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1.
Sci Rep ; 14(1): 19083, 2024 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-39154100

RESUMEN

Seagrasses provide critical ecosystem services but cumulative human pressure on coastal environments has seen a global decline in their health and extent. Key processes of anthropogenic disturbance can operate at local spatio-temporal scales that are not captured by conventional satellite imaging. Seagrass management strategies to prevent longer-term loss and ensure successful restoration require effective methods for monitoring these fine-scale changes. Current seagrass monitoring methods involve resource-intensive fieldwork or recurrent image classification. This study presents an alternative method using iteratively reweighted multivariate alteration detection (IR-MAD), an unsupervised change detection technique originally developed for satellite images. We investigate the application of IR-MAD to image data acquired using an unoccupied aerial vehicle (UAV). UAV images were captured at a 14-week interval over two seagrass beds in Brisbane Water, NSW, Australia using a 10-band Micasense RedEdge-MX Dual camera system. To guide sensor selection, a further three band subsets representing simpler sensor configurations (6, 5 and 3 bands) were also analysed using eight categories of seagrass change. The ability of the IR-MAD method, and for the four different sensor configurations, to distinguish the categories of change were compared using the Jeffreys-Matusita (JM) distance measure of spectral separability. IR-MAD based on the full 10-band sensor images produced the highest separability values indicating that human disturbances (propeller scars and other seagrass damage) were distinguishable from all other change categories. IR-MAD results for the 6-band and 5-band sensors also distinguished key seagrass change features. The IR-MAD results for the simplest 3-band sensor (an RGB camera) detected change features, but change categories were not strongly separable from each other. Analysis of IR-MAD weights indicated that additional visible bands, including a coastal blue band and a second red band, improve change detection. IR-MAD is an effective method for seagrass monitoring, and this study demonstrates the potential for multispectral sensors with additional visible bands to improve seagrass change detection.


Asunto(s)
Monitoreo del Ambiente , Monitoreo del Ambiente/métodos , Ecosistema , Dispositivos Aéreos No Tripulados , Australia , Análisis Multivariante , Imágenes Satelitales/métodos , Tecnología de Sensores Remotos/métodos , Tecnología de Sensores Remotos/instrumentación , Humanos , Alismatales , Conservación de los Recursos Naturales/métodos
2.
Mol Ecol ; : e17520, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39205506

RESUMEN

Animal gut microbiomes are critical to host physiology and fitness. The gut microbiomes of fishes-the most abundant and diverse vertebrate clade-have received little attention relative to other clades. Coral reef fishes, in particular, make up a wide range of evolutionary histories and feeding ecologies that are likely associated with gut microbiome diversity. The repeated evolution of herbivory in fishes and mammals also allows us to examine microbiome similarity in relationship to diet across the entire vertebrate tree of life. Here, we generate a large coral reef fish gut microbiome dataset (n = 499 samples, 19 species) and combine it with a diverse aggregation of public microbiome data (n = 447) to show that host diet drives significant convergence between coral reef fish and mammalian gut microbiomes. We demonstrate that this similarity is largely driven by carnivory and herbivory and that herbivorous and carnivorous hosts exhibit distinct microbial compositions across fish and mammals. We also show that fish and mammal gut microbiomes share prominent microbial taxa, including Ruminoccocus spp. and Akkermansia spp., and predicted metabolic pathways. Despite the major evolutionary and ecological differences between fishes and mammals, our results reveal that their gut microbiomes undergo similar dietary selective pressures. Thus, diet, in addition to phylosymbiosis must be considered even when comparing the gut microbiomes of distantly related hosts.

