Structure and function of MDM2 and MDM4 in health and disease.

Both mouse double-minute 2 (MDM2), an E3 ubiquitin ligase, and its closely related paralog, MDM4, which lacks E3 activity, play central roles in cellular homeostasis. MDM-linked dysfunction is associated with an increased risk of oncogenesis, primarily through targeting the tumor suppressor protein p53 for ubiquitination and degradation. Recent studies have revealed multifaceted roles of MDM proteins that are p53 independent with implications for their oncogenic properties.

AMPK associates with and causes fragmentation of the Golgi by phosphorylating the guanine nucleotide exchange factor GBF1.

AMP-activated protein kinase (AMPK) is an energy sensor that regulates cellular functions in response to changes in energy availability. However, whether AMPK activity is spatially regulated, and the implications for cell function, have been unclear. We now report that AMPK associates with the Golgi, and that its activation by two specific pharmacological activators leads to Golgi fragmentation similar to that caused by the antibiotic Golgicide A, an inhibitor of Golgi-specific Brefeldin A resistance factor-1 (GBF1), a guanine nucleotide exchange factor that targets ADP-ribosylation factor 1 (ARF1).

Use of Affimer technology for inhibition of α2-antiplasmin and enhancement of fibrinolysis.

Hypofibrinolysis is a documented abnormality in conditions with high risk of vascular occlusion. A key inhibitor of fibrinolysis is α2-antiplasmin (α2AP), and we hypothesize that the Affimer technology, comprising small conformational proteins with 2 9-amino-acid variable regions, can be used to modulate α2AP activity and facilitate fibrinolysis. Using a phage display system, a library of Affimers was screened against α2AP.

"Affimer" synthetic protein scaffolds block oxidized LDL binding to the LOX-1 scavenger receptor and inhibit ERK1/2 activation.

In multicellular organisms, a variety of lipid-protein particles control the systemic flow of triacylglycerides, cholesterol, and fatty acids between cells in different tissues. The chemical modification by oxidation of these particles can trigger pathological responses, mediated by a group of membrane proteins termed scavenger receptors. The lectin-like oxidized low-density lipoprotein (LOX-1) scavenger receptor binds to oxidized low-density lipoprotein (oxLDL) and mediates both signaling and trafficking outcomes.

prediction, characterization, molecular docking and dynamic simulation studies for screening potential fungicides against leaf rust of .

is an important crop worldwide, which is a large source of food grain. demands on developed countries will grow every year, this increase in the demand is profoundly serious especially in the light climate change which would lead to a 29% reduction in final productivity. Rust fungus attacks the , specifically newly planted plants, which block the vascular system, stun, and finally damage grain and tillers.

Virtual high throughput screening of natural peptides against ErbB1 and ErbB2 to identify potential inhibitors for cancer chemotherapy.

Human epidermal growth factor receptors (EGFR), namely ErbB1/HER1, ErbB2/HER2/neu, ErbB3/HER3, and ErbB4/HER4, the trans-membrane family of tyrosine kinase receptors, are overexpressed in many types of cancers. These receptors play an important role in cell proliferation, differentiation, invasion, metastasis and angiogenesis including unregulated activation of cancer cells. Overexpression of ErbB1 and ErbB2 that occurs in several types of cancers is associated with poor prognosis leading to resistance to ErbB1-directed therapies.

The E2 ubiquitin-conjugating enzymes UBE2D1 and UBE2D2 regulate VEGFR2 dynamics and endothelial function.

Vascular endothelial growth factor receptor 2 (VEGFR2, encoded by KDR) regulates endothelial function and angiogenesis. VEGFR2 undergoes ubiquitination that programs this receptor for trafficking and proteolysis, but the ubiquitin-modifying enzymes involved are ill-defined. Herein, we used a reverse genetics screen for the human E2 family of ubiquitin-conjugating enzymes to identify gene products that regulate VEGFR2 ubiquitination and proteolysis.

A research-led flexible cell biology practical for biological sciences undergraduate and postgraduate degree courses.

A challenge in the pandemic era is to implement effective but flexible practical teaching for biological sciences courses. Such teaching needs to deliver conceptual, analytical and practical skills training while having the option to rapidly respond to health and safety issues, local regulations, staff and student concerns. In this paper, we describe a set of cell biology practicals (mini-project) that meets many of these requirements and provides flexibility in providing skills training both through online and in practical laboratory environments.

