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Archivum Immunologiae Et Therapiae... Jan 2024Foot-and-mouth disease virus (FMDV) is a highly contagious and economically devastating pathogen that affects cloven-hoofed animals worldwide. FMDV infection causes... (Review)
Review
Foot-and-mouth disease virus (FMDV) is a highly contagious and economically devastating pathogen that affects cloven-hoofed animals worldwide. FMDV infection causes vesicular lesions in the mouth, feet, and mammary glands, as well as severe systemic symptoms such as fever, salivation, and lameness. The pathogenesis of FMDV infection involves complex interactions between the virus and the host immune system, which determine the outcome of the disease. FMDV has evolved several strategies to evade immune recognition and elimination, such as antigenic variation, receptor switching, immune suppression, and subversion of innate and adaptive responses. This review paper summarizes the current knowledge on the pathogenesis of FMDV infection and the mechanisms of immune evasion employed by the virus. It also discusses the challenges and opportunities for developing effective vaccines and therapeutics against this important animal disease.
Topics: Animals; Foot-and-Mouth Disease; Foot-and-Mouth Disease Virus; Immune Evasion; Immunity, Innate; Viral Vaccines; Adaptive Immunity; Humans; Host-Pathogen Interactions; Antigenic Variation
PubMed: 38910298
DOI: 10.2478/aite-2024-0013 -
BioRxiv : the Preprint Server For... May 2024During pregnancy, mammary tissue undergoes expansion and differentiation, leading to lactation, a process regulated by the hormone prolactin through the JAK2-STAT5...
During pregnancy, mammary tissue undergoes expansion and differentiation, leading to lactation, a process regulated by the hormone prolactin through the JAK2-STAT5 pathway. STAT5 activation is key to successful lactation making the mammary gland an ideal experimental system to investigate the impact of human missense mutations on mammary tissue homeostasis. Here, we investigated the effects of two human variants in the STAT5B SH2 domain, which convert tyrosine 665 to either phenylalanine (Y665F) or histidine (Y665H), both shown to activate STAT5B in cell culture. We ported these mutations into the mouse genome and found distinct and divergent functions. Homozygous mice failed to form functional mammary tissue, leading to lactation failure, with impaired alveolar development and greatly reduced expression of key differentiation genes. STAT5B failed to recognize mammary enhancers and impeded STAT5A binding. In contrast, mice carrying the mutation exhibited abnormal precocious development, accompanied by an early activation of the mammary transcription program and the induction of otherwise silent genetic programs. Physiological adaptation was observed in mice as continued exposure to pregnancy hormones led to lactation. In summary, our findings highlight that human STAT5B variants can modulate their response to cytokines and thereby impact mammary homeostasis and lactation.
PubMed: 38903072
DOI: 10.1101/2024.05.06.592736 -
Animal : An International Journal of... May 2024We now live in an era where metabolic data are increasingly accessible and available. Analysis of this data can be done using novel techniques (e.g., machine learning...
We now live in an era where metabolic data are increasingly accessible and available. Analysis of this data can be done using novel techniques (e.g., machine learning and artificial intelligence) but this does not alleviate scientists to use "human intelligence". The objective of this paper is to combine the information of a large database of biochemical reactions with a method and tool to make nutritional biochemistry more accessible to nutritionists. A script was developed to extract information from a database with more than 16 000 biochemical reactions so that it can be used for "biochemical bookkeeping". A system of more than 300 meta-reactions (i.e., the outcome reaction of a series of connected individual reactions) was constructed covering a wide range of metabolic pathways for macro- and micronutrients. Meta-reactions were constructed by identifying metabolic nodes, which are inputs or outputs of a metabolic system or that serve as connection points between meta-reactions. Complete metabolic pathways can be constructed by combining and balancing the meta-reactions using a simple Excel tool. To illustrate the use of meta-reactions and the tool in the teaching of nutritional biochemistry, examples are given to illustrate how much ATP can be synthesized from glucose, either directly or indirectly (i.e., via storage and mobilization or via transfer of intermediate metabolites between tissues and generations). To illustrate how meta-reactions and the tool can be used in research, nutrient balance data of the mammary gland of a dairy cow were used to construct a plausible pathway of nutrient metabolism of the whole mammary gland. The balance data included 34 metabolites taken up or exported by the mammary gland and 39 meta-reactions were used to construct a metabolic pathway that accounted for the uptake and output of metabolites. The results highlighted the importance of the synthesis of proline from arginine and the concomitant synthesis of urea by the mammary gland. It also raised the question of whether the availability of metabolic pathways or glucose uptake would be the more limiting factor for the synthesis of NADPH required for fatty acid synthesis. The availability of an open database with biochemical reactions, the concept of meta-reactions, and the provision of a tool allow users to construct metabolic pathways, which helps acquiring a more comprehensive and integrated view of metabolism and may raise issues that may be difficult to identify otherwise.
PubMed: 38897106
DOI: 10.1016/j.animal.2024.101204 -
Talanta Jun 2024Bovine mastitis is an inflammation of the mammary gland, and it is the most common infectious disease in dairy cattle. Mastitis reduces milk yield and quality, costing...
