Spheroid Model of Mammary Tumor Cells: Epithelial-Mesenchymal Transition and Doxorubicin Response.

Breast cancer is the most prevalent cancer among women worldwide. Therapeutic strategies to control tumors and metastasis are still challenging. Three-dimensional (3D) spheroid-type systems more accurately replicate the features of tumors in vivo, working as a better platform for performing therapeutic response analysis.

Endolithic Fungal Diversity in Antarctic Oligocene Rock Samples Explored Using DNA Metabarcoding.

In this study, we evaluated the fungal diversity present associated with cores of Oligocene rocks using a DNA metabarcoding approach. We detected 940,969 DNA reads grouped into 198 amplicon sequence variants (ASVs) representing the phyla , , , , , , , , , (Fungi) and the fungal-like (Stramenopila), in rank abundance order. , sp.

BRCA1 frameshift variants leading to extended incorrect protein C termini.

Carriers of BRCA1 germline pathogenic variants are at substantially higher risk of developing breast and ovarian cancer than the general population. Accurate identification of at-risk individuals is crucial for risk stratification and the implementation of targeted preventive and therapeutic interventions. Despite significant progress in variant classification efforts, a sizable portion of reported BRCA1 variants remain as variants of uncertain clinical significance (VUSs).

Assessment of small in-frame indels and C-terminal nonsense variants of BRCA1 using a validated functional assay.

BRCA1 (Breast Cancer 1, early onset) is linked to breast and ovarian cancer predisposition. Still, the risks conferred by a significant portion of BRCA1 variants identified in the population remains unknown. Most of these variants of uncertain significance are missense alterations.

Influence of the intertropical convergence zone on early cretaceous plant distribution in the South Atlantic.

The influence of the Intertropical Convergence Zone (ITCZ) in the emerging South Atlantic region during the late Aptian (Early Cretaceous) is reflected in the spatio-temporal distribution of plant communities recorded in eight Brazilian sedimentary basins. The distribution of the bioclimatic groups of hygrophytes, hydrophytes, tropical lowland flora, upland flora, and xerophytes was quantified using pollen and spores. A predominance of xerophytes from the tropical xerophytic shrubland biome characterized the pre-evaporitic, evaporitic, and post-evaporitic paleoclimatic phases, in particular the evaporitic phase.

Functional Restoration of Nonsense Mutations by Aminoglycoside-Induced Readthrough.

BRCA1 is a major tumor suppressor that functions in the accurate repair of DNA double-strand breaks via homologous recombination (HR). Nonsense mutations in lead to inactive truncated protein products and are associated with high risk of breast and ovarian cancer. These mutations generate premature termination codons (PTCs).

Rare germline variants in PALB2 and BRCA2 in familial and sporadic chordoma.

Chordoma is a rare bone tumor with genetic risk factors largely unknown. We conducted a whole-exome sequencing (WES) analysis of germline DNA from 19 familial chordoma cases in five pedigrees and 137 sporadic chordoma patients and identified 17 rare germline variants in PALB2 and BRCA2, whose products play essential roles in homologous recombination (HR) and tumor suppression. One PALB2 variant showed disease cosegregation in a family with four affected people or obligate gene carrier.

Two distinct mechanisms underlie estrogen-receptor-negative breast cancer susceptibility at the 2p23.2 locus.

Genome wide-association studies (GWAS) have established over 400 breast cancer risk loci defined by common single nucleotide polymorphisms (SNPs), including several associated with estrogen-receptor (ER)-negative disease. Most of these loci have not been studied systematically and the mechanistic underpinnings of risk are largely unknown. Here we explored the landscape of genomic features at an ER-negative breast cancer susceptibility locus at chromosome 2p23.

PALB2 Variants: Protein Domains and Cancer Susceptibility.

Since its discovery, partner and localizer of breast cancer 2 (BRCA2) (PALB2) has emerged as a major tumor suppressor gene linked to breast cancer (BC), pancreatic cancer (PC), and ovarian cancer (OC) susceptibility. Its protein product plays a pivotal role in the maintenance of genome integrity. Here we discuss the first functional evaluation of a large set of PALB2 missense variants of uncertain significance (VUSs).

Integration of functional assay data results provides strong evidence for classification of hundreds of BRCA1 variants of uncertain significance.

Purpose: BRCA1 pathogenic variant heterozygotes are at a substantially increased risk for breast and ovarian cancer. The widespread uptake of testing has led to a significant increase in the detection of missense variants in BRCA1, the vast majority of which are variants of uncertain clinical significance (VUS), posing a challenge to genetic counseling. Here, we harness a wealth of functional data for thousands of variants to aid in variant classification.

Galectin-3 mediates survival and apoptosis pathways during Trypanosoma cruzi-host cell interplay.

Neglected tropical diseases, such as Chagas disease caused by the protozoa Trypanosoma cruzi, affect millions of people worldwide but lack effective treatments that are accessible to the entire population, especially patients with the debilitating chronic phase. The recognition of host cells, invasion and its intracellular replicative success are essential stages for progression of the parasite life cycle and the development of Chagas disease. It is predicted that programmed cell death pathways (apoptosis) would be activated in infected cells, either via autocrine secretion or mediated by cytotoxic immune cells.

Network of Interactions between ZIKA Virus Non-Structural Proteins and Human Host Proteins.

