- Integrated clinical and genomic analysis identifies driver events and molecular evolution of colitis-associated cancers. [Journal Article]
- Inflammation has long been recognized to contribute to cancer development, particularly across the gastrointestinal tract. Patients with inflammatory bowel disease have an increased risk for bowel cancers, and it has been posited that a field of genetic changes may underlie this risk. Here, we define the clinical features, genomic landscape, and germline alterations in 174 patients with colitis-a…
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- Emerging Role of Targeted Therapy in Metastatic Pancreatic Adenocarcinoma. [Review]
- The aggressive biology of pancreatic ductal adenocarcinoma (PDAC), along with its limited sensitivity to many systemic therapies, presents a major challenge in the management of patients with metastatic PDAC. Over the past decade, the incorporation of combinatorial cytotoxic chemotherapy regimens has improved patient outcomes. Despite these advances, resistance to cytotoxic chemotherapy inevitabl…
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- Mechanism of Astrin in Head and Neck Squamous Cell Carcinoma. [Journal Article]Cell Mol Biol (Noisy-le-grand). 2022 Jul 31; 68(7):141-147.CM
- Head and neck squamous cell carcinoma(HNSCC) is a malignant epidermal tumor that seriously threatens human life and health. The main factors affecting the death of patients are local recurrence and lymph node metastasis. Astrin antibody is the basic component of the mitotic spindle required for normal chromosome separation and later development. There are few domestic studies on the mechanism of …
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- Integrative molecular analyses define correlates of high B7-H3 expression in metastatic castrate-resistant prostate cancer. [Journal Article]
- B7-H3 (CD276) is an immune checkpoint overexpressed in prostate cancer with minimal expression in normal tissues and associated with poor prognosis, making it an excellent therapy target. We interrogated B7-H3 expression and its regulation in metastatic castration-resistant prostate cancer (mCRPC). We found greater expression of B7-H3 transcript relative to other immunotherapy targets (CTLA-4, PD…
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- CCHCR1-astrin interaction promotes centriole duplication through recruitment of CEP72. [Journal Article]
- CONCLUSIONS: We conclude that HCR is localized and stabilized at the centrosome by directly binding to astrin. HCR are required for the centrosomal recruitment of MCPH proteins and centriolar duplication. Both HCR and astrin play key roles in keeping normal microtubule assembly and maintaining genomic stability.
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- Hypoxia-inducible factors, mTOR, and astrin constitute an integrative regulatory network in colon cancer cells. [Journal Article]
- Astrin/SPAG5 is a mitotic spindle protein found to be overexpressed in several human cancers, functioning as an oncogene. The expression of Astrin has not been reported so far in colon cancer, nor has it been related to HIFs expression or action. Since mTOR, Astrin, and hypoxia-inducible factors (HIFs) are involved in promoting the growth and survival of cancer cells, we investigated the possible…
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- The Astrin-SKAP complex reduces friction at the kinetochore-microtubule interface. [Journal Article]
- The kinetochore links chromosomes to spindle microtubules to drive chromosome segregation at cell division. While we know nearly all mammalian kinetochore proteins, how these give rise to the strong yet dynamic microtubule attachments required for function remains poorly understood. Here, we focus on the Astrin-SKAP complex, which localizes to bioriented kinetochores and is essential for chromoso…
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- CLUH controls astrin-1 expression to couple mitochondrial metabolism to cell cycle progression. [Journal Article]
- Proliferating cells undergo metabolic changes in synchrony with cell cycle progression and cell division. Mitochondria provide fuel, metabolites, and ATP during different phases of the cell cycle, however it is not completely understood how mitochondrial function and the cell cycle are coordinated. CLUH (clustered mitochondria homolog) is a post-transcriptional regulator of mRNAs encoding mitocho…
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- CREB5 reprograms FOXA1 nuclear interactions to promote resistance to androgen receptor-targeting therapies. [Journal Article]
- Metastatic castration-resistant prostate cancers (mCRPCs) are treated with therapies that antagonize the androgen receptor (AR). Nearly all patients develop resistance to AR-targeted therapies (ARTs). Our previous work identified CREB5 as an upregulated target gene in human mCRPC that promoted resistance to all clinically approved ART. The mechanisms by which CREB5 promotes progression of mCRPC o…
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- A genome-scale CRISPR screen reveals PRMT1 as a critical regulator of androgen receptor signaling in prostate cancer. [Journal Article]
- Androgen receptor (AR) signaling is the central driver of prostate cancer across disease states. While androgen deprivation therapy (ADT) is effective in the initial treatment of prostate cancer, resistance to ADT or to next-generation androgen pathway inhibitors invariably arises, most commonly through the re-activation of the AR axis. Thus, orthogonal approaches to inhibit AR signaling in advan…
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- YAP1 and PRDM14 converge to promote cell survival and tumorigenesis. [Journal Article]
- The transcriptional co-activator YAP1 oncogene is the downstream effector of the Hippo pathway, which regulates tissue homeostasis, organ size, regeneration, and tumorigenesis. Multiple cancers are dependent on sustained expression of YAP1 for cell proliferation, survival, and tumorigenesis, but the molecular basis of this oncogene dependency is not well understood. To identify genes that can fun…