3.
Eur J Nucl Med Mol Imaging ; 51(10): 3009-3025, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38853153

RESUMEN

PURPOSE: Prostate-specific membrane antigen (PSMA) is increasingly used to image prostate cancer in clinical practice. We sought to develop and test a humanised PSMA minibody IAB2M conjugated to the fluorophore IRDye 800CW-NHS ester in men undergoing robot-assisted laparoscopic radical prostatectomy (RARP) to image prostate cancer cells during surgery. METHODS: The minibody was evaluated pre-clinically using PSMA positive/negative xenograft models, following which 23 men undergoing RARP between 2018 and 2020 received between 2.5 mg and 20 mg of IR800-IAB2M intravenously, at intervals between 24 h and 17 days prior to surgery. At every step of the procedure, the prostate, pelvic lymph node chains and extra-prostatic surrounding tissue were imaged with a dual Near-infrared (NIR) and white light optical platform for fluorescence in vivo and ex vivo. Histopathological evaluation of intraoperative and postoperative microscopic fluorescence imaging was undertaken for verification. RESULTS: Twenty-three patients were evaluated to optimise both the dose of the reagent and the interval between injection and surgery and secure the best possible specificity of fluorescence images. Six cases are presented in detail as exemplars. Overall sensitivity and specificity in detecting non-lymph-node extra-prostatic cancer tissue were 100% and 65%, and 64% and 64% respectively for lymph node positivity. There were no side-effects associated with administration of the reagent. CONCLUSION: Intraoperative imaging of prostate cancer tissue is feasible and safe using IR800-IAB2M. Further evaluation is underway to assess the benefit of using the technique in improving completion of surgical excision during RARP. REGISTRATION: ISCRCTN10046036: https://www.isrctn.com/ISRCTN10046036 .


Asunto(s)
Antígenos de Superficie , Glutamato Carboxipeptidasa II , Imagen Óptica , Prostatectomía , Neoplasias de la Próstata , Masculino , Humanos , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/diagnóstico por imagen , Glutamato Carboxipeptidasa II/metabolismo , Antígenos de Superficie/metabolismo , Imagen Óptica/métodos , Periodo Intraoperatorio , Persona de Mediana Edad , Animales , Anciano , Cirugía Asistida por Computador/métodos , Ratones
4.
Int J Mol Sci ; 25(8)2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38673807

RESUMEN

Fluorescence lifetime imaging (FLIM) and confocal fluorescence studies of a porphyrin-based photosensitiser (meso-tetraphenylporphine disulfonate: TPPS2a) were evaluated in 2D monolayer cultures and 3D compressed collagen constructs of a human ovarian cancer cell line (HEY). TPPS2a is known to be an effective model photosensitiser for both Photodynamic Therapy (PDT) and Photochemical Internalisation (PCI). This microspectrofluorimetric study aimed firstly to investigate the uptake and subcellular localisation of TPPS2a, and evaluate the photo-oxidative mechanism using reactive oxygen species (ROS) and lipid peroxidation probes combined with appropriate ROS scavengers. Light-induced intracellular redistribution of TPPS2a was observed, consistent with rupture of endolysosomes where the porphyrin localises. Using the same range of light doses, time-lapse confocal imaging permitted observation of PDT-induced generation of ROS in both 2D and 3D cancer models using fluorescence-based ROS together with specific ROS inhibitors. In addition, the use of red light excitation of the photosensitiser to minimise auto-oxidation of the probes was investigated. In the second part of the study, the photophysical properties of TPPS2a in cells were studied using a time-domain FLIM system with time-correlated single photon counting detection. Owing to the high sensitivity and spatial resolution of this system, we acquired FLIM images that enabled the fluorescence lifetime determination of the porphyrin within the endolysosomal vesicles. Changes in the lifetime dynamics upon prolonged illumination were revealed as the vesicles degraded within the cells.


