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1.
Immunity ; 54(9): 2072-2088.e7, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34320366

RESUMO

Cardiac macrophages represent a heterogeneous cell population with distinct origins, dynamics, and functions. Recent studies have revealed that C-C Chemokine Receptor 2 positive (CCR2+) macrophages derived from infiltrating monocytes regulate myocardial inflammation and heart failure pathogenesis. Comparatively little is known about the functions of tissue resident (CCR2-) macrophages. Herein, we identified an essential role for CCR2- macrophages in the chronically failing heart. Depletion of CCR2- macrophages in mice with dilated cardiomyopathy accelerated mortality and impaired ventricular remodeling and coronary angiogenesis, adaptive changes necessary to maintain cardiac output in the setting of reduced cardiac contractility. Mechanistically, CCR2- macrophages interacted with neighboring cardiomyocytes via focal adhesion complexes and were activated in response to mechanical stretch through a transient receptor potential vanilloid 4 (TRPV4)-dependent pathway that controlled growth factor expression. These findings establish a role for tissue-resident macrophages in adaptive cardiac remodeling and implicate mechanical sensing in cardiac macrophage activation.


Assuntos
Cardiomiopatia Dilatada/metabolismo , Ativação de Macrófagos/fisiologia , Macrófagos/metabolismo , Remodelação Ventricular/fisiologia , Animais , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/patologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Mutação , Miocárdio/metabolismo , Troponina T/genética
2.
Mol Cell ; 79(3): 416-424.e5, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32645367

RESUMO

CRISPR-Cas12c/d proteins share limited homology with Cas12a and Cas9 bacterial CRISPR RNA (crRNA)-guided nucleases used widely for genome editing and DNA detection. However, Cas12c (C2c3)- and Cas12d (CasY)-catalyzed DNA cleavage and genome editing activities have not been directly observed. We show here that a short-complementarity untranslated RNA (scoutRNA), together with crRNA, is required for Cas12d-catalyzed DNA cutting. The scoutRNA differs in secondary structure from previously described tracrRNAs used by CRISPR-Cas9 and some Cas12 enzymes, and in Cas12d-containing systems, scoutRNA includes a conserved five-nucleotide sequence that is essential for activity. In addition to supporting crRNA-directed DNA recognition, biochemical and cell-based experiments establish scoutRNA as an essential cofactor for Cas12c-catalyzed pre-crRNA maturation. These results define scoutRNA as a third type of transcript encoded by a subset of CRISPR-Cas genomic loci and explain how Cas12c/d systems avoid requirements for host factors including ribonuclease III for bacterial RNA-mediated adaptive immunity.


Assuntos
Bactérias/genética , Proteínas de Bactérias/genética , Sistemas CRISPR-Cas , Endodesoxirribonucleases/genética , Genoma Bacteriano/imunologia , RNA Bacteriano/genética , Pequeno RNA não Traduzido/genética , Bactérias/classificação , Bactérias/imunologia , Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Sequência de Bases , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Endodesoxirribonucleases/metabolismo , Escherichia coli/genética , Escherichia coli/imunologia , Escherichia coli/metabolismo , Conformação de Ácido Nucleico , Filogenia , RNA Bacteriano/química , RNA Bacteriano/metabolismo , RNA Guia de Cinetoplastídeos/genética , RNA Guia de Cinetoplastídeos/metabolismo , Pequeno RNA não Traduzido/química , Pequeno RNA não Traduzido/metabolismo , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico
3.
EMBO Rep ; 25(5): 2375-2390, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38594391

RESUMO

Cancer patients undergoing treatment with antineoplastic drugs often experience chemotherapy-induced neuropathic pain (CINP), and the therapeutic options for managing CINP are limited. Here, we show that systemic paclitaxel administration upregulates the expression of neurotrophin-3 (Nt3) mRNA and NT3 protein in the neurons of dorsal root ganglia (DRG), but not in the spinal cord. Blocking NT3 upregulation attenuates paclitaxel-induced mechanical, heat, and cold nociceptive hypersensitivities and spontaneous pain without altering acute pain and locomotor activity in male and female mice. Conversely, mimicking this increase produces enhanced responses to mechanical, heat, and cold stimuli and spontaneous pain in naive male and female mice. Mechanistically, NT3 triggers tropomyosin receptor kinase C (TrkC) activation and participates in the paclitaxel-induced increases of C-C chemokine ligand 2 (Ccl2) mRNA and CCL2 protein in the DRG. Given that CCL2 is an endogenous initiator of CINP and that Nt3 mRNA co-expresses with TrkC and Ccl2 mRNAs in DRG neurons, NT3 likely contributes to CINP through TrkC-mediated activation of the Ccl2 gene in DRG neurons. NT3 may be thus a potential target for CINP treatment.


Assuntos
Quimiocina CCL2 , Gânglios Espinais , Neuralgia , Neurônios , Neurotrofina 3 , Paclitaxel , Receptor trkC , Animais , Feminino , Masculino , Camundongos , Antineoplásicos/efeitos adversos , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Gânglios Espinais/metabolismo , Gânglios Espinais/efeitos dos fármacos , Neuralgia/induzido quimicamente , Neuralgia/metabolismo , Neuralgia/genética , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Neurotrofina 3/metabolismo , Neurotrofina 3/genética , Paclitaxel/efeitos adversos , Paclitaxel/farmacologia , Receptor trkC/metabolismo , Receptor trkC/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Fatores de Crescimento Neural/genética , Fatores de Crescimento Neural/metabolismo
4.
Proc Natl Acad Sci U S A ; 120(44): e2307320120, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37871220

RESUMO

The selective photocatalytic conversion of CO2 and H2O to high value-added C2H4 remains a great challenge, mainly attributed to the difficulties in C-C coupling of reaction intermediates and desorption of C2H4* intermediates from the catalyst surface. These two key issues can be simultaneously overcome by alloying Ag with Cu which gives enhanced activity to both reactions. Herein, we developed a facile stepwise photodeposition strategy to load Cu-Ag alloy sub-nanoclusters (ASNCs) on TiO2 for CO2 photoreduction to produce C2H4. The optimized catalyst exhibits a record-high C2H4 formation rate (1110.6 ± 82.5 µmol g-1 h-1) with selectivity of 49.1 ± 1.9%, which is an order-of-magnitude enhancement relative to current work for C2H4 photosynthesis. The in situ FT-IR spectra combined with DFT calculations reveal the synergistic effect of Cu and Ag in Cu-Ag ASNCs, which enable an excellent C-C coupling capability like Ag and promoted C2H4* desorption property like Cu, thus advancing the selective and efficient production of C2H4. The present work provides a deeper understanding on cluster chemistry and C-C coupling mechanism for CO2 reduction on ASNCs and develops a feasible strategy for photoreduction CO2 to C2 fuels or industrial feedstocks.

