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Background: Immune checkpoint inhibitors (ICIs) are crucial in cancer treatment; however, they carry the risk of immune-related adverse events (irAEs), such as enteritis. Case presentation: This study investigated the role of the gut microbiota during the onset and remission of irAE enteritis in a patient with stage IV melanoma undergoing anti-PD-1 and anti-CTLA-4 therapy. Following commencement of ICI treatment, the patient developed severe diarrhea and was diagnosed with grade 3 irAE enteritis. Steroid and probiotic treatments provided swift symptom relief and remission, as confirmed by reduced fecal calprotectin levels and gastrointestinal imaging. Microbiota diversity analysis conducted via 16S rRNA gene sequencing identified a decrease in Streptococcus prevalence with improvement in enteritis symptoms. Conversely, genera Fusobacterium, Faecalibacterium, Bacteroides, Prevotella, and Bifidobacterium showed increased representation after remission. These genera are associated with anti-inflammatory properties and fibrous substrate degradation, aiding gut health. Immunological assessment demonstrated fluctuations in cytokine expression and the modulation of costimulatory molecules, aligning with therapeutic interventions and microbiota alterations. Conclusions: Our findings indicate a significant correlation between gut microbiota and immune responses in irAE enteritis. This underscores the potential utility of microbiome profiling in predicting irAE occurrence and in providing treatment strategies, thereby promoting a more comprehensive approach to managing the adverse effects of ICIs. [ABSTRACT FROM AUTHOR]

Phacoemulsification has emerged as the global standard for cataract surgery, and various novel methods, tools, and agents have promoted surgical efficiency and reduced complications. Conventionally, the phaco tip, which cleaves and aspirates the cataractous lens, has been mainly constructed of metal. In this study, the risk of anterior capsule rupture was evaluated under conditions of different power modes, longitudinal (Mode-L), torsional (Mode-T), or both (Mode-LT), and different aspiration powers (0 or 200 mmHg), using a traditional metal phaco tip (Group-M) or a new phaco tip with a high-strength polymer overmold on the needle edge (Group-P), which was developed to reduce the risk of capsule rupture. One hundred twenty porcine eyes were used for experiments within a setting of typical human physiological intraocular pressure. We found that Group-M showed capsule rupture with a smaller ultrasound power than did Group-P, regardless of power mode or aspiration power. In Group-M, there was no significant difference in risk of capsule rupture among power modes, however in Group-P, capsule rupture was least likely to occur with Mode-T. These results provide useful information for inexperienced ophthalmologists to improve surgical safety. [ABSTRACT FROM AUTHOR]

In the Japanese hagfish, Eptatretus burgeri, approximately 21% of the genomic DNA in germ cells (2n = 52) consists of 16 chromosomes (eliminated [E]-chromosomes) that are eliminated from presumptive somatic cells (2n = 36). To uncover the eliminated genome (E-genome), we have identified 16 eliminated repetitive DNA families from eight hagfish species, with 11 of these repeats being selectively amplified in the germline genome of E. burgeri. Furthermore, we have demonstrated that six of these sequences, namely EEEb1–6, are exclusively localized on all 16 E-chromosomes. This has led to the hypothesis that the eight pairs of E-chromosomes are derived from one pair of ancestral chromosomes via multiple duplication events over a prolonged evolutionary period. NGS analysis has recently facilitated the re-assembly of two distinct draft genomes of E. burgeri, derived from the testis and liver. This advancement allows for the prediction of not only nonrepetitive eliminated sequences but also over 100 repetitive and eliminated sequences, accomplished through K-mer-based analysis. In this study, we report four novel eliminated repetitive DNA sequences (designated as EEEb7–10) and confirm the relative chromosomal localization of all eliminated repeats (EEEb1–10) by fluorescence in situ hybridization (FISH). With the exception of EEEb10, all sequences were exclusively detected on EEEb1-positive chromosomes. Surprisingly, EEEb10 was detected as an intense signal on EEEb1-positive chromosomes and as a scattered signal on other chromosomes in germ cells. The study further divided the eight pairs of E-chromosomes into six groups based on the signal distribution of each DNA family, and fiber-FISH experiments showed that the EEEb2–10 family was dispersed in the EEEb1-positive extended chromatin fiber. These findings provide new insights into the mechanisms underlying chromosome elimination and the evolution of E-chromosomes, supporting our previous hypothesis. [ABSTRACT FROM AUTHOR]

We discovered that the aluminosilicate-stabilized silyl cations, which were created from a solid-acid catalyst, the proton-exchanged montmorillonite, and Et3 SiH, efficiently promoted the reductive benzylation of benzenes with aromatic carboxylic acid chlorides and Et3 SiH in one pot. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the age-related change in color visual acuity (CVA) in normal eyes. Methods: In total, 162 normal eyes (162 subjects, women: 52, men: 110, age range: 15–68 years) with best-corrected visual acuity (BCVA) ≥20/13 were enrolled. Fifteen colors from the New Color Test (chroma 6) were applied to Landolt "C" rings, white point D65 was applied as background, and a luminance of 30 cd/m2 was set for both the rings and the background. These rings were used to measure the chromatic spatial discrimination acuity as the CVA value, while changing the stimulus size. Correlations of the CVA value of each color and age were evaluated. Mean CVA values of all 15 colors (logarithm of the minimum angle of resolution) were compared between age groups in 10-year increments. Results: Nine CVA values (red, yellow-red, red-yellow, green, blue-green, green-blue, purple, red-purple, and purple-red) were negatively correlated with age (all p<0.05); the remaining six (yellow, green-yellow, yellow-green, blue, purple-blue, and blue-purple), as well as BCVA were not. The age groups with the best to worst mean CVA values of 15 colors were as follows: 20–29 (mean ± standard deviation, 0.303 ± 0.113), 30–39 (0.324 ± 0.096), 10–19 (0.333 ± 0.022), 50–59 (0.335 ± 0.078), 40–49 (0.339 ± 0.096), and 60–69 (0.379 ± 0.125) years. There were statistically significant differences between mean CVA values of the following groups: 20–29 and 40–49 years; 20–29 and 60–69 years; 30–39 and 60–69 years (all p<0.01). Conclusions: The CVA values related to the medium/long-wavelength-sensitive cones were more susceptible to aging than those related to the short-wavelength-sensitive cones. This differed from previous reports, and may be related to the difference in the range of foveal cone function evaluated with each examination. [ABSTRACT FROM AUTHOR]