Asunto(s)
Fármacos Fotosensibilizantes , Porfirinas , Especies Reactivas de Oxígeno , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Porfirinas/farmacología , Porfirinas/química , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Fotoquimioterapia/métodos , Imagen Óptica/métodos , Lisosomas/metabolismo , Lisosomas/efectos de los fármacos , Femenino , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Ováricas/tratamiento farmacológico
5.
Sci Rep ; 14(1): 3829, 2024 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-38360981

RESUMEN

Human impacts are dramatically changing ecological communities, motivating research on resilience. Tropical reefs are increasingly undergoing transitions to short algal turf, a successional community that mediates either recovery to coral by allowing recruitment or transitions to longer turf/macroalgae. Intense herbivory limits turf height; subsequently, overfishing erodes resilience of the desirable coral-dominated reef state. Increased sedimentation also erodes resilience through smothering and herbivory suppression. In spite of this critical role, most herbivory studies on tropical reefs focus on fishes, and the contribution of urchins remains under-studied. To test how different herbivory and sedimentation scenarios impact turf resilience, we experimentally simulated, in situ, four future overfishing scenarios derived from patterns of fish and urchin loss in other reef systems and two future sedimentation regimes. We found urchins were critical to short turf resilience, maintaining this state even with reduced fish herbivory and increased sediment. Further, urchins cleared sediment, facilitating fish herbivory. This study articulates the likelihood of increased reliance on urchins on impacted reefs in the Anthropocene.


Asunto(s)
Antozoos , Resiliencia Psicológica , Animales , Humanos , Conservación de los Recursos Naturales , Herbivoria , Explotaciones Pesqueras , Arrecifes de Coral , Erizos de Mar , Peces , Ecosistema
6.
R Soc Open Sci ; 10(10): 231305, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37830026

RESUMEN

The gut microbiome has a well-documented relationship with host fitness. Greater microbial diversity and abundance of specific microbes have been associated with improved fitness outcomes. Intestinal microbes also may be associated with patterns of social behaviour. However, these associations have been largely studied in captive animal models; we know less about microbiome composition as a potential driver of individual social behaviour and position in the wild. We used linear mixed models to quantify the relationship between fecal microbial composition, diversity and social network traits in a wild population of yellow-bellied marmots (Marmota flaviventer). We focused our analyses on microbes previously linked to sociability and neurobehavioural alterations in captive rodents, primates and humans. Using 5 years of data, we found microbial diversity (Shannon-Wiener and Faith's phylogenetic diversity) has a modest yet statistically significant negative relationship with the number of social interactions an individual engaged in. We also found a negative relationship between Streptococcus spp. relative abundance and two social network measures (clustering coefficient and embeddedness) that quantify an individual's position relative to others in their social group. These findings highlight a potentially consequential relationship between microbial composition and social behaviour in a wild social mammal.

7.
Trends Ecol Evol ; 38(8): 683-687, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37268526

RESUMEN

Racism permeates ecology, evolution, and conservation biology (EECB). Meaningfully advancing equity, inclusion, and belonging requires an interdisciplinary anti-racist pedagogical approach to educate our community in how racism shaped our field. Here, we apply this framework, highlight disparities and interdisciplinary practices across institutions globally, and emphasize that self-reflection is paramount before implementing anti-racist interventions.


Asunto(s)
Racismo , Biología
8.
PLoS One ; 18(6): e0260903, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37314989

RESUMEN

Surf zones are highly dynamic marine ecosystems that are subject to increasing anthropogenic and climatic pressures, posing multiple challenges for biomonitoring. Traditional methods such as seines and hook and line surveys are often labor intensive, taxonomically biased, and can be physically hazardous. Emerging techniques, such as baited remote underwater video (BRUV) and environmental DNA (eDNA) are promising nondestructive tools for assessing marine biodiversity in surf zones of sandy beaches. Here we compare the relative performance of beach seines, BRUV, and eDNA in characterizing community composition of bony (teleost) and cartilaginous (elasmobranch) fishes of surf zones at 18 open coast sandy beaches in southern California. Seine and BRUV surveys captured overlapping, but distinct fish communities with 50% (18/36) of detected species shared. BRUV surveys more frequently detected larger species (e.g. sharks and rays) while seines more frequently detected one of the most abundant species, barred surfperch (Amphistichus argenteus). In contrast, eDNA metabarcoding captured 88.9% (32/36) of all fishes observed in seine and BRUV surveys plus 57 additional species, including 15 that frequent surf zone habitats. On average, eDNA detected over 5 times more species than BRUVs and 8 times more species than seine surveys at a given site. eDNA approaches also showed significantly higher sensitivity than seine and BRUV methods and more consistently detected 31 of the 32 (96.9%) jointly observed species across beaches. The four species detected by BRUV/seines, but not eDNA were only resolved at higher taxonomic ranks (e.g. Embiotocidae surfperches and Sygnathidae pipefishes). In frequent co-detection of species between methods limited comparisons of richness and abundance estimates, highlighting the challenge of comparing biomonitoring approaches. Despite potential for improvement, results overall demonstrate that eDNA can provide a cost-effective tool for long-term surf zone monitoring that complements data from seine and BRUV surveys, allowing more comprehensive surveys of vertebrate diversity in surf zone habitats.


