We examined mitochondrial DNA (mtDNA) haplogroup and haplotype diversity in 188 individuals from three Chibchan (Kogi, Arsario, and Ijka) populations and one Arawak (Wayuú) group from northeast Colombia to determine the biological relationship between lower Central American and northern South American Chibchan speakers. mtDNA haplogroups were obtained for all individuals and mtDNA HVS-I sequence data were obtained for 110 samples. Resulting sequence data were compared to 16 other Caribbean, South, and Central American populations using diversity measures, neutrality test statistics, sudden and spatial mismatch models, intermatch distributions, phylogenetic networks, and a multidimensional scaling plot. Our results demonstrate the existence of a shared maternal genetic structure between Central American Chibchan, Mayan populations and northern South American Chibchan-speakers. Additionally, these results suggest an expansion of Chibchan-speakers into South America associated with a shift in subsistence strategies because of changing ecological conditions that occurred in the region between 10,000-14,000 years before present.

Degradation of proteins by the ubiquitin-proteasome system (UPS) is an essential biological process in the development of eukaryotic organisms. Dysregulation of this mechanism leads to numerous human neurodegenerative or neurodevelopmental disorders. Through a multi-center collaboration, we identified six de novo genomic deletions and four de novo point mutations involving PSMD12, encoding the non-ATPase subunit PSMD12 (aka RPN5) of the 19S regulator of 26S proteasome complex, in unrelated individuals with intellectual disability, congenital malformations, ophthalmologic anomalies, feeding difficulties, deafness, and subtle dysmorphic facial features. We observed reduced PSMD12 levels and an accumulation of ubiquitinated proteins without any impairment of proteasome catalytic activity. Our PSMD12 loss-of-function zebrafish CRISPR/Cas9 model exhibited microcephaly, decreased convolution of the renal tubules, and abnormal craniofacial morphology. Our data support the biological importance of PSMD12 as a scaffolding subunit in proteasome function during development and neurogenesis in particular; they enable the definition of a neurodevelopmental disorder due to PSMD12 variants, expanding the phenotypic spectrum of UPS-dependent disorders.

The Saccharomyces cerevisiae ynl294c⌬ (rim21⌬) mutant was identified in our lab owing to its moderate resistance to calcofluor, although it also displayed all of the phenotypic traits associated with its function as the putative sensor (Rim21p) of the RIM101 pathway. rim21⌬ also showed moderate hypersensitivity to sodium dodecyl sulfate, caffeine, and zymolyase, and the cell wall compensatory response in this mutant was very poor, as indicated by the almost complete absence of Slt2 phosphorylation and the modest increase in chitin synthesis after calcofluor treatment. However, the cell integrity pathway appeared functional after caffeine treatment or thermal stress. rim21⌬ and rim101⌬ mutant strains shared all of the cell-wall-associated phenotypes, which were reverted by the expression of Rim101-531p, the constitutively active form of this transcription factor. Therefore, the absence of a functional RIM101 pathway leads to cell wall defects. rim21⌬, as well as rim101⌬, was synthetic lethal with slt2⌬, a synthetic defect alleviated by osmotic stabilization of the media. The double mutants grown in osmotically stabilized media were extremely hypersensitive to zymolyase and showed thicker cell walls, with poorly defined mannoprotein layers. In contrast, rim21⌬ rlm1⌬ and rim101⌬ rlm1⌬ double mutants were fully viable. Taken together, these results show that the RIM101 pathway participates directly in cell wall assembly and that it acts in parallel with the protein kinase C pathway (PKC) in this process independently of the transcriptional effect of the compensatory response mediated by this route. In addition, these results provide new experimental evidence of the direct involvement of the PKC signal transduction pathway through the Sltp2 kinase in the construction of yeast cell walls.

Previous investigations of the population genetics of the scalloped hammerhead sharks (Sphyrna lewini) in the Eastern Tropical Pacific have lacked information about nursery areas. Such areas are key to promoting conservation initiatives that can protect young sharks from threats such as overfishing. Here, we investigated the genetic diversity, phylogeography, and connectivity of S. lewini found in 3 areas of Colombia's Pacific coast: around Malpelo Island and in 2 National Natural Parks on the Colombian Pacific mainland (Sanquianga and Ensenada de Utría). We analyzed mtDNA control region (CR) sequences and genotyped 15 microsatellite loci in 137 samples of adults and juveniles. The mtDNA analyses showed haplotypes shared between the Colombian Pacific individuals sampled in this investigation and other areas in the Eastern Tropical Pacific, the Indo-Pacific, and with sequences previously reported in Colombia (Buenaventura Port), as well as 4 unique haplotypes. Population assignment and paternity analyses detected 3 parent-offspring pairs between Malpelo and Sanquianga and 1 between Malpelo and Utría. These results indicate high genetic connectivity between Malpelo Island and the Colombian Pacific coast, suggesting that these 2 areas are nurseries for S. lewini. This is, to our knowledge, the first evidence of nursery areas identified for the scalloped hammerhead shark anywhere in the world. Additional conservation planning may be required to protect these nursery habitats of this endangered shark species.