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- Counteraction between Astrin-PP1 and Cyclin-B-CDK1 pathways protects chromosome-microtubule attachments independent of biorientation. [Journal Article]
- Defects in chromosome-microtubule attachment can cause chromosomal instability (CIN), frequently associated with infertility and aggressive cancers. Chromosome-microtubule attachment is mediated by a large macromolecular structure, the kinetochore. Sister kinetochores of each chromosome are pulled by microtubules from opposing spindle-poles, a state called biorientation which prevents chromosome …
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- The Aurora B gradient sustains kinetochore stability in anaphase. [Journal Article]
- Kinetochores assemble on chromosomes in mitosis to allow microtubules to attach and bring about accurate chromosome segregation. The kinases Cyclin B-Cdk1 and Aurora B are crucial for the formation of stable kinetochores. However, the activity of these two kinases appears to decline dramatically at centromeres during anaphase onset, precisely when microtubule attachments are required to move chro…
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- The dark side of pseudoscorpion diversity: The German Barcode of Life campaign reveals high levels of undocumented diversity in European false scorpions. [Journal Article]
- DNA barcoding is particularly useful for identification and species delimitation in taxa with conserved morphology. Pseudoscorpions are arachnids with high prevalence of morphological crypsis. Here, we present the first comprehensive DNA barcode library for Central European Pseudoscorpiones, covering 70% of the German pseudoscorpion fauna (35 out of 50 species). For 21 species, we provide the fir…
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- Are Current Metrics Adequate to Demonstrate the Value of Oncology Advanced Practitioners? [Journal Article]
- At JADPRO Live Virtual 2020, Jason Astrin, DMSc, MBA, PA-C, DFAAPA, defined the concepts of productivity and value and discussed strategies for measuring the value of oncology advanced practitioners in order to recognize advanced practitioner contributions to quality care and provide meaningful incentives.
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- Increased Expression of KNSTRN in Lung Adenocarcinoma Predicts Poor Prognosis: A Bioinformatics Analysis Based on TCGA Data. [Journal Article]
- Purpose: Available evidence indicates that kinetochore-localized astrin/SPAG5-binding protein (KNSTRN) is an oncogene in skin carcinoma. This study aimed to evaluate the prognostic value of KNSTRN in lung adenocarcinoma (LUAD) underlying the Cancer Genome Atlas (TCGA) database. Methods: The relationship between clinicopathological features and KNSTRN was analyzed with the Wilcoxon signed-rank tes…
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- DIAPH3 deficiency links microtubules to mitotic errors, defective neurogenesis, and brain dysfunction. [Journal Article]
- Diaphanous (DIAPH) three (DIAPH3) is a member of the formin proteins that have the capacity to nucleate and elongate actin filaments and, therefore, to remodel the cytoskeleton. DIAPH3 is essential for cytokinesis as its dysfunction impairs the contractile ring and produces multinucleated cells. Here, we report that DIAPH3 localizes at the centrosome during mitosis and regulates the assembly and …
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- The association of Plk1 with the astrin-kinastrin complex promotes formation and maintenance of a metaphase plate. [Journal Article]
- Errors in mitotic chromosome segregation can lead to DNA damage and aneuploidy, both hallmarks of cancer. To achieve synchronous error-free segregation, mitotic chromosomes must align at the metaphase plate with stable amphitelic attachments to microtubules emanating from opposing spindle poles. The astrin-kinastrin (astrin is also known as SPAG5 and kinastrin as SKAP) complex, also containing DY…
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- Towards retrieving the Promethean treasure: a first molecular assessment of the freshwater fish diversity of Georgia. [Journal Article]
- In this study, we provide a first estimation of the molecular diversity of the freshwater fishes of Georgia. In addition to field collections, we integrated DNA barcode data obtained from recent works and public databases (BOLD and NCBI GenBank). Currently, the DNA barcode reference library for freshwater fishes of Georgia comprises 352 DNA barcodes for 50 species, 36 genera and 15 families (52% …
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- Astrin: A Key Player in Mitosis and Cancer. [Review]
- Astrin, which is a spindle-associated protein, was found to be closely related to mitotic spindle formation and maintenance. It interacts with other spindle-related proteins to play a key role in maintaining the attachment of the kinetochore-microtubule and integrity of centrosomes and promoting the centriole duplication. In addition, Astrin was quite recently found to be abnormally highly expres…
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- Comparing diversity levels in environmental samples: DNA sequence capture and metabarcoding approaches using 18S and COI genes. [Journal Article]
- Environmental DNA studies targeting multiple taxa using metabarcoding provide remarkable insights into levels of species diversity in any habitat. The main drawbacks are the presence of primer bias and difficulty in identifying rare species. We tested a DNA sequence-capture method in parallel with the metabarcoding approach to reveal possible advantages of one method over the other. Both approach…
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- SPAG5: An Emerging Oncogene. [Journal Article]
- Sperm-associated Antigen 5 (SPAG5) is a mitotic spindle protein. Recent studies have found that it is overexpressed in many human cancers and functions as an oncogene. Here, we summarize the current underlying mechanisms for its oncogenic roles in regulating cellular behaviors of cancer cells and discuss the possibility of targeting SPAG5 for cancer treatment.