VEGFR endocytosis: Implications for angiogenesis.

The binding of vascular endothelial growth factor (VEGF) superfamily to VEGF receptor tyrosine kinases (VEGFRs) and co-receptors regulates vasculogenesis, angiogenesis and lymphangiogenesis. A recurring theme is that dysfunction in VEGF signaling promotes pathological angiogenesis, an important feature of cancer and pro-inflammatory disease states. Endocytosis of basal (resting) or activated VEGFRs facilitates signal attenuation and endothelial quiescence.

Effectiveness of a school-based nutrition education program on waist circumference and dietary behavior among overweight adolescents in Puducherry, India.

Background: The influence of western lifestyle such as high-caloric dense food and sedentary lifestyle has a great influence on Indian children, and the current prevalence of childhood overweight in India ranges between 4% and 22%. The primary aim of the study was to determine the change in growth parameters (waist circumference) as well as dietary behaviors at baseline and at the end of first, third, sixth, and ninth months among overweight adolescent girls and boys following a school-based nutritional education program.

Materials And Methods: The study was conducted in 2019 in four urban schools at Puducherry which were randomly assigned to study and control groups by lottery method, and 140 overweight children aged 11-14 years were in the study group and 140 children were in the control group.

Identification of FDA-approved drugs against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) through computational virtual screening.

Unlabelled: The SARS-CoV-2 coronavirus is responsible for the COVID-19 outbreak, which overwhelmed millions of people worldwide; hence, there is an urgency to identify appropriate antiviral drugs. This study focuses on screening compounds that inhibit RNA-dependent RNA-polymerase (RdRp) essential for RNA synthesis required for replication of positive-strand RNA viruses. Computational screening against RdRp using Food and Drug Administration (FDA)-approved drugs identified ten prominent compounds with binding energies of more than - 10.

Plasmin Inhibitor in Health and Diabetes: Role of the Protein as a Therapeutic Target.

The vascular obstructive thrombus is composed of a mesh of fibrin fibers with blood cells trapped in these networks. Enhanced fibrin clot formation and/or suppression of fibrinolysis are associated with an increased risk of vascular occlusive events. Inhibitors of coagulation factors and activators of plasminogen have been clinically used to limit fibrin network formation and enhance lysis.

TDO2 modulates liver cancer cell migration and invasion via the Wnt5a pathway.

Liver cancer is a malignant cancer phenotype for which there currently remains a lack of reliable biomarkers and therapeutic targets for disease management. Tryptophan 2,3‑dioxygenase (TDO2), a heme‑containing polyoxygenase enzyme, is primarily expressed in cells of the liver and nervous systems. In the present study, through the combination of cancer bioinformatics and analysis of clinical patient samples, it was shown that TDO2 expression in liver cancer tissue samples was significantly higher than that in normal tissues, and liver cancer patients with high TDO2 expression had a poor prognosis.

Monitoring VEGF-Stimulated Calcium Ion Flux in Endothelial Cells.

The endothelial response to vascular endothelial growth factor A (VEGF-A) regulates many aspects of animal physiology in health and disease. Such VEGF-A-regulated phenomena include vasculogenesis, angiogenesis, tumor growth and progression. VEGF-A binding to receptor tyrosine kinases such as vascular endothelial growth factor receptor 2 (VEGFR2 ) activates multiple signal transduction pathways and changes in homeostasis, metabolism, gene expression, cell proliferation, migration, and survival.

Affinity purification of fibrinogen using an Affimer column.

Background: Fibrinogen is an abundant plasma protein with an essential role in blood coagulation and haemostasis thus receiving significant research interest. However, protein purification is time consuming and commercial preparations often have protein contaminants. The aim of this study was to develop a new method to purify high quality and functional fibrinogen.

Purification and Analysis of Circulating Lipid Particles.

Lipid particles found in circulating extracellular fluids such as blood or lymph are essential for cellular homeostasis, metabolism and survival. Such particles provide essential lipids and fats which enable cells to synthesize new membranes and regulate different biochemical pathways. Imbalance in lipid particle metabolism can cause pathological states such as atherosclerosis.

