Insights in AAV-mediated antigen-specific immunity and a strategy for AAV vaccine dose reduction through AAV-extracellular vesicle association.

We previously showed therapeutic advantages of using a capsid-modified and encoded antigen-optimized AAV-based cancer vaccine to initiate strong antigen-specific immune responses and increase survival in a syngeneic mouse model of melanoma. In this study, we further explore AAV vaccine dose reduction and possible mechanisms of the immune response. Immunization with extracellular vesicle (EV)-associated AAV6-S663V encoded ovalbumin (OVA) or tyrosinase-related protein 1 (TRP-1) induced significantly higher levels of antigen-specific CD8 T cells compared with standard AAV in mice.

MYC directly transactivates CR2/CD21, the receptor of the Epstein-Barr virus, enhancing the viral infection of Burkitt lymphoma cells.

MYC is an oncogenic transcription factor dysregulated in about half of total human tumors. While transcriptomic studies reveal more than 1000 genes regulated by MYC, a much smaller fraction of genes is directly transactivated by MYC. Virtually all Burkitt lymphoma (BL) carry chromosomal translocations involving MYC oncogene.

NUAK Kinases: Brain-Ovary Axis.

Liver kinase B (LKB1) and adenosine monophosphate (AMP)-activated protein kinase (AMPK) are two major kinases that regulate cellular metabolism by acting as adenosine triphosphate (ATP) sensors. During starvation conditions, LKB1 and AMPK activate different downstream pathways to increase ATP production, while decreasing ATP consumption, which abrogates cellular proliferation and cell death. Initially, LKB1 was considered to be a tumor suppressor due to its loss of expression in various tumor types.

Minimum Effects of Sampling Time on the Apparent Digestibility of Nutrients and Blood Protein Catabolites in Light Lambs.

This experiment aimed to evaluate the effects of sampling time on organic matter (OM), crude protein (CP) and phosphorous (P) apparent digestibility and plasma urea and creatinine concentration in growing and finishing male Ripollesa lambs fed different CP concentrations in the diet. Twenty-four male Ripollesa lambs with 14.5 kg body weight (BW) were randomly assigned to two groups differing in CP content in the growing (14 to 19 kg of BW) and finishing (19 to 25 kg of BW) phases (20% vs.

AMPKα-like proteins as LKB1 downstream targets in cell physiology and cancer.

One of the key events in cancer development is the ability of tumor cells to overcome nutrient deprivation and hypoxia. Among proteins performing metabolic adaptation to the various cellular nutrient conditions, liver kinase B 1 (LKB1) and its main downstream target adenosine monophosphate (AMP)-activated protein kinase α (AMPKα) are important sensors of energy requirements within the cell. Although LKB1 was originally described as a tumor suppressor, given its role in metabolism, it potentially acts as a double-edged sword.

The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells.

The MAX network transcriptional repressor (MNT) is an MXD family transcription factor of the basic helix-loop-helix (bHLH) family. MNT dimerizes with another transcriptional regulator, MYC-associated factor X (MAX), and down-regulates genes by binding to E-boxes. MAX also dimerizes with MYC, an oncogenic bHLH transcription factor.

Myc stimulates cell cycle progression through the activation of Cdk1 and phosphorylation of p27.

Cell cycle stimulation is a major transforming mechanism of Myc oncoprotein. This is achieved through at least three concomitant mechanisms: upregulation of cyclins and Cdks, downregulation of the Cdk inhibitors p15 and p21 and the degradation of p27. The Myc-p27 antagonism has been shown to be relevant in human cancer.

Effects of maternal subnutrition during early pregnancy on cow hematological profiles and offspring physiology and vitality in two beef breeds.

This experiment evaluated the effects of subnutrition during early gestation on hematology in cows (Bos Taurus) and on hematological, metabolic, endocrine, and vitality parameters in their calves. Parda de Montaña and Pirenaica dams were inseminated and assigned to either a control (CONTROL, 100% requirements) or a nutrient-restricted group (SUBNUT, 65%) during the first third of gestation. Dam blood samples were collected on days 20 and 253 of gestation, and calf samples were obtained during the first days of life.