Bovine mastitis is an inflammation of the mammary gland, and it is the most common infectious disease in dairy cattle. Mastitis reduces milk yield and quality, costing dairy farmers millions of dollars each year. The aim of this study was to develop a point-of-need test for identifying mastitis pathogens that is field portable, cost-effective and can be used with minimal training. Using a proprietary polymer-based milk sample preparation method to rapidly extract pathogen DNA in milk samples, we demonstrated quantitative Polymerase Chain Reaction (qPCR) assays for six common bovine bacterial mastitis pathogens: Staphylococcus aureus, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus uberis, Mycoplasma bovis and Escherichia coli. We also implemented this sample preparation method on a prototype point-of-need system in a proof-of-concept field trial to evaluate user experience. Importantly, the protype system enabled a sample-to-result turnaround time of within 70 min to quantitatively detect all six target pathogens. The key advantage of our point-of-need prototype system is being culture-independent yet providing automated milk sample preparation for molecular identification of key mastitis pathogens by non-expert users. Our point-of-need prototype system showed a good correlation to laboratory-based qPCR for target pathogen detection outcomes, thus potentially removing the need for milk samples to be transported off-site for laboratory testing. Above all, we successfully achieved our objective of developing a point-of-need biosensor technology for mastitis and increased its readiness level with industry partners towards technology commercialization.
PubMed: 38897015
DOI: 10.1016/j.talanta.2024.126424 -
Nutrients Jun 2024Maternal breast milk plays a key role in providing newborns with passive immunity and stimulating the maturation of an infant's immune system, protecting them from many...
Maternal breast milk plays a key role in providing newborns with passive immunity and stimulating the maturation of an infant's immune system, protecting them from many diseases. It is known that diet can influence the immune system of lactating mothers and the composition of their breast milk. The aim of this study was to establish if a supplementation during the gestation and lactation of Lewis rats with extra virgin olive oil (EVOO), due to the high proportion of antioxidant components in its composition, has an impact on the mother's immune system and on the breast milk's immune composition. For this, 10 mL/kg of either EVOO, refined oil (control oil) or water (REF group) were orally administered once a day to rats during gestation and lactation periods. Immunoglobulin (Ig) concentrations and gene expressions of immune molecules were quantified in several compartments of the mothers. The EVOO group showed higher IgA levels in both the breast milk and the mammary glands than the REF group. In addition, the gene expression of IgA in mammary glands was also boosted by EVOO consumption. Overall, EVOO supplementation during gestation and lactation is safe and does not negatively affect the mother's immune system while improving breast milk immune composition by increasing the presence of IgA, which could be critical for an offspring's immune health.
Topics: Animals; Olive Oil; Female; Pregnancy; Lactation; Rats; Rats, Inbred Lew; Maternal Nutritional Physiological Phenomena; Immunoglobulin A; Immune System; Dietary Supplements; Mammary Glands, Animal; Milk; Milk, Human
PubMed: 38892716
DOI: 10.3390/nu16111785 -
International Journal of Molecular... Jun 2024In this study, our primary aim was to explore the genomic landscape of Barka cattle, a breed recognized for high milk production in a semi-arid environment, by focusing...
In this study, our primary aim was to explore the genomic landscape of Barka cattle, a breed recognized for high milk production in a semi-arid environment, by focusing on genes with known roles in milk production traits. We employed genome-wide analysis and three selective sweep detection methods (, ratio, and ) to identify candidate genes associated with milk production and composition traits. Notably, , , and were consistently identified by all methods. Functional annotation highlighted their roles in crucial biological processes such as fatty acid metabolism, mammary gland development, and milk protein synthesis. These findings contribute to understanding the genetic basis of milk production in Barka cattle, presenting opportunities for enhancing dairy cattle production in tropical climates. Further validation through genome-wide association studies and transcriptomic analyses is essential to fully exploit these candidate genes for selective breeding and genetic improvement in tropical dairy cattle.
Topics: Animals; Cattle; Genome-Wide Association Study; Milk; Female; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Lactation; Genome; Phenotype
PubMed: 38892330
DOI: 10.3390/ijms25116142 -
Animals : An Open Access Journal From... Jun 2024Cow's milk and dairy products are the primary sources of OBCFAs, which have beneficial health properties. The goal of this study was to identify the factors that... (Review)
Review
Cow's milk and dairy products are the primary sources of OBCFAs, which have beneficial health properties. The goal of this study was to identify the factors that influence the content of OBCFAs in cow's milk and to indicate which OBCFAs can serve as biomarkers for fermentation processes. The content of OBCFAs in milk depends on the species of ruminants, with studies showing that this varies between 3.33% (in goat's milk) and 5.02% (in buffalo's milk). These differences also stem from the animals' energy balance, lactation phases, forage-to-concentrate ratio, and the presence of bioactive compounds in feeds, as well as management practices and environmental conditions. The OBCFAs in milk fat mainly come from rumen bacteria, but can also be synthesized de novo in the mammary gland, making them potentially useful noninvasive indicators of rumen fermentation. The concentration of BCFA is lower in colostrum and transitional milk than in full lactation milk. The proportions of total OBCFAs are higher in first- and second-parity cows. The most effective predictors of the biohydrogenation of fatty acids in the rumen are likely C18:2 -9, -11, -C16:0, and -C13:0. OBCFAs have been identified as potential biomarkers for rumen function, because their synthesis depends on specific bacteria. Strong predictors of subclinical ruminal acidosis include -C14:0, -C13:0, and C15:0. The concentration of ∑ OBCFA >C16 in milk is associated with fat mobilization and serves as a significant marker of the energy balance in cows.