5.
Proc Natl Acad Sci U S A ; 119(7)2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35135880

RESUMO

The conversion of CO2 into fuels and chemicals is an attractive option for mitigating CO2 emissions. Controlling the selectivity of this process is beneficial to produce desirable liquid fuels, but C-C coupling is a limiting step in the reaction that requires high pressures. Here, we propose a strategy to favor C-C coupling on a supported Ru/TiO2 catalyst by encapsulating it within the polymer layers of an imine-based porous organic polymer that controls its selectivity. Such polymer confinement modifies the CO2 hydrogenation behavior of the Ru surface, significantly enhancing the C2+ production turnover frequency by 10-fold. We demonstrate that the polymer layers affect the adsorption of reactants and intermediates while being stable under the demanding reaction conditions. Our findings highlight the promising opportunity of using polymer/metal interfaces for the rational engineering of active sites and as a general tool for controlling selective transformations in supported catalyst systems.

6.
Proc Natl Acad Sci U S A ; 119(34): e2206399119, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35984900

RESUMO

Conversion of naturally occurring sugars, the most abundant biomass resources on Earth, to fuels and chemicals provides a sustainable and carbon-neutral alternative to the current fossil resource-based processes. Tungsten-based catalysts (e.g., WO3) are efficient for selectively cleaving C-C bonds of sugars to C2,3 oxygenate intermediates (e.g., glycolaldehyde) that can serve as platform molecules with high viability and versatility in the synthesis of various chemicals. Such C-C bond cleavage follows a mechanism distinct from the classical retro-aldol condensation. Kinetic, isotope 13C-labeling, and spectroscopic studies and theoretical calculations, reveal that the reaction proceeds via a surface tridentate complex as the critical intermediate on WO3, formed by chelating both α- and ß-hydroxyls of sugars, together with the carbonyl group, with two adjacent tungsten atoms (W-O-W) contributing to the ß-C-C bond cleavage. This mechanism provides insights into sugar chemistry and enables the rational design of catalytic sites and reaction pathways toward the efficient utilization of sugar-based feedstocks.

7.
J Allergy Clin Immunol ; 153(2): 447-460.e9, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37922997

RESUMO

BACKGROUND: Whether IgE affects eosinophil migration in chronic rhinosinusitis with nasal polyps (CRSwNP) remains largely unclear. Moreover, our understanding of local IgE, eosinophils, and omalizumab efficacy in CRSwNP remains limited. OBJECTIVE: We investigated whether IgE acts directly on eosinophils and determined its role in omalizumab therapy. METHODS: Eosinophils and their surface receptors were detected by hematoxylin and eosin staining and flow cytometry. IgE and its receptors, eosinophil peroxidase (EPX), eosinophilic cationic protein, and CCR3 were detected by immunohistochemistry and immunofluorescence. Functional analyses were performed on blood eosinophils and polyp tissues. Logistic regression was performed to screen for risk factors. Receiver operating characteristic curve was generated to evaluate the accuracy. RESULTS: Both FcεRI and CD23 were expressed on eosinophils. The expression of FcεRI and CD23 on eosinophil in nasal polyp tissue was higher than in peripheral blood (both P < .001). IgE and EPX colocalized in CRSwNP. IgE directly promoted eosinophil migration by upregulating CCR3 in CRSwNP but not in healthy controls. Omalizumab and lumiliximab were found to be effective in restraining this migration, indicating CD23 was involved in IgE-induced eosinophil migration. Both IgE+ and EPX+ cells were significantly reduced after omalizumab treatment in those who experienced response (IgE+ cells, P = .001; EPX+ cells, P = .016) but not in those with no response (IgE+ cells, P = .060; EPX+ cells, P = .151). Baseline IgE+ cell levels were higher in those with response compared to those without response (P = .024). The baseline local IgE+ cell count predicted omalizumab efficacy with an accuracy of 0.811. CONCLUSIONS: IgE directly promotes eosinophil migration, and baseline local IgE+ cell counts are predictive of omalizumab efficacy in CRSwNP.


Assuntos
Pólipos Nasais , Rinite , Rinossinusite , Humanos , Eosinófilos , Omalizumab/farmacologia , Omalizumab/uso terapêutico , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/metabolismo , Imunoglobulina E , Doença Crônica , Rinite/tratamento farmacológico , Rinite/metabolismo , Receptores CCR3
8.
J Infect Dis ; 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38271258

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS), a lethal tick-borne hemorrhagic fever, prompted our investigation into prognostic predictors and potential drug targets using plasma Olink Proteomics. METHODS: Employing the Olink assay, we analyzed 184 plasma proteins in 30 survivors and 8 non-survivors of SFTS. Validation was performed in a cohort of 154 SFTS patients using enzyme-linked immunosorbent assay. We utilized the Drug Gene Interaction database to identify protein-drug interactions. RESULTS: Non-survivors exhibited 110 differentially expressed proteins (DEPs) compared to survivors, with functional enrichment in the cell chemotaxis-related pathway. Thirteen DEPs, including C-C motif chemokine 20 (CCL20), calcitonin gene-related peptide alpha and Pleiotrophin, were associated with multiple organ dysfunction syndrome. CCL20 emerged as the top predictor of death, demonstrating an area under the curve of 1 (P = .0004) and 0.9033 (P < .0001) in the discovery and validation cohort, respectively. Patients with CCL20 levels exceeding 45.74 pg/mL exhibited a fatality rate of 45.65%, while no deaths occurred in those with lower CCL20 levels. Furthermore, we identified 202 FDA-approved drugs targeting 37 death-related plasma proteins. CONCLUSIONS: Distinct plasma proteomic profiles characterize SFTS patients with different outcomes, with CCL20 emerging as a novel, sensitive, accurate, and specific biomarker for predicting SFTS prognosis.

