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G3 (Bethesda, Md.) Jun 2024Elaeis guineensis and E. oleifera are the two species of oil palm. E. guineensis is the most widely cultivated commercial species, and introgression of desirable traits...
Elaeis guineensis and E. oleifera are the two species of oil palm. E. guineensis is the most widely cultivated commercial species, and introgression of desirable traits from E. oleifera is ongoing. We report an improved E. guineensis genome assembly with substantially increased continuity and completeness, as well as the first chromosome-scale E. oleifera genome assembly. Each assembly was obtained by integration of long-read sequencing, proximity ligation sequencing, optical mapping and genetic mapping. High interspecific genome conservation is observed between the two species. The study provides the most extensive gene annotation to date, including 46,697 E. guineensis and 38,658 E. oleifera gene predictions. Analyses of repetitive element families further resolve the DNA repeat architecture of both genomes. Comparative genomic analyses identified experimentally validated small structural variants between the oil palm species and resolved the mechanism of chromosomal fusions responsible for the evolutionary descending dysploidy from 18 to 16 chromosomes.
PubMed: 38918881
DOI: 10.1093/g3journal/jkae135 -
Parasites & Vectors Jun 2024The sand fly Nyssomyia neivai is one of the most abundant species in Southern Brazil. It is frequently found in areas that are foci of visceral leishmaniasis in the...
BACKGROUND
The sand fly Nyssomyia neivai is one of the most abundant species in Southern Brazil. It is frequently found in areas that are foci of visceral leishmaniasis in the state of Santa Catarina, caused by Leishmania infantum. In this region, the main vector of L. infantum, Lutzomyia longipalpis, has not been detected. In the absence of L. longipalpis, this study aimed to identify the sand fly fauna and diagnose any potential Leishmania spp. infection in sand flies and in dogs in a region of Southern Brazil that experienced a recent canine visceral leishmaniasis outbreak.
METHODS
This report includes a survey of the sand fly fauna at the Zoonosis Control Center of the Municipality of Tubarão (Santa Catarina, Brazil). Molecular tests were conducted to investigate Leishmania spp. natural infection in sand flies using polymerase chain reaction (PCR). In positive females, in addition to morphological identification, molecular analysis through DNA barcoding was performed to determine the sand fly species. Additionally, the dogs were tested for the presence of Leishmania spp. using a non-invasive technique for the collection of biological material, to be assessed by PCR.
RESULTS
A total of 3419 sand flies, belonging to five genera, were collected. Nyssomyia neivai was the most abundant species (85.8%), followed by Migonemyia migonei (13.3%), Pintomyia fischeri (0.8%), Evandromyia edwardsi (< 0.1%), and species of the genus Brumptomyia. (0.1%). Out of the 509 non-engorged females analyzed by PCR, two (0.4%) carried L. infantum DNA. The naturally infected females were identified as Ny. neivai, in both morphological and molecular analysis. In addition, two out of 47 conjunctival swabs from dogs tested positive for L. infantum, yielding an infection rate of 4.2%.
CONCLUSIONS
These results confirm the presence of Ny. neivai naturally infected with L. infantum in an area where dogs were also infected by the parasite, suggesting its potential role as a vector in Southern Brazil.
PubMed: 38918858
DOI: 10.1186/s13071-024-06336-z -
Biology Direct Jun 2024Prostate cancer (PCa) is the second leading cause of tumor-related mortality in men. Metastasis from advanced tumors is the primary cause of death among patients....
BACKGROUND
Prostate cancer (PCa) is the second leading cause of tumor-related mortality in men. Metastasis from advanced tumors is the primary cause of death among patients. Identifying novel and effective biomarkers is essential for understanding the mechanisms of metastasis in PCa patients and developing successful interventions.
METHODS
Using the GSE8511 and GSE27616 data sets, 21 metastasis-related genes were identified through the weighted gene co-expression network analysis (WGCNA) method. Subsequent functional analysis of these genes was conducted on the gene set cancer analysis (GSCA) website. Cluster analysis was utilized to explore the relationship between these genes, immune infiltration in PCa, and the efficacy of targeted drug IC50 scores. Machine learning algorithms were then employed to construct diagnostic and prognostic models, assessing their predictive accuracy. Additionally, multivariate COX regression analysis highlighted the significant role of POLD1 and examined its association with DNA methylation. Finally, molecular docking and immunohistochemistry experiments were carried out to assess the binding affinity of POLD1 to PCa drugs and its impact on PCa prognosis.
RESULTS
The study identified 21 metastasis-related genes using the WGCNA method, which were found to be associated with DNA damage, hormone AR activation, and inhibition of the RTK pathway. Cluster analysis confirmed a significant correlation between these genes and PCa metastasis, particularly in the context of immunotherapy and targeted therapy drugs. A diagnostic model combining multiple machine learning algorithms showed strong predictive capabilities for PCa diagnosis, while a transfer model using the LASSO algorithm also yielded promising results. POLD1 emerged as a key prognostic gene among the metastatic genes, showing associations with DNA methylation. Molecular docking experiments supported its high affinity with PCa-targeted drugs. Immunohistochemistry experiments further validated that increased POLD1 expression is linked to poor prognosis in PCa patients.
