HDAC6 inhibitors sensitize resistant t(11;14) multiple myeloma cells to a combination of bortezomib and BH3 mimetics.

Not available.

Antileukemic potential of methylated indolequinone MAC681 through immunogenic necroptosis and PARP1 degradation.

Background: Despite advancements in chronic myeloid leukemia (CML) therapy with tyrosine kinase inhibitors (TKIs), resistance and intolerance remain significant challenges. Leukemia stem cells (LSCs) and TKI-resistant cells rely on altered mitochondrial metabolism and oxidative phosphorylation. Targeting rewired energy metabolism and inducing non-apoptotic cell death, along with the release of damage-associated molecular patterns (DAMPs), can enhance therapeutic strategies and immunogenic therapies against CML and prevent the emergence of TKI-resistant cells and LSC persistence.

ATP1A1/BCL2L1 predicts the response of myelomonocytic and monocytic acute myeloid leukemia to cardiac glycosides.

Myelomonocytic and monocytic acute myeloid leukemia (AML) subtypes are intrinsically resistant to venetoclax-based regimens. Identifying targetable vulnerabilities would limit resistance and relapse. We previously documented the synergism of venetoclax and cardiac glycoside (CG) combination in AML.

Selective sorting of ancestral introgression in maize and teosinte along an elevational cline.

While often deleterious, hybridization can also be a key source of genetic variation and pre-adapted haplotypes, enabling rapid evolution and niche expansion. Here we evaluate these opposing selection forces on introgressed ancestry between maize (Zea mays ssp. mays) and its wild teosinte relative, mexicana (Zea mays ssp.

Unraveling the Complex Hybrid Ancestry and Domestication History of Cultivated Strawberry.

Cultivated strawberry (Fragaria × ananassa) is one of our youngest domesticates, originating in early eighteenth-century Europe from spontaneous hybrids between wild allo-octoploid species (Fragaria chiloensis and Fragaria virginiana). The improvement of horticultural traits by 300 years of breeding has enabled the global expansion of strawberry production. Here, we describe the genomic history of strawberry domestication from the earliest hybrids to modern cultivars.

Male Linked Genomic Region Determines Sex in Dioecious Amaranthus palmeri.

Dioecy, the separation of reproductive organs on different individuals, has evolved repeatedly in different plant families. Several evolutionary paths to dioecy have been suggested, but the mechanisms behind sex determination is not well understood. The diploid dioecious Amaranthus palmeri represents a well-suited model system to study sex determination in plants.

Genome Synteny Has Been Conserved Among the Octoploid Progenitors of Cultivated Strawberry Over Millions of Years of Evolution.

Allo-octoploid cultivated strawberry ( × ) originated through a combination of polyploid and homoploid hybridization, domestication of an interspecific hybrid lineage, and continued admixture of wild species over the last 300 years. While genes appear to flow freely between the octoploid progenitors, the genome structures and diversity of the octoploid species remain poorly understood. The complexity and absence of an octoploid genome frustrated early efforts to study chromosome evolution, resolve subgenomic structure, and develop a single coherent linkage group nomenclature.

Genomics of Long- and Short-Term Adaptation in Maize and Teosintes.

Maize is an excellent model for the study of plant adaptation. Indeed, post domestication maize quickly adapted to a host of new environments across the globe. And work over the last decade has begun to highlight the role of the wild relatives of maize-the teosintes Zea mays ssp.

Parallel altitudinal clines reveal trends in adaptive evolution of genome size in Zea mays.

While the vast majority of genome size variation in plants is due to differences in repetitive sequence, we know little about how selection acts on repeat content in natural populations. Here we investigate parallel changes in intraspecific genome size and repeat content of domesticated maize (Zea mays) landraces and their wild relative teosinte across altitudinal gradients in Mesoamerica and South America. We combine genotyping, low coverage whole-genome sequence data, and flow cytometry to test for evidence of selection on genome size and individual repeat abundance.

Dysregulation of expression correlates with rare-allele burden and fitness loss in maize.

Here we report a multi-tissue gene expression resource that represents the genotypic and phenotypic diversity of modern inbred maize, and includes transcriptomes in an average of 255 lines in seven tissues. We mapped expression quantitative trait loci and characterized the contribution of rare genetic variants to extremes in gene expression. Some of the new mutations that arise in the maize genome can be deleterious; although selection acts to keep deleterious variants rare, their complete removal is impeded by genetic linkage to favourable loci and by finite population size.

Construction of the third-generation Zea mays haplotype map.

Background: Characterization of genetic variations in maize has been challenging, mainly due to deterioration of collinearity between individual genomes in the species. An international consortium of maize research groups combined resources to develop the maize haplotype version 3 (HapMap 3), built from whole-genome sequencing data from 1218 maize lines, covering predomestication and domesticated Zea mays varieties across the world.

Results: A new computational pipeline was set up to process more than 12 trillion bp of sequencing data, and a set of population genetics filters was applied to identify more than 83 million variant sites.

The interplay of demography and selection during maize domestication and expansion.

Background: The history of maize has been characterized by major demographic events, including population size changes associated with domestication and range expansion, and gene flow with wild relatives. The interplay between demographic history and selection has shaped diversity across maize populations and genomes.

Results: We investigate these processes using high-depth resequencing data from 31 maize landraces spanning the pre-Columbian distribution of maize, and four wild teosinte individuals (Zea mays ssp.

The potential role of genetic assimilation during maize domestication.

Domestication research has largely focused on identification of morphological and genetic differences between extant populations of crops and their wild relatives. Little attention has been paid to the potential effects of environment despite substantial known changes in climate from the time of domestication to modern day. In recent research, the exposure of teosinte (i.

Genomic abundance is not predictive of tandem repeat localization in grass genomes.

Highly repetitive regions have historically posed a challenge when investigating sequence variation and content. High-throughput sequencing has enabled researchers to use whole-genome shotgun sequencing to estimate the abundance of repetitive sequence, and these methodologies have been recently applied to centromeres. Previous research has investigated variation in centromere repeats across eukaryotes, positing that the highest abundance tandem repeat in a genome is often the centromeric repeat.