9.
J Gene Med ; 26(6): e3708, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38837511

RESUMO

BACKGROUND: Lysophosphatidic acid (LPA) is a small bioactive lipid which acts as a potent regulator in various tumor progressions through six G-protein-coupled receptors (LPA1-LPA6). Our previous study demonstrated that the LPA-producing enzyme, autotaxin (ATX), was upregulated in esophageal squamous cell carcinoma (ESCC) and ATX high expression levels indicated a poor prognosis. Esophageal squamous cell carcinoma is a type of malignant tumor which originates from epithelial cells. Its progression can be affected by the interaction between cancer cells and normal cells. However, the impact of LPA on the interaction between esophageal epithelial cells and cancer cells in the development of ESCC remains uncertain. METHODS: MTS and Edu assays were performed to determine ESCC cell proliferation in culture medium (CM) derived from LPA-stimulated esophageal epithelial cells (Het-1a). A wound healing assay, transwell migration and an invasion assay were performed to assess the metastatic ability of ESCC cells. Cytokine array analysis was conducted to detect the differentially secreted cytokines in CM. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to uncover the pathways and cytokines that are influenced by LPA in ESCC. Immunohistochemical staining was employed to measure the expression of ATX and CCL2 in early-stage ESCC. Quantitative real-time PCR, western blot, enzyme-linked immunosorbent assay and an antibody neutralization assay were employed to measure the mechanism of LPA-mediated communication between epithelial cells and cancer cells. RESULTS: Functional experiments showed that exposing ESCC cancer cells to CM from LPA-treated Het-1a results in promoting proliferation, migration, invasion and epithelial-mesenchymal transition processes. Using cytokine array analysis, we discovered that LPA triggers the release of multiple cytokines from epithelial cells. After screening of the TCGA and GEO databases, CCL2 was identified and found to be correlated with ATX expression in ESCC. Furthermore, CCL2 levels in both mRNA expression and secretion were observed to be upregulated in epithelial cells upon stimulation with LPA. Blocking CCL2 effectively reduced the pro-migration influence of CM derived from LPA-treated Het-1a. Mechanism studies have demonstrated that LPA activated the NF-κB signaling pathway through LPA1/3, ultimately causing an increase in CCL2 expression and secretion in Het-1a. CONCLUSIONS: Our findings, taken together, demonstrate that CM from LPA-treated esophageal epithelial cells plays a significant role in promoting the progression of ESCC, with CCL2 acting as the primary regulator.


Assuntos
Movimento Celular , Proliferação de Células , Quimiocina CCL2 , Células Epiteliais , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Regulação Neoplásica da Expressão Gênica , Lisofosfolipídeos , Humanos , Lisofosfolipídeos/metabolismo , Lisofosfolipídeos/farmacologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Progressão da Doença , Transdução de Sinais/efeitos dos fármacos , Esôfago/metabolismo , Esôfago/patologia , Esôfago/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos
10.
Small ; : e2401872, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639027

RESUMO

Electrochemical glycerol oxidation features an attractive approach of converting bulk chemicals into high-value products such as glyceric acid. Nonetheless, to date, the major product selectivity has mostly been limited as low-value C1 products such as formate, CO, and CO2, due to the fast cleavage of carbon-carbon (C-C) bonds during electro-oxidation. Herein, the study develops an atomically ordered Ni3Sn intermetallic compound catalyst, in which Sn atoms with low carbon-binding and high oxygen-binding capability allow to tune the adsorption of glycerol oxidation intermediates from multi-valent carbon binding to mono-valent carbon binding, as well as enhance *OH binding and subsequent nucleophilic attack. The Ni3Sn electrocatalyst exhibits one of the highest glycerol-to-glyceric acid performances, including a high glycerol conversion rate (1199 µmol h-1) and glyceric acid selectivity (62 ± 3%), a long electrochemical stability of > 150 h, and the capability of direct conversion of crude glycerol (85% purity) into glyceric acid. The work features the rational design of highly ordered catalytic sites for tailoring intermediate binding and reaction pathways, thereby facilitating the efficient production of high-value chemical products.

11.
Genes Cells ; 28(12): 868-880, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37837427

RESUMO

Primary cilia on neural stem/progenitor cells (NSPCs) play an important role in determining cell fate, although the regulatory mechanisms involved in the ciliogenesis remain largely unknown. In this study, we analyzed the effect of the leukemia inhibitory factor (LIF) for the primary cilia in immortalized human NSPCs. LIF withdrawal elongated the primary cilia length, whereas the addition of LIF shortened it. Microarray gene expression analysis revealed that differentially expressed genes (DEGs) associated with LIF treatment were related with the multiple cytokine signaling pathways. Among the DEGs, C-C motif chemokine 2 (CCL2) had the highest ranking and its increase in the protein concentration in the NSPCs-conditioned medium after the LIF treatment was confirmed by ELISA. Interestingly, we found that CCL2 was a negative regulator of cilium length, and LIF-induced shortening of primary cilia was antagonized by CCL2-specific antibody, suggesting that LIF could influence cilia length via upregulating CCL2. The shortening effect of LIF and CCL2 on primary cilia was also observed in SH-SY5Y cells. The results of the study suggested that the LIF-CCL2 axis may well be a regulator of NSPCs and its primary cilia length, which could affect multiple cellular processes, including NSPC proliferation and differentiation.


