In order for cells to successfully multiply, a number of proteins are needed to correctly coordinate the replication and division process. In this study, students use fluorescence microscopy and molecular methods to study CCDC11, a protein critical in the formation of cilia. Interestingly, they uncover a new role for CCDC11, critical in the cell division across multiple human cell lines.
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High-throughput virtual screening of novel dihydropyrimidine monastrol analogs reveals robust structure-activity relationship to kinesin Eg5 binding thermodynamics
As cancer continues to take millions of lives worldwide, the need to create effective therapeutics for the disease persists. The kinesin Eg5 assembly motor protein is a promising target for cancer therapeutics as inhibition of this protein leads to cell cycle arrest. Monastrol, a small dihydropyrimidine-based molecule capable of inhibiting the kinesin Eg5 function, has attracted the attention of medicinal chemists with its potency, affinity, and specificity to the highly targeted loop5/α2/α3 allosteric binding pocket. In this work, we employed high-throughput virtual screening (HTVS) to identify potential small molecule Eg5 inhibitors from a designed set of novel dihydropyrimidine analogs structurally similar to monastrol.
Read More...Evolution of Neuroplastin-65
Human intelligence is correlated with variation in the protein neuroplastin-65, which is encoded by the NPTN gene. The authors examine the evolution of this gene across different animal species.
Read More...SOS-PVCase: A machine learning optimized lignin peroxidase with polyvinyl chloride (PVC) degrading properties
The authors looked at the primary structure of lignin peroxidase in an attempt to identify mutations that would improve both the stability and solubility of the peroxidase protein. The goal is to engineer peroxidase enzymes that are stable to help break down polymers, such as PVC, into monomers that can be reused instead of going to landfills.
Read More...The novel function of PMS2 mutation on ovarian cancer proliferation
With disruption of DNA repair pathways pertinent to the timeline of cancer, thorough evaluation of mutations relevant to DNA repair proteins is crucial within cancer research. One such mutation includes S815L PMS2 - a mutation that results in significant decrease of DNA repair function by PMS2 protein. While mutation of PMS2 is associated with significantly increased colorectal and endometrial cancer risk, much work is left to do to establish the functional effects of the S815L PMS2 mutation in ovarian cancer progression. In this article, researchers contribute to this essential area of research by uncovering the tumor-progressive effects of the S815L PMS2 mutation in the context of ovarian cancer cell lines.
Read More...Using the COmplex PAthway SImulator, Stage Analysis, and Chemical Kinetics to Develop a Novel Solution to Lower Tau Concentrations in Alzheimer’s Disease
In this study, the authors ask whether a Tau immunotherapy treatment, Hsp70 protein treatment, or dual treatment approach of both the Tau imunotherapy treatment and Hsp70 protein treatment leads to a greater reduction in Tau protein concentration in Alzheimer's disease. Overall, they conclude that the effectiveness of the treatment ultimately relies on the stage of Alzheimer’s.
Read More...Characterization of a UPEC DegS Mutant in vitro and in vivo
DegS is an integral inner membrane protein in E. coli that helps break down misfolded proteins. When it is mutated, there is a large increase in the production of outer membrane vesicles (OMVs), which are thought to play a role in pathogenesis. This study used mutant strains of uropathogenic E. coli (UPEC) to characterize the role of DegS and OMVs on UPEC virulence.
Read More...Identification of microwave-related changes in tissue using an ultrasound scan
Microwave energy (ME) is used in the medical field to denature protein structures, resulting in inactivation or destruction of abnormal cells. Identifying the extent of destruction of abnormal tissue (cancer tissue or tissue with abnormal electrical activity) is essential for accomplishing successful therapy and reducing collateral damage. Our study was an ex vivo assessment of the changes on ultrasound scans (US) in chicken tissue exposed to ME. We hypothesized that any changes in tissue structures would be recognized on the reflected ultrasound waves. Ultrasound scans of tissues change with exposure to microwaves with increasing reflection of ultrasound waves. With exposure to microwaves, surface level brightness on the ultrasound scans increases statistically significantly. The findings could be used in heat related (ME and radiofrequency) procedures where clinicians would be able to actively assess lesions in real-time. Further studies are required to assess changes in tissue during active exposure to different types of energies.
Read More...Assessing CDK5 as a Nanomotor for Chemotactic Drug Delivery
Enzyme chemotaxis is a thermodynamic phenomenon in which enzymes move along a substrate concentration gradient towards regions with higher substrate concentrations and can be used to steer nanovehicles towards targets along natural substrate concentrations. In patients with Alzheimer’s disease, a gradient of tau protein forms in the bloodstream. Tau protein is a substrate of the enzyme CDK5, which catalyzes the phosphorylation of tau protein and can travel using chemotaxis along tau protein gradients to increasing concentrations of tau and amyloid-beta proteins. The authors hypothesized that CDK5 would be able to overcome these barriers of Brownian motion and developed a quantitative model using Michaelis-Menten kinetics to define the necessary parameters to confirm and characterize CDK5’s chemotactic behavior to establish its utility in drug delivery and other applications.
Read More...In silico modeling of emodin’s interactions with serine/threonine kinases and chitosan derivatives
Here, through protein-ligand docking, the authors investigated the effect of the interaction of emodin with serine/threonine kinases, a subclass of kinases that is overexpressed in many cancers, which is implicated in phosphorylation cascades. Through molecular dynamics theyfound that emodin forms favorable interactions with chitosan and chitosan PEG (polyethylene glycol) copolymers, which could aid in loading drugs into nanoparticles (NPs) for targeted delivery to cancerous tissue. Both polymers demonstrated reasonable entrapment efficiencies, which encourages experimental exploration of emodin through targeted drug delivery vehicles and their anticancer activity.
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