the therapeutic control of inflammation.

immunology↗

Molecular and functional basis of a novel Amazonian Dark Earth Esterase 1 (Ade1) with hysteresis behavior and quorum-quenching activity

Amazon Dark Earth (ADE) soil is rich in organic compounds and its fertility has been associated with a high diversity of microorganisms. Herein, we investigate the biochemical and functional features of a novel esterase, Ade1, obtained from a metagenomic library of Amazonian Dark Earth soils of the Amazonian Rainforest, in Brazil. The esterases cleave ester bonds to form a carboxylic and an alcohol group. Esterases and lipases are enzymes found in almost all living organisms, demonstrating their biological relevance. We reported that Ade1 belongs to an /{beta}-hydrolase superfamily. We suggest that Ade1 is a moonlighting enzyme with hysteresis behavior and quorum-quenching activity, which may play a key role in the metabolism of a Gram-negative proteobacteria. In addition, molecular dynamics simulations reveal that the hysteresis behavior is directly associated with structural properties of the cap domain. Our findings reveal details of the molecular basis, catalytic and structural mechanisms of a novel /{beta}-hydrolase, which may be applied to other esterases of biotechnological, food, and/or pharmaceutical interest. O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

biochemistry↗

DRD2 and FOXP2 are implicated in the associations between computerized device use and psychiatric disorders

1.The societal health effects of ubiquitous computerized device use (CDU) is mostly unknown. Epidemiological evidence supports associations between CDU and psychiatric traits, but the underlying biological mechanisms are unclear. We investigated genetic overlaps, causal relationships, and molecular pathways shared between these traits using genome-wide data regarding CDU (UK Biobank; up to N=361,194 individuals) and Psychiatric Genomics Consortium phenotypes (14,477<N<150,064). The strongest genetic correlations were between \"weekly usage of mobile phone in last 3 months\" (PhoneUse) vs. attention deficit hyperactivity disorder (ADHD) (rg=0.425, p=4.59x10-11) and \"plays computer games\" (CompGaming) vs. schizophrenia (SCZ) (rg=-0.271, p=7.16x10-26). Latent causal variable analysis did not support causal relationships between these traits, but the observed genetic overlap was related to shared molecular pathways, including: dopamine transport (Gene Ontology:0015872, pSCZvsCompGaming=2.74x10-10) and DRD2 association (pSCZ=7.94x10-8; pCompGaming=3.98x10-25), and FOXP2 association (pADHD=9.32x10-7; pPhoneUse=9.00x10-11). Our results support epidemiological observations with genetic data, and uncover biological mechanisms underlying psychiatric disorders contribution to CDUs.

genomics↗