Assuntos
Células-Tronco Neurais , Neuroblastoma , Humanos , Cílios/metabolismo , Transdução de Sinais , Fator Inibidor de Leucemia/genética , Fator Inibidor de Leucemia/metabolismo , Fator Inibidor de Leucemia/farmacologia , Células-Tronco Neurais/metabolismo , Diferenciação Celular/fisiologia
12.
FASEB J ; 37(1): e22632, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36468785

RESUMO

Peritoneal fibrosis (PF) is an irreversible complication of peritoneal dialysis (PD) that leads to loss of peritoneal membrane function. We investigated PD effluent and serum levels and the tissue expression of chemokine (C-C motif) ligand 8 (CCL8) in patients with PD. Additionally, we investigated their association with PF in a mouse model. Eighty-two end-stage renal disease (ESRD) patients with PD were examined. CCL8 levels were measured via enzyme-linked immunosorbent assays in PD effluents and serum and analyzed with peritoneal transport parameters. Human peritoneal mesothelial cells (hPMCs) were obtained from the PD effluents of 20 patients. Primary cultured hPMCs were treated with recombinant (r) transforming growth factor (TGF)-ß, and CCL8 expression was assessed via western blotting. As the duration of PD increased, the concentration of CCL8 in PD effluents significantly increased. Correlations between peritoneal transport parameters and dialysate CCL8 levels were observed. Western blotting analysis showed that CCL8 was upregulated via rTGF-ß treatment, accompanied by increases in markers of inflammation, fibrosis, senescence, and apoptosis in hPMCs after induction of fibrosis with rTGF-ß. Anti-CCL8 monoclonal antibody (mAb) treatment suppressed the rTGF-ß-induced increase in all analyzed markers. Immunohistochemical analysis revealed that CCL8 along with fibrosis- and inflammation-related markers were significantly increased in the PF mouse model. Functional blockade of CCL8 using a CCR8 inhibitor (R243) abrogated peritoneal inflammation and fibrosis in vivo. In conclusion, high CCL8 levels in PD effluents may be associated with an increased risk of PD failure, and the CCL8 pathway is associated with PF. CCL8 blockade can ameliorate peritoneal inflammation and fibrosis.


Assuntos
Fibrose Peritoneal , Peritonite , Animais , Camundongos , Humanos , Fibrose Peritoneal/prevenção & controle , Quimiocina CCL8 , Peritônio , Quimiocinas , Ligantes , Inflamação , Modelos Animais de Doenças
13.
Cell Commun Signal ; 22(1): 364, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39014433

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality worldwide, characterized by persistent respiratory symptoms and airflow limitation. The involvement of C-C motif chemokine ligand 2 (CCL2) in COPD pathogenesis, particularly in macrophage regulation and activation, is poorly understood despite its recognized role in chronic inflammation. Our study aims to elucidate the regulatory role and molecular mechanisms of CCL2 in the pathogenesis of COPD, providing new insights for therapeutic strategies. METHODS: This study focused on the CCL2-CCR2 signaling pathway, exploring its role in COPD pathogenesis using both Ccl2 knockout (KO) mice and pharmacological inhibitors. To dissect the underlying mechanisms, we employed various in vitro and in vivo methods to analyze the secretion patterns and pathogenic effects of CCL2 and its downstream molecular signaling through the CCL2-CCR2 axis. RESULTS: Elevated Ccl2 expression was confirmed in the lungs of COPD mice and was associated with enhanced recruitment and activation of macrophages. Deletion of Ccl2 in knockout mice, as well as treatment with a Ccr2 inhibitor, resulted in protection against CS- and LPS-induced alveolar injury and airway remodeling. Mechanistically, CCL2 was predominantly secreted by bronchial epithelial cells in a process dependent on STAT1 phosphorylation and acted through the CCR2 receptor on macrophages. This interaction activated the PI3K-AKT signaling pathway, which was pivotal for macrophage activation and the secretion of inflammatory cytokines, further influencing the progression of COPD. CONCLUSIONS: The study highlighted the crucial role of CCL2 in mediating inflammatory responses and remodeling in COPD. It enhanced our understanding of COPD's molecular mechanisms, particularly how CCL2's interaction with the CCR2 activates critical signaling pathways. Targeting the CCL2-CCR2 axis emerged as a promising strategy to alleviate COPD pathology.


Assuntos
Quimiocina CCL2 , Macrófagos , Camundongos Knockout , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Doença Pulmonar Obstrutiva Crônica , Receptores CCR2 , Transdução de Sinais , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Animais , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Receptores CCR2/metabolismo , Receptores CCR2/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Humanos , Camundongos Endogâmicos C57BL , Masculino
14.
J Neurooncol ; 168(3): 457-471, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38652401

RESUMO

PURPOSE: A strong immunosuppressive tumor microenvironment (TME) represents the major barrier responsible for the failure of current immunotherapy approaches in treating Glioblastoma Multiforme (GBM). Within the TME, the regulatory T cells (Tregs) exert immunosuppressive effects on CD8+ T cell - mediated anti-cancer immune killing. Consequently, targeting and inhibiting their immunosuppressive function emerges as an effective therapeutic strategy for GBM. The present study aimed to investigate the mechanisms and effects of Suberanilohydroxamic Acid (SAHA), a histone deacetylase inhibitor, on immunosuppressive Tregs. METHODS: The tumor-infiltrating immune cells in the immunocompetent GBM intracranial implanted xenograft mouse model were analyzed by immunohistochemistry and flow cytometry techniques. The mRNA expressions were assessed through the RT-qPCR method, while the related protein expressions were determined using western blot, ELISA, immunofluorescence (IF), and flow cytometry techniques. The relationship between c-Myc and C-C motif Chemokine Ligand 1 (CCL1) promotor was validated through a dual-luciferase reporter assay system and chromatin immunoprecipitation. RESULTS: SAHA suppressed effectively tumor growth and extended significantly overall survival in the immunocompetent GBM intracranial xenograft mouse model. Additionally, it promoted the infiltration of CD8+ T lymphocytes while suppressed the infiltration of CD4+ CD25+ Tregs. Furthermore, SAHA enhanced anti-PD-L1 immune therapy in the intracranial xenograft of mice. Mechanistically, SAHA exerted its effects by inhibiting histone deacetylase 2 (HDAC2), thereby suppressing the binding between c-Myc and the CCL1 promotor. CONCLUSION: SAHA inhibited the binding of c-Myc with the CCL1 promoter and then suppressed the transcription of CCL1.Additionally, it effectively blocked the interplay of CCL1-CCR8, resulting in reduced activity of Tregs and alleviation of tumor immunosuppression.


