ATM: Functions of ATM Kinase and Its Relevance to Hereditary Tumors

Ataxia–telangiectasia mutated (ATM) functions as a key initiator and coordinator of DNA damage and cellular stress responses. ATM signaling pathways contain many downstream targets that regulate multiple important cellular processes, including DNA damage repair, apoptosis, cell cycle arrest, oxidative sensing, and proliferation. Over the past few decades, associations between germline ATM pathogenic variants and cancer risk have been reported, particularly for breast and pancreatic cancers. In addition, given that ATM plays a critical role in repairing double-strand breaks, inhibiting other DNA repair pathways could be a synthetic lethal approach. Based on this rationale, several DNA damage response inhibitors are currently being tested in ATM-deficient cancers. In this review, we discuss the current knowledge related to the structure of the ATM gene, function of ATM kinase, clinical significance of ATM germline pathogenic variants in patients with hereditary cancers, and ongoing efforts to target ATM for the benefit of cancer patients.     

Characterization of a GH Family 20 Exo-β-N-acetylhexosaminidase with Antifungal Activity from Streptomyces avermitilis

We characterized SaHEX, which is a glycoside hydrolase (GH) family 20 exo-β-N-acetylhexosaminidase found in Streptomyces avermitilis. SaHEX exolytically hydrolyzed chitin oligosaccharides from their non-reducing ends, and yielded N-acetylglucosamine (GlcNAc) as the end product. According to the initial rate of substrate hydrolysis, the rates of (GlcNAc)₃ and (GlcNAc)₅ hydrolysis were greater than the rates for the other oligosaccharides. The enzyme exhibited antifungal activity against Aspergillus niger, which was probably due to hydrolytic activity with regard to chitin in the hyphal tips. Therefore, SaHEX has potential for use in GlcNAc production and food preservation.     

Structural modifications of sugar beet pectin and the relationship of structure to functionality

The emulsifying properties of sugar beet pectin (SBP) were investigated in relation to its molecular structure. SBP has been subjected to an enhancement process, and this material was here compared with conventional non-enhanced SBP. The oil-in-water emulsification properties of both were compared at 1.5% concentration at pH 3.25, using 15% middle-chain triglyceride as the oil phase. Their emulsification behavior after various enzyme treatments decreased in the order: protease > arabinanase/galactanase mixture > polygalacturonase. The enzyme treatment also decreased the molecular weight of SBP. Protease degraded the high molecular weight carbohydrate–protein complex. Arabinanase/galactanase mixture was more effective in decreasing the emulsification performance than polygalacturonase. The results confirm the key role of protein as the anchor for the oil droplets and identify also the contribution of the neutral lateral chains in stabilizing emulsions by forming a hydrated layer. Protein also aggregates, which functions as a linker for the association of the carbohydrate chains consequent to the enhancement process.     

Swallowing profiles of food polysaccharide gels in relation to bolus rheology

Swallowing profiles of food polysaccharide gels were investigated in relation to bolus rheology. Polysaccharide gel from either gellan gum or a mixture of gellan gum and psyllium seed gum was used as a model food. Acoustic analysis and sensory evaluation were carried out to investigate the swallowing profiles using the same human subjects. Model bolus was prepared through instrumental mastication using a mechanical simulator to mimic the action of the human jaw in the presence or absence of artificial saliva and was subjected to dynamic viscoelasticity measurements to investigate the rheological properties. Bolus from the binary gel was shorter in time required to transfer through the pharyngeal phase due to mass flow and was scored higher in sensory perceived cohesiveness (bolus forming) than that from gellan gum gel. Model bolus from the binary gel showed a rheologically weak gel (or structured fluid) behavior and was higher in structural homogeneity than that from gellan gum gel. Also, dynamic viscoelasticity parameters of the binary gel were less dependent on the addition level of saliva. Results indicate that the viscoelasticity balance is a key for texture design of dysphagia foods in relation to the saliva miscibility.     

Enantioselective Hydrogenation of Olefins using Commercially Available Pd/C. Chiral Heterogeneous Catalyst Applicable for High-Throughput Screening

Cinchonidine-modified Pd/C applicable for the high-throughput-guided study was developed. Commercial Pd/C catalysts were employed for the enantioselective hydrogenation of phenylcinnamic acid after the pretreatment, and some of the catalysts were found to result in the sufficient enantioselectivity. The Pd/C catalysts suitable for the cinchonidine modification were characterized by TEM and XAFS to have highly dispersed metal, 2.2 nm of the mean particles size for the best catalyst. The pre-modified Pd/C could be stored in a suspension accompanying with gradual decease in the product ee. The pre-modified catalyst was applicable for the high-throughput screening by using a parallel reactor in the 1/5-scale reactions.     

In Vitro Cytological Responses against Laser Photobiomodulation for Periodontal Regeneration

Periodontal disease is a chronic inflammatory disease caused by periodontal bacteria. Recently, periodontal phototherapy, treatment using various types of lasers, has attracted attention. Photobiomodulation, the biological effect of low-power laser irradiation, has been widely studied. Although many types of lasers are applied in periodontal phototherapy, molecular biological effects of laser irradiation on cells in periodontal tissues are unclear. Here, we have summarized the molecular biological effects of diode, Nd:YAG, Er:YAG, Er,Cr:YSGG, and CO₂ lasers irradiation on cells in periodontal tissues. Photobiomodulation by laser irradiation enhanced cell proliferation and calcification in osteoblasts with altering gene expression. Positive effects were observed in fibroblasts on the proliferation, migration, and secretion of chemokines/cytokines. Laser irradiation suppressed gene expression related to inflammation in osteoblasts, fibroblasts, human periodontal ligament cells (hPDLCs), and endothelial cells. Furthermore, recent studies have revealed that laser irradiation affects cell differentiation in hPDLCs and stem cells. Additionally, some studies have also investigated the effects of laser irradiation on endothelial cells, cementoblasts, epithelial cells, osteoclasts, and osteocytes. The appropriate irradiation power was different for each laser apparatus and targeted cells. Thus, through this review, we tried to shed light on basic research that would ultimately lead to clinical application of periodontal phototherapy in the future.     

Strong Binding and Off–On Signaling Functions of Deep-Red Fluorescent TO-PRO-3 for Influenza A Virus RNA Promoter Region

The RNA promoter region of the influenza A virus has recently attracted much attention as an RNA target for the development of anti-influenza drugs. However, there are very few reports on small RNA-binding ligands targeting this region. In this work, it is reported that TO-PRO-3, a thiazole orange analogue with a trimethine bridge, exhibits strong and selective binding to the internal loop structure of the influenza A virus RNA promoter. This binding accompanies the remarkable light-up response of TO-PRO-3 in the deep-red spectral region. By virtue of these binding and fluorescence signaling functions, TO-PRO-3 can act as a useful indicator for the assessment of the binding capabilities of various test compounds for this RNA region, with a view toward the development of anti-influenza drug candidates.