A transporter of the multidrug and toxic compound extrusion (MATE) family, Nicotiana tabacum MATE2 (NtMATE2), is located in the vacuole membrane of the tobacco plant root and is involved in the transportation of nicotine, a secondary or specialized metabolic compound in Solanaceae. Here, we report the crystal structures of NtMATE2 in its outward‐facing forms. The overall structure has a bilobate V‐shape with pseudo‐symmetrical assembly of the N‐ and C‐lobes. In one crystal structure, the C‐lobe cavity of NtMATE2 interacts with an unidentified molecule that may partially mimic a substrate. In addition, NtMATE2‐specific conformational transitions imply that an unprecedented movement of the transmembrane α‐helix 7 is related to the release of the substrate into the vacuolar lumen. [ABSTRACT FROM AUTHOR]

The development of near‐infrared (NIR) fluorophores that have both excellent chemical stability and photostability, as well as efficient cell permeability, is highly demanded. In this study, we present phospha‐rhodamine (POR) dyes which display significantly improved performance for protein labeling. This is achieved by incorporating a 2‐carboxy‐3‐benzothiophenyl group at the 9‐position of the xanthene scaffold. The resulting cis and trans isomers were successfully isolated and structurally characterized using X‐ray diffraction. The HaloTag ligand conjugates of the two isomers exhibited different staining abilities in live cells. While the cis isomer showed non‐specific accumulation on the organelle membranes, the trans isomer selectively labeled the HaloTag‐fused proteins, enabling the long‐term imaging of cell division and the 5‐color imaging of cell organelles. Molecular dynamics simulations of the HaloTag ligand conjugates within the lipid membrane suggested that the cis isomer is more prone to forming oligomers in the membrane. In contrast, the oligomerization of the trans isomer is effectively suppressed by its interaction with the lipid molecules. By taking advantage of the superior labeling performance of the trans isomer and its NIR‐emissive properties, multi‐color time‐lapse super‐resolution 3D imaging, namely super‐resolution 5D‐imaging, of the interconnected network between the endoplasmic reticulum and microtubules was achieved in living cells. [ABSTRACT FROM AUTHOR]

The development of near‐infrared (NIR) fluorophores that have both excellent chemical stability and photostability, as well as efficient cell permeability, is highly demanded. In this study, we present phospha‐rhodamine (POR) dyes which display significantly improved performance for protein labeling. This is achieved by incorporating a 2‐carboxy‐3‐benzothiophenyl group at the 9‐position of the xanthene scaffold. The resulting cis and trans isomers were successfully isolated and structurally characterized using X‐ray diffraction. The HaloTag ligand conjugates of the two isomers exhibited different staining abilities in live cells. While the cis isomer showed non‐specific accumulation on the organelle membranes, the trans isomer selectively labeled the HaloTag‐fused proteins, enabling the long‐term imaging of cell division and the 5‐color imaging of cell organelles. Molecular dynamics simulations of the HaloTag ligand conjugates within the lipid membrane suggested that the cis isomer is more prone to forming oligomers in the membrane. In contrast, the oligomerization of the trans isomer is effectively suppressed by its interaction with the lipid molecules. By taking advantage of the superior labeling performance of the trans isomer and its NIR‐emissive properties, multi‐color time‐lapse super‐resolution 3D imaging, namely super‐resolution 5D‐imaging, of the interconnected network between the endoplasmic reticulum and microtubules was achieved in living cells. [ABSTRACT FROM AUTHOR]

Abstract YidC/Alb3/Oxa1 family proteins are involved in the insertion and assembly of membrane proteins. The core five transmembrane regions of YidC, which are conserved in the protein family, form a positively charged cavity open to the cytoplasmic side. The cavity plays an important role in membrane protein insertion. In all reported structural studies of YidC, the second cytoplasmic loop (C2 loop) was disordered, limiting the understanding of its role. Here, we determined the crystal structure of YidC including the C2 loop at 2.8 Å resolution with R / R free = 21.8/27.5. This structure and subsequent molecular dynamics simulation indicated that the intrinsic flexible C2 loop covered the positively charged cavity. This crystal structure provides the coordinates of the complete core region including the C2 loop, which is valuable for further analyses of YidC. [ABSTRACT FROM AUTHOR]

Investigates the primary photochemistry of gas phase dichlorine monoxide (Cl[sub 2]O) and of hypochlorous acid after excitation at 235 nanometers. Angular distributions by chlorine spin orbits; Description of the ground state atom partnering by ClO fragments; Rationalization of findings in terms of model potential energy surface.

Purpose: To evaluate the color visual acuity (CVA) of young healthy subjects using colored Landolt rings and the effect of background luminance level on the CVA. Materials and methods: We measured the CVA of 20 young healthy subjects (age: 23.8 ± 3.8 years) with different colors using a computer and a liquid crystal display, with 15 Landolt ring colors (30 cd/m2) with a background luminance of 30 cd/m2, and then 100 cd/m2. We then used different background luminance levels (15–50 cd/m2) using four Landolt ring colors (red, green–yellow, green, and blue–green) to evaluate the effect of the background luminance level on CVA. Results: The CVA significantly differed among the colors with a background luminance of 30 cd/m2 (p < 0.0001). Green–yellow and blue–purple had poor CVA (high LogMAR value; 0.808 ± 0.107 and 0.633 ± 0.150, respectively) with a background luminance of 30 cd/m2 (same luminance as the Landolt rings). There were no significant differences in the CVAs among the colors with a background luminance of 100 cd/m2 (p = 0.5999). There were no significant difference in the CVA between background luminance 30 cd/m2 and other luminance level ranging from 28 to 32 cd/m2 for colors of red, green–yellow, green, and blue–green. Conclusions: The results reveal that the background luminance of Landolt rings affects the CVA. Distinctive CVAs for each color are measured by equalizing the luminance between the Landolt ring and the background. We consider that the poor CVAs of these colors reflect the visual function of S-cone, because GY and BP are included in the confusion locus of tritan axis on the chromaticity diagram. We believe that CVA assessment may be useful for individuals who have known or suspected ocular dysfunction or color vision deficiencies. [ABSTRACT FROM AUTHOR]

The delignification of Japanese beech ( Fagus crenata) has been evaluated under conditions of subcritical phenol (230°C/1.2 MPa) and subcritical water (230°C/2.9 MPa). In the former, more than 90% of the original lignin was decomposed and removed, while in subcritical water, around half of the original lignin was left as insoluble residue. Ultraviolet (UV) microscopic images of the insoluble residues showed that the lignin in the secondary walls is decomposed and removed under both conditions. These images also revealed that the lignin in the compound middle lamella (CML) is resistant to subcritical water, but not to subcritical phenol. Results of alkaline nitrobenzene oxidation of the residual lignin confirmed these observations. Lignin in Japanese beech wood was phenolated by subcritical phenol, which was efficiently removed due to its high solubility in the reactant. It is obvious that CML is rich in condensed-type linkages facilitating rapid solvolysis by phenol. The topochemistry of the plant has a pronounced impact on its delignification behavior. [ABSTRACT FROM AUTHOR]

