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Nature Communications Apr 2024Lactation insufficiency affects many women worldwide. During lactation, a large portion of mammary gland alveolar cells become polyploid, but how these cells balance the...
Lactation insufficiency affects many women worldwide. During lactation, a large portion of mammary gland alveolar cells become polyploid, but how these cells balance the hyperproliferation occurring during normal alveologenesis with terminal differentiation required for lactation is unknown. Here, we show that DNA damage accumulates due to replication stress during pregnancy, activating the DNA damage response. Modulation of DNA damage levels in vivo by intraductal injections of nucleosides or DNA damaging agents reveals that the degree of DNA damage accumulated during pregnancy governs endoreplication and milk production. We identify a mechanism involving early mitotic arrest through CDK1 inactivation, resulting in a heterogeneous alveolar population with regards to ploidy and nuclei number. The inactivation of CDK1 is mediated by the DNA damage response kinase WEE1 with homozygous loss of Wee1 resulting in decreased endoreplication, alveologenesis and milk production. Thus, we propose that the DNA damage response to replication stress couples proliferation and endoreplication during mammary gland alveologenesis. Our study sheds light on mechanisms governing lactogenesis and identifies non-hormonal means for increasing milk production.
Topics: Pregnancy; Animals; Female; Humans; Alveolar Epithelial Cells; Mammary Glands, Human; Endoreduplication; Mammary Glands, Animal; Lactation; Milk
PubMed: 38627401
DOI: 10.1038/s41467-024-47668-9 -
Nature Genetics Apr 2024Coffea arabica, an allotetraploid hybrid of Coffea eugenioides and Coffea canephora, is the source of approximately 60% of coffee products worldwide, and its cultivated...
Coffea arabica, an allotetraploid hybrid of Coffea eugenioides and Coffea canephora, is the source of approximately 60% of coffee products worldwide, and its cultivated accessions have undergone several population bottlenecks. We present chromosome-level assemblies of a di-haploid C. arabica accession and modern representatives of its diploid progenitors, C. eugenioides and C. canephora. The three species exhibit largely conserved genome structures between diploid parents and descendant subgenomes, with no obvious global subgenome dominance. We find evidence for a founding polyploidy event 350,000-610,000 years ago, followed by several pre-domestication bottlenecks, resulting in narrow genetic variation. A split between wild accessions and cultivar progenitors occurred ~30.5 thousand years ago, followed by a period of migration between the two populations. Analysis of modern varieties, including lines historically introgressed with C. canephora, highlights their breeding histories and loci that may contribute to pathogen resistance, laying the groundwork for future genomics-based breeding of C. arabica.
Topics: Coffea; Coffee; Genome, Plant; Metagenomics; Plant Breeding
PubMed: 38622339
DOI: 10.1038/s41588-024-01695-w -
Cell Reports Methods May 2024Precision medicine's emphasis on individual genetic variants highlights the importance of haplotype-resolved assembly, a computational challenge in bioinformatics given...
Precision medicine's emphasis on individual genetic variants highlights the importance of haplotype-resolved assembly, a computational challenge in bioinformatics given its combinatorial nature. While classical algorithms have made strides in addressing this issue, the potential of quantum computing remains largely untapped. Here, we present the vehicle routing problem (VRP) assembler: an approach that transforms this task into a vehicle routing problem, an optimization formulation solvable on a quantum computer. We demonstrate its potential and feasibility through a proof of concept on short synthetic diploid and triploid genomes using a D-Wave quantum annealer. To tackle larger-scale assembly problems, we integrate the VRP assembler with Google's OR-Tools, achieving a haplotype-resolved local assembly across the human major histocompatibility complex (MHC) region. Our results show encouraging performance compared to Hifiasm with phasing accuracy approaching the theoretical limit, underscoring the promising future of quantum computing in bioinformatics.
Topics: Humans; Haplotypes; Diploidy; Polyploidy; Computational Biology; Algorithms; Quantum Theory; Genome, Human; Major Histocompatibility Complex
PubMed: 38614089
DOI: 10.1016/j.crmeth.2024.100754 -
Plants (Basel, Switzerland) Mar 2024Acyl carrier proteins (ACPs) have been reported to play a crucial role in responding to biotic and abiotic stresses, regulating growth and development. However, the...