Asunto(s)
Monitoreo Biológico , ADN Ambiental , Animales , Ecosistema , Peces/genética , Biodiversidad , ADN Ambiental/genética
9.
Br J Cancer ; 128(2): 245-254, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36352028

RESUMEN

BACKGROUND: Epidermal growth factor receptor (EGFR) is a therapeutic target to which HER2/HER3 activation may contribute resistance. This Phase I/II study examined the toxicity and efficacy of high-dose pulsed AZD8931, an EGFR/HER2/HER3 inhibitor, combined with chemotherapy, in metastatic colorectal cancer (CRC). METHODS: Treatment-naive patients received 4-day pulses of AZD8931 with irinotecan/5-FU (FOLFIRI) in a Phase I/II single-arm trial. Primary endpoint for Phase I was dose limiting toxicity (DLT); for Phase II best overall response. Samples were analysed for pharmacokinetics, EGFR dimers in circulating exosomes and Comet assay quantitating DNA damage. RESULTS: Eighteen patients received FOLFIRI and AZD8931. At 160 mg bd, 1 patient experienced G3 DLT; 160 mg bd was used for cohort expansion. No grade 5 adverse events (AE) reported. Seven (39%) and 1 (6%) patients experienced grade 3 and grade 4 AEs, respectively. Of 12 patients receiving 160 mg bd, best overall response rate was 25%, median PFS and OS were 8.7 and 21.2 months, respectively. A reduction in circulating HER2/3 dimer in the two responding patients after 12 weeks treatment was observed. CONCLUSIONS: The combination of pulsed high-dose AZD8931 with FOLFIRI has acceptable toxicity. Further studies of TKI sequencing may establish a role for pulsed use of such agents rather than continuous exposure. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number: NCT01862003.


Asunto(s)
Neoplasias Colorrectales , Receptor ErbB-3 , Humanos , Receptor ErbB-3/metabolismo , Transducción de Señal , Quinazolinas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/inducido químicamente , Fluorouracilo , Leucovorina/efectos adversos , Camptotecina , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo
10.
J Phycol ; 59(1): 277-280, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36308024

RESUMEN

Coral reefs are shifting from coral to algal-dominated ecosystems worldwide. Recently, Turbinaria ornata, a marine alga native to coral reefs of the South Pacific, has spread in both range and habitat usage. Given dense stands of T. ornata can function as an alternative stable state on coral reefs, it is imperative to understand the factors that underlie its success. We tested the hypothesis that T. ornata demonstrates ontogenetic variation in allocation to anti-herbivore defense, specifically that blade toughness varied nonlinearly with thallus size. We quantified the relationship between T. ornata blade toughness and thallus size for individual thalli within algal stands (N = 345) on seven fringing reefs along the north shore of Moorea, French Polynesia. We found that blade toughness was greatest at intermediate sizes that typically form canopies, with overall reduced toughness in both smaller individuals that refuge within the understory and older reproductive individuals that ultimately detach and form floating rafts. We posit this variation in blade toughness reduces herbivory on the thalli that are most exposed to herbivores and may facilitate reproduction in dispersing stages, both of which may aid the proliferation of T. ornata.


