Simulation-Based Approach to the Matching of a Dielectric-Filled Circular Waveguide Aperture.

The circular waveguide aperture or open-end radiator, one of the canonical antenna elements, can be filled with a dielectric material for miniaturization. With dielectric filling, the aperture reflection increases and impedance matching is necessary. This paper presents a simple but innovative simulation-based approach to the aperture matching of a dielectric-filled circular waveguide aperture. By properly loading the aperture with two- or three-section dielectric rings, the impedance matching is possible over a wide frequency range starting slightly above the TE11-mode cutoff and continuing upward. The material for the aperture matching is the same as that filling the waveguide. The proposed matching structure is analyzed and optimized using a simulation tool for the dielectric constant εr of the filling material ranging from 1.8 to 10. For εr ≥ 5, the unmatched reflection coefficient ranges from -6.0 dB to -0.9 dB while the matched reflection coefficient is from -20.4 dB to -10.0 dB. The impedance matching has been achieved over more than an octave bandwidth.

A New Technique for Broadband Matching of Open-Ended Rectangular Waveguide Radiator.

The maximum reflection at an open end of a standard rectangular waveguide is about -10 dB in its operating frequency range. It is often used without matching. For critical applications, it is desirable to further reduce the reflection coefficient. In this paper, a new technique is presented for the broadband impedance matching of an open-ended rectangular waveguide. The proposed technique employs three thin capacitive matching elements placed at proper intervals via a low-loss dielectric material. The capacitance of, and distance between, the matching elements are optimized for broadband impedance matching using a simulation tool. Based on the proposed technique, two design examples are presented for the matching of a WR75 waveguide radiator. A reflection coefficient of less than -16 dB and -20 dB has been achieved over a ratio bandwidth of 2.13:1 and 1.62:1, respectively.

Surface Engineering of Cu2O Photocathodes via Facile Graphene Oxide Decoration for Improved Photoelectrochemical Water Splitting.

Copper oxide (Cu2O) has attracted significant interest as an efficient photocathode for photoelectrochemical (PEC) water splitting owing to its abundance, suitable band gap, and band-edge potential. Nevertheless, a high charge recombination rate restricts its practical photoconversion efficiency and reduces the PEC water-splitting performance. To address this challenge, we present the facile electrodeposition of graphene oxide (GO) on the Cu2O photocathode surface. To determine the effect of varying GO weight percentages on PEC performance, varying amounts of GO were deposited on the Cu2O photocathode surface. The optimally deposited GO-Cu2O photocathode exhibited a photocurrent density of -0.39 to -1.20 mA/cm2, which was three times that of a photocathode composed of pristine Cu2O. The surface decoration of Cu2O with GO reduced charge recombination and improved the PEC water-splitting performance. These composites can be utilized in strategies designed to address the challenges associated with low-efficiency Cu2O photocathodes. The physicochemical properties of the prepared samples were comprehensively characterized by field-emission scanning electron microscopy, energy-dispersive spectroscopy, X-ray diffraction, Raman spectroscopy, UV-visible spectroscopy, and X-ray photoelectron spectroscopy. We believe that this research will pave the way for developing efficient Cu2O-based photocathodes for PEC water splitting.

Comparative Analysis of T4SS Molecular Architectures.

The recently published high-resolution R388 T4SS structure provides exciting new details about the complete complex of T4SS, including the components making up the stalk and arches, numerous symmetry mismatches between regions of the complex, and an intriguing interpretation of the closed stalk and radial symmetry of the inner membrane complex, which is related to pilus biogenesis assembly. However, there are a few unidentified densities in the electron microscopy map and portions of the identified component sequences for which the structure is not yet known. It is also unclear how well this minimized DNA-transporting T4SS predicts the structure of other T4SSs, such as expanded systems and those that transport proteins rather than DNA. In this review, we evaluate what can be inferred from the recent high-resolution structure of the R388 T4SS with respect to the Cag and Dot/Icm systems. These systems were selected because, given what is currently known about these systems, we expect them to present most structural differences compared to the R388 T4SS structure. Furthermore, we discuss bacterial physiology and diversity, the T4SS structures and their variations between different bacterial species. These insights may prove beneficial for researchers who elucidate the structure and functions of T4SS in different bacterial species.

Studies of functional properties of espin 1: Its interaction to actin filaments.