We are going to perform an inclusive spectroscopy experiment of η′ mesic nuclei with the C( p, d) reaction to study in-medium properties of the η′ meson. In nuclear medium, the η′ meson mass may be reduced due to partial restoration of chiral symmetry. In case of sufficiently large mass reduction and small absorption width of η′ at normal nuclear density, peak structures of η′ mesic states in C will be observed near the η′ emission threshold even in an inclusive spectrum. The experiment will be carried out at GSI with proton beam supplied by SIS using FRS as a spectrometer. The detail of the experiment is described. [ABSTRACT FROM AUTHOR]

Multidrug and toxic compound extrusion (MATE) family transporters are conserved in the three primary domains of life (Archaea, Bacteria and Eukarya), and export xenobiotics using an electrochemical gradient of H+ or Na+ across the membrane. MATE transporters confer multidrug resistance to bacterial pathogens and cancer cells, thus causing critical reductions in the therapeutic efficacies of antibiotics and anti-cancer drugs, respectively. Therefore, the development of MATE inhibitors has long been awaited in the field of clinical medicine. Here we present the crystal structures of the H+-driven MATE transporter from Pyrococcus furiosus in two distinct apo-form conformations, and in complexes with a derivative of the antibacterial drug norfloxacin and three in vitro selected thioether-macrocyclic peptides, at 2.1-3.0 Å resolutions. The structures, combined with functional analyses, show that the protonation of Asp 41 on the amino (N)-terminal lobe induces the bending of TM1, which in turn collapses the N-lobe cavity, thereby extruding the substrate drug to the extracellular space. Moreover, the macrocyclic peptides bind the central cleft in distinct manners, which correlate with their inhibitory activities. The strongest inhibitory peptide that occupies the N-lobe cavity may pave the way towards the development of efficient inhibitors against MATE transporters. [ABSTRACT FROM AUTHOR]

Abstract: A new sledge net system using propulsion vehicles has been developed to sample more efficiently the demersal juveniles of marine organisms. A net attached to a sledge maneuvered by a SCUBA diver who uses operating switches on a steering handle to adjust the altitude of the sledge and the position of the tickler chains to ensure that the footcloth of the mouth of the net remains in constant contact with the bottom surface. Video camera, flow meter, compass, and dive computers are positioned on the sledge net in the view of the diver. Given that the system can attain speeds of 70cms−1, the net can be employed to capture highly mobile fish. Unlike most boat-based net sampling methods, the use of propulsion vehicles means that there are no sound or vibration disturbances due to the boat and tow ropes typically used to maneuver these types of sampling nets. Marine fauna was collected at monthly intervals over a two-year period in a sampling area along the southern coast of Hokkaido, Japan. A total of 2641 specimens comprising 61 species and including five species which were the first records for the region were collected. These findings suggest that the new sledge net system employing propulsion vehicles was effective for sampling demersal juveniles, particularly in situations where sledge nets towed by boats or push nets cannot be deployed. [Copyright &y& Elsevier]

The magnesium ion Mg2+ is a vital element involved in numerous physiological processes. Mg2+ has the largest hydrated radius among all cations, whereas its ionic radius is the smallest. It remains obscure how Mg2+ transporters selectively recognize and dehydrate the large, fully hydrated Mg2+ cation for transport. Recently the crystal structures of the CorA Mg2+ transporter were reported. The MgtE family of Mg2+ transporters is ubiquitously distributed in all phylogenetic domains, and human homologues have been functionally characterized and suggested to be involved in magnesium homeostasis. However, the MgtE transporters have not been thoroughly characterized. Here we determine the crystal structures of the full-length Thermus thermophilus MgtE at 3.5 Å resolution, and of the cytosolic domain in the presence and absence of Mg2+ at 2.3 Å and 3.9 Å resolutions, respectively. The transporter adopts a homodimeric architecture, consisting of the carboxy-terminal five transmembrane domains and the amino-terminal cytosolic domains, which are composed of the superhelical N domain and tandemly repeated cystathionine-β-synthase domains. A solvent-accessible pore nearly traverses the transmembrane domains, with one potential Mg2+ bound to the conserved Asp 432 within the pore. The transmembrane (TM)5 helices from both subunits close the pore through interactions with the ‘connecting helices’, which connect the cystathionine-β-synthase and transmembrane domains. Four putative Mg2+ ions are bound at the interface between the connecting helices and the other domains, and this may lock the closed conformation of the pore. A structural comparison of the two states of the cytosolic domains showed the Mg2+-dependent movement of the connecting helices, which might reorganize the transmembrane helices to open the pore. These findings suggest a homeostasis mechanism, in which Mg2+ bound between cytosolic domains regulates Mg2+ flux by sensing the intracellular Mg2+ concentration. Whether this presumed regulation controls gating of an ion channel or opening of a secondary active transporter remains to be determined. [ABSTRACT FROM AUTHOR]

The MgtE family of Mg2+ transporters is ubiquitously conserved in all domains of life. The cytosolic domains of the MgtE Mg2+ transporters include a cystathionine-β-synthase (CBS) domain which is known to play a regulatory function in transporter proteins. The cytosolic domain of MgtE from Thermus thermophilus was overexpressed, purified and crystallized in the presence and absence of Mg2+. The crystals formed in the presence of Mg2+ diffracted X-rays to 2.3 Å resolution using synchrotron radiation, belong to space group P6522 with unit-cell parameters a = b = 57.7, c = 317.6 Å and are expected to contain one molecule in the asymmetric unit. The crystals formed in the absence of Mg2+ diffracted X-rays to 3.5 Å resolution using synchrotron radiation, belong to space group P212121 with unit-cell parameters a = 77.0, b = 100.3, c = 100.3 Å and are expected to contain two molecules in the asymmetric unit. [ABSTRACT FROM AUTHOR]

Abstract: Although thromboxane (TX)A2 is involved in allergic rhinitis, the mechanisms inducing nasal blockage have not been elucidated. We evaluated the roles of nasal mucosal vascular changes following intranasal instillation of the TXA2 analog U-46619 or leukotriene (LT)D4 to induce nasal blockage in a guinea pig model of allergic rhinitis. Both U-46619- and LTD4-induced nasal blockages in sensitized animals were swiftly and completely suppressed by a vasoconstrictor, naphazoline. The nitric oxide synthase inhibitor N ω-nitro-l-arginine methyl ester relieved LTD4-induced nasal blockage, but not U-46619-induced nasal blockage. Although both agonists produced vasodilatation of nasal mucosa in vivo, LTD4 caused vasodilatation while U-46619 caused vasoconstriction in vitro. Both LTD4- and U-46619-induced nasal blockages in vivo should depend on vasodilatation of nasal mucosa. LTD4-induced nasal blockage is induced by direct vasodilatation via nitric oxide. In contrast, U-46619-induced nasal blockage may be associated with contraction of a certain vein that should exist at the exit of capacitance vessels, leading to congestion of the nasal mucosa. [Copyright &y& Elsevier]

