tion’, implying that most patients ‘should’ receive a particular action. In contrast, level 2 guidelines are essentially ‘suggestions’ and are deemed to be ‘weak’ or discretionary, recognising that management decisions may vary in different clinical contexts. Each recommendation was further graded from A to D by the quality of evidence underpinning them, with grade A referring to a high quality of evidence whilst grade D recognised a ‘very low’ evidence base. The overall strength and quality of the supporting evidence is summarised in table 1 . The guidelines focused on 4 key domains: (1) AKI definition, (2) prevention and treatment of AKI, (3) contrastinduced AKI (CI-AKI) and (4) dialysis interventions for the treatment of AKI. The full summary of clinical practice statements is available at www.kdigo.org, but a few key recommendation statements will be highlighted here.

/pdf/kdigo-clinical-practice-guidelines-for-acute-kidney-injury-27tybolw7l.pdf

KDIGO clinical practice guidelines for acute kidney injury.

https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

/pdf/metal-organic-frameworks-and-self-assembled-supramolecular-2xs948xxr9.pdf

Metal–Organic Frameworks and Self-Assembled Supramolecular Coordination Complexes: Comparing and Contrasting the Design, Synthesis, and Functionality of Metal–Organic Materials

In addition to their role in binding antigen, antibodies can regulate immune responses through interacting with Fc receptors (FcRs). In recent years, significant progress has been made in understanding the mechanisms that regulate the activity of IgG antibodies in vivo. In this Review, we discuss recent studies addressing the multifaceted roles of FcRs for IgG (FcgammaRs) in the immune system and how this knowledge could be translated into novel therapeutic strategies to treat human autoimmune, infectious or malignant diseases.

/pdf/fcg-receptors-as-regulators-of-immune-responses-46isonwygz.pdf

Fcγ receptors as regulators of immune responses

Fascination with supramolecular chemistry over the last few decades has led to the synthesis of an ever-increasing number of elegant and intricate functional structures with sizes that approach nanoscopic dimensions Today, it has grown into a mature field of modern science whose interfaces with many disciplines have provided invaluable opportunities for crossing boundaries both inside and between the fields of chemistry, physics, and biology This chemistry is of continuing interest for synthetic chemists; partly because of the fascinating physical and chemical properties and the complex and varied aesthetically pleasing structures that supramolecules possess For scientists seeking to design novel molecular materials exhibiting unusual sensing, magnetic, optical, and catalytic properties, and for researchers investigating the structure and function of biomolecules, supramolecular chemistry provides limitless possibilities Thus, it transcends the traditional divisional boundaries of science and represents a highly interdisciplinary field

In the early 1960s, the discovery of ‘crown ethers’, ‘cryptands’ and ‘spherands’ by Pedersen,1 Lehn,2 and Cram3 respectively, led to the realization that small, complementary molecules can be made to recognize each other through non-covalent interactions such as hydrogen-bonding, charge-charge, donor-acceptor, π-π, van der Waals, etc Such ‘programmed’ molecules can thus be self-assembled by utilizing these interactions in a definite algorithm to form large supramolecules that have different physicochemical properties than those of the precursor building blocks Typical systems are designed such that the self-assembly process is kinetically reversible; the individual building blocks gradually funnel towards an ensemble that represents the thermodynamic minimum of the system via numerous association and dissociation steps By tuning various reaction parameters, the reaction equilibrium can be shifted towards the desired product As such, self-assembly has a distinct advantage over traditional, stepwise synthetic approaches when accessing large molecules

It is well known that nature has the ability to assemble relatively simple molecular precursors into extremely complex biomolecules, which are vital for life processes Nature’s building blocks possess specific functionalities in configurations that allow them to interact with one another in a deliberate manner Protein folding, nucleic acid assembly and tertiary structure, phospholipid membranes, ribosomes, microtubules, etc are but a selective, representative example of self-assembly in nature that is of critical importance for living organisms Nature makes use of a variety of weak, non-covalent interactions such as hydrogen–bonding, charge–charge, donor–acceptor, π-π, van der Waals, hydrophilic and hydrophobic, etc interactions to achieve these highly complex and often symmetrical architectures In fact, the existence of life is heavily dependent on these phenomena The aforementioned structures provide inspiration for chemists seeking to exploit the ‘weak interactions’ described above to make scaffolds rivaling the complexity of natural systems