Asunto(s)
Antozoos , Phaeophyceae , Animales , Arrecifes de Coral , Ecosistema , Herbivoria , Variación Genética
11.
Elife ; 112022 12 23.
Artículo en Inglés | MEDLINE | ID: mdl-36562609

RESUMEN

Background: Advanced head and neck squamous cell carcinoma (HNSCC) is associated with a poor prognosis, and biomarkers that predict response to treatment are highly desirable. The primary aim was to predict progression-free survival (PFS) with a multivariate risk prediction model. Methods: Experimental covariates were derived from blood samples of 56 HNSCC patients which were prospectively obtained within a Phase 2 clinical trial (NCT02633800) at baseline and after the first treatment cycle of combined platinum-based chemotherapy with cetuximab treatment. Clinical and experimental covariates were selected by Bayesian multivariate regression to form risk scores to predict PFS. Results: A 'baseline' and a 'combined' risk prediction model were generated, each of which featuring clinical and experimental covariates. The baseline risk signature has three covariates and was strongly driven by baseline percentage of CD33+CD14+HLADRhigh monocytes. The combined signature has six covariates, also featuring baseline CD33+CD14+HLADRhigh monocytes but is strongly driven by on-treatment relative change of CD8+ central memory T cells percentages. The combined model has a higher predictive power than the baseline model and was successfully validated to predict therapeutic response in an independent cohort of nine patients from an additional Phase 2 trial (NCT03494322) assessing the addition of avelumab to cetuximab treatment in HNSCC. We identified tissue counterparts for the immune cells driving the models, using imaging mass cytometry, that specifically colocalized at the tissue level and correlated with outcome. Conclusions: This immune-based combined multimodality signature, obtained through longitudinal peripheral blood monitoring and validated in an independent cohort, presents a novel means of predicting response early on during the treatment course. Funding: Daiichi Sankyo Inc, Cancer Research UK, EU IMI2 IMMUCAN, UK Medical Research Council, European Research Council (335326), Merck Serono. Cancer Research Institute, National Institute for Health Research, Guy's and St Thomas' NHS Foundation Trust and The Institute of Cancer Research. Clinical trial number: NCT02633800.


Asunto(s)
Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Cetuximab/uso terapéutico , Supervivencia sin Progresión , Teorema de Bayes , Neoplasias de Cabeza y Cuello/tratamiento farmacológico
12.
PeerJ ; 10: e14071, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36405018

RESUMEN

Environmental DNA (eDNA) metabarcoding is a powerful tool that can enhance marine ecosystem/biodiversity monitoring programs. Here we outline five important steps managers and researchers should consider when developing eDNA monitoring program: (1) select genes and primers to target taxa; (2) assemble or develop comprehensive barcode reference databases; (3) apply rigorous site occupancy based decontamination pipelines; (4) conduct pilot studies to define spatial and temporal variance of eDNA; and (5) archive samples, extracts, and raw sequence data. We demonstrate the importance of each of these considerations using a case study of eDNA metabarcoding in the Ports of Los Angeles and Long Beach. eDNA metabarcoding approaches detected 94.1% (16/17) of species observed in paired trawl surveys while identifying an additional 55 native fishes, providing more comprehensive biodiversity inventories. Rigorous benchmarking of eDNA metabarcoding results improved ecological interpretation and confidence in species detections while providing archived genetic resources for future analyses. Well designed and validated eDNA metabarcoding approaches are ideally suited for biomonitoring applications that rely on the detection of species, including mapping invasive species fronts and endangered species habitats as well as tracking range shifts in response to climate change. Incorporating these considerations will enhance the utility and efficacy of eDNA metabarcoding for routine biomonitoring applications.