Actin is a multifunctional biomolecule that forms not only basic structural bodies such as filopodia and lamellipodia, but also large microvilli-like organelles like stereocilia. Actin consists of four sub-domains (S1, S2, S3, and S4), and the "target-binding groove" formed between S1 and S3 is the major binding site for various actin binding proteins. Actin filament dynamics are regulated by numerous actin binding proteins with different mechanisms of actin binding, assembly, and disassembly such as actin severing, branching, and bundling. Ectoplasmic specialization protein 1 (espin 1) is an actin binding and bundling protein that is specifically implicated in the elongation and stabilization of stereocilia as a binding partner with myosin III. However, little is known about the molecular structure, actin bundling, and stabilizing mechanism of espin 1; hence, we investigated the interaction between actin and espin 1 through structural data. In this study, we first purified human espin 1 in an E. coli system following a new detergent-free approach and then demonstrated the 2D structure of full-length espin 1 using transmission electron microscopy along with Nickel nitrilotriacetic acid nanogold labeling and 2D averaging using SPIDER. Furthermore, we also determined the espin 1 binding domain of actin using a co-sedimentation assay along with gelsolin and myosin S1. These findings are not only beneficial for understanding the actin binding and bundling mechanism of espin 1, but also shed light on its elongation, stabilization, and tip-localization mechanisms with myosin III. This study thus provides a basis for understanding the molecular structure of espin 1 and can contribute to various hearing-related diseases, such as hearing loss and vestibular dysfunction.

Crystal structure of yeast Gid10 in complex with Pro/N-degron.

The cellular glucose level has to be tightly regulated by a variety of cellular processes. One of them is the degradation of gluconeogenic enzymes such as Fbp1, Icl1, Mdh2, and Pck1 by GID (glucose-induced degradation deficient) E3 ubiquitin ligase. The Gid4 component of the GID ligase complex is responsible for recognizing the N-terminal proline residue of the target substrates under normal conditions. However, an alternative N-recognin Gid10 controls the degradation process under stressed conditions. Although Gid10 shares a high sequence similarity with Gid4, their substrate specificities are quite different. Here, we report the structure of Gid10 from Saccharomyces cerevisiae in complex with Pro/N-degron, Pro-Tyr-Ile-Thr, which is almost identical to the sequence of the natural substrate Art2. Although Gid10 shares many structural features with the Gid4 protein from yeast and humans, the current structure explains the unique structural difference for the preference of bulky hydrophobic residue at the second position of Pro/N-degron. Therefore, this study provides a fundamental basis for understanding of the structural diversity and substrate specificity of recognition components in the GID E3 ligase complex involved in the Pro/N-degron pathway.

Sex Differences in the Incidence of Obesity-Related Gastrointestinal Cancer.

Cancer is the second leading cause of death worldwide, with 9.6 million people estimated to have died of cancer in 2018. Excess body fat deposition is a risk factor for many types of cancer. Men and women exhibit differences in body fat distribution and energy homeostasis regulation. This systematic review aimed to understand why sex disparities in obesity are associated with sex differences in the incidence of gastrointestinal cancers. Cancers of the esophagus, liver, and colon are representative gastrointestinal cancers, and obesity is a convincing risk factor for their development. Numerous epidemiological studies have found sex differences in the incidence of esophageal, liver, and colorectal cancers. We suggest that these sexual disparities are partly explained by the availability of estrogens and other genetic factors regulating inflammation, cell growth, and apoptosis. Sex differences in gut microbiota composition may contribute to differences in the incidence and phenotype of colorectal cancer. To establish successful practices in personalized nutrition and medicine, one should be aware of the sex differences in the pathophysiology and associated mechanisms of cancer development.

Structural basis for the N-degron specificity of ClpS1 from Arabidopsis thaliana.

