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1.
Nat Commun ; 12(1): 1717, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741967

RESUMO

Myeloid-derived suppressor cells (MDSC) are pathologically activated neutrophils and monocytes with potent immune suppressive activity. These cells play an important role in accelerating tumor progression and undermining the efficacy of anti-cancer therapies. The natural mechanisms limiting MDSC activity are not well understood. Here, we present evidence that type I interferons (IFN1) receptor signaling serves as a universal mechanism that restricts acquisition of suppressive activity by these cells. Downregulation of the IFNAR1 chain of this receptor is found in MDSC from cancer patients and mouse tumor models. The decrease in IFNAR1 depends on the activation of the p38 protein kinase and is required for activation of the immune suppressive phenotype. Whereas deletion of IFNAR1 is not sufficient to convert neutrophils and monocytes to MDSC, genetic stabilization of IFNAR1 in tumor bearing mice undermines suppressive activity of MDSC and has potent antitumor effect. Stabilizing IFNAR1 using inhibitor of p38 combined with the interferon induction therapy elicits a robust anti-tumor effect. Thus, negative regulatory mechanisms of MDSC function can be exploited therapeutically.


Assuntos
Interferon Tipo I/metabolismo , Células Supressoras Mieloides/imunologia , Neoplasias/metabolismo , Receptor de Interferon alfa e beta/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antineoplásicos/farmacologia , Medula Óssea , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Monócitos/imunologia , Neutrófilos/imunologia , Receptor de Interferon alfa e beta/genética , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
2.
Microbiome ; 9(1): 48, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597033

RESUMO

BACKGROUND: Salt marshes are major natural repositories of sequestered organic carbon with high burial rates of organic matter, produced by highly productive native flora. Accumulated carbon predominantly exists as lignocellulose which is metabolised by communities of functionally diverse microbes. However, the organisms that orchestrate this process and the enzymatic mechanisms employed that regulate the accumulation, composition and permanence of this carbon stock are not yet known. We applied meta-exo-proteome proteomics and 16S rRNA gene profiling to study lignocellulose decomposition in situ within the surface level sediments of a natural established UK salt marsh. RESULTS: Our studies revealed a community dominated by Gammaproteobacteria, Bacteroidetes and Deltaproteobacteria that drive lignocellulose degradation in the salt marsh. We identify 42 families of lignocellulolytic bacteria of which the most active secretors of carbohydrate-active enzymes were observed to be Prolixibacteracea, Flavobacteriaceae, Cellvibrionaceae, Saccharospirillaceae, Alteromonadaceae, Vibrionaceae and Cytophagaceae. These families secreted lignocellulose-active glycoside hydrolase (GH) family enzymes GH3, GH5, GH6, GH9, GH10, GH11, GH13 and GH43 that were associated with degrading Spartina biomass. While fungi were present, we did not detect a lignocellulolytic contribution from fungi which are major contributors to terrestrial lignocellulose deconstruction. Oxidative enzymes such as laccases, peroxidases and lytic polysaccharide monooxygenases that are important for lignocellulose degradation in the terrestrial environment were present but not abundant, while a notable abundance of putative esterases (such as carbohydrate esterase family 1) associated with decoupling lignin from polysaccharides in lignocellulose was observed. CONCLUSIONS: Here, we identify a diverse cohort of previously undefined bacteria that drive lignocellulose degradation in the surface sediments of the salt marsh environment and describe the enzymatic mechanisms they employ to facilitate this process. Our results increase the understanding of the microbial and molecular mechanisms that underpin carbon sequestration from lignocellulose within salt marsh surface sediments in situ and provide insights into the potential enzymatic mechanisms regulating the enrichment of polyphenolics in salt marsh sediments. Video Abstract.


