Structural Insights into the Epimerization of β-1,4-Linked Oligosaccharides Catalyzed by Cellobiose 2-Epimerase, the Sole Enzyme Epimerizing Non-anomeric Hydroxyl Groups of Unmodified Sugars

Cellobiose 2-epimerase (CE) reversibly converts d-glucose residues into d-mannose residues at the reducing end of unmodified β1,4-linked oligosaccharides, including β-1,4-mannobiose, cellobiose, and lactose. CE is responsible for conversion of β1,4-mannobiose to 4-O-β-d-mannosyl-d-glucose in mannan metabolism. However, the detailed catalytic mechanism of CE is unclear due to the lack of structural data in complex with ligands. We determined the crystal structures of halothermophile Rhodothermus marinus CE (RmCE) in complex with substrates/products or intermediate analogs, and its apo form. The structures in complex with the substrates/products indicated that the residues in the β5-β6 loop as well as those in the inner six helices form the catalytic site. Trp-322 and Trp-385 interact with reducing and non-reducing end parts of these ligands, respectively, by stacking interactions. The architecture of the catalytic site also provided insights into the mechanism of reversible epimerization. His-259 abstracts the H2 proton of the d-mannose residue at the reducing end, and consistently forms the cis-enediol intermediate by facilitated depolarization of the 2-OH group mediated by hydrogen bonding interaction with His-200. His-390 subsequently donates the proton to the C2 atom of the intermediate to form a d-glucose residue. The reverse reaction is mediated by these three histidines with the inverse roles of acid/base catalysts. The conformation of cellobiitol demonstrated that the deprotonation/reprotonation step is coupled with rotation of the C2-C3 bond of the open form of the ligand. Moreover, it is postulated that His-390 is closely related to ring opening/closure by transferring a proton between the O5 and O1 atoms of the ligand

Gauged U(1)XU(1)_X breaking as origin of neutrino masses, dark matter and leptogenesis at TeV scale

We propose a new mechanism which simultaneously explains tiny neutrino masses, stability of dark matter and baryon asymmetry of the Universe via leptogenesis due to the common origin: a spontaneous breaking of a $U(1)_X$ gauge symmetry at TeV scale. The $U(1)_X$ breaking provides small Majorana masses of vector-like leptons which generate small mass differences among them, and enhance their CP-violating decays via the resonant effect. Such CP-violation and lepton number violation turns out to be a sufficient amount of the observed baryon asymmetry through leptogenesis. The Majorana masses from the $U(1)_X$ breaking also induce radiative generation of masses for active neutrinos at one-loop level. Furthermore, a $Z_2$ symmetry appears as a remnant of the $U(1)_X$ breaking, which guarantees the stability of dark matter. We construct a simple renormalizable model to realize the above mechanism, and show a benchmark point which can explain observed neutrino oscillations, dark matter data and the baryon asymmetry at the same time.Comment: Version accepted for publication in PRD, 6 pages, 5 figure

Local Conceptual Engineering in a Linguistic Subgroup and the Implementation Problem

In this paper, I examine Max Deutsch’s dilemma for the implementation of newly engineered concepts. In the debate over this dilemma, the goal of conceptual engineering tends to be set either too high or too low. As a result, implementation tends to be seen as either very unlikely to succeed or too easily achievable. This paper aims to offer a way out of this dilemma. I argue that the success conditions for implementation can be better understood if we distinguish between different stages in the implementation process. Implementation is a complex process involving several stages, each of which can be evaluated as a success or a failure. I argue that even if an implementation does not reach the final stage in which a new concept is widely used in the society at large, it may not be a complete failure: conceptual engineers may not even aim for a new concept to be widely used in the society at large; or even if they do and a new concept only circulates in a smaller subgroup, this can still be a significant achievement. The upshot is that we should take more seriously the possibility that conceptual engineering can be implemented locally at the subgroup level