Asunto(s)
ADN Ambiental , Ecosistema , ADN Ambiental/genética , Código de Barras del ADN Taxonómico/métodos , Monitoreo del Ambiente/métodos , Biodiversidad
13.
Nucleic Acids Res ; 50(8): 4557-4573, 2022 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-35438764

RESUMEN

Lineage-determining transcription factors (LD-TFs) drive the differentiation of progenitor cells into a specific lineage. In CD4+ T cells, T-bet dictates differentiation of the TH1 lineage, whereas GATA3 drives differentiation of the alternative TH2 lineage. However, LD-TFs, including T-bet and GATA3, are frequently co-expressed but how this affects LD-TF function is not known. By expressing T-bet and GATA3 separately or together in mouse T cells, we show that T-bet sequesters GATA3 at its target sites, thereby removing GATA3 from TH2 genes. This redistribution of GATA3 is independent of GATA3 DNA binding activity and is instead mediated by the T-bet DNA binding domain, which interacts with the GATA3 DNA binding domain and changes GATA3's sequence binding preference. This mechanism allows T-bet to drive the TH1 gene expression program in the presence of GATA3. We propose that redistribution of one LD-TF by another may be a common mechanism that could explain how specific cell fate choices can be made even in the presence of other transcription factors driving alternative differentiation pathways.


Asunto(s)
Factor de Transcripción GATA3 , Proteínas de Dominio T Box/metabolismo , Células Th2 , Animales , Linaje de la Célula , ADN/metabolismo , Factor de Transcripción GATA3/genética , Factor de Transcripción GATA3/metabolismo , Expresión Génica , Ratones , Proteínas de Dominio T Box/genética , Células Th2/citología , Células Th2/metabolismo
14.
Clin Teach ; 19(3): 240-246, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35274454

RESUMEN

BACKGROUND: Most undergraduate medical students (UMS) do not receive any formal exposure to quality improvement (QI) efforts in healthcare during the entirety of their undergraduate programme. This is despite the rising interest amongst UMS and the unique potential that UMS hold as an innovator unencumbered by previous biases. To explore this, we implemented an undergraduate training programme that provides experiential QI education. APPROACH: The 15-week Summer Healthcare Improvement Programme (SHIP) was established in 2017, supported by a regional physician QI leadership coalition, a QI consultant preceptor who is linked to both the local university and health organisation and an UMS leadership group. Students were assigned QI projects that were aligned with the health organisation's purpose and scope. Students co-led the project to completion with mentorship from both physician QI leaders, and residents. Student competencies were formatively assessed by completing QI activities and a programme survey. RESULTS: From 2017 to 2019, 19 students completed 22 QI projects, academic posters and publications, and all received QI certification. The majority (72%) of students felt involvement in SHIP increased their QI knowledge and skills, 90% believed SHIP would benefit their peers, and 71% of students felt it directly applied to their future careers. DISCUSSION: Benefits of the programme were threefold: provided students with early experiential QI exposure, provided student QI leaders who possess dedicated time and effort to complete projects over the summer months and provided a physician QI learning continuum implemented with minimal to no additional cost to either the university or health organisation.


Asunto(s)
Estudiantes de Medicina , Curriculum , Humanos , Grupo Paritario , Aprendizaje Basado en Problemas , Mejoramiento de la Calidad
15.
Mol Cancer Ther ; 21(4): 667-676, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35086953

RESUMEN

Prostate cancer remains a major cause of male mortality. Genetic alteration of the PI3K/AKT/mTOR pathway is one of the key events in tumor development and progression in prostate cancer, with inactivation of the PTEN tumor suppressor being very common in this cancer type. Extensive evaluation has been performed on the therapeutic potential of PI3K/AKT/mTOR inhibitors and the resistance mechanisms arising in patients with PTEN-mutant background. However, in patients with a PTEN wild-type phenotype, PI3K/AKT/mTOR inhibitors have not demonstrated efficacy, and this remains an area of clinical unmet need. In this study, we have investigated the response of PTEN wild-type prostate cancer cell lines to the dual PI3K/mTOR inhibitor DS-7423 alone or in combination with HER2 inhibitors or mGluR1 inhibitors. Upon treatment with the dual PI3K/mTOR inhibitor DS-7423, PTEN wild-type prostate cancer CWR22/22RV1 cells upregulate expression of the proteins PSMA, mGluR1, and the tyrosine kinase receptor HER2, while PTEN-mutant LNCaP cells upregulate androgen receptor and HER3. PSMA, mGluR1, and HER2 exert control over one another in a positive feedback loop that allows cells to overcome treatment with DS-7423. Concomitant targeting of PI3K/mTOR with either HER2 or mGluR1 inhibitors results in decreased cell survival and tumor growth in xenograft studies. Our results suggest a novel therapeutic possibility for patients with PTEN wild-type PI3K/AKT-mutant prostate cancer based in the combination of PI3K/mTOR blockade with HER2 or mGluR1 inhibitors.