Assuntos
Sedimentos Geológicos/microbiologia , Lignina/metabolismo , Microbiota/fisiologia , Áreas Alagadas , Microbiota/genética , RNA Ribossômico 16S/genética , Reino Unido
3.
Artigo em Inglês | MEDLINE | ID: mdl-33443928

RESUMO

Factor V inhibitors are a rare cause of life-threatening bleeding. We present a case of an acquired factor V inhibitor likely caused by coronavirus disease 2019 infection. Bleeding was manifested by severe anemia requiring frequent red-cell transfusion, left psoas muscle hematoma, and left retroperitoneal cavity hematoma. Factor V activity was less than 1% and the factor V inhibitor titer was 31.6 Bethesda units. Severe acute respiratory syndrome coronavirus 2 RNA testing of the nasopharynx was positive 2 weeks before presentation and continued to be positive for 30 days. The patient failed treatment with intravenous immunoglobulin and dexamethasone. Three cycles of plasmapheresis with fresh frozen plasma replacement resulted in correction of the bleeding and laboratory coagulopathy. This is the first reported case of a factor V inhibitor in a coronavirus disease 2019 patient and suggests that plasmapheresis may be a successful treatment strategy.

4.
Inorg Chem ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33404221

RESUMO

Lead (Pb)-containing solids find widespread commercial use in batteries, piezoelectrics, and as starting materials for synthesis. Here, we combine density functional theory (DFT) and thermodynamics in a DFT + solvent ion model to compare the surface reactivity of Pb oxides and carbonates, specifically litharge, massicot, and cerussite, in contact with water. The information provided by this model is used to delineate structure-property relationships for surfaces that are able to release Pb as Pb2+. We find that Pb2+ release is dependent on pH and chemical bonding environment and go on to correlate changes in the surface bonding to key features of the electronic structure through a projected density of states analysis. Collectively, our analyses link the atomistic structure to i) specific electronic states and ii) the thermodynamics of surface transformations, and the results presented here can be used to guide synthetic efforts of Pb2+-containing materials in aqueous media or be used to better understand the initial steps in solid decomposition.

5.
Cell Rep ; 33(13): 108571, 2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33378668

RESUMO

Here, we report that functional heterogeneity of macrophages in cancer could be determined by the nature of their precursors: monocytes (Mons) and monocytic myeloid-derived suppressor cells (M-MDSCs). Macrophages that are differentiated from M-MDSCs, but not from Mons, are immune suppressive, with a genomic profile matching that of M-MDSCs. Immune-suppressive activity of M-MDSC-derived macrophages is dependent on the persistent expression of S100A9 protein in these cells. S100A9 also promotes M2 polarization of macrophages. Tissue-resident- and Mon-derived macrophages lack expression of this protein. S100A9-dependent immune-suppressive activity of macrophages involves transcription factor C/EBPß. The presence of S100A9-positive macrophages in tumor tissues is associated with shorter survival in patients with head and neck cancer and poor response to PD-1 antibody treatment in patients with metastatic melanoma. Thus, this study reveals the pathway of the development of immune-suppressive macrophages and suggests an approach to their selective targeting.

6.
Cureus ; 12(10): e11164, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33251071

RESUMO

A 67-year-old female with a history of colon cancer underwent colonoscopy. An 8 mm semi-pedunculated, friable, and ulcerated lesion of the ascending colon was removed completely using a hot snare. Immunohistochemical staining showed strong positivity for transcription factor binding to IGHM enhancer 3 (TFE-3) and was partially positive for Human Melanoma Black (HMB-45), consistent with a diagnosis of perivascular epithelioid cell tumor (PEComa). The patient underwent endoscopic submucosal dissection of the residual lesion in the ascending colon without complications. Here, we discuss the clinical and histopathologic characterizations that helped guide the diagnosis and management of this exceedingly rare entity.

7.
Conserv Biol ; 34(6): 1331-1332, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044011

RESUMO

Article impact statement: COVID-19 has demonstrated the need to optimize research activity, convey the gravity of loss, and reevaluate merit in conservation science.