The breadth of supramolecular chemistry has progressively increased with the synthesis of numerous unique supramolecules each year Based on the interactions used in the assembly process, supramolecular chemistry can be broadly classified in to three main branches: i) those that utilize H-bonding motifs in the supramolecular architectures, ii) processes that primarily use other non-covalent interactions such as ion-ion, ion-dipole, π–π stacking, cation-π, van der Waals and hydrophobic interactions, and iii) those that employ strong and directional metal-ligand bonds for the assembly process However, as the scale and degree of complexity of desired molecules increases, the assembly of small molecular units into large, discrete supramolecules becomes an increasingly daunting task This has been due in large part to the inability to completely control the directionality of the weak forces employed in the first two classifications above Coordination-driven self-assembly, which defines the third approach, affords a greater control over the rational design of 2D and 3D architectures by capitalizing on the predictable nature of the metal-ligand coordination sphere and ligand lability to encode directionality Thus, this third strategy represents an alternative route to better execute the “bottom-up” synthetic strategy for designing molecules of desired dimensions, ranging from a few cubic angstroms to over a cubic nanometer For instance, a wide array of 2D systems: rhomboids, squares, rectangles, triangles, etc, and 3D systems: trigonal pyramids, trigonal prisms, cubes, cuboctahedra, double squares, adamantanoids, dodecahedra and a variety of other cages have been reported As in nature, inherent preferences for particular geometries and binding motifs are ‘encoded’ in certain molecules depending on the metals and functional groups present; these moieties help to control the way in which the building blocks assemble into well-defined, discrete supramolecules4

Since the early pioneering work by Lehn5 and Sauvage6 on the feasibility and usefulness of coordination-driven self-assembly in the formation of infinite helicates, grids, ladders, racks, knots, rings, catenanes, rotaxanes and related species,7 several groups - Stang,8 Raymond,9 Fujita,10 Mirkin,11 Cotton12 and others13,14 have independently developed and exploited novel coordination-based paradigms for the self-assembly of discrete metallacycles and metallacages with well-defined shapes and sizes In the last decade, the concepts and perspectives of coordination-driven self-assembly have been delineated and summarized in several insightful reviews covering various aspects of coordinationdriven self-assembly15 In the last decade, the use of this synthetic strategy has led to metallacages dubbed as “molecular flasks” by Fujita,16 and Raymond and Bergman,17 which due to their ability to encapsulate guest molecules, allowed for the observation of unique chemical phenomena and unusual reactions which cannot be achieved in the conventional gas, liquid or solid phases Furthermore, these assemblies found applications in supramolecular catalysis18,19 and as nanomaterials as developed by Hupp20 and others21,22

This review focuses on the journey of early coordination-driven self-assembly paradigms to more complex and discrete 2D and 3D supramolecular ensembles over the last decade We begin with a discussion of various approaches that have been developed by different groups to assemble finite supramolecular architectures The subsequent sections contain detailed discussions on the synthesis of discrete 2D and 3D systems, their functionalizations and applications

Supramolecular coordination: self-assembly of finite two- and three-dimensional ensembles.