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- Kinetochores attached to microtubule-ends are stabilised by Astrin bound PP1 to ensure proper chromosome segregation. [Journal Article]
- Microtubules segregate chromosomes by attaching to macromolecular kinetochores. Only microtubule-end attached kinetochores can be pulled apart; how these end-on attachments are selectively recognised and stabilised is not known. Using the kinetochore and microtubule-associated protein, Astrin, as a molecular probe, we show that end-on attachments are rapidly stabilised by spatially-restricted del…
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- New records of bats and terrestrial small mammals from the Seli River in Sierra Leone before the construction of a hydroelectric dam. [Journal Article]
- Sierra Leone is situated at the western edge of the Upper Guinean Forests in West Africa, a recognised biodiversity hotspot which is increasingly threatened by habitat degradation and loss through anthropogenic impacts. The small mammal fauna of Sierra Leone is poorly documented, although bats and rodents account for the majority of mammalian diversity. Based on morphological, genetic and echoloc…
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- Loss of Kif18A Results in Spindle Assembly Checkpoint Activation at Microtubule-Attached Kinetochores. [Journal Article]
- The spindle assembly checkpoint (SAC) halts anaphase progression until all kinetochores have obtained bipolar, stable attachments to the mitotic spindle. Upon initial attachment, chromosomes undergo oscillatory movements to reach metaphase. Once a chromosome is correctly attached and positioned, these oscillatory movements are reduced by the motor protein Kif18A, and loss of Kif18A results in chr…
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- Climate and host-plant associations shaped the evolution of ceutorhynch weevils throughout the Cenozoic. [Journal Article]
- Using molecular phylogenetic data and methods we inferred divergence times and diversification patterns for the weevil subfamily Ceutorhynchinae in the context of host-plant associations and global climate over evolutionary time. We detected four major diversification shifts that correlate with both host shifts and major climate events. Ceutorhynchinae experienced an increase in diversification r…
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- The 2018 Revision of the ISBER Best Practices: Summary of Changes and the Editorial Team's Development Process. [Guideline]
- An increased need for specimens of reliable and consistent quality for research purposes requires the development of standardized policies and practices for the collection, handling, storage, retrieval, and distribution of specimens and specimen-related data. Providers of specimen resources should strive to incorporate new technologies and state-of-the-science approaches and thus ensure the avail…
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- Astrin-SKAP complex reconstitution reveals its kinetochore interaction with microtubule-bound Ndc80. [Journal Article]
- Chromosome segregation requires robust interactions between the macromolecular kinetochore structure and dynamic microtubule polymers. A key outstanding question is how kinetochore-microtubule attachments are modulated to ensure that bi-oriented attachments are selectively stabilized and maintained. The Astrin-SKAP complex localizes preferentially to properly bi-oriented sister kinetochores, repr…
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- Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells. [Journal Article]
- Human chromosomes are captured along microtubule walls (lateral attachment) and then tethered to microtubule-ends (end-on attachment) through a multi-step end-on conversion process. Upstream regulators that orchestrate this remarkable change in the plane of kinetochore-microtubule attachment in human cells are not known. By tracking kinetochore movements and using kinetochore markers specific to …
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- Critical roles of Astrin in the mitosis of immature rat Sertoli cells. [Journal Article]
- Male hypogonadism (hgn/hgn) rats show testicular hypoplasia accompanied by dysplastic development of seminiferous tubules due to loss-of-function mutation of the gene encoding Astrin, which is required for mitotic progression in the division cycle of HeLa cells. In the present study, we examined the cytological base leading to the decrease of Sertoli cells in hgn/hgn testes. In hgn/hgn testes on …
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