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1.
Folia Primatol (Basel) ; 91(6): 558-574, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32663822

RESUMO

Madagascar's dramatic climatic fluctuations mean most lemurs adjust behaviors seasonally as resource availability fluctuates. Many lemurs will adopt one of two strategies, a resource maximizer or an area minimizer, when adjusting to seasonal shifts in resource availability. However, it is unknown if and how aye-aye (Daubentonia madagascariensis) ranging behavior is influenced by seasonality. We explored whether habitat use changed seasonally. We followed two aye-ayes, an adult male and an adult female, in the undisturbed forest of Torotorofotsy, Madagascar, from April 2012 to December 2017. We used instantaneous focal-animal sampling to collect behavioral data every 5 min and GPS locations every 20 min. We used the minimum convex polygon (MCP) to determine overall home range, and the Brownian bridge movement model (BBMM) to estimate overall and seasonal home range of the female aye-aye from November 2014 to October 2017. We used Wilcoxon signed-rank tests to determine whether there were significant differences in home range sizes between seasons across years and to examine whether there were seasonal differences in height of invertebrate foraging, generalized linear models to assess seasonal differences in travel rates and nesting locations, and χ2 tests to determine whether there were differences in forest strata use when foraging on invertebrates. The male's MCP home range was 2,586 ha, and the female's MCP home range was 765 ha. The seasonal BBMM for the female varied between 443.6 and 1,010.0 ha, though infant rearing appears to have influenced these values. There were no significant differences in seasonal home range, travel rates, nesting locations, or height of invertebrate feeding. However, canopy level invertebrate foraging occurred more often than understory or ground levels. It appears aye-ayes in this undisturbed forest were not influenced by seasonal shifts and had larger home ranges than any previously reported. These findings may indicate that aye-ayes in an undisturbed forest are resource maximizers, closely linked to invertebrate assemblages.


Assuntos
Ecossistema , Comportamento de Retorno ao Território Vital , Strepsirhini , Animais , Comportamento Apetitivo , Comportamento Animal , Feminino , Sistemas de Informação Geográfica , Invertebrados , Locomoção , Madagáscar , Masculino , Comportamento de Nidação , Estações do Ano
2.
Nat Commun ; 15(1): 8218, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300140

RESUMO

In the United States, Black individuals have higher rates of cancer mortality than any other racial group. Here, we examine chromosome copy number changes in cancers from more than 1800 self-reported Black patients. We find that tumors from self-reported Black patients are significantly more likely to exhibit whole-genome duplications (WGDs), a genomic event that enhances metastasis and aggressive disease, compared to tumors from self-reported white patients. This increase in WGD frequency is observed across multiple cancer types, including breast, endometrial, and lung cancer, and is associated with shorter patient survival. We further demonstrate that combustion byproducts are capable of inducing WGDs in cell culture, and cancers from self-reported Black patients exhibit mutational signatures consistent with exposure to these carcinogens. In total, these findings identify a type of genomic alteration that is associated with environmental exposures and that may influence racial disparities in cancer outcomes.


Assuntos
Negro ou Afro-Americano , Genoma Humano , Neoplasias , Humanos , Neoplasias/genética , Neoplasias/etnologia , Neoplasias/mortalidade , Feminino , Negro ou Afro-Americano/genética , Masculino , Variações do Número de Cópias de DNA , Estados Unidos/epidemiologia , População Branca/genética , Mutação , Pessoa de Meia-Idade
3.
bioRxiv ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36711674

RESUMO

Most cancers exhibit aneuploidy, but its functional significance in tumor development is controversial. Here, we describe ReDACT (Restoring Disomy in Aneuploid cells using CRISPR Targeting), a set of chromosome engineering tools that allow us to eliminate specific aneuploidies from cancer genomes. Using ReDACT, we created a panel of isogenic cells that have or lack common aneuploidies, and we demonstrate that trisomy of chromosome 1q is required for malignant growth in cancers harboring this alteration. Mechanistically, gaining chromosome 1q increases the expression of MDM4 and suppresses TP53 signaling, and we show that TP53 mutations are mutually-exclusive with 1q aneuploidy in human cancers. Thus, specific aneuploidies play essential roles in tumorigenesis, raising the possibility that targeting these "aneuploidy addictions" could represent a novel approach for cancer treatment.

4.
Science ; 381(6660): eadg4521, 2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-37410869

RESUMO

Most cancers exhibit aneuploidy, but its functional significance in tumor development is controversial. Here, we describe ReDACT (Restoring Disomy in Aneuploid cells using CRISPR Targeting), a set of chromosome engineering tools that allow us to eliminate specific aneuploidies from cancer genomes. Using ReDACT, we created a panel of isogenic cells that have or lack common aneuploidies, and we demonstrate that trisomy of chromosome 1q is required for malignant growth in cancers harboring this alteration. Mechanistically, gaining chromosome 1q increases the expression of MDM4 and suppresses p53 signaling, and we show that TP53 mutations are mutually exclusive with 1q aneuploidy in human cancers. Thus, tumor cells can be dependent on specific aneuploidies, raising the possibility that these "aneuploidy addictions" could be targeted as a therapeutic strategy.


Assuntos
Proteínas de Ciclo Celular , Edição de Genes , Neoplasias , Oncogenes , Trissomia , Proteína Supressora de Tumor p53 , Humanos , Proteínas de Ciclo Celular/genética , Mutação , Neoplasias/genética , Neoplasias/terapia , Proteínas Proto-Oncogênicas/metabolismo , Edição de Genes/métodos , Proteína Supressora de Tumor p53/genética , Carcinogênese/genética
5.
Genes (Basel) ; 13(6)2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35741788

RESUMO

The most comprehensive phylogenomic reconstruction to date was generated on all nominal taxa within the lemur genus Propithecus. Over 200 wild-caught individuals were included in this study to evaluate the intra and interspecific relationships across this genus. Ultraconserved Elements (UCEs) resulted in well-supported phylogenomic trees. Complete mitochondrial genomes (CMGs) largely agreed with the UCEs, except where a mitochondrial introgression was detected between one clade of the diademed sifaka (Propithecus diadema) and the Milne-Edwards sifaka (P. edwardsi). Additionally, the crowned (P. coronatus) and Von der Decken's (P. deckeni) sifakas belonged to a single admixed lineage from UCEs. Further sampling across these two species is warranted to determine if our sampling represents a hybrid zone. P. diadema recovered two well-supported clades, which were dated and estimated as being ancient as the split between the Perrier's (P. perrierii) and silky (P. candidus) sifakas. The reconstructed demographic history of the two clades also varied over time. We then modeled the modern ecological niches of the two cryptic P. diadema clades and found that they were significantly diverged (p < 0.01). These ecological differences result in a very limited zone of geographic overlap for the P. diadema clades (<60 km2). Niche models also revealed that the Onive River acts as a potential barrier to dispersal between P. diadema and P. edwardsi. Further taxonomic work is required on P. diadema to determine if its taxonomic status should be revised. This first genomic evaluation of the genus resolved the relationships between the taxa and the recovered cryptic diversity within one species.


Assuntos
Indriidae , Animais , Ecossistema , Humanos , Indriidae/classificação , Mitocôndrias , Filogenia , Ouriços-do-Mar
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