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1.
Sci Rep ; 13(1): 18345, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884544

RESUMO

High-throughput proteomic analysis of archaeological skeletal remains provides information about past fauna community compositions and species dispersals in time and space. Archaeological skeletal remains are a finite resource, however, and therefore it becomes relevant to optimize methods of skeletal proteome extraction. Ancient proteins in bone specimens can be highly degraded and consequently, extraction methods for well-preserved or modern bone might be unsuitable for the processing of highly degraded skeletal proteomes. In this study, we compared six proteomic extraction methods on Late Pleistocene remains with variable levels of proteome preservation. We tested the accuracy of species identification, protein sequence coverage, deamidation, and the number of post-translational modifications per method. We find striking differences in obtained proteome complexity and sequence coverage, highlighting that simple acid-insoluble proteome extraction methods perform better in highly degraded contexts. For well-preserved specimens, the approach using EDTA demineralization and protease-mix proteolysis yielded a higher number of identified peptides. The protocols presented here allowed protein extraction from ancient bone with a minimum number of working steps and equipment and yielded protein extracts within three working days. We expect further development along this route to benefit large-scale screening applications of relevance to archaeological and human evolution research.


Assuntos
Proteoma , Proteômica , Humanos , Proteoma/análise , Proteômica/métodos , Restos Mortais , Peptídeos , Sequência de Aminoácidos
2.
Phys Life Rev ; 38: 55-106, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34088608

RESUMO

Understanding how genotypes map onto phenotypes, fitness, and eventually organisms is arguably the next major missing piece in a fully predictive theory of evolution. We refer to this generally as the problem of the genotype-phenotype map. Though we are still far from achieving a complete picture of these relationships, our current understanding of simpler questions, such as the structure induced in the space of genotypes by sequences mapped to molecular structures, has revealed important facts that deeply affect the dynamical description of evolutionary processes. Empirical evidence supporting the fundamental relevance of features such as phenotypic bias is mounting as well, while the synthesis of conceptual and experimental progress leads to questioning current assumptions on the nature of evolutionary dynamics-cancer progression models or synthetic biology approaches being notable examples. This work delves with a critical and constructive attitude into our current knowledge of how genotypes map onto molecular phenotypes and organismal functions, and discusses theoretical and empirical avenues to broaden and improve this comprehension. As a final goal, this community should aim at deriving an updated picture of evolutionary processes soundly relying on the structural properties of genotype spaces, as revealed by modern techniques of molecular and functional analysis.


Assuntos
Genótipo , Fenótipo
3.
Hum Brain Mapp ; 35(9): 4440-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24596026

RESUMO

The subthalamic nucleus (STN) is an important node of the cortico-basal ganglia network and the main target of deep brain stimulation (DBS) in Parkinson's disease. Histological studies have revealed an inhomogeneous iron distribution within the STN, which has been related to putative subdivisions within this nucleus. Here, we investigate the iron distribution in more detail using quantitative susceptibility mapping (QSM), a novel magnetic resonance imaging (MRI) contrast mechanism. QSM allows for detailed assessment of iron content in both in vivo and postmortem tissue. Twelve human participants and 7 postmortem brain samples containing the STN were scanned using ultra-high field 7 Tesla (T) MRI. Iron concentrations were found to be higher in the medial-inferior tip of the STN. Using quantitative methods we show that the increase of iron concentration towards the medial-inferior tip is of a gradual rather than a discrete nature.


Assuntos
Ferro/metabolismo , Núcleo Subtalâmico/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/instrumentação , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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