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Garcia, C.

Publications and source records attributed to Garcia, C..

47 records · Page 3Linked to original sources

Does male mate choice select for female colouration in a promiscuous primate species?

The traditional view of sex roles and sexual selection emphasises the evolution of male ornaments as a result of female mate choice and male-male competition. Female ornaments are now receiving more attention, although their roles in mating decision are still less well understood, especially considering cases in which colourful ornaments are expressed by both sexes. In this study, we analysed whether female skin colouration (luminance and redness of the face and hindquarters) influenced male mate choice and sexual behaviours in relation to intra-cycle (cycle phase), inter-cycle (number of consecutive cycles, conceptive nature of the cycle), and inter-individual (age, social rank, weight, and parity) variation in a captive population of Japanese macaques (Macaca fuscata). Males did not preferentially choose darker/redder females. Moreover, males did not appear to use female skin colouration to apportion their mating efforts on the most fertile period of the menstrual cycle or during cycles that lead to conception, or to discriminate between females. To our knowledge, our study is among the few to report a lack of male choice for female colouration in a species where both sexes potentially display ornamentation. While female colouration appeared to contain information about intra-cycle, inter-cycle, and inter-individual variation in fecundity, this study further demonstrates that this trait may not have been sexually selected and that males mated regardless of such variation across females. This study adds to the growing research on the role and evolution of female colouration in the context of sexual signalling and mate attraction.

animal behavior and cognition↗

Screening of Cultivars for Tissue Culture Response and Establishment of Genetic Transformation in a High-yielding and Disease-resistant Cultivar of Theobroma cacao

A highly efficient transformation protocol is a prerequisite to developing genetically modified and genome-edited crops. A tissue culture system spanning the initiation of floral material to the regeneration of plantlets into soil has been tested and improved in cacao. Fourteen cultivars were screened for their tissue culture response and transfer DNA (T-DNA) delivery efficiency via Agrobacterium. These key factors were used to determine the genetic transformability of various cultivars. The high-yielding, disease-resistant cultivar INIAPG-038 was selected for stable transformation and the method was further optimized. Multiple transgenic events were produced using two vectors containing both yellow fluorescent protein and neomycin phosphotransferase II genes. A two-fold strategy to improve both T-DNA delivery and secondary somatic embryogenesis rates was conducted to improve overall transformation frequency. The use of Agrobacterium strain AGL1 and cotyledon tissue derived from immature somatic embryos ranging in size between 4-10 mm resulted in the highest T-DNA delivery efficiency. Furthermore, the use of higher concentrations of basal salts and cupric sulfate in secondary callus growth medium increased the percentage of explants producing greater than ten embryos by 504% and 443%, respectively. Consequently, an optimal combination of all these components resulted in a successful transformation of INIAPG-038 with 3.7% frequency at the T0 plant level. Grafting transgenic scions with undeveloped roots to wild-type seedlings with strong, healthy roots helped make plantlets survive and facilitated quick transplantation to the soil. The present methods can be applied to improve tissue culture response and transformation frequency in other cacao cultivars. Key messageTissue culture and genetic transformation methods for a high-yielding, disease-resistant cultivar of Theobroma cacao were established while factors affecting T-DNA delivery and somatic embryogenesis were identified.

plant biology↗

Tuning TPO-R signaling to influence hematopoietic stem cell differentiation and inhibit essential thrombocythemia