Assuntos
Antígeno B7-H1 , Neoplasias Encefálicas , Quimiocina CCL1 , Inibidores de Histona Desacetilases , Células-Tronco Neoplásicas , Linfócitos T Reguladores , Vorinostat , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Camundongos , Humanos , Inibidores de Histona Desacetilases/farmacologia , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/imunologia , Vorinostat/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Quimiocina CCL1/metabolismo , Quimiocina CCL1/antagonistas & inibidores , Glioma/tratamento farmacológico , Glioma/metabolismo , Glioma/patologia , Glioma/imunologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Microambiente Tumoral/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioblastoma/imunologia
15.
Conserv Biol ; 38(3): e14228, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38441344

RESUMO

Raptors are threatened by anthropogenic land modifications, but targeted quantitative assessment of these impacts is lacking. We conducted the first global quantitative evaluation of the impacts of human-modified land on raptors. We used eBird data from 2001 to 2020 on 425 raptor species and occupancy models to assess the impacts of human-modified land on raptor distribution. The mean spatiotemporal correlations of human settlement, cropland, and pasture with raptor occupancy probability were -0.048 (SE 0.031), -0.134 (0.032), and -0.145 (0.032), respectively. The mean sensitivity of raptor occupancy probability to settlement, cropland, and pasture was -5.760 (2.266), -3.128 (1.540), and -2.402 (1.551), respectively. The occupancy probability of raptors with a large body mass was more negatively correlated with cropland (phylogenetic generalized least squares regressions: slope = -0.052 [SE 0.022], t = -2.335, df = 1, 407, p = 0.020, λ = 0.006) and more positively correlated with pasture (slope = 0.047 [0.022], t = 2.118, df = 1, 407, p = 0.035, λ = 0.013). The occupancy probability of raptors with a more extensive range size was more positively correlated with cropland (slope = 0.002 [0.004], t = 0.399, df = 1, 407, p < 0.001, λ = 0.000). Raptors that prefer open habitats were more positively correlated with cropland (analysis of variance: F = 3.424, df = 2, p = 0.034, λ = 0.000) and pasture (F = 6.577, df = 2, p = 0.002, λ = 0.000). In Africa and South America, where raptor species are most abundant, raptor occupancy probability decreased over 20 years, most likely due to habitat fragmentation associated with human land modification. Although raptors with different ecological characteristics had different responses to human land modification, the impacts of settlement, cropland, and pasture on mean raptor occupancy probability were negative, regardless of space and time.


Evaluación cuantitativa del impacto global de la modificación humana del uso de suelo sobre las rapaces Resumen Las rapaces se encuentran amenazadas por las modificaciones de suelo antropogénicas, pero la evaluación cuantitativa focalizada de estos impactos es muy escasa. Realizamos la primera evaluación cuantitativa mundial del impacto del suelo modificado por humanos sobre las rapaces. Usamos datos de eBird desde 2001 hasta 2020 sobre 425 especies rapaces y modelos de ocupación para evaluar el impacto del suelo modificado por humanos sobre la distribución de estas especies. La correlación espaciotemporal media de los asentamientos humanos, las tierras de cultivo y las pasturas con probabilidad de ocupación por rapaces fueron ­0,048 (SE 0,031), ­0,134 (0,032) y ­0,145 (0,032), respectivamente. La sensibilidad media de la probabilidad de ocupación de las rapaces a los asentamientos, las tierras de cultivo y las pasturas fue de ­5,760 (2,266), ­3,128 (1,540) y ­2,402 (1,551), respectivamente. La probabilidad de ocupación de las rapaces con gran masa corporal tuvo una correlación más negativa con las tierras de cultivo (regresiones filogenéticas por mínimos cuadrados generalizados: pendiente =­0. 052 [SE 0,022], t = ­2,335, gl = 1, 407, p = 0,020, λ = 0,006) y una correlación más positiva con los pastos (pendiente = 0,047 [0,022], t = 2,118, gl = 1, 407, p = 0,035, λ = 0,013). La probabilidad de ocupación de las rapaces con un área de distribución más extensa tuvo una correlación más positiva con las tierras de cultivo (pendiente = 0,002 [0,004], t = 0,399, gl = 1, 407, p < 0,001, λ = 0,000). Las rapaces que prefieren hábitats abiertos tuvieron una correlación más positiva con las tierras de cultivo (análisis de la varianza: F = 3,424, gl = 2, p = 0,034, λ = 0,000) y los pastos (F = 6,577, df = 2, p = 0,002, λ = 0,000). En África y América del Sur, en donde son más abundantes las especies rapaces, la probabilidad de ocupación de las rapaces disminuyó a lo largo de 20 años, probablemente debido a la fragmentación de hábitat asociada con la modificación del suelo por humanos. Aunque las rapaces con características ecológicas diferentes tienen diferentes respuestas a estas modificaciones, el impacto de los asentamientos, las tierras de cultivo y las pasturas fue negativo para la probabilidad de ocupación media de las rapaces, sin importar el espacio ni el tiempo.