The Zika virus (ZIKV) is a mosquito-borne Flavivirus and can be transmitted through an infected mosquito bite or through human-to-human interaction by sexual activity, blood transfusion, breastfeeding, or perinatal exposure. After the 2015-2016 outbreak in Brazil, a strong link between ZIKV infection and microcephaly emerged. ZIKV specifically targets human neural progenitor cells, suggesting that proteins encoded by ZIKV bind and inactivate host cell proteins, leading to microcephaly.

DNA damage response and repair in perspective: Aedes aegypti, Drosophila melanogaster and Homo sapiens.

Background: The maintenance of genomic integrity is the responsibility of a complex network, denominated the DNA damage response (DDR), which controls the lesion detection and DNA repair. The main repair pathways are base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination repair (HR) and non-homologous end joining repair (NHEJ). They correct double-strand breaks (DSB), single-strand breaks, mismatches and others, or when the damage is quite extensive and repair insufficient, apoptosis is activated.

Functional characterization of 84 PALB2 variants of uncertain significance.

Purpose: Inherited pathogenic variants in PALB2 are associated with increased risk of breast and pancreatic cancer. However, the functional and clinical relevance of many missense variants of uncertain significance (VUS) identified through clinical genetic testing is unclear. The ability of patient-derived germline missense VUS to disrupt PALB2 function was assessed to identify variants with potential clinical relevance.

A global functional analysis of missense mutations reveals two major hotspots in the PALB2 tumor suppressor.

While biallelic mutations in the PALB2 tumor suppressor cause Fanconi anemia subtype FA-N, monoallelic mutations predispose to breast and familial pancreatic cancer. Although hundreds of missense variants in PALB2 have been identified in patients to date, only a few have clear functional and clinical relevance. Herein, we investigate the effects of 44 PALB2 variants of uncertain significance found in breast cancer patients and provide detailed analysis by systematic functional assays.

Low cytomolecular diversification in the genus Stylosanthes Sw. (Papilionoideae, Leguminosae).

Stylosanthes (Papilionoideae, Leguminosae) is a predominantly Neotropical genus with ~48 species that include worldwide important forage species. This study presents the chromosome number and morphology of eight species of the genus Stylosanthes (S. acuminata, S.

Impact of amino acid substitutions at secondary structures in the BRCT domains of the tumor suppressor BRCA1: Implications for clinical annotation.

Genetic testing for , a DNA repair protein, can identify carriers of pathogenic variants associated with a substantially increased risk for breast and ovarian cancers. However, an association with increased risk is unclear for a large fraction of variants present in the human population. Most of these variants of uncertain clinical significance lead to amino acid changes in the BRCA1 protein.

Loss of constitutive expression in breast cancer associated with worse prognosis.

gene encodes an adenosine 5'-triphosphate-binding cassette transporter, which not only confers multidrug resistance phenotype in malignant cells, but is also present in several nonmalignant tissues. For the last thirty years, expression in breast cancer has been described by many authors, but the extent of expression differs among the studies, and there is no consensus regarding its potential role in carcinogenesis or in the tumor response to antineoplastic drugs. This study aimed to characterize the expression of in breast tumors as a function of genetic, clinical, and histopathological variables.

DNA repair genes PAXIP1 and TP53BP1 expression is associated with breast cancer prognosis.

Despite remarkable advances in diagnosis, prognosis and treatment, advanced or recurrent breast tumors have limited therapeutic approaches. Many treatment strategies try to explore the limitations of DNA damage response (DDR) in tumor cells to selectively eliminate them. BRCT (BRCA1 C-terminal) domains are present in a superfamily of proteins involved in cell cycle checkpoints and the DDR.

BRCA1 recruitment to damaged DNA sites is dependent on CDK9.

Double strand break lesions, the most toxic type of DNA damage, are repaired primarily through 2 distinct pathways: homology-directed recombination (HR) and non-homologous end-joining (NHEJ). BRCA1 and 53BP1, 2 proteins containing the BRCT modular domain, play an important role in DNA damage response (DDR) by orchestrating the decision between HR and NHEJ, but the precise mechanisms regarding both pathways are not entirely understood. Previously, our group identified a putative interaction between BRCA1 and BARD1 (BRCA1-associated RING domain 1) and the cyclin-dependent kinase (CDK9).

Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance.

Variants of Uncertain Significance (VUS) are genetic variants whose association with a disease phenotype has not been established. They are a common finding in sequencing-based genetic tests and pose a significant clinical challenge. The objective of this study was to assess the use of functional data to classify variants according to pathogenicity.

Enhancer scanning to locate regulatory regions in genomic loci.

This protocol provides a rapid, streamlined and scalable strategy to systematically scan genomic regions for the presence of transcriptional regulatory regions that are active in a specific cell type. It creates genomic tiles spanning a region of interest that are subsequently cloned by recombination into a luciferase reporter vector containing the simian virus 40 promoter. Tiling clones are transfected into specific cell types to test for the presence of transcriptional regulatory regions.

Santonian dinocyst assemblages of the Santa Marta Formation, Antarctic Peninsula: Inferences for paleoenvironments and paleoecology.

To better understand the paleoenvironments of the lower-middle Santonian, dinocyst data were obtained from the Santa Marta Formation, Larsen Basin, James Ross Island, Antarctic Peninsula. This study provides the first available quantitative dinocyst data for the Santa Marta Formation, which should more clearly reflect detailed changes in paleoenvironments, as recorded by fluctuations in diversity and abundance. To record the Santonian dinocyst assemblages from the Larsen Basin, 30 samples from an outcrop of the Lachman Crags Member (LC section) were analyzed.