CONCLUSIONS
The developed diagnostic and metastasis models provide substantial value for patients with prostate cancer. The discovery of POLD1 as a novel biomarker related to prostate cancer metastasis offers a promising avenue for enhancing treatment of prostate cancer metastasis.
PubMed: 38918844
DOI: 10.1186/s13062-024-00494-x -
Cell & Bioscience Jun 2024Polyamines (PA) are polycations with pleiotropic functions in cellular physiology and pathology. In particular, PA have been involved in the regulation of cell... (Review)
Review
Polyamines (PA) are polycations with pleiotropic functions in cellular physiology and pathology. In particular, PA have been involved in the regulation of cell homeostasis and proliferation participating in the control of fundamental processes like DNA transcription, RNA translation, protein hypusination, autophagy and modulation of ion channels. Indeed, their dysregulation has been associated to inflammation, oxidative stress, neurodegeneration and cancer progression. Accordingly, PA intracellular levels, derived from the balance between uptake, biosynthesis, and catabolism, need to be tightly regulated. Among the mechanisms that fine-tune PA metabolic enzymes, emerging findings highlight the importance of noncoding RNAs (ncRNAs). Among the ncRNAs, microRNA, long noncoding RNA and circRNA are the most studied as regulators of gene expression and mRNA metabolism and their alteration have been frequently reported in pathological conditions, such as cancer progression and brain diseases. In this review, we will discuss the role of ncRNAs in the regulation of PA genes, with a particular emphasis on the changes of this modulation observed in health disorders.
PubMed: 38918813
DOI: 10.1186/s13578-024-01235-3 -
World Journal of Surgical Oncology Jun 2024Prior research exploring the correlation between the XRCC3 Thr241Met polymorphism and the susceptibility to pancreatic cancer has yielded conflicting outcomes. To date,...
BACKGROUND
Prior research exploring the correlation between the XRCC3 Thr241Met polymorphism and the susceptibility to pancreatic cancer has yielded conflicting outcomes. To date, there has been a notable absence of studies examining this polymorphism. The primary aim of the current investigation is to elucidate the potential role of the XRCC3 Thr241Met polymorphism as a risk factor in the development of pancreatic cancer.
METHODS
The comprehensive literature search was meticulously conducted across primary databases, including PubMed, Embase, and CNKI (China National Knowledge Infrastructure), spanning from the inception of each database through January 2024. To synthesize the data, a meta-analysis was performed using either a fixed or random-effects model, as appropriate, to calculate the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs).
RESULTS
The analysis revealed significant associations between the XRCC3 Thr241Met polymorphism and an increased risk of pancreatic cancer. This was evidenced through various genetic model comparisons: allele contrast (T vs. C: OR = 0.77, 95% CI = 0.70-0.86, P < 0.001), homozygote comparison (TT vs. CC: OR = 0.71, 95% CI = 0.58-0.88, P = 0.001), heterozygote comparison (TC vs. CC: OR = 0.67, 95% CI = 0.52-0.87, P = 0.003), and a dominant genetic model (TT/TC vs. CC: OR = 0.68, 95% CI = 0.57-0.81, P < 0.001). Additionally, subgroup analyses based on ethnicity disclosed that these associations were particularly pronounced in the Caucasian population, with all genetic models showing significance (P < 0.05).
CONCLUSIONS
The XRCC3 Thr241Met polymorphism has been identified as contributing to a reduced risk of pancreatic cancer in the Caucasian population. This finding underscores the need for further research to validate and expand upon our conclusions, emphasizing the urgency for continued investigations in this domain.
PubMed: 38918791
DOI: 10.1186/s12957-024-03450-1 -
BMC Bioinformatics Jun 2024Promoters are essential elements of DNA sequence, usually located in the immediate region of the gene transcription start sites, and play a critical role in the...
Promoters are essential elements of DNA sequence, usually located in the immediate region of the gene transcription start sites, and play a critical role in the regulation of gene transcription. Its importance in molecular biology and genetics has attracted the research interest of researchers, and it has become a consensus to seek a computational method to efficiently identify promoters. Still, existing methods suffer from imbalanced recognition capabilities for positive and negative samples, and their recognition effect can still be further improved. We conducted research on E. coli promoters and proposed a more advanced prediction model, iProL, based on the Longformer pre-trained model in the field of natural language processing. iProL does not rely on prior biological knowledge but simply uses promoter DNA sequences as plain text to identify promoters. It also combines one-dimensional convolutional neural networks and bidirectional long short-term memory to extract both local and global features. Experimental results show that iProL has a more balanced and superior performance than currently published methods. Additionally, we constructed a novel independent test set following the previous specification and compared iProL with three existing methods on this independent test set.