Regulation of follistatin-like 3 expression by miR-486-5p modulates gastric cancer cell proliferation, migration and tumor progression.

Cancer development and progression can be regulated by the levels of endogenous factors. Gastric cancer is an aggressive disease state with poor patient prognosis, needing the development of new diagnostics and therapeutic strategies. We investigated the close association between follistatin-like 3 (FSTL3) and different cancers, and focused on its role in gastric cancer cell function.

Prognostic value of members of NFAT family for pan-cancer and a prediction model based on NFAT2 in bladder cancer.

Bladder cancer (BLCA) is one of the common malignant tumors of the urinary system. The poor prognosis of BLCA patients is due to the lack of early diagnosis and disease recurrence after treatment. Increasing evidence suggests that gene products of the nuclear factor of activated T-cells (NFAT) family are involved in BLCA progression and subsequent interaction(s) with immune surveillance.

Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease Therapy.

Vascular endothelial growth factors (VEGFs) bind to membrane receptors on a wide variety of cells to regulate diverse biological responses. The VEGF-A family member promotes vasculogenesis and angiogenesis, processes which are essential for vascular development and physiology. As angiogenesis can be subverted in many disease states, including tumour development and progression, there is much interest in understanding the mechanistic basis for how VEGF-A regulates cell and tissue function.

Scavenger Receptors as Biomarkers and Therapeutic Targets in Cardiovascular Disease.

The process of atherosclerosis leads to the formation of plaques in the arterial wall, resulting in a decreased blood supply to tissues and organs and its sequelae: morbidity and mortality. A class of membrane-bound proteins termed scavenger receptors (SRs) are closely linked to the initiation and progression of atherosclerosis. Increasing interest in understanding SR structure and function has led to the idea that these proteins could provide new routes for cardiovascular disease diagnosis, management, and treatment.

Fibrinogen interaction with complement C3: a potential therapeutic target to reduce thrombosis risk.

Complement C3 binds fibrinogen and compromises fibrin clot lysis thereby enhancing thrombosis risk. We investigated the role of fibrinogen-C3 interaction as a novel therapeutic target to reduce thrombosis risk by analysing: i) consistency in the fibrinolytic properties of C3, ii) binding sites between fibrinogen and C3 and iii) modulation of fibrin clot lysis by manipulating fibrinogen-C3 interactions. Purified fibrinogen and C3 from the same individuals (n=24) were used to assess inter-individual variability in the anti-fibrinolytic effects of C3.

Unilateral external jugular vein fenestration with variant anatomy of the retromandibular and facial vein.

External jugular vein (EJV), a significant superficial vein draining head and neck (H&N) region is been increasingly used for cannulation in diverse diagnostic purposes and intravenous therapies. The variant anatomy of formation and draining patterns of EJV and retromandibular veins were reported earlier. In the present case, EJV showed significant variation in one of the male cadaver, during routine H&N dissection.

ATF-2 and Tpl2 regulation of endothelial cell cycle progression and apoptosis.

Cells respond to soluble and membrane-bound factors to activate signalling cascades that control cell proliferation and cell death. Vascular endothelial growth factor A (VEGF-A) is a soluble ligand that modulates a variety of cellular responses including cell proliferation and apoptosis. It is not well understood how VEGF-A signalling pathways regulate cell proliferation and cell death.

Chemical activation of the Piezo1 channel drives mesenchymal stem cell migration via inducing ATP release and activation of P2 receptor purinergic signaling.

In this study, we examined the Ca -permeable Piezo1 channel, a newly identified mechanosensing ion channel, in human dental pulp-derived mesenchymal stem cells (MSCs) and hypothesized that activation of the Piezo1 channel regulates MSC migration via inducing ATP release and activation of the P2 receptor purinergic signaling. The Piezo1 mRNA and protein were readily detected in hDP-MSCs from multiple donors and, consistently, brief exposure to Yoda1, the Piezo1 channel-specific activator, elevated intracellular Ca concentration. Yoda1-induced Ca response was inhibited by ruthenium red or GsMTx4, two Piezo1 channel inhibitors, and also by Piezo1-specific siRNA.