Objective was to compare the accuracy of three formulas (IA; Sanders, Retzlaff, and Kraff/Theoretical (SRK/T); and Barrett Universal II (BUII)), in achieving emmetropia in eyes implanted with TFNT lenses (Alcon). Patients and Methods: A total of 145 eyes of 145 patients were included in the evaluation. Preoperative data were obtained from IOLMaster 700, while intraoperative data were collected from ORA SYSTEMTM. Visual acuity ≥ 0.8 at the 3-month post-surgery mark was confirmed. We assessed refractive prediction error (RPE), which is the difference between predicted refraction (PR) and postoperative subjective refraction. This evaluation aimed to identify the optimal IOL power with the implemented algorithm. Results: Among the 145 eyes evaluated, 55.9%, 78.7%, and 97.2% achieved postoperative subjective refraction within ± 0.13 Diopters (D), ± 0.25 D, and ± 0.50 D, respectively. The percentages of eyes within ± 0.25 D of PR varied by formula type, with values of 57%, 57%, and 54% for IA, BUII, and SRK/T, respectively. For eyes with short to medium axial length (AL< 26.00 mm), the percentages within ± 0.25 D of RPE were 52%, 58%, and 58% for IA, SRK/T, and BUII, respectively. In contrast, for eyes with long axial length (≥ 26.00 mm) the percentages were 68%, 52%, and 45% for IA, BUII, and SRK/T, respectively. Conclusion: The proposed majority decision algorithm incorporating IA and two IOL frequency formulas was effective in reducing postoperative refractive error. IA was particularly beneficial for eyes with long axial length. These findings suggest the algorithm has potential to optimize IOL power selection to improve quality of life of patients and clinical practice outcomes. [ABSTRACT FROM AUTHOR]

With the widespread use of digital pen tablets and touch displays, sketch-based interactive computer-aided design (CAD) user interfaces have attracted considerable attention. In an existing interface called the Sketch Input Tracer (SKIT), however, the editing operation performed via an over-sketching stroke can target only a single geometric object at any given time. To overcome this limitation, in this study, we propose a new general-purpose sketch-based interface developed for use in two-dimensional CAD systems. In the proposed interface, a sketch-based editing operation can simultaneously modify the geometry and topology of multiple geometric objects via over-sketching. The interface was developed based on the fuzzy logic-based strategy of SKIT. With this interface, a user can draw in a creative manner; for example, they can begin with a rough sketch and progressively create a detailed design through repeated over-sketches. The results of experiments conducted demonstrate that experts can control the proposed interactive drawing interface and beginners can habituate to controlling it. [Display omitted] • A new general-purpose sketch-based interface for 2D CAD systems is proposed. • The interface is based on the SKIT fuzzy-logic strategy. • An editing operation via over-sketching can modify multiple geometric objects. • Users can repeatedly over-sketch on a rough drawing to obtain a detailed design. • Adequate controllability by trained users of the interface is shown quantitatively. [ABSTRACT FROM AUTHOR]

The cation diffusion facilitator (CDF) family proteins are ubiquitously distributed in the three domains of life and transport metals such as zinc and various heavy metals. Prokaryotic CDF proteins consists of an N-terminal putative six-transmembrane domain followed by a C-terminal cytosolic domain. The cytosolic domain of the CDF-family protein from Thermotoga maritima has been overexpressed, purified and crystallized. The selenomethionine-substituted crystals diffracted X-rays to 2.5 Å resolution using synchrotron radiation, belonged to space group R32, with unit-cell parameters a = b = 97.7, c = 83.4 Å, and are expected to contain one molecule in each asymmetric unit. [ABSTRACT FROM AUTHOR]

The MgtE family of Mg2+ transporters are ubiquitously conserved in all three domains. The genes encoding full-length MgtE from seven different species were cloned. Three of the seven MgtE transporters were overexpressed and purified for use in crystallization trials. Only Thermus thermophilus MgtE was successfully crystallized using the sitting-drop vapour-diffusion method. Selenomethionine-substituted (SeMet) crystals were obtained by cross-microseeding using the native microcrystals. The SeMet crystals diffracted X-rays to 3.5 Å resolution using synchrotron radiation and belong to space group C2221, with unit-cell parameters a = 118.3, b = 134.9, c = 366.2 Å. Structure determination is in progress. [ABSTRACT FROM AUTHOR]

The article titled "Innentitelbild: Stereochemistry-Dependent Labeling of Organelles with a Near-Infrared-Emissive Phosphorus-Bridged Rhodamine Dye in Live-Cell Imaging" presents a new photostable near-infrared (NIR) labeling agent developed by Masayasu Taki, Yasushi Okada, Florence Tama, Shigehiro Yamaguchi, and their colleagues. The compounds, which are stereoisomers based on phosphorus-bridged rhodamine, have different staining abilities in live cells. The trans-isomer can permeate organelle membranes and label target proteins, while the cis-isomer accumulates nonspecifically on lipid bilayers. The authors of the article are Qian Wu, Masayasu Taki, Yoshiki Tanaka, Manish Kesherwani, Quan Manh Phung, Sawako Enoki, Yasushi Okada, Florence Tama, and Shigehiro Yamaguchi. [Extracted from the article]

The article titled "Inside Cover: Stereochemistry-Dependent Labeling of Organelles with a Near-Infrared-Emissive Phosphorus-Bridged Rhodamine Dye in Live-Cell Imaging" presents a new photostable near-infrared labeling agent developed by Masayasu Taki, Yasushi Okada, Florence Tama, Shigehiro Yamaguchi, and their team. The compounds, which are stereoisomers based on phosphorus-bridged rhodamine, have different staining abilities in live cells. The trans-isomer can permeate organelle membranes and label target proteins, while the cis-isomer accumulates nonspecifically on lipid bilayers. The authors of the article are Qian Wu, Masayasu Taki, Yoshiki Tanaka, Manish Kesherwani, Quan Manh Phung, Sawako Enoki, Yasushi Okada, Florence Tama, and Shigehiro Yamaguchi. [Extracted from the article]