8.
Nat Commun ; 11(1): 4668, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963244

RESUMO

Funds to combat biodiversity loss are insufficient, requiring conservation managers to make trade-offs between costs for actions to avoid further loss and costs for research and monitoring to guide effective actions. Using species' management plans for 2328 listed species from three countries we show that 50% of species' proposed recovery plan budgets are allocated to research and monitoring. The proportion of budgets allocated to research and monitoring vary among jurisdictions and taxa, but overall, species with higher proportions of budgets allocated to research and monitoring have poorer recovery outcomes. The proportion allocated to research and monitoring is lower for more recent recovery plans, but for some species, plans have allocated the majority of funds to information gathering for decades. We provide recommendations for careful examination of the value of collecting new information in recovery planning to ensure that conservation programs emphasize action or research and monitoring that directly informs action.

9.
Cureus ; 12(7): e9083, 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32676257

RESUMO

A 73-year-old female with past medical history of essential hypertension, hyperlipidemia, seasonal allergies, and chronic back pain presented to the hospital with complaints of headaches, fevers, fatigue, generalized body aches, shortness of breath, and diarrhea. Initial complete blood count was remarkable for leukopenia with an absolute lymph count of 0.60 K/µL and severe thrombocytopenia (platelet count < 3 K/µL). She was tested for COVID-19 via nasopharyngeal swab polymerase chain reaction (PCR) testing and found positive. Additional labs showed an elevated D-dimer, C-reactive protein, fibrinogen, and lactate dehydrogenase. Vitamin B12 and folate levels were obtained and found to be normal. Peripheral smear showed no schistocytes or additional hematologic abnormalities apart from thrombocytopenia. The patient was transfused one unit of platelets with no improvement in platelet count. Fibrinogen count was obtained and found in normal range at 458 mg/dL. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR) were all found to be normal. Immune thrombocytopenia purpura (ITP) was suspected and intravenous immunoglobulin (IVIG) was administered at a dose of 1 g/kg/day for two doses. By day 4, the patient had marked response to treatment with platelet recovery to 105 K/µL and subsequently discharged by day 5 with complete resolution of symptoms and platelet count of 146 K/µL. Twenty-eight days after discharge, she presented to hematology clinic with platelet count of 8 K/µL. Repeat nasopharyngeal swab PCR COVID testing was negative and she was treated with IVIG and pulse dexamethasone with prompt response, confirming suspicion of underlying, undiagnosed ITP prior to COVID infection.

10.
Ecol Evol ; 10(11): 5001-5014, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32551077

RESUMO

Species distribution models (SDMs) are used to test ecological theory and to direct targeted surveys for species of conservation concern. Several studies have tested for an influence of species traits on the predictive accuracy of SDMs. However, most used the same set of environmental predictors for all species and/or did not use truly independent data to test SDM accuracy. We built eight SDMs for each of 24 plant species of conservation concern, varying the environmental predictors included in each SDM version. We then measured the accuracy of each SDM using independent presence and absence data to calculate area under the receiver operating characteristic curve (AUC) and true positive rate (TPR). We used generalized linear mixed models to test for a relationship between species traits and SDM accuracy, while accounting for variation in SDM performance that might be introduced by different predictor sets. All traits affected one or both SDM accuracy measures. Species with lighter seeds, animal-dispersed seeds, and a higher density of occurrences had higher AUC and TPR than other species, all else being equal. Long-lived woody species had higher AUC than herbaceous species, but lower TPR. These results support the hypothesis that the strength of species-environment correlations is affected by characteristics of species or their geographic distributions. However, because each species has multiple traits, and because AUC and TPR can be affected differently, there is no straightforward way to determine a priori which species will yield useful SDMs based on their traits. Most species yielded at least one useful SDM. Therefore, it is worthwhile to build and test SDMs for the purpose of finding new populations of plant species of conservation concern, regardless of these species' traits.