Anti-mucin1 (MUC1) antibodies have been widely used for breast cancer diagnosis and treatment. This is based on the fact that MUC1 undergoes aberrant glycosylation upon cancer progression, and anti-MUC1 antibodies differentiate changes in glycan structure. MY.1E12 is a promising anti-MUC1 antibody with a distinct specificity toward MUC1 modified with an immature O-glycan (NeuAcα(2-3)Galβ(1-3)GalNAc) on a specific Thr. However, the structural basis for the interaction between MY.1E12 and MUC1 remains unclear. The aim of this study is to elucidate the mode of interaction between MY.1E12 and MUC1 O-glycopeptide by NMR, molecular dynamics (MD) and docking simulations. NMR titration using MUC1 O-glycopeptides suggests that the epitope is located within the O-linked glycan and near the O-glycosylation site. MD simulations of MUC1 glycopeptide showed that the O-glycosylation significantly limits the flexibility of the peptide backbone and side chain of the O-glycosylated Thr. Docking simulations using modeled MY.1E12 Fv and MUC1 O-glycopeptide, suggest that VH mainly contributes to the recognition of the MUC1 peptide portion while VL mainly binds to the O-glycan part. The VH/VL-shared recognition mode of this antibody may be used as a template for the rational design and development of anti-glycopeptide antibodies.

/pdf/o-glycan-dependent-interaction-between-muc1-glycopeptide-and-15ztk5t9.pdf

O-Glycan-Dependent Interaction between MUC1 Glycopeptide and MY.1E12 Antibody by NMR, Molecular Dynamics and Docking Simulations

This article reports the development of a muon monitoring system that utilizes SiC p+n junction diodes as the primary sensing element, integrated with FPGAs for signal processing and control. The system will be designed to detect muons, which are subatomic particles that penetrate deep into materials and have applications in various fields such as particle physics, geology, and radiography. The use of SiC p+n junction diodes is advantageous due to their high radiation hardness, fast response time, and low noise characteristics, which make them well-suited for high-energy particle detection. The FPGAs will provide real-time signal processing capabilities, enabling efficient data analysis and monitoring. This FPGA-based detector system has the potential to provide a cost-effective and reliable solution for muon monitoring applications.

FPGA-based detector with SiC sensing for real-time monitoring of muon beams: A preliminary report of the SCIBER-1 system in COMET Phase-α

Mammalian glycolipids play a variety of roles, often coupled with interactions with endogenous and exogenous molecules. The interactions can induce intracellular signaling and are the means by which glycolipids express biological phenotypes. Insights into the structure-function relationships of glycolipids (both glycan and lipid moieties) provide the basis for gaining an understanding of the mechanisms at play, an important area for further study. Solution nuclear magnetic resonance (NMR) spectroscopy is a unique and powerful method employed to provide, at the atomic level, structural information on glycolipids and other biomolecules in solutions. This chapter briefly describes how we measure NMR spectra of glycolipids and the information gained from NMR spectral analysis. 

NMR Analysis of Mammalian Glycolipids.

The anticancer function of superoxide dismutases (SODs) is still controversial. Removing superoxide and/or producing oxygen and hydrogen peroxide exhibits both pro- and anti-tumor effects. SOD3 is an extracellular superoxide dismutase and contains a single N-glycan chain. Although we reported previously that the N-glycosylation of SOD3 was essential for its secretion, the role played by the N-glycosylation of SOD3, as it relates to lung cancer, is poorly understood. We report herein that the fucose structure of the N-glycan in SOD3 was increased in the sera of patients with lung cancer. In cell lines of non-small lung cancer cell (NSCLC), we also found a high level of the core fucose structure in the N-glycan of SOD3, as determined by lectin blotting and mass spectrometry analysis. To address the roles of the core fucose structure of SOD3, we generated FUT8 (α1,6-fucosyltransferase) gene knockout A549 cells. Using these cells, we found that the core fucose structure of SOD3 was required for its secretion and enzymatic activity, which contributes to the suppression of cell growth of NSCLC cells. These data demonstrate that N-glycans, especially those with core fucose structures, regulate the anti-tumor functions of SOD3 against NSCLC.

Core fucosylation is required for the secretion of and the enzymatic activity of SOD3 in non-small cell lung cancer cells.