Uptake of thiosulfate ions as an inorganic sulfur source from the environment is important for bacterial sulfur assimilation. Recently, a selective thiosulfate uptake pathway involving a membrane protein YeeE (TsuA) in Escherichia coli was characterized. YeeE-like proteins are conserved in some bacteria, archaea, and eukaryotes. However, the precise function of YeeE, along with its potential partner protein in the thiosulfate ion uptake pathway, remained unclear. Here, we assessed selective thiosulfate transport via Spirochaeta thermophila YeeE in vitro and characterized E. coli YeeD (TsuB) as an adjacent and essential protein for YeeE-mediated thiosulfate uptake in vivo. We further showed that S. thermophila YeeD possesses thiosulfate decomposition activity and that a conserved cysteine in YeeD was modified to several forms in the presence of thiosulfate. Finally, the crystal structures of S. thermophila YeeE-YeeD fusion proteins at 3.34-Å and 2.60-Å resolutions revealed their interactions. The association was evaluated by a binding assay using purified S. thermophila YeeE and YeeD. Based on these results, a model of the sophisticated uptake of thiosulfate ions by YeeE and YeeD is proposed. YeeE is a bacterial membrane protein that mediates thiosulfate uptake, but whether it acts alone it is unclear. This study identifies YeeD as a necessary partner of YeeE, characterizing the cooperation of the two proteins -which is based on the thiosulfate ion decomposition activity of YeeD- at both structural and functional levels. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the influence of aging on color vision in a large normal population using Standard Pseudoisochromatic Plates part-3 (SPP-3), which is a pseudoisochromatic plate test used to detect congenital or acquired color vision deficiency (CVD). Materials and methods: We retrospectively reviewed SPP-3 test results of 23,565 normal eyes of 23,565 subjects (women: 12,035; men: 11,530), who were examined between July 1993 and December 2010. The subjects had a mean age of 46.9 ± 18.5 years, ranging from 5 to 89 years, and they were evaluated following categorization into age groups with five-year increments. Subjects whose best-corrected visual acuity (BCVA) was 20/20 or better, with no history of ocular diseases, were included. Subjects with congenital CVD were excluded. Results: We found a negative correlation between age and the total number of correct answers in SPP-3 (Spearman's correlation coefficient, r = −0.5743; p <.0001). The total number of correct answers was the highest in subjects aged 10–14, 15–19, and 20–24 years (17.2 ± 0.9 [mean ±SD]). The total number of correct answers of these groups had significant differences from those in the 5–9 years age group and those aged >30 years (Dunn's post-hoc test: p <.0001). Among the 19 detection numerals in SPP-3, we found that the correct answer rates of six numerals decreased with aging, and the colors of the numerals and their backgrounds all located parallel to the tritanopic confusion line. Conclusions: Using SPP-3, we confirmed that aging influenced color vision, even in normal eyes with a good BCVA (20/20 or better). The total number of correct answers of SPP-3 was the highest in subjects aged 10–24 years and had already begun to decline in those in their 30s. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have attracted a great deal of interest as a therapeutic tool for renal fibrosis. Although both adipose-derived and bone marrow-derived MSCs (ADSCs and BMSCs, respectively) suppress renal fibrosis, which of these two has a stronger therapeutic effect remains unclear. This study aimed to compare the antifibrotic effects of ADSCs and BMSCs extracted from adipose tissue and bone marrow derived from the same rats. When cultured in serum-containing medium, ADSCs had a more potent inhibitory effect than BMSCs on renal fibrosis induced by ischemia-reperfusion injury in rats. ADSCs and BMSCs cultured in serum-free medium were equally effective in suppressing renal fibrosis. Mice infused with ADSCs (serum-containing or serum-free cultivation) had a higher death rate from pulmonary embolism than those infused with BMSCs. In vitro, mRNA levels of tissue factor, tumor necrosis factor-α-induced protein 6 and prostaglandin E synthase were higher in ADSCs than in BMSCs, while that of vascular endothelial growth factor was higher in BMSCs than in ADSCs. Although ADSCs had a stronger antifibrotic effect, these findings support the consideration of thromboembolism risk in clinical applications. Our results emphasize the importance of deciding between ADSCs and BMSCs based upon the target disease and culture method. [ABSTRACT FROM AUTHOR]

Summary The multidrug and toxic compound extrusion (MATE) family of proteins consists of transporters responsible for multidrug resistance in prokaryotes. In plants, a number of MATE proteins were identified by recent genomic and functional studies, which imply that the proteins have substrate-specific transport functions instead of multidrug extrusion. The three-dimensional structure of eukaryotic MATE proteins, including those of plants, has not been reported, preventing a better understanding of the molecular mechanism of these proteins. Here, we describe the crystal structure of a MATE protein from the plant Camelina sativa at 2.9 Å resolution. Two sets of six transmembrane α helices, assembled pseudo-symmetrically, possess a negatively charged internal pocket with an outward-facing shape. The crystal structure provides insight into the diversity of plant MATE proteins and their substrate recognition and transport through the membrane. [ABSTRACT FROM AUTHOR]

Background and Aim: Fluoropyrimidines (FPs) are key drugs in many chemotherapy regimens; however, recipients are often prone to diarrhea due to gastrointestinal toxicity. Disruption of the intestinal epithelial barrier function by FPs leads to dysbiosis, which may exacerbate intestinal epithelial cell damage as a secondary effect and trigger diarrhea. However, despite studies on chemotherapy-induced changes in the intestinal microbiome of humans, the relationship between dysbiosis and diarrhea is unclear. In this study, we aimed to investigate the relationship between chemotherapy-induced diarrhea and the intestinal microbiome. Methods: We conducted a single-center prospective observational study. Twenty-three patients who received chemotherapy, including FPs as first-line chemotherapy for colorectal cancer, were included. Stool samples were collected before the start of chemotherapy and after one cycle of treatment to analyze intestinal microbiome composition and perform PICRUSt predictive metagenomic analysis. Results: Gastrointestinal toxicity was observed in 7 of 23 patients (30.4%), diarrhea was observed in 4 (17.4%), and nausea and anorexia were observed in 3 (13.0%). In 19 patients treated with oral FPs, the α diversity of the microbial community decreased significantly following chemotherapy only in the diarrheal group. At the phylum level, the diarrheal group showed a significant decrease in the abundance of Firmicutes and a significant increase in the abundance of Bacteroidetes with chemotherapy (p = 0.013 and 0.011, respectively). In the same groups, at the genus level, Bifidobacterium abundance was significantly decreased (p = 0.019). In contrast, in the non-diarrheal group, Actinobacteria abundance increased significantly with chemotherapy at the phylum level (p = 0.011). Further, Bifidobacterium, Fusicatenibacter, and Dorea abundance significantly increased at the genus level (p = 0.006, 0.019, and 0.011, respectively). The PICRUSt predictive metagenomic analysis revealed that chemotherapy caused significant differences in membrane transport in KEGG pathway level 2 and in 8 KEGG pathway level 3, including transporters and oxidative phosphorylation in the diarrhea group. Conclusion: Organic-acid-producing bacteria seem to be involved in diarrhea associated with chemotherapy, including FPs. [ABSTRACT FROM AUTHOR]