Asunto(s)
Fosfatidilinositol 3-Quinasas , Neoplasias de la Próstata , Línea Celular Tumoral , Proliferación Celular , Humanos , Inhibidores mTOR , Masculino , Fosfohidrolasa PTEN/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de Glutamato Metabotrópico , Serina-Treonina Quinasas TOR/metabolismo
16.
PLoS One ; 16(11): e0253104, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34735443

RESUMEN

Environmental DNA (eDNA) metabarcoding is an increasingly important tool for surveying biodiversity in marine ecosystems. However, the scale of temporal and spatial variability in eDNA signatures, and how this variation may impact eDNA-based marine biodiversity assessments, remains uncertain. To address this question, we systematically examined variation in vertebrate eDNA signatures across depth (0 m to 10 m) and horizontal space (nearshore kelp forest and surf zone) over three successive days in Southern California. Across a broad range of teleost fish and elasmobranchs, results showed significant variation in species richness and community assemblages between surface and depth, reflecting microhabitat depth preferences of common Southern California nearshore rocky reef taxa. Community assemblages between nearshore and surf zone sampling stations at the same depth also differed significantly, consistent with known habitat preferences. Additionally, assemblages also varied across three sampling days, but 69% of habitat preferences remained consistent. Results highlight the sensitivity of eDNA in capturing fine-scale vertical, horizontal, and temporal variation in marine vertebrate communities, demonstrating the ability of eDNA to capture a highly localized snapshot of marine biodiversity in dynamic coastal environments.


Asunto(s)
Biodiversidad , ADN Ambiental/genética , Monitoreo del Ambiente , Peces/genética , Kelp/genética , Animales , California
17.
Mol Ecol Resour ; 21(7): 2546-2564, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34235858

RESUMEN

DNA metabarcoding is an important tool for molecular ecology. However, its effectiveness hinges on the quality of reference sequence databases and classification parameters employed. Here we evaluate the performance of MiFish 12S taxonomic assignments using a case study of California Current Large Marine Ecosystem fishes to determine best practices for metabarcoding. Specifically, we use a taxonomy cross-validation by identity framework to compare classification performance between a global database comprised of all available sequences and a curated database that only includes sequences of fishes from the California Current Large Marine Ecosystem. We demonstrate that the regional database provides higher assignment accuracy than the comprehensive global database. We also document a tradeoff between accuracy and misclassification across a range of taxonomic cutoff scores, highlighting the importance of parameter selection for taxonomic classification. Furthermore, we compared assignment accuracy with and without the inclusion of additionally generated reference sequences. To this end, we sequenced tissue from 597 species using the MiFish 12S primers, adding 252 species to GenBank's existing 550 California Current Large Marine Ecosystem fish sequences. We then compared species and reads identified from seawater environmental DNA samples using global databases with and without our generated references, and the regional database. The addition of new references allowed for the identification of 16 additional native taxa representing 17.0% of total reads from eDNA samples, including species with vast ecological and economic value. Together these results demonstrate the importance of comprehensive and curated reference databases for effective metabarcoding and the need for locus-specific validation efforts.