11.
PeerJ ; 8: e9258, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32518737

RESUMO

The resources available for conserving biodiversity are limited, and so protected areas need to be established in places that will achieve objectives for minimal cost. Two of the main algorithms for solving systematic conservation planning problems are Simulated Annealing (SA) and exact integer linear programing (EILP) solvers. Using a case study in BC, Canada, we compare the cost-effectiveness and processing times of SA used in Marxan versus EILP using both commercial and open-source algorithms. Plans for expanding protected area systems based on EILP algorithms were 12-30% cheaper than plans using SA, due to EILP's ability to find optimal solutions as opposed to approximations. The best EILP solver we examined was on average 1,071 times faster than the SA algorithm tested. The performance advantages of EILP solvers were also observed when we aimed for spatially compact solutions by including a boundary penalty. One practical advantage of using EILP over SA is that the analysis does not require calibration, saving even more time. Given the performance of EILP solvers, they can be used to generate conservation plans in real-time during stakeholder meetings and can facilitate rapid sensitivity analysis, and contribute to a more transparent, inclusive, and defensible decision-making process.

12.
Surg Oncol Clin N Am ; 29(1): 1-13, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31757306

RESUMO

Translational and clinical research advances have unveiled extensive cancer tumor cell heterogenicity. New understanding has prompted the practice-changing treatment of each cancer specific to its unique genetic construct. Among the earliest applications of this model was melanoma treatment. Survival rates increased significantly, with improvement each year. Genetic profiling allows further lesion classification, resulting in more personalized follow-up and treatment plans. Gene expression profiling allows the identification of specific mutations to direct targeted therapy and provides invaluable prognostic data. This article reviews the newest and most up-to-date advances in precision medicine within melanoma practice.

13.
Conserv Biol ; 34(1): 276-281, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31264731

RESUMO

Bias toward legally protecting and prioritizing charismatic taxonomic groups, such as mammals and birds, and against others, such as insects and plants, is well documented. However, the relative costs of conserving various taxonomic groups and the potential of these costs to interact with existing biases have been much less explored. We analyzed conservation programs across more than 2,000 species in 3 countries to investigate the costs of conserving species within taxonomic groups and how these costs might affect conservation planning. For each data set, we tested for differences in mean annual cost among taxonomic groups. For the data set from the United States, recovery plans differed in duration, so we also tested for differences in total costs among taxonomic groups. Although the costs for individual species varied widely, there were strong international consistencies. For example, mammals cost 8-26 times more on average to conserve than plants and 13-19 times more to conserve than aquatic invertebrates. On average, bird species cost 5-30 times more to conserve than plants and 6-14 times more to conserve than aquatic invertebrates. These cost differences could exacerbate unequal resource allocation among taxonomic groups such that more charismatic groups both receive more attention and require more resources, leading to neglect of other taxonomic groups.


Assuntos
Conservação dos Recursos Naturais , Espécies em Perigo de Extinção , Animais , Biodiversidade , Aves , Invertebrados , Mamíferos , Estados Unidos
14.
Biotechnol Biofuels ; 12: 265, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31719844