Acyl carrier proteins (ACPs) have been reported to play a crucial role in responding to biotic and abiotic stresses, regulating growth and development. However, the biological function of the gene family in the genus has been limited until now. In this study, we conducted a comprehensive analysis and identified a total of 120 genes across six species in the genus. Among these, there were 27, 26, and 30 genes in the allotetraploid , , and , respectively, and 14, 13, and 10 genes in the diploid , , and , respectively. These genes were further classified into six subclades, each containing conserved motifs and domains. Interestingly, the majority of genes exhibited high conservation among the six species, suggesting that the genome evolution and polyploidization processes had relatively minor effects on the gene family. The duplication modes of the six species were diverse, and the expansion of most in occurred primarily through dispersed duplication (DSD) events. Furthermore, most of the genes were under purifying selection during the process of evolution. Subcellular localization experiments demonstrated that genes in species are localized in chloroplasts and mitochondria. -acting element analysis revealed that most of the genes were associated with various abiotic stresses. Additionally, RNA-seq data revealed differential expression levels of genes across various tissues in , with particularly high expression in seeds and buds. qRT-PCR analysis further indicated that genes play a significant role in salt stress tolerance. These findings provide a comprehensive understanding of genes in plants and will facilitate further functional analysis of these genes.
PubMed: 38611479
DOI: 10.3390/plants13070950 -
Plants (Basel, Switzerland) Mar 2024We performed next-generation sequencing of the 18S rDNA-ITS1-5.8S rDNA region along with traditional Sanger sequencing of L, K, F, and ITS1-5.8S rDNA-ITS2 to clarify the...
We performed next-generation sequencing of the 18S rDNA-ITS1-5.8S rDNA region along with traditional Sanger sequencing of L, K, F, and ITS1-5.8S rDNA-ITS2 to clarify the hybridization pattern in the subtribe Alopecurinae and in the genus in particular. Our data support the hybrid origin of × from hybridization between (sect. ) and (sect. ). Moreover, in the rDNA of hybrid × , only -like ribotypes from tetraploid participated. Surprisingly, we found the traces of introgression of -like ribotypes not only in hybrid × ( × ) but in s. str. as well. A high-polyploid group from the section , . aggr. has undoubted hybrid origin: e. g., has rDNA from the sect. . , with its allies, is clearly distinct from other members of the sect. (especially by maternal line) and thus we can re-establish a previous opinion about the separate group to which belongs. Species from the section (presumably Alpine grasses from Ancient Mediterranean region) probably hybridized with the group. Even (sect. ) that could be referred to the separate genus has ribotypes common with the species of the section (, ) in one of the accessions. Additionally, we found that the possible polyphyletic origin of the genus . is very close to according to NGS data, while is more or less distinct from other studied species of the genus .
PubMed: 38611448
DOI: 10.3390/plants13070919 -
Frontiers in Oncology 2024Breast cancer is the most prevalent malignancy among women worldwide. Despite significant advances in treatment, it remains one of the leading causes of female... (Review)
Review
Breast cancer is the most prevalent malignancy among women worldwide. Despite significant advances in treatment, it remains one of the leading causes of female mortality. The inability to effectively treat advanced and/or treatment-resistant breast cancer demonstrates the need to develop novel treatment strategies and targeted therapies. Centrosomes and their associated proteins have been shown to play key roles in the pathogenesis of breast cancer and thus represent promising targets for drug and biomarker development. Centrosomes are fundamental cellular structures in the mammalian cell that are responsible for error-free execution of cell division. Centrosome amplification and aberrant expression of its associated proteins such as Polo-like kinases (PLKs), Aurora kinases (AURKs) and Cyclin-dependent kinases (CDKs) have been observed in various cancers, including breast cancer. These aberrations in breast cancer are thought to cause improper chromosomal segregation during mitosis, leading to chromosomal instability and uncontrolled cell division, allowing cancer cells to acquire new genetic changes that result in evasion of cell death and the promotion of tumor formation. Various chemical compounds developed against PLKs and AURKs have shown meaningful antitumorigenic effects in breast cancer cells and . The mechanism of action of these inhibitors is likely related to exacerbation of numerical genomic instability, such as aneuploidy or polyploidy. Furthermore, growing evidence demonstrates enhanced antitumorigenic effects when inhibitors specific to centrosome-associated proteins are used in combination with either radiation or chemotherapy drugs in breast cancer. This review focuses on the current knowledge regarding the roles of centrosome and centrosome-associated proteins in breast cancer pathogenesis and their utility as novel targets for breast cancer treatment.
PubMed: 38606093
DOI: 10.3389/fonc.2024.1370565 -
Comparative Cytogenetics 2024Polyploidy is a condition in which a cell has multiple diploid sets of chromosomes. Two forms of polyploidy are known. One of them, generative polyploidy, is...
Polyploidy is a condition in which a cell has multiple diploid sets of chromosomes. Two forms of polyploidy are known. One of them, generative polyploidy, is characteristic of all cells of the organism, while the other form develops only in some somatic tissues at certain stages of postnatal ontogenesis. Whole genome duplication has played a particularly important role in the evolution of plants and animals, while the role of cellular (somatic) polyploidy in organisms remains largely unclear. In this work we investigated the contribution of cellular polyploidy to the normal and the reparative liver growth of (Berkenhout, 1769) and Linnaeus, 1758. It is shown that polyploidy makes a significant contribution to the increase of the liver mass both in the course of normal postnatal development and during pathological process.