Thrombopoietin (TPO) and the TPO-receptor (TPO-R, or c-MPL)) are essential for hematopoietic stem cell (HSC) maintenance and megakaryocyte differentiation. Agents that can modulate TPO-R signaling are highly desirable, both experimentally and clinically. We have developed a series of surrogate protein-ligands for TPO-R, in the form of diabodies, that homodimerize the TPO-R on the cell surface in different geometries, in effect tuning downstream signaling responses. These surrogate ligands exhibit diverse pharmacological properties, inducing graded signaling outputs, from full to partial TPO agonism and antagonism, thus decoupling the dual functions of TPO/TPO-R. Using scRNA sequencing and HSC self-renewal assays we find that partial agonistic diabodies preserved the stem-like properties of cultured HSCs, but also blocked oncogenic colony formation in Essential Thrombocythemia (ET) through inverse agonism. Our data suggest that dampening downstream TPO signaling is a powerful approach not only for HSC preservation in culture, but also for inhibiting oncogenic signaling through the TPO-R. Significance StatementThe TPO cytokine, which signals through its receptor c-MPL (or TPO-R), is essential for megakaryocyte differentiation and maintenance of hematopoietic stem cells (HSCs). Its signaling is deregulated in Essential Thrombocythemia (ET). Here, we engineered diabodies (DBs) against the TPO-R as surrogate TPO ligands to manipulate TPO-R signaling, from full to partial to antagonism, thus decoupling the dual functions of TPO/TPO-R (i.e, HSC maintenance versus megakaryopoiesis). We subsequently discovered that partial agonistic DBs, by reducing the strength of the TPO-R signal, not only preserved HSCs in culture, but also blocked oncogenic signaling in ET. This finding has the potential to improve HSC cultures for transplants, as well as serve as a unique therapeutic approach for ET.

cell biology↗

The chaos in calibrating crop models

Calibration, the estimation of model parameters based on fitting the model to experimental data, is among the first steps in many applications of system models and has an important impact on simulated values. Here we propose and illustrate a novel method of developing guidelines for calibration of system models. Our example is calibration of the phenology component of crop models. The approach is based on a multi-model study, where all teams are provided with the same data and asked to return simulations for the same conditions. All teams are asked to document in detail their calibration approach, including choices with respect to criteria for best parameters, choice of parameters to estimate and software. Based on an analysis of the advantages and disadvantages of the various choices, we propose calibration recommendations that cover a comprehensive list of decisions and that are based on actual practices. HighlightsO_LIWe propose a new approach to deriving calibration recommendations for system models C_LIO_LIApproach is based on analyzing calibration in multi-model simulation exercises C_LIO_LIResulting recommendations are holistic and anchored in actual practice C_LIO_LIWe apply the approach to calibration of crop models used to simulate phenology C_LIO_LIRecommendations concern: objective function, parameters to estimate, software used C_LI

plant biology↗

Fine-tuning of Epithelial EGFR signals Supports Coordinated Mammary Gland Development

During puberty, robust morphogenesis occurs in the mammary gland; stem- and progenitor-cells develop into mature basal- and luminal-cells to form the ductal tree. The receptor signals that govern this process in mammary epithelial cells (MECs) are incompletely understood. The EGFR has been implicated and here we focused on EGFRs downstream pathway component Rasgrp1. We find that Rasgrp1 dampens EGF-triggered signals in MECs. Biochemically and in vitro, Rasgrp1 perturbation results in increased EGFR-Ras-PI3K-AKT and mTORC1-S6 kinase signals, increased EGF-induced proliferation, and aberrant branching-capacity in 3D cultures. However, in vivo, Rasgrp1 perturbation results in delayed ductal tree maturation with shortened branches and reduced cellularity. Rasgrp1-deficient MEC organoids revealed lower frequencies of basal cells, the compartment that incorporates stem cells. Molecularly, EGF effectively counteracts Wnt signal-driven stem cell gene signature in organoids. Collectively, these studies demonstrate the need for fine-tuning of EGFR signals to properly instruct mammary epithelium during puberty.

cell biology↗

How well do crop models predict phenology, with emphasis on the effect of calibration?

