Temporal dynamics of woolly mammoth genome erosion prior to extinction.

A number of species have recently recovered from near-extinction. Although these species have avoided the immediate extinction threat, their long-term viability remains precarious due to the potential genetic consequences of population declines, which are poorly understood on a timescale beyond a few generations. Woolly mammoths (Mammuthus primigenius) became isolated on Wrangel Island around 10,000 years ago and persisted for over 200 generations before becoming extinct around 4,000 years ago. To study the evolutionary processes leading up to the mammoths' extinction, we analyzed 21 Siberian woolly mammoth genomes. Our results show that the population recovered quickly from a severe bottleneck and remained demographically stable during the ensuing six millennia. We find that mildly deleterious mutations gradually accumulated, whereas highly deleterious mutations were purged, suggesting ongoing inbreeding depression that lasted for hundreds of generations. The time-lag between demographic and genetic recovery has wide-ranging implications for conservation management of recently bottlenecked populations.

Effectiveness of inactivated COVID-19 vaccine CoronaVac in children aged less than 3 years old during Omicron wave in Hong Kong.

The COVID-19 pandemic has affected people of all ages worldwide. However, there is still no information on the vaccine effectiveness (VE) of inactivated COVID-19 vaccines in children aged less than 3 years old. This study highlighted that 2 doses of CoronaVac were effective in preventing COVID-19, with a VE of 83.1 %.

Neanderthal introgression in SCN9A impacts mechanical pain sensitivity.

The Nav1.7 voltage-gated sodium channel plays a key role in nociception. Three functional variants in the SCN9A gene (encoding M932L, V991L, and D1908G in Nav1.7), have recently been identified as stemming from Neanderthal introgression and to associate with pain symptomatology in UK BioBank data. In 1000 genomes data, these variants are absent in Europeans but common in Latin Americans. Analysing high-density genotype data from 7594 Latin Americans, we characterized Neanderthal introgression in SCN9A. We find that tracts of introgression occur on a Native American genomic background, have an average length of ~123 kb and overlap the M932L, V991L, and D1908G coding positions. Furthermore, we measured experimentally six pain thresholds in 1623 healthy Colombians. We found that Neanderthal ancestry in SCN9A is significantly associated with a lower mechanical pain threshold after sensitization with mustard oil and evidence of additivity of effects across Nav1.7 variants. Our findings support the reported association of Neanderthal Nav1.7 variants with clinical pain, define a specific sensory modality affected by archaic introgression in SCN9A and are consistent with independent effects of the Neanderthal variants on Nav1.7 function.

Caracterización sociodemográfica, clínica y ecográfica de la enfermedad de nódulos tiroideos y su relación con la malignidad en un centro de alta complejidad colombiano / Sociodemographic, clinical and ultrasound characterization of thyroid nodule pathology and its association with malignancy in a Colombian high-complexity center

Antecedentes y objetivo Los nódulos tiroideos se encuentran entre las dolencias más frecuentes, con un 10% de riesgo de malignidad. El objetivo es describir la frecuencia de las características demográficas, clínicas y ecográficas de la enfermedad de nódulos tiroideos en adultos y explorar la relación con la malignidad del tumor. Métodos Estudio transversal analítico, retrospectivo, en adultos con nódulos tiroideos y aspiración con aguja fina nodular realizada en pacientes adultos de un centro de referencia colombiano entre 2009-2019. Los datos se obtuvieron de la historia clínica y se estimaron medidas descriptivas de las variables demográficas, clínicas y ecográficas de los pacientes y se exploró su relación con la malignidad del tumor. Resultados Se incluyeron 445 pacientes y 515 nódulos. La mediana de edad fue de 55 años (RIQ 44-64), 86,8% mujeres, 54,8% tenía lesión única. El 80,2 y el 19,8% eran nódulos benignos y malignos, con una mediana de 15,7mm (RIQ 11-25) y 12,7mm (RIQ 8,5-18,3), respectivamente (p<0,001). El hipotiroidismo y el consumo de levotiroxina fueron mayores en quienes tenían nódulos malignos, (p<0,001). Las características ecográficas fueron diferentes estadísticamente entre los nódulos: en los malignos hubo mayor frecuencia de composición sólida, hipoecogenicidad y margen irregular, mientras que en los benignos se destacó la ausencia de foco ecogénico (p<0,001). Conclusión Las características ecográficas son fundamentales para definir el riesgo de malignidad de un nódulo tiroideo, por lo cual, considerar las más frecuentes puede ayudar en el abordaje más adecuado desde la atención primaria (AU)

Background and objective Thyroid nodules are among the most frequent conditions, with a 10% risk of malignancy. The objective is to describe the frequency of demographic, clinical, and ultrasonographic characteristics of thyroid nodule pathology in adults and to explore the relationship with tumor malignancy. Methods An analytical, retrospective cross-sectional study in adults with thyroid nodules and nodular fine-needle aspiration performed in adult patients from a Colombian reference center between 2009-2019. Data were obtained from the clinical history, descriptive measures of the patient's demographic, clinical, and ultrasound variables were estimated, and their relationship with the malignancy of the tumor was explored. Results A total of 445 patients and 515 nodules were included. The median age was 55 years (IQR 44-64), 86.8% of women, and 54.8% had a single lesion. Percentages of 80.2 and 19.8 were benign and malignant nodules, with a median of 15.7mm (IQR 11-25) and 12.7mm (IQR 8.5-18.3), respectively (p<0.001). Hypothyroidism and levothyroxine consumption were higher in those with malignant nodules (p<0.001). The echographic characteristics were statistically different between the nodules. In the malignant ones, there was a higher frequency of solid composition, hypoechogenicity, and irregular margins. In contrast, in the benign ones, the absence of echogenic focus stood out (p<0.001). Conclusion The ultrasound characteristics are essential to define the risk of malignancy of a thyroid nodule. Therefore, considering the most frequent ones can help in the most appropriate approach to primary care (AU)

[Sociodemographic, clinical and ultrasound characterization of thyroid nodule pathology and its association with malignancy in a Colombian high-complexity center]. / Caracterización sociodemográfica, clínica y ecográfica de la enfermedad de nódulos tiroideos y su relación con la malignidad en un centro de alta complejidad colombiano.