Abstract The β-barrel assembly machinery (BAM) complex mediates the assembly of β-barrel membrane proteins in the outer membrane. BepA, formerly known as YfgC, interacts with the BAM complex and functions as a protease/chaperone for the enhancement of the assembly and/or degradation of β-barrel membrane proteins. To elucidate the molecular mechanism underlying the dual functions of BepA, its full-length three-dimensional structure is needed. Here, we report the crystal structure of full-length BepA at 2.6-Å resolution. BepA possesses an N-terminal protease domain and a C-terminal tetratricopeptide repeat domain, which interact with each other. Domain cross-linking by structure-guided introduction of disulfide bonds did not affect the activities of BepA in vivo , suggesting that the function of this protein does not involve domain rearrangement. The full-length BepA structure is compatible with the previously proposed docking model of BAM complex and tetratricopeptide repeat domain of BepA. Graphical Abstract Unlabelled Image Highlights • Crystal structure (2.6 Å) of full-length BepA, β-barrel assembly-enhancing protease BepA • Crystal structure represents both its functional and resting states. • Functional model of BepA was proposed. [ABSTRACT FROM AUTHOR]

Purpose: Analyzing the gut microbiome is essential for planning treatment strategies to manage esophageal squamous cell carcinoma. This study aimed to characterize the gut microbiome of patients with esophageal squamous cell carcinoma and to identify alterations in its composition during treatment. Methods: We observed alterations in the gut microbiome in 21 consecutive patients with esophageal squamous cell carcinoma at five different time points, from neoadjuvant treatment to postoperative surgery. Ten healthy individuals were used as a non-cancer control group. Fecal samples were collected and analyzed using 16S ribosomal ribonucleic acid sequencing. Results: Before treatment, participants with esophageal squamous cell carcinoma had different alpha and beta diversity in comparison to healthy controls. The number of Streptococcus, a facultative anaerobic bacterium, was significantly higher, whereas that of Faecalibacterium, an obligate anaerobic bacterium, was significantly lower. Both alpha and beta diversity remained unchanged during neoadjuvant treatment, but the alterations were pronounced after surgery. The increase in the relative abundance of Streptococcus and the decrease in that of Faecalibacterium also tended to be more pronounced after surgery. Conclusions: The gut microbiome in patients with esophageal squamous cell carcinoma is altered with surgical intervention. [ABSTRACT FROM AUTHOR]

BepA (formerly YfgC) is an Escherichia coli periplasmic protein consisting of an N-terminal protease domain and a C-terminal tetratricopeptide repeat (TPR) domain. We have previously shown that BepA is a dual functional protein with chaperone-like and proteolytic activities involved in membrane assembly and proteolytic quality control of LptD, a major component of the outer membrane lipopolysaccharide translocon. Intriguingly, BepA can associate with the BAM complex: the β-barrel assembly machinery (BAM) driving integration of β-barrel proteins into the outer membrane. However, the molecular mechanism of BepA function and its association with the BAM complex remains unclear. Here, we determined the crystal structure of the BepA TPR domain, which revealed the presence of two subdomains formed by four TPR motifs. Systematic site-directed in vivo photo-cross-linking was used to map the protein-protein interactions mediated by the BepA TPR domain, showing that this domain interacts both with a substrate and with the BAM complex. Mutational analysis indicated that these interactions are important for the BepA functions. These results suggest that the TPR domain plays critical roles in BepA functions through interactions both with substrates and with the BAM complex. Our findings provide insights into the mechanism of biogenesis and quality control of the outer membrane. [ABSTRACT FROM AUTHOR]

Simple Summary: In this retrospective study of 198 HCC patients receiving ablation therapy, participants were divided into two groups based on body mass index (BMI): overweight patients (BMI ≥ 25) and non-overweight patients (BMI < 25). The technical success rate (TSR) in the first session was significantly higher in non-overweight patients than in overweight patients (90.3% vs. 78.4%, p = 0.03). Fifteen (20.3%) overweight and eleven (8.9%) non-overweight patients required additional ablation therapy for residual tumors, resulting in almost similar TSRs at the final session (95.9% vs. 99.2%, p = 0.3). Local tumor progression and distant recurrence rates were not significantly different between the two groups, but overall survival was better in overweight patients than in non-overweight patients (p < 0.001). Despite the potential adverse impact of being overweight on public health problems, the present findings showed the relationship between being overweight and improved survival. The negative aspects of being overweight might remain as minor technical issues in HCC patients receiving ablation therapy. This study aimed to investigate the effect of being overweight on the outcome of ablation therapy for patients with early-stage hepatocellular carcinoma (HCC). This retrospective study included 198 patients with HCC who underwent radiofrequency ablation or microwave ablation at Gunma Saiseikai Maebashi Hospital between April 2017 and December 2021. We divided the patients into two groups based on their body mass index (BMI): overweight (BMI ≥ 25 kg/m2, n = 74 (37.4%)) and non-overweight (BMI < 25 kg/m2, n = 124 (62.6%)). The technical success rates (TSRs) in the first session were 78.4% and 90.3% in overweight and non-overweight patients, respectively, with a significant difference (p = 0.03). Additional ablation therapy for residual tumors was required in 15 (20.3%) overweight and 11 (8.9%) non-overweight patients (p = 0.03), resulting in 95.9% and 99.2% TSRs at the final session, respectively, without a significant difference (p = 0.3). While local tumor progression and distant recurrence rates were not significantly different between the two groups, overall survival was better in overweight patients than in non-overweight patients (p < 0.001). Despite the potential adverse impact of being overweight on public health problems, the present findings showed the relationship between being overweight and improved survival. The negative aspects of being overweight might remain as minor technical issues in HCC patients receiving ablation therapy. [ABSTRACT FROM AUTHOR]

The bacterial peptidoglycan enclosing the cytoplasmic membrane is a fundamental cellular architecture. The integral membrane protein MurJ plays an essential role in flipping the cell wall building block Lipid II across the cytoplasmic membrane for peptidoglycan biosynthesis. Previously reported crystal structures of MurJ have elucidated its V-shaped inward- or outward-facing forms with an internal cavity for substrate binding. MurJ transports Lipid II using its cavity through conformational transitions between these two forms. Here, we report two crystal structures of inward-facing forms from Arsenophonus endosymbiont MurJ and an unprecedented crystal structure of Escherichia coli MurJ in a "squeezed" form, which lacks a cavity to accommodate the substrate, mainly because of the increased proximity of transmembrane helices 2 and 8. Subsequent molecular dynamics simulations supported the hypothesis that the squeezed form is an intermediate conformation. This study fills a gap in our understanding of the Lipid II flipping mechanism. [Display omitted] • Crystal structures of bacterial MurJ reveal its squeezed and inward forms • The squeezed form does not contain an internal cavity required for substrate binding • Transmembrane helices 2, 7, and 8 contribute to MurJ structural transitions • The squeezed form occurs during outward-to-inward conformational changes Kohga et al. present an unprecedented "squeezed" structure of MurJ, a Lipid II flippase that is essential for peptidoglycan biogenesis in gram-negative bacteria. The "squeezed" form is proposed to be an intermediate during outward-to-inward conformational changes after substrate release, which is further supported by molecular dynamics simulations. [ABSTRACT FROM AUTHOR]