Sellars, Analyticity, and a Dynamic Picture of Language

Even after Quine’s critique of the analytic-synthetic distinction in “Two Dogmas of Empiricism,” Wilfrid Sellars maintained some forms of analyticity or truth in virtue of meaning. This paper aims to reconstruct his neglected account of the analytic-synthetic distinction and the revisability of analytic sentences, its connection to his inferentialist account of meaning, and his response to Quine. While Sellars’s account of how analytic sentences can be revised bears certain similarities with Carnap’s and Grice and Strawson’s accounts, it is still striking in that it is part of his broader picture of how our language develops dynamically in our ongoing inquiry. I aim to show how it relates within his broader picture to his account of how the diachronic continuity in meaning, language, or conceptual framework can be preserved through a revision of analytic sentences, and to his evolutionary account of the development of our language or conceptual framework

Extensive Bilateral Patellar Tendon Ossification in a Spinal Cord Injury Patient

This is the first report of extensive bilateral patellar tendon ossification occurring over a prolonged time after a unilateral knee injury. An 84-year-old Japanese man with a spinal cord injury caused by a burst fracture of the T12 vertebra presented with a bony hard prominence on the left knee, which was injured in a traffic accident when he was 77 years old. Radiography revealed extensive ossification of the bilateral patellar tendons. We review the English literature with a focus on the localization of bilateral heterotopic ossification of the knee in patients who had a central nervous system injury

Effect of dentin desensitizers on resin cement bond strengths

Introduction: The crown preparation promotes the exposure of dentin tubules. Thus, to avoid post-operative sensitivity, the first approach involves the use of dentin adhesives, and the second one the use of dentin desensitizers. Objective: This study evaluated the effect of dentin desensitizers on microtensile bond strengths (µTBSs) of a resin cement to dentin. Material and methods: Twenty bovine teeth were prepared until obtaining flat dentin surfaces. A standardized smear layer was created (#600-grit SiC paper). The samples were randomly divided into the following four groups (n = 5): no treatment (Control), treatment with Gluma Desensitizer (Heraeus Kulzer), Super Seal (Phoenix Dental) and Teethmate Desensitizer (Kuraray Noritake Dental). The dentin surfaces were then treated with ED Primer II (Kuraray Noritake Dental). Twenty composite blocks, 4 mm thick (Estenia C&B, Kuraray Noritake Dental) were used. The composite surfaces were abraded with aluminum oxide (50 µm), and then silanized. The composite block was bonded to the dentin surface with a resin cement (Panavia F 2.0, Kuraray Noritake Dental) according to he manufacturer’s instructions. After 24-hour storage (37ºC, 100% RH), the bonded samples were cut into beam–shaped microtensile specimens and loaded in tension until failure. Data were analyzed with one-way ANOVA and the Dunnett’s test (α = 0.05). An SEM was used to examine the failure modes. Results: The µTBSs (MPa ± SD) were: 24.4 ± 3.2 (Control), 14.0 ± 5.6 (Gluma Desensitizer), 8.6 ± 4.7 (Super Seal), and 34.7 ± 4.6 (Teethmate Desensitizer), in which there were significant differences among the four groups (p < 0.05). The Teethmate Desensitizer group showed the highest µTBS, while the Super Seal group showed the lowest mean of µTBS to dentin. Conclusion: The efficacy of the desensitizers is material-dependent; Gluma Desensitizer and Super Seal decreased the µTBSs, however, Teethmate Desensitizer improved it

High Efficacy of Preoperative Low-Dose Radiotherapy with Sanazole (AK-2123) for Extraskeletal Ewing's Sarcoma: A Case Report

Extraskeletal Ewing's sarcoma is a rare soft tissue tumor that is morphologically indistinguishable from Ewing's sarcoma of bone. We report a case of extraskeletal Ewing's sarcoma with several systemic problems. A 69-year-old man presented with a 5-month history of a rapidly enlarging mass in the right thigh. Because preoperative radiotherapy with sanazole (AK-2123) contributed the tumor mass reduction down to 40% in size, the tumor was successfully resected with clear surgical margins and repaired with a musculocutaneous flap. The high efficacy of pre-operative low-dose radiotherapy with sanazole was histologically confirmed that the resected tumor specimen involved no viable tumor cells and showed 100% necrosis. Based on clinical outcomes in this case, the combined modality of pre-operative low-dose radiotherapy with hypoxic cell radiosensitizer and adequate surgical resection might provide for the useful clinical application of extraskeletal Ewing's sarcoma treatment