BACKGROUND AND OBJECTIVE: Thyroid nodules are among the most frequent conditions, with a 10% risk of malignancy. The objective is to describe the frequency of demographic, clinical, and ultrasonographic characteristics of thyroid nodule pathology in adults and to explore the relationship with tumor malignancy. METHODS: An analytical, retrospective cross-sectional study in adults with thyroid nodules and nodular fine-needle aspiration performed in adult patients from a Colombian reference center between 2009-2019. Data were obtained from the clinical history, descriptive measures of the patient's demographic, clinical, and ultrasound variables were estimated, and their relationship with the malignancy of the tumor was explored. RESULTS: A total of 445 patients and 515 nodules were included. The median age was 55 years (IQR 44-64), 86.8% of women, and 54.8% had a single lesion. Percentages of 80.2 and 19.8 were benign and malignant nodules, with a median of 15.7mm (IQR 11-25) and 12.7mm (IQR 8.5-18.3), respectively (p<0.001). Hypothyroidism and levothyroxine consumption were higher in those with malignant nodules (p<0.001). The echographic characteristics were statistically different between the nodules. In the malignant ones, there was a higher frequency of solid composition, hypoechogenicity, and irregular margins. In contrast, in the benign ones, the absence of echogenic focus stood out (p<0.001). CONCLUSION: The ultrasound characteristics are essential to define the risk of malignancy of a thyroid nodule. Therefore, considering the most frequent ones can help in the most appropriate approach to primary care.

Automatic landmarking identifies new loci associated with face morphology and implicates Neanderthal introgression in human nasal shape.

We report a genome-wide association study of facial features in >6000 Latin Americans based on automatic landmarking of 2D portraits and testing for association with inter-landmark distances. We detected significant associations (P-value <5 × 10-8) at 42 genome regions, nine of which have been previously reported. In follow-up analyses, 26 of the 33 novel regions replicate in East Asians, Europeans, or Africans, and one mouse homologous region influences craniofacial morphology in mice. The novel region in 1q32.3 shows introgression from Neanderthals and we find that the introgressed tract increases nasal height (consistent with the differentiation between Neanderthals and modern humans). Novel regions include candidate genes and genome regulatory elements previously implicated in craniofacial development, and show preferential transcription in cranial neural crest cells. The automated approach used here should simplify the collection of large study samples from across the world, facilitating a cosmopolitan characterization of the genetics of facial features.

Genomics of adaptive evolution in the woolly mammoth.

Ancient genomes provide a tool to investigate the genetic basis of adaptations in extinct organisms. However, the identification of species-specific fixed genetic variants requires the analysis of genomes from multiple individuals. Moreover, the long-term scale of adaptive evolution coupled with the short-term nature of traditional time series data has made it difficult to assess when different adaptations evolved. Here, we analyze 23 woolly mammoth genomes, including one of the oldest known specimens at 700,000 years old, to identify fixed derived non-synonymous mutations unique to the species and to obtain estimates of when these mutations evolved. We find that at the time of its origin, the woolly mammoth had already acquired a broad spectrum of positively selected genes, including ones associated with hair and skin development, fat storage and metabolism, and immune system function. Our results also suggest that these phenotypes continued to evolve during the last 700,000 years, but through positive selection on different sets of genes. Finally, we also identify additional genes that underwent comparatively recent positive selection, including multiple genes related to skeletal morphology and body size, as well as one gene that may have contributed to the small ear size in Late Quaternary woolly mammoths.

Evolutionary consequences of genomic deletions and insertions in the woolly mammoth genome.

Woolly mammoths had a set of adaptations that enabled them to thrive in the Arctic environment. Many mammoth-specific single nucleotide polymorphisms (SNPs) responsible for unique mammoth traits have been previously identified from ancient genomes. However, a multitude of other genetic variants likely contributed to woolly mammoth evolution. In this study, we sequenced two woolly mammoth genomes and combined these with previously sequenced mammoth and elephant genomes to conduct a survey of mammoth-specific deletions and indels. We find that deletions are highly enriched in non-coding regions, suggesting selection against structural variants that affect protein sequences. Nonetheless, at least 87 woolly mammoth genes contain deletions or indels that modify the coding sequence, including genes involved in skeletal morphology and hair growth. These results suggest that deletions and indels contributed to the unique phenotypic adaptations of the woolly mammoth, and were potentially critical to surviving in its natural environment.

Disentangling Signatures of Selection Before and After European Colonization in Latin Americans.

Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. Although classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations, we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ∼4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico, and Peru. Our approach replicates previous reports of selection in the human leukocyte antigen region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas.

La contaminación citológica de la aguja de punción en ecobroncoscopia / Cytologic Contamination of the Sampling Needle in Endobronchial Ultrasound

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[Translated article] Cytologic Contamination of the Sampling Needle in Endobronchial Ultrasound / La contaminación citológica de la aguja de punción en ecobroncoscopia

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