RESUMO

Background: Efficient deconstruction of lignocellulosic biomass into simple sugars in an economically viable manner is a prerequisite for its global acceptance as a feedstock in bioethanol production. This is achieved in nature by suites of enzymes with the capability of efficiently depolymerizing all the components of lignocellulose. Here, we provide detailed insight into the repertoire of enzymes produced by microorganisms enriched from the gut of the crop pathogen rice yellow stem borer (Scirpophaga incertulas). Results: A microbial community was enriched from the gut of the rice yellow stem borer for enhanced rice straw degradation by sub-culturing every 10 days, for 1 year, in minimal medium with rice straw as the main carbon source. The enriched culture demonstrated high cellulolytic and xylanolytic activity in the culture supernatant. Metatranscriptomic and metaexoproteomic analysis revealed a large array of enzymes potentially involved in rice straw deconstruction. The consortium was found to encode genes ascribed to all five classes of carbohydrate-active enzymes (GHs, GTs, CEs, PLs, and AAs), including carbohydrate-binding modules (CBMs), categorized in the carbohydrate-active enzymes (CAZy) database. The GHs were the most abundant class of CAZymes. Predicted enzymes from these CAZy classes have the potential to digest each cell-wall components of rice straw, i.e., cellulose, hemicellulose, pectin, callose, and lignin. Several identified CAZy proteins appeared novel, having an unknown or hypothetical catalytic counterpart with a known class of CBM. To validate the findings, one of the identified enzymes that belong to the GH10 family was functionally characterized. The enzyme expressed in E. coli efficiently hydrolyzed beechwood xylan, and pretreated and untreated rice straw. Conclusions: This is the first report describing the enrichment of lignocellulose degrading bacteria from the gut of the rice yellow stem borer to deconstruct rice straw, identifying a plethora of enzymes secreted by the microbial community when growing on rice straw as a carbon source. These enzymes could be important candidates for biorefineries to overcome the current bottlenecks in biomass processing.

15.
Glob Chang Biol ; 25(12): 4222-4233, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31502733

RESUMO

Globally, lake fish communities are being subjected to a range of scale-dependent anthropogenic pressures, from climate change to eutrophication, and from overexploitation to species introductions. As a consequence, the composition of these communities is being reshuffled, in most cases leading to a surge in taxonomic similarity at the regional scale termed homogenization. The drivers of homogenization remain unclear, which may be a reflection of interactions between various environmental changes. In this study, we investigate two potential drivers of the recent changes in the composition of freshwater fish communities: recreational fishing and climate change. Our results, derived from 524 lakes of Ontario, Canada sampled in two periods (1965-1982 and 2008-2012), demonstrate that the main contributors to homogenization are the dispersal of gamefish species, most of which are large predators. Alternative explanations relating to lake habitat (e.g., area, phosphorus) or variations in climate have limited explanatory power. Our analysis suggests that human-assisted migration is the primary driver of the observed compositional shifts, homogenizing freshwater fish community among Ontario lakes and generating food webs dominated by gamefish species.


Assuntos
Mudança Climática , Lagos , Animais , Ecossistema , Eutrofização , Peixes , Humanos , Ontário
16.
Sci Total Environ ; 696: 134000, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31465915

RESUMO

Discussions around the "slow science movement" abound in environmental sciences, yet they are generally counterproductive. Researchers must focus on producing robust and transparent knowledge, regardless of speed. Slow versus fast science is irrelevant - what we need is reproducible research to support evidence-based decision making and tackle urgent and costly environmental problems.

17.
CNS Oncol ; 8(2): CNS37, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31290679

RESUMO

Aim: Glioblastoma multiforme (GBM) carries a dismal prognosis. Integrated proteogenomic analysis was performed to understand GBM pathophysiology. Patients & methods: 17 patient samples were analyzed for driver mutations, oncogenes, major pathway alterations and molecular changes at gene and protein level. Clinical, treatment and survival data were collected. Results: Significantly mutated genes included TP53, EGFR, PIK3R1, PTEN, NF1, RET and STAG2. EGFR mutations noted included EGFRvIII-expression, EGFR-L816Q missense mutation-exon 21 and EGFR fusion (FGFR3-TACC3). TP53 mutations were noticed in COSMIC hot-spot driver gene and accompany IDH1 and ATRX mutations suggesting low- to high-grade glioma transformation. Proteomics showed higher (53%) EGFR expression than genomic expression (23%). MGMT methylation was present in two-thirds of cases. Conclusion: This study identifies a distinct biological process that may characterize each GBM differently. Proteogenomic data identify potential therapeutic targets of GBM.


