Characterization of BRCA2 R3052Q variant in mice supports its functional impact as a low-risk variant.

Pathogenic variants in BRCA2 are known to significantly increase the lifetime risk of developing breast and ovarian cancers. Sequencing-based genetic testing has resulted in the identification of thousands of BRCA2 variants that are considered to be variants of uncertain significance (VUS) because the disease risk associated with them is unknown. One such variant is p.

Utilization of Bioinorganic Nanodrugs and Nanomaterials for the Control of Infectious Diseases Using Deep Learning.

As one of the main causes of morbidity and mortality, viral infections have a major impact on the well-being and economics of every nation in the globe. The ability to predictably diagnose viral infections improves the provision of good healthcare as well as the control and prevention of these conditions. Nanomaterials have gained widespread usage in the medical industry recently due to the rapid advancement of nanotechnology and their exceptional chemical and physical qualities, such as their small size and synthesized surface properties.

Growth factor dependency in mammary organoids regulates ductal morphogenesis during organ regeneration.

Signaling pathways play an important role in cell fate determination in stem cells and regulate a plethora of developmental programs, the dysregulation of which can lead to human diseases. Growth factors (GFs) regulating these signaling pathways therefore play a major role in the plasticity of adult stem cells and modulate cellular differentiation and tissue repair outcomes. We consider murine mammary organoid generation from self-organizing adult stem cells as a tool to understand the role of GFs in organ development and tissue regeneration.

BRCA2-DSS1 interaction is dispensable for RAD51 recruitment at replication-induced and meiotic DNA double strand breaks.

The interaction between tumor suppressor BRCA2 and DSS1 is essential for RAD51 recruitment and repair of DNA double stand breaks (DSBs) by homologous recombination (HR). We have generated mice with a leucine to proline substitution at position 2431 of BRCA2, which disrupts this interaction. Although a significant number of mutant mice die during embryogenesis, some homozygous and hemizygous mutant mice undergo normal postnatal development.

Determination of five antimicrobial families in droppings of therapeutically treated broiler chicken by high-performance liquid chromatography-tandem mass spectrometry.

Antimicrobials are currently used in poultry for disease treatment. However, their excretion in bird feces may contaminate the environment. Considering this, the objective of this work was to quantify antimicrobials residues concentrations in therapeutically treated broiler chicken droppings throughout the post-treatment period.

Detection of Antimicrobial Residues in Poultry Litter: Monitoring a Risk through a Selective and Sensitive HPLC-MS/MS Method.

Tetracyclines, sulphonamides, and quinolones are families of antimicrobials (AMs) widely used in the poultry industry and can excrete up to 90% of AMs administrated, which accumulate in poultry litter. Worryingly, poultry litter is widely used as an agriculture fertilizer, contributing to the spread AMs residues in the environment. The aim of this research was to develop a method that could simultaneously identify and quantify three AMs families in poultry litter by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

Evaluation of Antibiotic Dissemination into the Environment and Untreated Animals, by Analysis of Oxytetracycline in Poultry Droppings and Litter.

Oxytetracycline (OTC) is widely used in broiler chickens. During and after treatment a fraction of OTC is excreted in its original form and as its epimer, 4-epi-OTC in droppings. To address the transfer of OTC into the environment, we evaluated the dissemination of OTC and 4-epi-OTC from treated birds to the environment and sentinels, through the simultaneous analysis of broiler droppings and litter.

Innate Biomineralization.

In vertebrates, biomineralization is a feature considered unique to mature osteoblasts and odontoblasts by which they synthesize hydroxyapatite (HAP), which is deposited in the collagen matrix to construct endoskeleton. For many decades, the mechanisms that modulate differentiation and maturation of these specialized cells have been sought as a key to understanding bone-remodeling defects. Here, we report that biomineralization is an innate ability of all mammalian cells, irrespective of cell type or maturation stage.

Assessment of Consumer Perceptions on the Use of Antimicrobials in Production Animals in Chile.

Successful treatment of diseases that sicken food-producing animals requires the use of antimicrobials. However, these drugs could result in serious consequences for human, animal, and environmental health. The emergence of antimicrobial resistance requires better communication with consumers to inform them about the risks associated with the use of these drugs, as well as the benefits gained from their rational use.

Determination of Chlortetracycline Residues, Antimicrobial Activity and Presence of Resistance Genes in Droppings of Experimentally Treated Broiler Chickens.

Tetracyclines are important antimicrobial drugs for poultry farming that are actively excreted via feces and urine. Droppings are one of the main components in broiler bedding, which is commonly used as an organic fertilizer. Therefore, bedding becomes an unintended carrier of antimicrobial residues into the environment and may pose a highly significant threat to public health.

BRE/BRCC45 regulates CDC25A stability by recruiting USP7 in response to DNA damage.

BRCA2 is essential for maintaining genomic integrity. BRCA2-deficient primary cells are either not viable or exhibit severe proliferation defects. Yet, BRCA2 deficiency contributes to tumorigenesis.

Survival of BRCA2-Deficient Cells Is Promoted by , a Novel Genetic Interactor of .

loss-of-heterozygosity (LOH) is frequently observed in -mutated tumors, but its biallelic loss causes embryonic lethality in mice and inhibits proliferation of normal somatic cells. Therefore, it remains unclear how loss of BRCA2 contributes to tumorigenesis. One possibility is that mutation in potential genetic interactors of , such as , is required for cell survival/proliferation in the absence of BRCA2.