The incidence of HC after haplo with post-HSCT Cy is high and is associated with morbidity, especially in high-risk patients such as those with a previous transplant history and with impaired immune reconstitution.

Clinically useful pre-transplant predictive factors of acute graft-versus-host-disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT) are lacking. We prospectively analyzed HSC graft content in CD34, NK, conventional T, regulatory T and invariant natural killer T (iNKT) cells in 117 adult patients before allo-SCT. Results were correlated with occurrence of aGVHD and relapse. In univariate analysis, iNKT cells were the only graft cell populations associated with occurrence of aGVHD. In multivariate analysis, CD4 iNKT/T cell frequency could predict grade II-IV aGVHD in bone marrow and peripheral blood stem cell (PBSC) grafts, while CD4 iNKT expansion capacity was predictive in PBSC grafts. Receiver operating characteristic analyses determined the CD4 iNKT expansion factor as the best predictive factor of aGVHD. Incidence of grade II-IV aGVHD was reduced in patients receiving a graft with an expansion factor above versus below 6.83 (9.7 vs 80%, P<0.0001), while relapse incidence at two years was similar (P=0.5).The test reached 94% sensitivity and 100% specificity in the subgroup of patients transplanted with human leukocyte antigen 10/10 PBSCs without active disease. Analysis of this CD4 iNKT expansion capacity test may represent the first diagnostic tool allowing selection of the best donor to avoid severe aGVHD with preserved graft-versus-leukemia effect after peripheral blood allo-SCT.

Introducción. Los restos óseos arcaicos son fuente privilegiada de información biológica y su caracterización genética permite confirmar o descartar filiaciones propuestas por otras aproximaciones científicas. La historia precolombina de los Andes orientales se divide en tres periodos principales: i) un poblamiento temprano por parte de grupos cazadores-recolectores; ii) un periodo intermedio (Herrera) de pueblos con agricultura incipiente, y iii) un periodo tardío de pueblos chibchas, agrícolas y alfareros (agroalfarero). Objetivo. Analizar el ADN mitocondrial de restos óseos del periodo Herrera. Materiales y métodos. Se analizaron 11 individuos pertenecientes al yacimiento arqueológico Madrid 2-41, con una edad aproximada de 2.000 años. Un fragmento (192 pb) del segmento hipervariable I fue amplificado y secuenciado, siguiendo criterios estrictos de autenticidad de ADN arcaico. Las secuencias se compararon con las existentes en bases de datos de Norteamérica y Europa usando herramientas bioinformáticas. Resultados. Todas las secuencias resultaron idénticas y fueron clasificadas como haplogrupo B. Esto puede relacionarse con el tipo de entierro ritual practicado en Madrid 2-41, es decir, probablemente los individuos analizados hagan parte de una familia jerárquicamente importante en la antigua sociedad Herrera. La búsqueda de secuencias homólogas en las bases de datos estadounidense y europea no arrojó coincidencias exactas, aunque existe el reporte de un individuo amazónico de ~4.000 años de antigüedad (Brasil) cuya secuencia coincide con la hallada en Madrid 2-41. Conclusión. Los individuos del yacimiento arqueológico Madrid 2-41 están estrechamente emparentados entre sí por línea materna y presentan una secuencia aparentemente ausente en poblaciones actuales.Palabras clave: ADN mitocondrial/análisis, polimorfismo de nucleótido simple, haplotipos, arqueología, población indígena, Colombia.

Ancient DNA was recovered from 17 individuals found in a rock shelter in the district of "La Purnia" (Santander, Colombia). This region is the homeland of pre-Columbian Guane, whom spread over the "Río Suarez" to the "Río de Oro", and were surrounded to the west by the Central Andes, south and east by foothills of Eastern Andes, and north by the "Chicamocha" river canyon. Guanes established in a region that straddles the Andes and the northern Amazon basin, possibly making it an unavoidable conduit for people moving to and from South America. We amplified mtDNA hypervariable region I (HVI) segments from ancient bone remains, and the resulting sequences were compared with both ancient and modern mitochondrial haplogroups from American and non-American populations. Samples showed a distribution of 35% for haplogroup A, 41% for haplogroup B and 24% for haplogroup D. Nine haplotypes were found in 17 samples, indicating an unusually high genetic diversity on a single site ancient population. Among them, three haplotypes have not been previously found in America, two are shared in Asia, and one is a private haplotype. Despite geographical barriers that eventually isolated them, an important influence of gene flow from neighboring pre-Columbian communities, mainly Muiscas, could explain the high genetic polymorphism of this community before the Spanish conquest, and argues against Guanes as being a genetic isolate.