The N-degron pathway determines the half-life of proteins in both prokaryotes and eukaryotes by precisely recognizing the N-terminal residue (N-degron) of substrates. ClpS proteins from bacteria bind to substrates containing hydrophobic N-degrons (Leu, Phe, Tyr, and Trp) and deliver them to the caseinolytic protease system ClpAP. This mechanism is preserved in organelles such as mitochondria and chloroplasts. Bacterial ClpS adaptors bind preferentially to Leu and Phe N-degrons; however, ClpS1 from Arabidopsis thaliana (AtClpS1) shows a difference in that it binds strongly to Phe and Trp N-degrons and only weakly to Leu. This difference in behavior cannot be explained without structural information due to the high sequence homology between bacterial and plant ClpS proteins. Here, we report the structure of AtClpS1 at 2.0 Å resolution in the presence of a bound N-degron. The key determinants for α-amino group recognition are conserved among all ClpS proteins, but the α3-helix of eukaryotic AtClpS1 is significantly shortened, and consequently, a loop forming a pocket for the N-degron is moved slightly outward to enlarge the pocket. In addition, amino acid replacement from Val to Ala causes a reduction in hydrophobic interactions with Leu N-degron. A combination of the fine-tuned hydrophobic residues in the pocket and the basic gatekeeper at the entrance of the pocket controls the N-degron selectivity of the plant ClpS protein.

Targeted Degradation of Transcription Coactivator SRC-1 through the N-Degron Pathway.

Aberrantly elevated steroid receptor coactivator-1 (SRC-1) expression and activity are strongly correlated with cancer progression and metastasis. Here we report, for the first time, the development of a proteolysis targeting chimera (PROTAC) that is composed of a selective SRC-1 binder linked to a specific ligand for UBR box, a unique class of E3 ligases recognizing N-degrons. We showed that the bifunctional molecule efficiently and selectively induced the degradation of SRC-1 in cells through the N-degron pathway. Importantly, given the ubiquitous expression of the UBR protein in most cells, PROTACs targeting the UBR box could degrade a protein of interest regardless of cell types. We also showed that the SRC-1 degrader significantly suppressed cancer cell invasion and migration in vitro and in vivo. Together, these results demonstrate that the SRC-1 degrader can be an invaluable chemical tool in the studies of SRC-1 functions. Moreover, our findings suggest PROTACs based on the N-degron pathway as a widely useful strategy to degrade disease-relevant proteins.

Use of the LC3B-fusion technique for biochemical and structural studies of proteins involved in the N-degron pathway.

The N-degron pathway, formerly the N-end rule pathway, is a protein degradation process that determines the half-life of proteins based on their N-terminal residues. In contrast to the well-established in vivo studies over decades, in vitro studies of this pathway, including biochemical characterization and high-resolution structures, are relatively limited. In this study, we have developed a unique fusion technique using microtubule-associated protein 1A/1B light chain 3B, a key marker protein of autophagy, to tag the N terminus of the proteins involved in the N-degron pathway, which enables high yield of homogeneous target proteins with variable N-terminal residues for diverse biochemical studies including enzymatic and binding assays and substrate identification. Intriguingly, crystallization showed a markedly enhanced probability, even for the N-degron complexes. To validate our results, we determined the structures of select proteins in the N-degron pathway and compared them with the Protein Data Bank-deposited proteins. Furthermore, several biochemical applications of this technique were introduced. Therefore, this technique can be used as a general tool for the in vitro study of the N-degron pathway.

Z-ajoene from Crushed Garlic Alleviates Cancer-Induced Skeletal Muscle Atrophy.

Skeletal muscle atrophy is one of the major symptoms of cancer cachexia. Garlic (Allium sativum), one of the world's most commonly used and versatile herbs, has been employed for the prevention and treatment of diverse diseases for centuries. In the present study, we found that ajoene, a sulfur compound found in crushed garlic, exhibits protective effects against muscle atrophy. Using CT26 tumor-bearing BALB/c mice, we demonstrate in vivo that ajoene extract alleviated muscle degradation by decreasing not only myokines secretion but also janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) and SMADs/forkhead box (FoxO) signaling pathways, thereby suppressing muscle-specific E3 ligases. In mouse skeletal myoblasts, Z-ajoene enhanced myogenesis as evidenced by increased expression of myogenic markers via p38 mitogen-activated protein kinase (MAPK) activation. In mature myotubes, Z-ajoene protected against muscle protein degradation induced by conditioned media from CT26 colon carcinoma cells, by suppressing expression of muscle specific E3 ligases and nuclear transcription factor kappa B (NF-κB) phosphorylation which contribute to muscle atrophy. Moreover, Z-ajoene treatment improved myofiber formation via stimulation of muscle protein synthesis. These findings suggest that ajoene extract and Z-ajoene can attenuate skeletal muscle atrophy induced by cancer cachexia through suppressing inflammatory responses and the muscle wasting as well as by promoting muscle protein synthesis.