Assuntos
Conservação dos Recursos Naturais , Aves Predatórias , Aves Predatórias/fisiologia , Animais , Atividades Humanas , Humanos , Agricultura , Ecossistema , Distribuição Animal
16.
Conserv Biol ; 38(3): e14231, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38111980

RESUMO

Deserts are often highly biodiverse and provide important habitats for many threatened species. Fire is a dominant disturbance in deserts, and prescribed burning is increasingly being used by conservation managers and Indigenous peoples to mitigate the damaging effects of climate change, invasive plants, and land-use change. The size, severity, and patchiness of fires can affect how animals respond to fire. However, there are almost no studies examining such burn characteristics in desert environments, which precludes the use of such information in conservation planning. Using a before-after control-impact approach with 20 sampling sites, we studied the outcomes of 10 prescribed burns of varying size (5-267 ha), severity, and patchiness to identify which variables best predicted changes in small mammal and reptile species richness and abundance. Three of the 13 species showed a clear response to fire. Captures increased for 2 species (1 mammal, 1 reptile) and decreased for 1 species (a reptile) as the proportional area burned around traps increased. Two other mammal species showed weaker positive responses to fire. Total burn size and burn patchiness were not influential predictors for any species. Changes in capture rates occurred only at sites with the largest and most severe burns. No fire-related changes in capture rates were observed where fires were small and very patchy. Our results suggest that there may be thresholds of fire size or fire severity that trigger responses to fire, which has consequences for management programs underpinned by the patch mosaic burning paradigm. The prescribed burns we studied, which are typical in scale and intensity across many desert regions, facilitated the presence of some taxa and are unlikely to have widespread or persistent negative impacts on small mammal or reptile communities in this ecosystem provided that long unburned habitat harboring threatened species is protected.


Prueba experimental de la respuesta animal al tamaño y gravedad de los incendios controlados Resumen Los desiertos suelen contar con mucha biodiversidad y proporcionar hábitats importantes para una variedad de especies amenazadas. El fuego es una perturbación que domina en los desiertos, y los incendios controlados cada vez se usan más por los gestores de la conservación y los pueblos indígenas para mitigar los efectos dañinos del cambio climático, las plantas invasoras y el cambio de uso de suelo. El tamaño, gravedad y fragmentación de los incendios pueden afectar cómo los animales responden al fuego. Sin embargo, casi no existen estudios que analicen dichas características de la quema en los ambientes desérticos, lo que excluye a dicha información de la planeación de la conservación. Usamos una estrategia de antes­después del control­impacto en 20 sitios de muestreo para estudiar los resultados de diez incendios controlados de diferentes tamaños (5­267 ha), gravedad y fragmentación para identificar cuáles variables pronostican mejor los cambios en la riqueza de especies y abundancia de mamíferos pequeños y reptiles. Tres de las 13 especies mostraron una respuesta clara al incendio. Las capturas incrementaron en dos especies (una de mamífero y una de reptil) y disminuyeron en una especie (un reptil) conforme incrementó el área proporcional incendiada alrededor de las trampas. Otras dos especies de mamíferos mostraron respuestas positivas más débiles ante el fuego. El tamaño total y la fragmentación del incendio no fueron influyentes sobre los pronosticadores de cualquier especie. Los cambios en las tasas de captura ocurrieron solamente en los sitios con los incendios más graves y grandes. No observamos cambios relacionados al incendio en las tasas de captura en donde los incendios fueron pequeños y muy fragmentados. Nuestros resultados sugieren que podría haber umbrales del tamaño o gravedad del incendio que provocan las respuestas al fuego, lo que tiene consecuencias para los programas de manejo sustentados en el paradigma del mosaico de fragmentos del incendio. Los incendios controlados que estudiamos, que son típicos en escala e intensidad en muchas regiones desérticas, facilitaron la presencia de algunos taxones y no tuvieron probabilidad de tener un impacto negativo extenso o persistente sobre las comunidades de mamíferos pequeños y reptiles en este ecosistema, siempre y cuando se proteja el hábitat que lleva mucho tiempo sin incendios y en donde viven las especies amenazadas.


Assuntos
Conservação dos Recursos Naturais , Incêndios , Mamíferos , Répteis , Animais , Conservação dos Recursos Naturais/métodos , Mamíferos/fisiologia , Répteis/fisiologia , Clima Desértico , Biodiversidade , Ecossistema
17.
Conserv Biol ; : e14312, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38894638

RESUMO

Introgressive hybridization between wolves and dogs is a conservation concern due to its potentially deleterious long-term evolutionary consequences. European legislation requires that wolf-dog hybridization be mitigated through effective management. We developed an individual-based model (IBM) to simulate the life cycle of gray wolves that incorporates aspects of wolf sociality that affect hybridization rates (e.g., the dissolution of packs after the death of one/both breeders) with the goal of informing decision-making on management of wolf-dog hybridization. We applied our model by projecting hybridization dynamics in a local wolf population under different mate choice and immigration scenarios and contrasted results of removal of admixed individuals with their sterilization and release. In several scenarios, lack of management led to complete admixture, whereas reactive management interventions effectively reduced admixture in wolf populations. Management effectiveness, however, strongly depended on mate choice and number and admixture level of individuals immigrating into the wolf population. The inclusion of anthropogenic mortality affecting parental and admixed individuals (e.g., poaching) increased the probability of pack dissolution and thus increased the probability of interbreeding with dogs or admixed individuals and boosted hybridization and introgression rates in all simulation scenarios. Recognizing the necessity of additional model refinements (appropriate parameterization, thorough sensitivity analyses, and robust model validation) to generate management recommendations applicable in real-world scenarios, we maintain confidence in our model's potential as a valuable conservation tool that can be applied to diverse situations and species facing similar threats.


Simulación de la eficiencia de la gestión de híbridos de perro y lobo con modelos basados en individuos Resumen La hibridación introgresiva entre perros y lobos es un tema de conservación por las posibles consecuencias evolutivas deletéreas a largo plazo. Las leyes europeas requieren que estos híbridos se mitiguen mediante una gestión efectiva. Desarrollamos un modelo basado en individuos (MBI) para simular el ciclo de vida del lobo gris que además incorpora los aspectos sociales de los lobos que afectan las tasas de hibridación (p. ej.: la disolución de las manadas después de la muerte de uno o ambos reproductores) con el objetivo de guiar las decisiones de gestión de estos híbridos. Aplicamos nuestro modelo con la proyección de las dinámicas de hibridación en una población local de lobos bajo diferentes selecciones de pareja y escenarios de inmigración y contrastamos los resultados de la extirpación de individuos mezclados con su esterilización y liberación. En varios escenarios, la falta de gestión llevó a una mezcla completa, mientras que las intervenciones de gestión reactiva redujeron de forma efectiva la mezcla en las poblaciones de lobos. Sin embargo, la eficiencia de la gestión dependió en su mayoría de la selección de pareja y el número y nivel de mezcla de los individuos inmigrantes a la población de lobos. La inclusión de la mortalidad antropogénica que afecta a los individuos parentales y mezclados (p. ej.: la cacería) incrementó la probabilidad de que se disolviera la manada y por lo tanto incrementara la probabilidad del entrecruzamiento con perros o individuos mezclados, además de que aumentó la hibridación y las tasas de introgresión en todos los escenarios de simulación. Reconocemos la necesidad de refinar el modelo (parametrización adecuada, análisis detallados de sensibilidad y validación del modelo robusto) para generar recomendaciones de gestión aplicables en escenarios reales y mantenemos la confianza en el potencial de nuestro modelo como una herramienta valiosa de conservación que podría aplicarse a diferentes situaciones y especies que enfrentan amenazas similares.