Physicochemical characteristics of pristine and functionalized graphene.

Graphene-based nanomaterials have received significant attention in the last decade due to their interesting properties. Its electrical and thermal conductivity and strength make graphene well suited for a variety of applications, particularly for use as a composite material in plastics. Furthermore, much work is taking place to utilize graphene as a biomaterial for uses such as drug delivery and tissue regeneration scaffolds.

Determination of Oxytetracycline and 4-Epi-Oxytetracycline Residues in Feathers and Edible Tissues of Broiler Chickens Using Liquid Chromatography Coupled with Tandem Mass Spectrometry.

Antibiotics have been widely used in poultry production for the treatment of bacterial diseases. However, drug residues can remain in products derived from animals after the cessation of the drug therapies. Feathers, in particular, have shown an affinity for antibiotics such as tetracycline, suggesting the persistence of these drugs in nonedible tissue.

Synthetic viability by BRCA2 and PARP1/ARTD1 deficiencies.

Poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib has been approved for treatment of advanced ovarian cancer associated with BRCA1 and BRCA2 mutations. BRCA1- and BRCA2-mutated cells, which are homologous recombination (HR) deficient, are hypersensitive to PARPi through the mechanism of synthetic lethality. Here we examine the effect of PARPi on HR-proficient cells.

Interaction with PALB2 Is Essential for Maintenance of Genomic Integrity by BRCA2.

Human breast cancer susceptibility gene, BRCA2, encodes a 3418-amino acid protein that is essential for maintaining genomic integrity. Among the proteins that physically interact with BRCA2, Partner and Localizer of BRCA2 (PALB2), which binds to the N-terminal region of BRCA2, is vital for its function by facilitating its subnuclear localization. A functional redundancy has been reported between this N-terminal PALB2-binding domain and the C-terminal DNA-binding domain of BRCA2, which undermines the relevance of the interaction between these two proteins.

BRCA2 minor transcript lacking exons 4-7 supports viability in mice and may account for survival of humans with a pathogenic biallelic mutation.

The breast cancer gene, BRCA2, is essential for viability, yet patients with Fanconi anemia-D1 subtype are born alive with biallelic mutations in this gene. The hypomorphic nature of the mutations is believed to support viability, but this is not always apparent. One such mutation is IVS7+2T>G, which causes premature protein truncation due to skipping of exon 7.

Loss of oncogenic miR-155 in tumor cells promotes tumor growth by enhancing C/EBP-β-mediated MDSC infiltration.

The oncogenic role of microRNA-155 (miR-155) in leukemia is well established but its role in other cancers, especially breast cancer, is gradually emerging. In this study we examined the effect of mir-155 loss in a well-characterized spontaneous breast cancer mouse model where Brca1 and Trp53 are deleted by K14-Cre. miR-155 is known to be up-regulated in BRCA1-deficient tumors.

Functional evaluation of BRCA2 variants mapping to the PALB2-binding and C-terminal DNA-binding domains using a mouse ES cell-based assay.

Single-nucleotide substitutions and small in-frame insertions or deletions identified in human breast cancer susceptibility genes BRCA1 and BRCA2 are frequently classified as variants of unknown clinical significance (VUS) due to the availability of very limited information about their functional consequences. Such variants can most reliably be classified as pathogenic or non-pathogenic based on the data of their co-segregation with breast cancer in affected families and/or their co-occurrence with a pathogenic mutation. Biological assays that examine the effect of variants on protein function can provide important information that can be used in conjunction with available familial data to determine the pathogenicity of VUS.

Increased urinary glucocorticoid metabolites are associated with metabolic syndrome, hypoadiponectinemia, insulin resistance and β cell dysfunction.

Metabolic syndrome (MetS) may have increased cortisol (F) production caused by 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in liver and adipose tissue and/or by HPA axis dysregulation. F is then mainly metabolized by liver reductases into inactive tetrahydrometabolites (THMs). We measured THM levels in patients with or without MetS and evaluate the correlation between THMs and anthropometric and biochemical parameters.

Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155.

BRCA1, a well-known tumor suppressor with multiple interacting partners, is predicted to have diverse biological functions. However, so far its only well-established role is in the repair of damaged DNA and cell cycle regulation. In this regard, the etiopathological study of low-penetrant variants of BRCA1 provides an opportunity to uncover its other physiologically important functions.

Expression of human BRCA1 variants in mouse ES cells allows functional analysis of BRCA1 mutations.

To date, inheritance of a mutant BRCA1 or BRCA2 gene is the best-established indicator of an increased risk of developing breast cancer. Sequence analysis of these genes is being used to identify BRCA1/2 mutation carriers, though these efforts are hampered by the high frequency of variants of unknown clinical significance (VUSs). Functional evaluation of such variants has been restricted due to lack of a physiologically relevant assay.

Loss of Rad51c leads to embryonic lethality and modulation of Trp53-dependent tumorigenesis in mice.

RecA/Rad51 protein family members (Rad51, Rad51b, Rad51c, Rad51d, Xrcc2, and Xrcc3) are essential for DNA repair by homologous recombination, and their role in cancers has been anticipated. Here we provide the first direct evidence for a tumor suppressor function for a member of the Rad51 family. We show that Rad51c deficiency leads to early embryonic lethality, which can be delayed on a Trp53-null background.