Asunto(s)
ADN Ambiental , Ecosistema , Animales , Biodiversidad , Código de Barras del ADN Taxonómico , Peces/genética , Agua de Mar
18.
Mar Pollut Bull ; 169: 112522, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34098526

RESUMEN

Human-induced nutrient pollution threatens coral reefs worldwide. Although eutrophication disrupts coral microbiomes, often leading to coral mortality, it is unknown whether eutrophication impacts the microbiomes of other coral reef organisms. Of particular interest are herbivorous fishes, whose algae consumption is critical in maintaining healthy corals. To examine the effects of eutrophication on fish gut microbiomes, we experimentally enriched territories of Stegastes nigricans, a predominantly herbivorous damselfish that farms turf algae. Using 16S RNA sequencing, we demonstrate that hindgut and foregut microbiomes have significantly higher alpha diversity in nutrient-enriched territories as compared to unenriched controls. S. nigricans gut microbiomes also exhibited significantly different compositions across treatments. In contrast, these changes were not observed in the microbiomes of the turf algae consumed by S. nigricans, indicating that the gut microbiome changes were autochthonous. Combined, our results provide a novel example of endogenous microbial shifts in wild vertebrates caused by simulated anthropogenic stress.


Asunto(s)
Antozoos , Microbioma Gastrointestinal , Animales , Arrecifes de Coral , Peces , Humanos , Nutrientes
19.
Proc Biol Sci ; 288(1952): 20210407, 2021 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-34102891

RESUMEN

Understanding how evolutionary forces interact to drive patterns of selection and distribute genetic variation across a species' range is of great interest in ecology and evolution, especially in an era of global change. While theory predicts how and when populations at range margins are likely to undergo local adaptation, empirical evidence testing these models remains sparse. Here, we address this knowledge gap by investigating the relationship between selection, gene flow and genetic drift in the yellowtail clownfish, Amphiprion clarkii, from the core to the northern periphery of the species range. Analyses reveal low genetic diversity at the range edge, gene flow from the core to the edge and genomic signatures of local adaptation at 56 single nucleotide polymorphisms in 25 candidate genes, most of which are significantly correlated with minimum annual sea surface temperature. Several of these candidate genes play a role in functions that are upregulated during cold stress, including protein turnover, metabolism and translation. Our results illustrate how spatially divergent selection spanning the range core to the periphery can occur despite the potential for strong genetic drift at the range edge and moderate gene flow from the core populations.


Asunto(s)
Peces/genética , Flujo Genético , Genética de Población , Selección Genética , Adaptación Fisiológica , Animales , Flujo Génico , Genoma , Genómica , Polimorfismo de Nucleótido Simple
20.
PLoS One ; 16(6): e0245314, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34086697

RESUMEN

Environmental DNA (eDNA) is increasingly used to measure biodiversity of marine ecosystems, yet key aspects of the temporal dynamics of eDNA remain unknown. Of particular interest is in situ persistence of eDNA signals in dynamic marine environments, as eDNA degradation rates have predominantly been quantified through mesocosm studies. To determine in situ eDNA residence times, we introduced an eDNA signal from a non-native fish into a protected bay of a Southern California rocky reef ecosystem, and then measured changes in both introduced and background eDNA signals across a fixed transect over 96 hours. Foreign eDNA signal was no longer detected only 7.5 hours after introduction, a time substantially shorter than the multi-day persistence times in laboratory studies. Moreover, the foreign eDNA signal spread along the entire 38 m transect within 1.5 hours after introduction, indicating that transport and diffusion play a role in eDNA detectability even in protected low energy marine environments. Similarly, native vertebrate eDNA signals varied greatly over the 96 hours of observation as well as within two additional nearby fixed transects sampled over 120 hours. While community structure did significantly change across time of day and tidal direction, neither accounted for the majority of observed variation. Combined, results show that both foreign and native eDNA signatures can exhibit substantial temporal heterogeneity, even on hourly time scales. Further work exploring eDNA decay from lagrangian perspective and quantifying effects of sample and technical replication are needed to better understand temporal variation of eDNA signatures in nearshore marine environments.


Asunto(s)
ADN Ambiental/genética , Vertebrados/genética , Animales , Biodiversidad , Conservación de los Recursos Naturales/métodos , Código de Barras del ADN Taxonómico/métodos , Ecosistema , Monitoreo del Ambiente/métodos
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