18.
Conserv Biol ; 38(4): e14245, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38456548

RESUMO

Understanding which species will be extirpated in the aftermath of large-scale human disturbance is critical to mitigating biodiversity loss, particularly in hyperdiverse tropical biomes. Deforestation is the strongest driver of contemporary local extinctions in tropical forests but may occur at different tempos. The 2 most extensive tropical forest biomes in South America-the Atlantic Forest and the Amazon-have experienced historically divergent pathways of habitat loss and biodiversity decay, providing a unique case study to investigate rates of local species persistence on a single continent. We quantified medium- to large-bodied mammal species persistence across these biomes to elucidate how landscape configuration affects their persistence and associated ecological functions. We collected occurrence data for 617 assemblages of medium- to large-bodied mammal species (>1 kg) in the Atlantic Forest and the Amazon. Analyzing natural habitat cover based on satellite data (1985-2022), we employed descriptive statistics and generalized linear models (GLMs) to investigate ecospecies occurrence patterns in relation to habitat cover across the landscapes. The subregional erosion of Amazonian mammal assemblage diversity since the 1970s mirrors that observed since the colonial conquest of the Atlantic Forest, given that 52.8% of all Amazonian mammals are now on a similar trajectory. Four out of 5 large mammals in the Atlantic Forest were prone to extirpation, whereas 53% of Amazonian mammals were vulnerable to extirpation. Greater natural habitat cover increased the persistence likelihood of ecospecies in both biomes. These trends reflected a median local species loss 63.9% higher in the Atlantic Forest than in the Amazon, which appears to be moving toward a turning point of forest habitat loss and degradation. The contrasting trajectories of species persistence in the Amazon and Atlantic Forest domains underscore the importance of considering historical habitat loss pathways and regional biodiversity erosion in conservation strategies. By focusing on landscape configuration and identifying essential ecological functions associated with large vertebrate species, conservation planning and management practices can be better informed.


Uso de la pérdida histórica de hábitat para predecir la desaparición de mamíferos contemporáneos en los bosques neotropicales Resumen Tener conocimiento de cuáles especies desaparecerán después de una perturbación humana es de suma importancia para mitigar la pérdida de la biodiversidad, particularmente en los biomas híper diversos. La deforestación es la principal causante de las extinciones locales contemporáneas en los bosques tropicales, aunque puede ocurrir en diferentes tiempos. Los dos bosques tropicales más extensos de América del Sur ­ el Bosque Atlántico y la Amazonia ­ han experimentado formas históricamente divergentes de pérdida de hábitat y decadencia de biodiversidad, lo que proporciona un caso único de estudio para investigar las tasas de persistencia de las especies locales en un solo continente. Cuantificamos la persistencia de las especies de mamíferos de talla mediana a grande en estos dos bosques para aclarar cómo la configuración del paisaje afecta su persistencia y las funciones ecológicas asociadas. Recolectamos datos de presencia de 617 ensambles de especies de mamíferos de talla mediana a grande (>1 kg) en el Bosque Atlántico y en la Amazonia. Analizamos la cobertura natural del hábitat con base en datos satelitales (1985­2022) y empleamos estadística descriptiva y modelos lineales generalizados (MLG) para investigar los patrones de presencia de las eco especies en relación con la cobertura del hábitat en los distintos paisajes. La erosión subregional de la diversidad de ensambles de mamíferos en la Amazonia desde los 70s es igual a la observada en el Bosque Atlántico desde la conquista colonial, dado que 52.8% de todos los mamíferos amazónicos se encuentran en una trayectoria similar. Cuatro de los cinco grandes mamíferos en el Bosque Atlántico estaban propensos a desaparecer, mientras que el 53% de los mamíferos amazónicos estaban vulnerables a desaparecer. Una mayor cobertura natural del hábitat incrementó la probabilidad de persistencia de las eco especies en ambos bosques. Estas tendencias reflejaron una pérdida mediana de especies locales 63.9% mayor en el Bosque Atlántico que en la Amazonia, lo cual parece dirigirse hacia un momento decisivo para la degradación y pérdida del hábitat del bosque. Las trayectorias contrastantes de la persistencia de especies en el Bosque Atlántico y la Amazonia destacan la importancia de considerar dentro de las estrategias de conservación las maneras en las que se ha perdido históricamente el hábitat y la erosión de la biodiversidad regional. Si nos enfocamos en la configuración del paisaje y en la identificación de las funciones ecológicas esenciales asociadas con las especies grandes de vertebrados, podemos informar de mejor manera a la planeación de la conservación y las prácticas de manejo.


