Glycosylation in Indolent,Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling

The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients’ serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies.     

ACE2, the Receptor that Enables Infection by SARS-CoV-2: Biochemistry,Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators

Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein.     

Towards a Better Prediction of Cell Settling on Nanostructure Arrays—Simple Means to Complicated Ends

Vertical arrays of nanostructures (NSs) are emerging as promising platforms for probing and manipulating live mammalian cells. The broad range of applications requires different types of interfaces, but cell settling on NS arrays is not yet fully controlled and understood. Cells are both seen to deform completely into NS arrays and to stay suspended like tiny fakirs, which have hitherto been explained with differences in NS spacing or density. Here, a better understanding of this phenomenon is provided by using a model that takes into account the extreme membrane deformation needed for a cell to settle into a NS array. It is shown that, in addition to the NS density, cell settling depends strongly on the dimensions of the single NS, and that the settling can be predicted for a given NS array geometry. The predictive power of the model is confirmed by experiments and good agreement with cases from the literature. Furthermore, the influence of cell‐related parameters is evaluated theoretically and a generic method of tuning cell settling through surface coating is demonstrated experimentally. These findings allow a more rational design of NS arrays for the numerous exciting biological applications where the mode of cell settling is crucial.     

Fundamental Evaluation of Power Supply and Rectifiers for Wireless Power Transfer Using Magnetic Resonant Coupling

This paper provides a fundamental analysis of a power supply and rectifiers for wireless power transfer using magnetic resonant coupling (MRC). MRC enables efficient wireless power transfer over middle‐range transfer distances. MRC for wireless power transfer should operate at a high frequency in the industry science medical band, such as 13.56 MHz, because the size of the transfer device decreases at higher transfer frequencies. Therefore, the output frequency of the power supply on the transmitting side should be 13.56 MHz. In addition, the rectifier on the receiving side is operated at a high frequency. This paper focuses on the reflected power in the power supply and rectifiers. Thus, the parametric design method is clarified for the power supply, including a low‐pass filter to match the output, the impedance of the power supply with the characteristic impedance of the transmission line. In addition, the effects on the rectifiers of silicon carbide and gallium nitride diodes are confirmed by performing an experiment and a loss analysis.     

Cell-Free Synthesis of Selenoproteins in High Yield and Purity for Selective Protein Tagging

The selenol group of selenocysteine is much more nucleophilic than the thiol group of cysteine. Selenocysteine residues in proteins thus offer reactive points for rapid post-translational modification. Herein, we show that selenoproteins can be expressed in high yield and purity by cell-free protein synthesis by global substitution of cysteine by selenocysteine. Complete alkylation of solvent-exposed selenocysteine residues was achieved in 10 minutes with 4-chloromethylene dipicolinic acid (4Cl-MDPA) under conditions that left cysteine residues unchanged even after overnight incubation. Gd^III−Gd^III distances measured by double electron–electron resonance (DEER) experiments of maltose binding protein (MBP) containing two selenocysteine residues tagged with 4Cl-MDPA-Gd^III were indistinguishable from Gd^III−Gd^III distances measured of MBP containing cysteine reacted with 4Br-MDPA tags.     

Pressure drop and optimization meta-models for arbitrary low-height pleated filter shapes and flowrates

Journal of Mechanical Science and Technology - This study delivers equations useful for low-height pleated fibrous filter design: two pressure drop equations and one set of optimum design equations...     

Chemical-Shift Perturbations Reflect Bile Acid Binding to Norovirus Coat Protein: Recognition Comes in Different Flavors

Bile acids have been reported as important cofactors promoting human and murine norovirus (NoV) infections in cell culture. The underlying mechanisms are not resolved. Through the use of chemical shift perturbation (CSP) NMR experiments, we identified a low-affinity bile acid binding site of a human GII.4 NoV strain. Long-timescale MD simulations reveal the formation of a ligand-accessible binding pocket of flexible shape, allowing the formation of stable viral coat protein–bile acid complexes in agreement with experimental CSP data. CSP NMR experiments also show that this mode of bile acid binding has a minor influence on the binding of histo-blood group antigens and vice versa. STD NMR experiments probing the binding of bile acids to virus-like particles of seven different strains suggest that low-affinity bile acid binding is a common feature of human NoV and should therefore be important for understanding the role of bile acids as cofactors in NoV infection.     

Deliberately Losing Control of C−H Activation Processes in the Design of Small-Molecule-Fragment Arrays Targeting Peroxisomal Metabolism

Combined photochemical arylation, “nuisance effect” (S_NAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with S_NAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.     

Characteristics of tiger nut milk: effects of milling

A standard method for the extraction of tiger nut milk has been introduced. It has been shown that, although milling duration improves the yield of tiger nut milk solids and its nutrient composition, there is a quantifiable loss of nutrient in the pressing residue during milk extraction. Milling duration improved the colloidal stability of the milk against creaming during 16 h of storage. A higher milling intensity resulted in the aggregation of biological polymers which resulted in colloidal destabilisation. Milling improved the lightness and stability and reduced browning rate of the tiger nut milk during storage. This report is important for the production of tiger nut milk of consistent and comparable characteristics. Milling has been introduced as a processing method for the qualitative and quantitative modulation of the properties of tiger nut milk. It is recommended to develop further strategies to improve the colloidal stability of tiger nut milk as a beverage.