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Despite their biological importance, the role of stem cells in human aging remains to be elucidated. In this work, we applied a machine learning methodology to GTEx transcriptome data and assigned stemness scores to 17,382 healthy samples from 30 human tissues aged between 20 and 79 years. We found that ~60% of the studied tissues exhibit a significant negative correlation between the subject's age and stemness score. The only significant exception was the uterus, where we observed an increased stemness with age. Moreover, we observed that stemness is positively correlated with cell proliferation and negatively correlated with cellular senescence. Finally, we also observed a trend that hematopoietic stem cells derived from older individuals might have higher stemness scores. In conclusion, we assigned stemness scores to human samples and show evidence of a pan-tissue loss of stemness during human aging, which adds weight to the idea that stem cell deterioration may contribute to human aging.

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INTRODUCTION: Understanding changes in cell identity in cancer and ageing is of great importance. In this work, we analyzed how gene expression changes in human tissues are associated with tissue specificity during cancer and ageing using transcriptome data from TCGA and GTEx. RESULTS: We found significant downregulation of tissue-specific genes during ageing in 40% of the tissues analyzed, which suggests loss of tissue identity with age. For most cancer types, we have noted a consistent pattern of downregulation in genes that are specific to the tissue from which the tumor originated. Moreover, we observed in cancer an activation of genes not usually expressed in the tissue of origin as well as an upregulation of genes specific to other tissues. These patterns in cancer were associated with patient survival. The age of the patient, however, did not influence these patterns. CONCLUSION: We identified loss of cellular identity in 40% of the tissues analysed during human ageing, and a clear pattern in cancer, where during tumorigenesis cells express genes specific to other organs while suppressing the expression of genes from their original tissue. The loss of cellular identity observed in cancer is associated with prognosis and is not influenced by age, suggesting that it is a crucial stage in carcinogenesis.

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Cetaceans are the longest-living species of mammals and the largest in the history of the planet. They have developed mechanisms against diseases such cancer, although the underlying molecular bases of these remain unknown. The goal of this study was to investigate the role of natural selection in the evolution of 1077 tumour suppressor genes (TSGs) in cetaceans. We used a comparative genomic approach to analyse two sources of molecular variation in the form of dN/dS rates and gene copy number variation. We found a signal of positive selection in the ancestor of cetaceans within the CXCR2 gene, an important regulator of DNA damage, tumour dissemination and immune system. Further, in the ancestor of baleen whales, we found six genes exhibiting positive selection relating to diseases such as breast carcinoma, lung neoplasm (ADAMTS8) and leukaemia (ANXA1). The TSGs turnover rate (gene gain and loss) was almost 2.4-fold higher in cetaceans when compared with other mammals, and notably even faster in baleen whales. The molecular variants in TSGs found in baleen whales, combined with the faster gene turnover rate, could have favoured the evolution of their particular traits of anti-cancer resistance, gigantism and longevity. Additionally, we report 71 genes with duplications, of which 11 genes are linked to longevity (e.g. NOTCH3 and SIK1) and are important regulators of senescence, cell proliferation and metabolism. Overall, these results provide evolutionary evidence that natural selection in TSGs could act on species with large body sizes and extended lifespan, providing novel insights into the genetic basis of disease resistance.

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Cancer is a disease of multicellularity; it originates when cells become dysregulated due to mutations and grow out of control, invading other tissues and provoking discomfort, disability, and eventually death. Human life expectancy has greatly increased in the last two centuries, and consequently so has the incidence of cancer. However, how cancer patterns in humans compare to those of other species remains largely unknown. In this review, we search for clues about cancer and its evolutionary underpinnings across the tree of life. We discuss data from a wide range of species, drawing comparisons with humans when adequate, and interpret our findings from an evolutionary perspective. We conclude that certain cancers are uniquely common in humans, such as lung, prostate, and testicular cancer; while others are common across many species. Lymphomas appear in almost every animal analysed, including in young animals, which may be related to pathogens imposing selection on the immune system. Cancers unique to humans may be due to our modern environment or may be evolutionary accidents: random events in the evolution of our species. Finally, we find that cancer-resistant animals such as whales and mole-rats have evolved cellular mechanisms that help them avoid neoplasia, and we argue that there are multiple natural routes to cancer resistance.

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Objective To describe axillary approach for axillary nerve transfer with radial nerve branch in brachial plexus lesions. Methods Six patients aged 24 to 54 (mean 30) years with traumatic superior trunk brachial plexus injury underwent axillary approach between October 2011 and April 2012. On physical examination prior to surgery, they could not perform shoulder abduction, external rotation, or elbow flexion. Surgical approach was made through axillary pathway without any muscular section. The transfer was done with the radial branch to the medial head of triceps. In addition to transfer to axillary nerve, each patient had spinal accessory nerve transferred to suprascapular nerve and ulnar nerve fascicle transferred to musculocutaneous nerve. Conclusion The axillary approach allows easy access to axillary nerve and, therefore, is a feasible pathway to transferences involving this nerve.(AU)

Objetivo Apresentar via axilar por transferência de nervo axilar com ramo de nervo radial em lesões do plexus braquial. Métodos Seis pacientes com idade entre 24 e 54 anos (média de 30) com lesão braquial traumática do plexus no tronco superior submetidos a via axilar entre outubro de 2011 e abril de 2012. Em exame físico pré-cirúrgico, não foram capazes de executar abdução do ombro, rotação externa, ou flexão do cotovelo. Abordagem cirúrgica foi realizada por passagem axilar sem qualquer seção muscular. A transferência ocorreu como ramo radial do tríceps medial da cabeça. Somada à transferência ao nervo axilar, cada paciente teve nervo acessório espinhal transferido para o nervo supraescapular, e o fascículo do nervo ulnar transferido para o nervo musculocutâneo. Conclusão A via axilar facilita acesso ao nervo axilar e, por isso, é um caminho factível para transferências envolvendo este nervo.(AU)

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Evaluate carpal tunnel release in leprosy. Methods: The authors operated upon 60 patientswith median nerve involvement by leprosy between February 2008 and February 2012. The outpatientswere under local anesthesia submitted to carpal tunnel release. Results: All the patients showed postoperativeimprovement in pain and sensation. Conclusion: The surgical approach is a cost effectivenessprocedure adequate to developing countries...

Avaliar a descompressão do túnel do carpo na lepra. Métodos: Os autores operaram 60pacientes ambulatoriais com envolvimento do nervo mediano pela lepra, entre fevereiro de 2008 efevereiro de 2012. Os pacientes foram submetidos a anestesia local e cirurgia de túnel do carpo.Resultados: Todos os pacientes experimentaram melhora no pós-operatório da sensibilidade e da dor.Conclusão: A abordagem cirúrgica é um procedimento de custo-efetividade satisfatório, adequadapara países em desenvolvimento...

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