Assuntos
Biodiversidade , Conservação dos Recursos Naturais , Extinção Biológica , Florestas , Mamíferos , Animais , Mamíferos/fisiologia , Clima Tropical , Ecossistema , Brasil
19.
Conserv Biol ; : e14290, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38708868

RESUMO

The conservation-invasion paradox (CIP) refers to a long-term phenomenon wherein species threatened in their native range can sustain viable populations when introduced to other regions. Understanding the drivers of CIP is helpful for conserving threatened species and managing invasive species, which is unfortunately still lacking. We compiled a global data set of 1071 introduction events, including 960 CIP events (successful establishment of threatened species outside its native range) and 111 non-CIP events (unsuccessful establishment of threatened species outside its native range after introduction), involving 174 terrestrial vertebrates. We then tested the relative importance of various predictors at the location, event, and species levels with generalized linear mixed models and model averaging. Successful CIP events occurred across taxonomic groups and biogeographic realms, especially for the mammal group in the Palearctic and Australia. Locations of successful CIP events had fewer native threat factors, especially less climate warming in invaded regions. The probability of a successful CIP event was highest when species introduction efforts were great and there were more local congeners and fewer natural enemies. These results can inform threatened species ex situ conservation and non-native invasive species mitigation.


Causantes mundiales de la paradoja conservación­invasión Resumen La paradoja de conservación­invasión (PCI) se refiere al evento a largo plazo en el que las especies amenazadas en su distribución nativa puedan mantener poblaciones viables cuando se les introduce a otras regiones. Es de mucha ayuda para la conservación de especies amenazadas y el manejo de especies invasoras entender las causantes de la PCI, entendimiento que todavía es escaso. Compilamos un conjunto mundial de datos de 174 vertebrados terrestres en 1071 eventos de introducción, incluyendo 960 eventos de PCI (el establecimiento exitoso de especies amenazadas fuera de su distribución nativa) y 111 eventos no PCI (el fracaso en el establecimiento de especies amenazadas fuera de su distribución nativa después de la introducción). Después analizamos con modelos lineales mixtos generalizados y promedio de modelos la importancia relativa de varios pronosticadores en la localidad, en el evento y a nivel de especie. Los eventos exitosos de PCI ocurrieron en todos los grupos taxonómicos y en todos los reinos biogeográficos, especialmente para los mamíferos del Paleártico y Australia. Las localidades de los eventos exitosos de PCI tuvieron menos factores nativos de amenaza, especialmente un menor calentamiento climático en las regiones invadidas. La probabilidad de que un evento de PCI sea exitoso fue mayor cuando los esfuerzos de introducción fueron mayores y hubo más congéneres locales y menos enemigos naturales. Estos resultados pueden orientar la conservación ex situ de especies y la mitigación de especies invasoras no nativas.

20.
Conserv Biol ; 38(1): e14106, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37144483

RESUMO

In 2010, the introduction of other effective area-based conservation measures (OECMs) into international policy caused a paradigm shift in area-based conservation, which included consideration of areas outside formal protected areas and places where biodiversity conservation may not be a management objective for the site. Despite the importance of this shift for global conservation, conservation science and policy have been slow to engage with the concept of OECMs. As the world moves toward protecting 30% of the Earth by 2030, it is imperative to develop evidence-based guidance for how to identify effective conservation measures, especially tools to help evaluate and monitor the biodiversity outcomes associated with potential OECMs. To understand the current progress in developing the concept of OECMs, I evaluated the peer-reviewed literature to consolidate and synthesize current knowledge. I conducted a thematic analysis of papers to identify the types of challenges and opportunities being discussed and lessons from studies evaluating the effectiveness of OECMs. Only 105 studies mentioned OECMs, and those that did rarely move beyond superficial mention of OECMs as part of area-based conservation. Around one-half of studies listed potential risks or benefits of OECMs but none provided evidence these issues have materialized. Twenty-three studies attempted to identify potential OECMs, although specific case studies were rare. The 7 studies that evaluated existing OECMs were highly critical of how they had been implemented to date. Studies that evaluated conservation outcomes were extremely rare, and suggested effectiveness must be judged on a case-by-case basis. The current literature not only leaves many gaps in the science required to operationalize the concept of OECMs, but also often raises additional questions that need to be addressed. If these gaps are not filled by robust science, the promised benefits for biodiversity from OECMs may never be realized.


Progreso en el desarrollo del concepto de otras medidas efectivas de conservación basadas en el área Resumen En 2010, la introducción de otras medidas eficaces de conservación basadas en zonas geográficas específicas (OECM) en la política internacional provocó un cambio de paradigma en la conservación basada en el área, que incluyó la consideración de zonas situadas fuera de las áreas protegidas formales y lugares donde la conservación de la biodiversidad puede no ser un objetivo de gestión para el sitio. A pesar de la importancia de este cambio para la conservación mundial, la ciencia y la política de la conservación han tardado en comprometerse con el concepto de OECM. A medida que el mundo avanza hacia la protección del 30% de la Tierra para 2030, es imperativo desarrollar orientaciones basadas en pruebas sobre cómo identificar medidas de conservación eficaces, especialmente herramientas que ayuden a evaluar y supervisar los resultados de biodiversidad asociados a posibles OECM. Para comprender los avances actuales en el desarrollo del concepto de OECM, evalué la bibliografía revisada por pares para consolidar y sintetizar los conocimientos actuales. Realicé un análisis temático de los artículos para identificar los tipos de retos y oportunidades que se debatían y las lecciones extraídas de los estudios que evaluaban la eficacia de las OECM. Sólo 105 estudios mencionaron las OECM, y los que lo hicieron rara vez iban más allá de la mención superficial de las OECM como parte de la conservación basada en el área. Aproximadamente la mitad de los estudios mencionaron los riesgos o beneficios potenciales de las OECM, pero ninguno aportó pruebas de que estos problemas se hubieran materializado. Veintitrés estudios intentaron identificar OECM potenciales, aunque los estudios de casos fueron escasos. Los siete estudios que evaluaron las OECM existentes fueron muy críticos con la forma en que se habían aplicado hasta la fecha. Los estudios que evaluaban los resultados de la conservación eran muy escasos y sugerían que la eficacia debía juzgarse caso por caso. La bibliografía actual no sólo deja muchos vacíos en la ciencia necesaria para hacer operativo el concepto de OECM, sino que a menudo plantea cuestiones adicionales que deben abordarse. Si estos vacíos no se cubren con una ciencia sólida, es posible que los beneficios prometidos de las OECM para la biodiversidad nunca lleguen a materializarse.


Assuntos
Biodiversidade , Conservação dos Recursos Naturais , Política Pública
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