An 81‐year‐old man initially underwent right hepatic lobectomy for liver cancer and was pathologically diagnosed with combined hepatocellular and cholangiocarcinoma (CHC). At 13 months after resection, multiple lymph node metastases were observed. We started atezolizumab plus bevacizumab (Atez/Bev), achieving a 7.5‐month progression‐free survival. Atez/Bev might exhibit efficacy for CHC patients. [ABSTRACT FROM AUTHOR]

Dicopper complexes [Cu2(μ-OH)(Ln)](ClO4)2 [n = 1 (1) and 2 (2)] with a novel phenanthrene amide-tether ligand conjugate (HL1) and the original p-cresol-2,6-bis(amidecyclen) (HL2) were synthesized. A phenanthrene unit of 1 enhances the DNA-binding by 9-fold, enabling 1 to convert supercoiled plasmid DNA with H2O2 to a linear one in a 9.3-fold higher yield than 2. 1 reacts with H2O2 to form the μ-1,1-hydroperoxodicopper(II) complex 3 as the active species. The IC50 values of 1 against cancer cells of the lung and pancreas are 23.8 and 18.4 μM, respectively, 12-fold more toxic than the 284 and 241 μM of 2. Confocal microscopy, fluorescence-activated cell sorting, and caspase activity assays using HeLa cells revealed that 1 induces mitochondrial apoptosis. A DNA-targeting phenanthrene unit of 1 enhances the cancer-cell-selective toxicity via mitochondrial apoptosis. [ABSTRACT FROM AUTHOR]

Despite improvements in surgical techniques and perioperative management, postoperative pancreatic fistula (PF) is often difficult to treat and can be fatal due to various complications without effective drainage. Here, we report a case of PF following surgery for congenital biliary dilatation (CBD) successfully managed by endoscopic ultrasound (EUS)-guided transduodenal drainage. A 55-year-old woman underwent extrahepatic bile duct resection, including the gallbladder, and biliary tract reconstruction for CBD. On the 10th postoperative day (POD), computed tomography (CT) showed fluid retention observed from the upper edge of the pancreatic head to the surface of the right lobe of the liver. First, percutaneous fine-needle aspiration was performed on the fluid retention in the lateral part of the liver on the 11th POD. The amylase level in the drainage was high (30,156 U/L), and we diagnosed it as PF. Percutaneous drainage was difficult for fluid retention on the cut surface of the pancreas; thus, drainage under EUS guidance was decided. On the 13th POD, EUS was performed, a scan of the duodenal bulb revealed fluid retention with debris inside, and approximately 20-mL fluid was aspirated (amylase: 139,200 U/L). Although the inflammatory response temporarily improved, it recurred, so we decided to perform continuous drainage. On the 21st POD, EUS was performed again; a 19-G needle was used; a 0.025-in angle-type Jagwire was advanced into the fluid retention and expanded using a 7-Fr dilator; and then, a 6-Fr endoscopic nasoabscess drain (ENAD) tube was placed. On the 29th POD, CT showed that the fluid retention on the upper edge of the head of the pancreas had shrunk to a thickness of approximately 20 mm. On the 30th POD, the patient started eating. The ENAD tube was removed on the 38th POD. The patient was discharged from the hospital on the 45th POD without any symptoms. EUS-guided transduodenal drainage is an effective treatment option for postoperative PF following surgery for CBD. [ABSTRACT FROM AUTHOR]

The freshwater amphipod Crangonyx floridanus (Amphipoda: Crangonyctidae) is considered to have been recently introduced from North America to Japan, and the recorded sites at which it has been collected now cover nearly all of Japan except for the northern part. In this study, we surveyed further areas outside of its known distribution range, and examined the population genetic structure and the phylogenetic relationships between Japanese and North American populations of this species based on nuclear (18S rRNA) and mitochondrial (COI) DNA sequences. We found that this amphipod has already reached Hokkaido, northernmost Japan, which suggests that it has undergone rapid expansion in a pattern of concentric circles from the central part of Japan. Genetic analysis showed that the Japanese population is genetically homogeneous, in contrast to the genetic diversification of this species seen in North American Crangonyx populations. The process of introducing, establishing, and expanding this amphipod in Japan may be explained as follows. A limited number of individuals from a North American native population were probably inadvertently introduced and established somewhere within the Kanto region. The local population size then increased and its distribution range expanded rapidly across Japan. [ABSTRACT FROM AUTHOR]

This Article describes an enantioselective synthesis of cephalostatin 1. Key steps of this synthesis are a unique methyl group selective allylic oxidation, directed C-H hydroxylation of a sterol at C12, Au(I)- catalyzed 5-endo-dig cyclization, and a kinetic spiroketalization. [ABSTRACT FROM AUTHOR]

Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-018-30943-3, published online 17 August 2018 The original version of this Article contained an error in the legend of Figure 4. The original article can be found online at https://doi.org/10.1038/s41598-018-30943-3. [Extracted from the article]

Background and Aim: Gut microbiota composition is associated with the pathogenesis of non‐alcoholic fatty liver disease. However, the association between gut microbiota composition and non‐alcoholic fatty liver disease in non‐obese patients remains unclear. We compared clinical parameters and gut microbiota profiles of healthy controls and non‐obese and obese patients with non‐alcoholic fatty liver disease. Methods: We examined the clinical parameters and gut microbiota profiles by 16S rRNA sequences and short‐chain fatty acid levels in fecal samples from 51 non‐obese patients with non‐alcoholic fatty liver disease (body mass index <25 kg/m2) and 51 obese patients with non‐alcoholic fatty liver disease (body mass index ≥30 kg/m2) who underwent pathological examination and 87 controls at five hospitals in Japan. Results: Although no significant differences between the non‐obese and other groups were observed in alpha diversity, a significant difference was found in beta diversity. We observed a significant decrease in serum alanine aminotransferase levels, Eubacterium population, and butyric acid levels in non‐obese patients with non‐alcoholic fatty liver disease compared with those in obese patients with non‐alcoholic fatty liver disease. A significant negative correlation was found between the stage of hepatic fibrosis and Eubacterium abundance in non‐obese patients with non‐alcoholic fatty liver disease. Conclusions: The decrease in the abundance of Eubacterium that produces butyric acid may play an important role in the development of non‐alcoholic fatty liver disease in non‐obese individuals. This study was registered at the University Hospital Medical Information Network clinical trial registration system (UMIN000020917). [ABSTRACT FROM AUTHOR]