Predicting phenology is essential for adapting varieties to different environmental conditions and for crop management. Therefore, it is important to evaluate how well different crop modeling groups can predict phenology. Multiple evaluation studies have been previously published, but it is still difficult to generalize the findings from such studies since they often test some specific aspect of extrapolation to new conditions, or do not test on data that is truly independent of the data used for calibration. In this study, we analyzed the prediction of wheat phenology in Northern France under observed weather and current management, which is a problem of practical importance for wheat management. The results of 27 modeling groups are evaluated, where modeling group encompasses model structure, i.e. the model equations, the calibration method and the values of those parameters not affected by calibration. The data for calibration and evaluation are sampled from the same target population, thus extrapolation is limited. The calibration and evaluation data have neither year nor site in common, to guarantee rigorous evaluation of prediction for new weather and sites. The best modeling groups, and also the mean and median of the simulations, have a mean absolute error (MAE) of about 3 days, which is comparable to the measurement error. Almost all models do better than using average number of days or average sum of degree days to predict phenology. On the other hand, there are important differences between modeling groups, due to model structural differences and to differences between groups using the same model structure, which emphasizes that model structure alone does not completely determine prediction accuracy. In addition to providing information for our specific environments and varieties, these results are a useful contribution to a knowledge base of how well modeling groups can predict phenology, when provided with calibration data from the target population.

plant biology↗

Splicing inhibition enhances the antitumor immune response through increased tumor antigen presentation and altered MHC-I immunopeptidome

The success of cancer immunotherapy relies on the induction of an immunoprotective response targeting tumor antigens (TAs) presented by tumor cells on MHC class I molecules. Alternative translation events emerged as a rich source of TAs and generate the so-called Pioneer Translation Products (PTPs), which are peptides generated from unspliced mRNA. We demonstrated in vitro and in vivo that the splicing inhibitor isoginkgetin and a derived water-soluble and less toxic molecule, IP2, act at the production stage of the PTPs. We showed that IP2 increases PTP-derived antigen presentation in cancer cells in vitro and decreases tumor growth in vivo in an immune-dependent manner. Furthermore, IP2 treatment induces a long-lasting antitumor response. Finally, we observed that the epitope repertoire displayed on MHC-I molecules is altered upon treatment with IP2 with the modulation of pre-existing peptides and the emergence of novel antigens derived from both coding and allegedly non-coding sequences.\n\nSignificanceIP2 is a new efficient \"first in class\" immunomodulator of the MHC I presentation pathway. IP2 reduces the growth of sarcoma MCA205 and melanoma B16F10 tumors bearing the PTP-derived SL8 epitope and significantly extends mice survival. IP2 treatment reshape the cancer cell MHC-I immunopeptidome. These findings add to the understanding of the role of the splicing machinery in antigen production and presentation and identify the spliceosome as a druggable target to enhance cancer immunosurveillance.

immunology↗

A phenotypic small-molecule screen identifies halogenated salicylanilides as inhibitors of fungal morphogenesis, biofilm formation and host cell invasion

A poorly exploited paradigm in the antimicrobial therapy field is to target virulence traits for drug development. In contrast to target-focused approaches, antivirulence phenotypic screens enable identification of bioactive molecules that induce a desirable biological readout without making a priori assumption about the cellular target. Here, we screened a chemical library of 678 small molecules against the invasive hyphal growth of the human opportunistic yeast Candida albicans. We found that a halogenated salicylanilide (N1-(3,5-dichlorophenyl)-5-chloro-2-hydroxybenzamide) and one of its analog, Niclosamide, an FDA-approved anthelmintic in humans, exhibited both antifilamentation and antibiofilm activities against C. albicans and the multi-resistant yeast C. auris. The antivirulence activity of halogenated salicylanilides were also expanded to C. albicans resistant strains with different resistance mechanisms. We also found that Niclosamide protected the intestinal epithelial cells against invasion by C. albicans. Transcriptional profiling of C. albicans challenged with Niclosamide exhibited a signature that is characteristic of the mitochondria-to-nucleus retrograde response. Our chemogenomic analysis showed that halogenated salicylanilides compromise the potential-dependant mitochondrial protein translocon machinery. Given the fact that the safety of Niclosamide is well established in humans, this molecule could represent the first clinically approved antivirulence agent against a pathogenic fungus.

microbiology↗

Neuronal thresholds and correlations in the peripheral vestibular system during rotation discrimination

