PDE8, a type of phosphodiesterase (PDE), is proven to be crucial in various cellular activities and physiological activities by influencing second messenger systems. It is involved in a wide range of diseases, including Alzheimer’s disease and various heart diseases. However, there is limited information about PDE8 selective inhibitors. This work aimed to improve the solubility and yield of PDE8 in the supernatant by exploring suitable culture conditions, including temperatures and different additives.
Osteosarcoma is a type of bone cancer that affects young adults and children. Early diagnosis of osteosarcoma is crucial to successful treatment. The current methods of diagnosis, which include imaging tests and biopsy, are time consuming and prone to human error. Hence, we used deep learning to extract patterns and detect osteosarcoma from histological images. We hypothesized that the combination of two different technologies (transfer learning and data augmentation) would improve the efficacy of osteosarcoma detection in histological images. The dataset used for the study consisted of histological images for osteosarcoma and was quite imbalanced as it contained very few images with tumors. Since transfer learning uses existing knowledge for the purpose of classification and detection, we hypothesized it would be proficient on such an imbalanced dataset. To further improve our learning, we used data augmentation to include variations in the dataset. We further evaluated the efficacy of different convolutional neural network models on this task. We obtained an accuracy of 91.18% using the transfer learning model MobileNetV2 as the base model with various geometric transformations, outperforming the state-of-the-art convolutional neural network based approach.
Control of voluntary and involuntary movements is one of the most important aspects of human neurological function, but the mechanisms of motor control are not completely understood. In this study, the authors use transcranial magnetic stimulation (TMS) to stimulate a portion of the motor cortex while subjects performed either discrete (e.g. throwing) or rhythmic (e.g. walking) movements. By recording electrical activity in the muscles during this process, the authors showed that motor evoked potentials (MEPs) measured in the muscles during TMS stimulation are larger in amplitude for discrete movements than for rhythmic movements. Interestingly, they also found that MEPs during transitions between rhythmic and discrete movements were nearly identical and larger in amplitude than those recorded during either rhythmic or discrete movements. This research provides important insights into the mechanisms of neurological control of movement and will serve as the foundation for future studies to learn more about temporal variability in neural activity during different movement types.
Although the 5-year survival rate for colorectal cancer is below 10%, it increases to greater than 90% if it is diagnosed early. We hypothesized from our research that analyzing non-synonymous single nucleotide variants (SNVs) in a patient's exome sequence would be an indicator for high genetic risk of developing colorectal cancer.
Anticholinergics are used in treating asthma, a chronic inflammation of the airways. These drugs block human M1 and M2 muscarinic acetylcholine receptors, inhibiting bronchoconstriction. However, studies have reported complications of anticholinergic usage, such as exacerbated eosinophil production and worsened urinary retention. Modification of known anticholinergics using bioisosteric replacements to increase efficacy could potentially minimize these complications. The present study focuses on identifying viable analogs of anticholinergics to improve binding energy to the receptors compared to current treatment options. Glycopyrrolate (G), ipratropium (IB), and tiotropium bromide (TB) were chosen as parent drugs of interest, due to the presence of common functional groups within the molecules, specifically esters and alcohols. Docking score analysis via AutoDock Vina was used to evaluate the binding energy between drug analogs and the muscarinic acetylcholine receptors. The final results suggest that G-A3, IB-A3, and TB-A1 are the most viable analogs, as binding energy was improved when compared to the parent drug. G-A4, IB-A4, IB-A5, TB-A3, and TB-A4 are also potential candidates, although there were slight regressions in binding energy to both muscarinic receptors for these analogs. By researching the effects of bioisosteric replacements of current anticholinergics, it is evident that there is a potential to provide asthmatics with more effective treatment options.
Here, recognizing the important role of bacterial biofilms in many life-threatening chronic infections, the authors investigated the effectiveness of a combination treatment on biofilms composed of up to three different common species within the lungs of cystic fibrosis patients with computational analysis. They found that a triple cocktail therapy targeting three different signaling pathways has significant potential as both a treatment and prophylaxis.
Antibiotics are one of the most common treatments for bacterial infections, but the emergence of antibiotic resistance is a major threat to the control of infectious diseases. Many factors contribute to the development of antibiotic resistance. One is bacterial conjugation from Gram-positive to Gram-negative bacteria where there is a transfer of resistance genes from Gram-positive to Gram-negative bacteria that could increase antibiotic resistance in the latter. In light of these observations, we decided to test whether Gram-negative bacteria that came into contact with Gram-positive bacteria had a higher resistance to the antimicrobial properties of spices than Gram-negative bacteria that did not come into contact with Gram-positive bacteria.
In this article, the authors systematically study whether the type of a star is correlated with the number of planets it can support. Their study shows that medium-sized stars are likely to support more than one planet, just like the case in our solar system. They predict that, of the hundreds of planets beyond our solar system, 6% might be habitable. As humans work to travel further and further into space, some of those might truly be suited for human life.
Understanding how bacteria respond to other bacteria could facilitate their ability to initiate and maintain their infectiousness. The phenomenon by which bacteria signal to each other via chemical signals is called quorum sensing, which could be targeted to deter bacterial infection in some cases if better understood. In this article, the authors study how a bacterium called V. fischeri uses quorum sensing to change bioluminescence, an easy readout that facilitates studying quorum sensing in this strain.