PubMed: 38891752
DOI: 10.3390/ani14111706 -
Cells May 2024Subcutaneous adipocytes are crucial for mammary gland epithelial development during pregnancy. Our and others' previous data have suggested that adipo-epithelial...
Subcutaneous adipocytes are crucial for mammary gland epithelial development during pregnancy. Our and others' previous data have suggested that adipo-epithelial transdifferentiation could play a key role in the mammary gland alveolar development. In this study, we tested whether adipo-epithelial transdifferentiation occurs in vitro. Data show that, under appropriate co-culture conditions with mammary epithelial organoids (MEOs), mature adipocytes lose their phenotype and acquire an epithelial one. Interestingly, even in the absence of MEOs, extracellular matrix and diffusible growth factors are able to promote adipo-epithelial transdifferentiation. Gene and protein expression studies indicate that transdifferentiating adipocytes exhibit some characteristics of milk-secreting alveolar glands, including significantly higher expression of milk proteins such as whey acidic protein and β-casein. Similar data were also obtained in cultured human multipotent adipose-derived stem cell adipocytes. A miRNA sequencing experiment on the supernatant highlighted mir200c, which has a well-established role in the mesenchymal-epithelial transition, as a potential player in this phenomenon. Collectively, our data show that adipo-epithelial transdifferentiation can be reproduced in in vitro models where this phenomenon can be investigated at the molecular level.
Topics: Cell Transdifferentiation; Humans; Female; Adipocytes; Epithelial Cells; Animals; MicroRNAs; Mammary Glands, Animal; Organoids; Coculture Techniques; Mice; Models, Biological
PubMed: 38891075
DOI: 10.3390/cells13110943 -
Nature Communications Jun 2024In many cancers, a stem-like cell subpopulation mediates tumor initiation, dissemination and drug resistance. Here, we report that cancer stem cell (CSC) abundance is...
In many cancers, a stem-like cell subpopulation mediates tumor initiation, dissemination and drug resistance. Here, we report that cancer stem cell (CSC) abundance is transcriptionally regulated by C-terminally phosphorylated p27 (p27pT157pT198). Mechanistically, this arises through p27 co-recruitment with STAT3/CBP to gene regulators of CSC self-renewal including MYC, the Notch ligand JAG1, and ANGPTL4. p27pTpT/STAT3 also recruits a SIN3A/HDAC1 complex to co-repress the Pyk2 inhibitor, PTPN12. Pyk2, in turn, activates STAT3, creating a feed-forward loop increasing stem-like properties in vitro and tumor-initiating stem cells in vivo. The p27-activated gene profile is over-represented in STAT3 activated human breast cancers. Furthermore, mammary transgenic expression of phosphomimetic, cyclin-CDK-binding defective p27 (p27CK-DD) increases mammary duct branching morphogenesis, yielding hyperplasia and microinvasive cancers that can metastasize to liver, further supporting a role for p27pTpT in CSC expansion. Thus, p27pTpT interacts with STAT3, driving transcriptional programs governing stem cell expansion or maintenance in normal and cancer tissues.
Topics: Neoplastic Stem Cells; Humans; Cyclin-Dependent Kinase Inhibitor p27; Animals; STAT3 Transcription Factor; Female; Phosphorylation; Breast Neoplasms; Hyperplasia; Mice; Gene Expression Regulation, Neoplastic; Cell Self Renewal; Cell Line, Tumor; Mammary Glands, Animal; Jagged-1 Protein
PubMed: 38886396
DOI: 10.1038/s41467-024-48742-y -
Cureus May 2024Secretory carcinoma of the salivary gland (SCSG) is a rare head and neck tumor in adults and exceptional at the pediatric age. Its varied histological subtypes and...
Secretory carcinoma of the salivary gland (SCSG) is a rare head and neck tumor in adults and exceptional at the pediatric age. Its varied histological subtypes and distinct clinical presentation pose diagnostic and therapeutic challenges. Therefore, standardized guidelines are of utmost importance for the care of these patients, especially in children. Here we present an 11-year-old male presented with a left cheek mass initially diagnosed as lipoma. A wide resection was performed and SCSG was revealed in the histopathologic and immunohistochemistry analysis. The presentation of this case provides valuable information on the diagnostic and therapeutic complexities of SCSG. It emphasizes the need for standardized guidelines and further research to optimize pediatric patient outcomes. Overall, this case report is a crucial resource for clinicians and researchers, highlighting the importance of interdisciplinary collaboration and early intervention in managing SCSG.
PubMed: 38883019
DOI: 10.7759/cureus.60355