PubMed: 38601956
DOI: 10.3897/compcytogen.18.121459 -
Frontiers in Plant Science 2024Under changing climatic scenarios, grassland conservation and development have become imperative to impart functional sustainability to their ecosystem services. These... (Review)
Review
Under changing climatic scenarios, grassland conservation and development have become imperative to impart functional sustainability to their ecosystem services. These goals could be effectively and efficiently achieved with targeted genetic improvement of native grass species. To the best of our literature search, very scant research findings are available pertaining to gene editing of non-cultivated grass species (switch grass, wild sugarcane, Prairie cordgrass, Bermuda grass, Chinese silver grass, etc.) prevalent in natural and semi-natural grasslands. Thus, to explore this novel research aspect, this study purposes that gene editing techniques employed for improvement of cultivated grasses especially sugarcane might be used for non-cultivated grasses as well. Our hypothesis behind suggesting sugarcane as a model crop for genetic improvement of non-cultivated grasses is the intricacy of gene editing owing to polyploidy and aneuploidy compared to other cultivated grasses (rice, wheat, barley, maize, etc.). Another reason is that genome editing protocols in sugarcane ( = 10-13) have been developed and optimized, taking into consideration the high level of genetic redundancy. Thus, as per our knowledge, this review is the first study that objectively evaluates the concept and functioning of the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 technique in sugarcane regarding high versatility, target specificity, efficiency, design simplicity, and multiplexing capacity in order to explore novel research perspectives for gene editing of non-cultivated grasses against biotic and abiotic stresses. Additionally, pronounced challenges confronting sugarcane gene editing have resulted in the development of different variants (Cas9, Cas12a, Cas12b, and SpRY) of the CRISPR tool, whose technicalities have also been critically assessed. Moreover, different limitations of this technique that could emerge during gene editing of non-cultivated grass species have also been highlighted.
PubMed: 38601306
DOI: 10.3389/fpls.2024.1369416 -
JCEM Case Reports Apr 202448 XXYY syndrome is a rare polyploidy often compared with Klinefelter syndrome because of shared features such as tall stature, neurocognitive diseases, hypogonadism,...
48 XXYY syndrome is a rare polyploidy often compared with Klinefelter syndrome because of shared features such as tall stature, neurocognitive diseases, hypogonadism, and cardiac malformations. This population is believed to be predisposed to type 2 diabetes because of the presence of hypogonadism and central adiposity. We present a patient with XXYY syndrome who had an atypical and difficult-to-manage diabetes presentation. The patient was nonadherent to medication regimen with poorly controlled diabetes and hemoglobin A1c ranging from 12% to 14% (16.5-19.6 mmol/L). He lacked history of diabetes ketoacidosis, raising the question of maturity-onset diabetes of the young. Workup was negative for glutamic acid decarboxylase-65 and pancreatic islet cell antibody testing. Genetic testing for 5-gene panel for maturity-onset diabetes of the young was also negative. Distinct parts of his presentation make an accurate diabetes diagnosis very challenging. Clinicians should be aware of diabetes associations in patients with XXYY syndrome for optimization of care.
PubMed: 38601067
DOI: 10.1210/jcemcr/luae014 -
Nature Communications Apr 2024Island systems provide important contexts for studying processes underlying lineage migration, species diversification, and organismal extinction. The Hawaiian endemic...
Island systems provide important contexts for studying processes underlying lineage migration, species diversification, and organismal extinction. The Hawaiian endemic mints (Lamiaceae family) are the second largest plant radiation on the isolated Hawaiian Islands. We generated a chromosome-scale reference genome for one Hawaiian species, Stenogyne calaminthoides, and resequenced 45 relatives, representing 34 species, to uncover the continental origins of this group and their subsequent diversification. We further resequenced 109 individuals of two Stenogyne species, and their purported hybrids, found high on the Mauna Kea volcano on the island of Hawai'i. The three distinct Hawaiian genera, Haplostachys, Phyllostegia, and Stenogyne, are nested inside a fourth genus, Stachys. We uncovered four independent polyploidy events within Stachys, including one allopolyploidy event underlying the Hawaiian mints and their direct western North American ancestors. While the Hawaiian taxa may have principally diversified by parapatry and drift in small and fragmented populations, localized admixture may have played an important role early in lineage diversification. Our genomic analyses provide a view into how organisms may have radiated on isolated island chains, settings that provided one of the principal natural laboratories for Darwin's thinking about the evolutionary process.
Topics: Humans; Mentha; Phylogeny; Hawaii; Biological Evolution
PubMed: 38600100
DOI: 10.1038/s41467-024-47247-y