Assuntos
Glioblastoma/genética , Glioblastoma/metabolismo , Adulto , Idoso , Metilação de DNA , Feminino , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteogenômica/métodos , Adulto Jovem
18.
Cureus ; 11(5): e4725, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31355085

RESUMO

Isolated spontaneous dissection of the superior mesenteric artery (SMA) is a rare entity that is increasingly becoming recognized due to an improvement in imaging techniques. The pathogenesis of a spontaneous SMA dissection has yet to be fully elucidated. Here, we present the case of isolated SMA dissection in a 65-year-old female who was seen in the emergency room with acute substernal chest and left upper quadrant abdominal pain. She was managed for atrial fibrillation with a rapid ventricular response. She underwent computed tomography (CT) angiogram of the chest, abdomen, and pelvis, which revealed focal dissection involving SMA measuring 2.7 cm in width. Vascular surgery recommended conservative management with low-dose daily aspirin and the optimization of blood pressure control. She subsequently was seen as an outpatient with complete resolution of abdominal pain. Given the low incidence rate, vascular surgery evaluation may be required to determine the best course of management. Treatment needs to be individualized for each patient. Since abdominal pain is a common complaint for which patients are seen in each clinical setting, it is important to highlight this case to create awareness regarding the possibility of isolated SMA dissection as one of the underlying etiologies.

19.
Cureus ; 11(5): e4654, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31316875

RESUMO

Histoplasmosis and cryptococcosis are systemic fungal diseases frequently encountered in immunocompromised hosts, particularly in patients with HIV/AIDS with low CD4 counts. However, co-infection with histoplasmosis and cryptococcosis is an uncommon clinical scenario, hence carrying the risk of under diagnosis by medical professionals. For instance, when one infection is identified, most health professionals will have a low suspicion for an additional co-infection. Here, we report the case of a 71-year-old gentleman with a new diagnosis of myasthenia gravis (MG) requiring recent steroid therapy who presented with recurrent respiratory symptoms despite treatment for community acquired pneumonia. Bronchoscopy and bronchoalveolar lavage (BAL) were performed; BAL samples revealed presence of Cryptococcus neoformans and histoplasma antigen (Ag). Serum cryptococcal Ag and urine histoplasma Ag returned positive as well. The patient then required inpatient treatment with amphotericin B, with eventual transition to oral fluconazole at discharge. Pulmonology and Infectious disease consults assisted in appropriate diagnosis and management of this rare presentation. Given the high prevalence of immunocompromised states in a myriad of medical co-morbidities, it is important to highlight this case to create awareness regarding possibility of concomitant systemic fungal diseases.

20.
J Exp Med ; 216(9): 2150-2169, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31239386

RESUMO

We have identified a precursor that differentiates into granulocytes in vitro and in vivo yet belongs to the monocytic lineage. We have termed these cells monocyte-like precursors of granulocytes (MLPGs). Under steady state conditions, MLPGs were absent in the spleen and barely detectable in the bone marrow (BM). In contrast, these cells significantly expanded in tumor-bearing mice and differentiated to polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Selective depletion of monocytic cells had no effect on the number of granulocytes in naive mice but decreased the population of PMN-MDSCs in tumor-bearing mice by 50%. The expansion of MLPGs was found to be controlled by the down-regulation of Rb1, but not IRF8, which is known to regulate the expansion of PMN-MDSCs from classic granulocyte precursors. In cancer patients, putative MLPGs were found within the population of CXCR1+CD15-CD14+HLA-DR-/lo monocytic cells. These findings describe a mechanism of abnormal myelopoiesis in cancer and suggest potential new approaches for selective targeting of MDSCs.


Assuntos
Monócitos/patologia , Células Supressoras Mieloides/patologia , Neoplasias/patologia , Neutrófilos/patologia , Adulto , Idoso , Animais , Diferenciação Celular , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Proteínas de Ligação a Retinoblastoma/metabolismo
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