タンパク質に付加された糖鎖は,細胞外において細 胞間相互作用などのシグナルとして働いている.一方 細胞内においては,糖鎖はタンパク質の成熟・輸送・ 分解の過程において「目印」としての役割を果たして いる.小胞体内で翻訳された新生タンパク質の折りた たみの補助とゴルジ体への輸送,折りたたみに失敗し たタンパク質の細胞質への輸送と分解といった一連の 過程は,糖鎖とそれを認識するレクチンの相互作用を 通じて決定されている.小胞体における糖タンパク質 の品質管理機構を解明するためにはレクチンと糖鎖の 相互作用の詳細を明らかにすることが重要となる.本 稿では,小胞体レクチン OS-9の結果を中心に,糖鎖 を目印とするタンパク質の品質管理機構の構造機能解 析研究の進展について紹介する. 2. 糖鎖を目印とする糖タンパク質の小胞体品質 管理機構 小胞体では,N結合型糖鎖を目印としたタンパク質 の品質管理が行われており,さまざまなレクチンが機 能している(図 1).カルネキシンサイクルは,その 代表例の 1つであり,UDP-グルコース糖タンパク質 グルコース転移酵素(UGGT)によるモノグルコシル 化,レクチン(カルネキシン)によるモノグルコシル 化糖タンパク質の認識,小胞体グルコシダーゼ IIに よる脱グルコシル化,などが協同的に機能すること で,新生タンパク質の折りたたみの補助が行われ る .また一方で,タンパク質が正しい高次構造を形 成できなかった場合,そのような異常タンパク質を細 胞質へ放出し分解する小胞体関連分解(ERAD)も同 時に機能している.ERADにおける糖鎖の役割はこれ まで不明な点が多かったが,近年新たに,マンノース 6-リン酸受容体相同(MRH)ドメインをもつ小胞体 レクチン・OS-9が同定され,OS-9レクチンおよび関 連分子の新規機能が明らかにされた.OS-9ファミ リーはその重要性と新規性から大きな注目を集め国際 的に熾烈な競争となった .OS-9は折りたたみに失 敗した糖タンパク質と結合することで ERADを促進 すること,OS-9のMRHドメインは小胞体マンノシ ダーゼ様タンパク質 EDEMの α1,2マンノシダーゼ活 性により生成したマンノース 1残基がトリミングされ たManα1,6Manα1,6Man部分(α(1-6)結合が 2つつな がっている;図 2の点線で囲った 3つのマンノース) を認識するという糖鎖特異性が明らかにされた. 筆者らはこれまでに,糖タンパク質の細胞内輸送を 行う糖鎖認識型の輸送レクチン(VIP36)の構造機能 解析を行い,VIP36がグルコシダーゼ IIにより脱グル コシル化された高マンノース型糖鎖の D1アームの Manα1,2Manα1,2Man部分と Ca依存的に結合する構 造基盤を明らかにしてきた (図 2).一方,ERADに かかわるMRHドメインをもつ小胞体レクチンの構造 的な知見は得られておらず,糖鎖認識の仕組みは不明 であった.このような研究背景のなか,筆者らはヒト OS-9のMRHドメインに注目し糖鎖複合体の立体構 造解析に挑んだ. 3. OS-9のMRHドメインはWWモチーフを介して トリミングされた高マンノース型糖鎖を認識する OS-9のMRHドメインの糖鎖結合部位は,マンノー 生物物理 52(1),032-033(2012)

Yoshiki Yamaguchi

Papers

O-Glycan-Dependent Interaction between MUC1 Glycopeptide and MY.1E12 Antibody by NMR, Molecular Dynamics and Docking Simulations

FPGA-based detector with SiC sensing for real-time monitoring of muon beams: A preliminary report of the SCIBER-1 system in COMET Phase-α

NMR Analysis of Mammalian Glycolipids.

Core fucosylation is required for the secretion of and the enzymatic activity of SOD3 in non-small cell lung cancer cells.

Elucidation of Molecular Mechanism of Glycan-mediated Protein Quality Control