PubMed: 38918692
DOI: 10.1186/s12859-024-05849-9 -
Physiological regulation of neuronal Wnt activity is essential for TDP-43 localization and function.The EMBO Journal Jun 2024Nuclear exclusion of the RNA- and DNA-binding protein TDP-43 can induce neurodegeneration in different diseases. Diverse processes have been implicated to influence...
Nuclear exclusion of the RNA- and DNA-binding protein TDP-43 can induce neurodegeneration in different diseases. Diverse processes have been implicated to influence TDP-43 mislocalization, including disrupted nucleocytoplasmic transport (NCT); however, the physiological pathways that normally ensure TDP-43 nuclear localization are unclear. The six-transmembrane enzyme glycerophosphodiester phosphodiesterase 2 (GDE2 or GDPD5) cleaves the glycosylphosphatidylinositol (GPI) anchor that tethers some proteins to the membrane. Here we show that GDE2 maintains TDP-43 nuclear localization by regulating the dynamics of canonical Wnt signaling. Ablation of GDE2 causes aberrantly sustained Wnt activation in adult neurons, which is sufficient to cause NCT deficits, nuclear pore abnormalities, and TDP-43 nuclear exclusion. Disruption of GDE2 coincides with TDP-43 abnormalities in postmortem tissue from patients with amyotrophic lateral sclerosis (ALS). Further, GDE2 deficits are evident in human neural cell models of ALS, which display erroneous Wnt activation that, when inhibited, increases mRNA levels of genes regulated by TDP-43. Our study identifies GDE2 as a critical physiological regulator of Wnt signaling in adult neurons and highlights Wnt pathway activation as an unappreciated mechanism contributing to nucleocytoplasmic transport and TDP-43 abnormalities in disease.
PubMed: 38918634
DOI: 10.1038/s44318-024-00156-8 -
Scientific Reports Jun 2024The benefits of breastfeeding for the health and wellbeing of both infants and mothers are well documented, yet global breastfeeding rates are low. One factor associated...
The benefits of breastfeeding for the health and wellbeing of both infants and mothers are well documented, yet global breastfeeding rates are low. One factor associated with low breast feeding is maternal body mass index (BMI), which is used as a measure of obesity. The negative relationship between maternal obesity and breastfeeding is likely caused by a variety of social, psychological, and physiological factors. Maternal obesity may also have a direct biological association with breastfeeding through changes in maternal DNA methylation. Here, we investigate this potential biological association using data from a UK-based cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC). We find that pre-pregnancy body mass index (BMI) is associated with lower initiation to breastfeed and shorter breastfeeding duration. We conduct epigenome-wide association studies (EWAS) of pre-pregnancy BMI and breastfeeding outcomes, and run candidate-gene analysis of methylation sites associated with BMI identified via previous meta-EWAS. We find that DNA methylation at cg11453712, annotated to PHTP1, is associated with pre-pregnancy BMI. From our results, neither this association nor those at candidate-gene sites are likely to mediate the link between pre-pregnancy BMI and breastfeeding.
Topics: Humans; DNA Methylation; Breast Feeding; Body Mass Index; Female; Pregnancy; Adult; Longitudinal Studies; Genome-Wide Association Study; United Kingdom; Obesity; Epigenesis, Genetic
PubMed: 38918574
DOI: 10.1038/s41598-024-65605-0 -
Nature Reviews. Genetics Jun 2024DNA damage is a threat to genome integrity and can be a cause of many human diseases, owing to either changes in the chemical structure of DNA or conversion of the... (Review)
Review
DNA damage is a threat to genome integrity and can be a cause of many human diseases, owing to either changes in the chemical structure of DNA or conversion of the damage into a mutation, that is, a permanent change in DNA sequence. Determining the exact positions of DNA damage and ensuing mutations in the genome are important for identifying mechanisms of disease aetiology when characteristic mutations are prevalent and probably causative in a particular disease. However, this approach is challenging particularly when levels of DNA damage are low, for example, as a result of chronic exposure to environmental agents or certain endogenous processes, such as the generation of reactive oxygen species. Over the past few years, a comprehensive toolbox of genome-wide methods has been developed for the detection of DNA damage and rare mutations at single-nucleotide resolution in mammalian cells. Here, we review and compare these methods, describe their current applications and discuss future research questions that can now be addressed.
PubMed: 38918545
DOI: 10.1038/s41576-024-00748-4 -
Nature Reviews. Genetics Jun 2024Microbiomes occupy a range of niches and, in addition to having diverse compositions, they have varied functional roles that have an impact on agriculture, environmental... (Review)
Review
Microbiomes occupy a range of niches and, in addition to having diverse compositions, they have varied functional roles that have an impact on agriculture, environmental sciences, and human health and disease. The study of microbiomes has been facilitated by recent technological and analytical advances, such as cheaper and higher-throughput DNA and RNA sequencing, improved long-read sequencing and innovative computational analysis methods. These advances are providing a deeper understanding of microbiomes at the genomic, transcriptional and translational level, generating insights into their function and composition at resolutions beyond the species level.
PubMed: 38918544
DOI: 10.1038/s41576-024-00746-6