Neuronal and behavioral thresholds were measured simultaneously as trained male macaques performed a yaw rotation discrimination task in darkness. When corrected to account for variations in neuronal direction preferences, neurons in the vestibular nuclei and semicircular canal afferents had discrimination thresholds that were only two-fold smaller than behavioral thresholds. There was no significant trial-by-trial correlation between neuronal activity and perceptual decisions, despite the presence of significant pair-wise noise correlations. The lack of choice-related activity during rotation discrimination contrasts with the robust correlations observed previously between brainstem neurons and choices during translation perception. These results suggest task-dependent differences in subcortical processing of vestibular signals, as well as how signals related to perceptual decisions may propagate back to early stages of sensory processing.\n\nSIGNIFICANCE STATEMENTThis is the first ever simultaneous recordings of neural and behavioral thresholds during rotation discrimination. Its importance lies on the fact that the vestibular system provides an excellent model to probe origins of perception because directional selectivity signals are similar at many levels of processing, from afferents to cortex. The findings of similar neuronal and behavioral discrimination thresholds, significant inter-neuronal correlations, but lack of correlations between behavior and neuronal activity of both afferents and central brainstem neurons are intriguing and suggest task-dependent organization of early sensory areas.

neuroscience↗

First natural crossover recombination of intact ORFs between two distinct species of the family Closteroviridae

Lettuce chlorosis virus-SP (LCV-SP) (family Closteroviridae, genus Crinivirus), is a new strain of LCV which is able to infect green bean plants and incapable of infecting lettuce crops. In the present study, high throughput and Sanger sequencing of RNA was used to obtain the LCV-SP full-length sequence. The LCV-SP genome comprises 8825 nt and 8672 nt equivalent with RNA1 and RNA2 respectively. RNA1 of LCV-SP contains four ORFs, the proteins encoded by the ORF1a and ORF1b are closely related to LCV RNA1 from California (FJ380118) whereas the 3{acute} end encodes proteins which share high amino acid sequence identity with RNA1 of BnYDV (EU191904). The genomic sequence of RNA2 consists of 8 ORFs, instead of 10 ORFs contained in LCV-California isolate. The distribution of vsiRNA (virus-derived small interfering RNA) along the LCV-SP genome suggested the presence of subgenomic RNAs corresponding with HSP70, P6.4 and P60. Results of the analysis using RDP4 and Simplot programs are the proof of the evidence that LCV-SP is the first recombinant of the family Closteroviridae by crossover recombination of intact ORFs, being the LCV RNA1 (FJ380118) and BnYDV RNA1 (EU191904) the origin of the new LCV strain. Genetic diversity values of virus isolates in the recombinant region obtained after sampling LCV-SP infected green bean between 2011 and 2017 might suggest that the recombinant virus event occurred in the area before this period. The presence of LCV-SP shows the role of recombination as a driving force of evolution within the genus Crinivirus, a globally distributed, emergent genus.

plant biology↗

Daam2 Driven Degradation Of VHL Promotes Gliomagenesis

Von Hippel-Landau (VHL) protein is a potent tumor suppressor regulating numerous pathways that drive cancer, but mutations in VHL are restricted to limited subsets of malignancies. Here we identified a novel mechanism for VHL suppression in tumors that do not have inactivating mutations. Using developmental processes to uncover new pathways contributing to tumorigenesis, we found that Daam2 promotes glioma formation. Protein expression screening identified an inverse correlation between Daam2 and VHL expression across a host of cancers, including glioma. These in silico insights guided corroborating functional studies, which revealed that Daam2 promotes tumorigenesis by suppressing VHL expression. Furthermore, biochemical analyses demonstrate that Daam2 associates with VHL and facilitates its ubiquitination and degradation. Together, these studies are the first to define an upstream mechanism regulating VHL suppression in cancer and describe the role of Daam2 in tumorigenesis.\n\nStatement of SignificanceWe found that the glial developmental factor Daam2 promotes glioma tumorigenesis by suppressing VHL expression. Our studies show, for the first time, a regulatory mechanism that operates upstream of VHL in cancer and provides an explanation for how VHL expression is extinguished in tumors that do not have inactivating mutations.

cancer biology↗