A 73-year-old woman with idiopathic pulmonary fibrosis (IPF) had an elevated serum CA19-9 level, but not KL-6. Her condition worsened and she subsequently died and this was associated with a rise in the serum KL-6 level. At autopsy, the lung showed a honeycomb appearance macroscopically and, microscopically, hyaline membrane formation was seen. Immunohistochemical staining revealed partial colocalization of KL-6 and CA19-9 to dilated bronchiolar cells. These features suggest that the mechanisms that cause the synthesis and release of CA19-9 and KL-6 from damaged lung tissue in IPF are likely to differ from those in diffuse alveolar damage. In addition, serum KL-6 levels may reflect the severity of disease more sensitively than CA19-9 levels. [ABSTRACT FROM AUTHOR]

A treatment option for constipation that improves the quality of life is needed since available laxatives do not effectively improve the quality of life in patients with constipation. A significant association between gut dysbiosis and constipation is recognized, suggesting that probiotics may be an important option for management of constipation. The underlying mechanism by which probiotics improve constipation remains unclear. In this study, we aimed to evaluate the effects of the probiotic Bifidobacterium bifidum G9-1 (BBG9-1) on loperamide-induced delayed colonic transit constipation and to elucidate its mechanism of action. First, the effect of BBG9-1 was evaluated in a rat model of constipation induced by subcutaneous administration of loperamide. BBG9-1 improved constipation parameters (number of feces, fecal water content, and fecal hardness) in constipated rats. Next, the relationship of organic acids and neurotransmitters to gut microbiota was investigated. BBG9-1 improved dysbiosis and prevented a decrease in butyric acid concentration in the gut, increased serum serotonin, and suppressed an increase in dopamine and a decrease in acetylcholine in serum. Further, an increase in the expression level of tryptophan hydroxylase 1, a 5-HT-synthetizing enzyme, was observed. These results suggest that BBG9-1 improves dysbiosis, which results in an increase in organic acids and improvement of neurotransmission. These actions may increase intestinal mobility, finally leading to alleviating constipation. The probiotic BBG9-1 may, therefore, be a potential option for the treatment of constipation. [ABSTRACT FROM AUTHOR]

Mucosal incision and submucosal dissection during gel immersion ESD were performed using a new electrosurgical knife (GoldKnife T-type 1.5 mm; Micro-Tech Co., Ltd, Nanjing, China), which allowed local injection of hyaluronic acid solution. Colorectal endoscopic submucosal dissection (ESD) is now widely used for the treatment of colorectal tumors using several strategies. [Extracted from the article]

Introduction: The disadvantage of conventional armrests is the difficulty to adjust their height and position during surgery. Objectives: We investigated whether a freely movable armrest (FMA) that follows the surgeon's arm is useful for reducing surgeon fatigue and arm tremors and for improving surgical accuracy. Methods: In the basic study, a corneal suture was placed in porcine eyes with FMA (FMA group) or without FMA (non-FMA group). The suture was intended to pass through two points. Tremor was quantified using motion-tracking software when the needle was held. Subjective symptoms of arm-related fatigue were scored using a questionnaire. Suturing accuracy was compared between the groups. In the clinical study, the same surgeon performed corneal transplantation, cataract surgery, and glaucoma surgery with or without FMA. Fatigue scores from the questionnaire were then compared. Results: In the basic study, hand tremor at rest was significantly improved with FMA (p < 0.0001). The subjective arm fatigue score was significantly reduced (p = 0.0465), while the subjective tremor score was also significantly improved (p = 0.0453). There were no differences in the accuracy of corneal suturing with or without FMA. In the clinical study, the total and arm-related fatigue scores during corneal transplantation and glaucoma surgery tended to improve. Conclusions: FMA is a useful tool for fixing the surgeon's arm in any position and may improve the quality of ophthalmic surgery by reducing hand tremor and fatigue. [ABSTRACT FROM AUTHOR]

Summary Multidrug and toxic compound extrusion (MATE) transporters efflux toxic compounds using a Na+ or H+ gradient across the membrane. Although the structures of MATE transporters have been reported, the cation-coupled substrate transport mechanism remains controversial. Here we report crystal structures of VcmN, a Vibrio cholerae MATE transporter driven by the H+ gradient. High-resolution structures in two distinct conformations associated with different pHs revealed that the rearrangement of the hydrogen-bonding network around the conserved Asp35 induces the bending of transmembrane helix 1, as in the case of the H+-coupled Pyrococcus furiosus MATE transporter. We also determined the crystal structure of the D35N mutant, which captured a unique conformation of TM1 facilitated by an altered hydrogen-bonding network. Based on the present results, we propose a common step in the transport cycle shared among prokaryotic H+-coupled MATE transporters. Graphical Abstract Highlights • Crystal structures of VcmN, an H+-coupled MATE transporter from Vibrio cholerae • Distinct conformations associated with different pHs and the D35N mutation in TM1 • Coupling of rearrangement of hydrogen bond network around Asp35 to the TM1 bending • Common step in the transport cycle shared among prokaryotic H+-driven MATE proteins Kusakizako et al. determined the crystal structures of VcmN, an H+-coupled MATE transporter from Vibrio cholerae. A structural comparison of distinct conformations associated with different pH conditions and the D35N mutation in TM1 reveals the common step in the transport cycle shared among prokaryotic H+-coupled MATE transporters. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical significance of color visual acuity (CVA) in preperimetric glaucoma (PPG) and open-angle glaucoma (OAG). Methods: A total of 123 eyes of 73 subjects (22 normal eyes, 14 PPG eyes, and 87 OAG eyes; mean age: 44.9 ± 10.1 years, age range: 21–64 years) were enrolled. CVA was tested for red, green-yellow, blue-green and blue-purple with a newly developed test. Results: There was no statistical difference in clinical background factors, including age, sex, intraocular pressure, or spherical equivalent between the three groups. Red VA and blue-green VA were significantly worse in the OAG eyes than in the normal eyes (P = 0.008 and P = 0.015, respectively), although green-yellow VA and blue-purple VA were not significantly worse. Furthermore, red VA and blue-green VA were significantly correlated with MD in a group of eyes with either PPG or OAG (r = -0.23, P = 0.023; r = -0.25, P = 0.012, respectively), but green-yellow VA and blue-purple VA were not. Conclusion: Red VA and blue-green VA were detectably worse in eyes with OAG, in close association with the degree of functional loss. This suggests that measuring CVA with the new color test described here may be a promising supplement to existing methods of detecting glaucoma and evaluating its severity. [ABSTRACT FROM AUTHOR]