Crystal structure of human METTL6, the m3C methyltransferase

In tRNA, the epigenetic m3C modification at position 32 in the anticodon loop is highly conserved in eukaryotes, which maintains the folding and basepairing functions of the anticodon. However, the responsible enzymes METTL2 and METTL6 were identified only in recent years. The loss of human METTL6 (hMETTL6) affects the translational process and proteostasis in cells, while in mESCs cells, it leads to defective pluripotency potential. Despite its important functions, the catalytic mechanism of the C32 methylation by this enzyme is poorly understood. Here we present the 1.9 Å high-resolution crystal structure of hMETTL6 bound by SAH. The key residues interacting with the ligand were identified and their roles were confirmed by ITC. We generated a docking model for the hMETTL6-SAH-CMP ternary complex. Interestingly, the CMP molecule binds into a cavity in a positive patch with the base ring pointing to the inside, suggesting a flipped-base mechanism for methylation. We further generated a model for the quaternary complex with tRNASer as a component, which reasonably explained the biochemical behaviors of hMETTL6. Taken together, our crystallographic and biochemical studies provide important insight into the molecular recognition mechanism by METTL6 and may aid in the METTL-based rational drug design in the future.

On the State Approach Representations of Convolutional Codes over Rings of Modular Integers

In this study, we prove the existence of minimal first-order representations for convolutional codes with the predictable degree property over principal ideal artinian rings. Further, we prove that any such first-order representation leads to an input/state/output representation of the code provided the base ring is local. When the base ring is a finite field, we recover the classical construction, studied in depth by J. Rosenthal and E. V. York. This allows us to construct observable convolutional codes over such rings in the same way as is carried out in classical convolutional coding theory. Furthermore, we prove the minimality of the obtained representations. This completes the study of the existence of input/state/output representations of convolutional codes over rings of modular integers.

Asymptotic behavior of $j$-multiplicities

Let $R= \oplus_{n\in \mathbb{N}_0}R_n$ be a Noetherian homogeneous ring with local base ring $(R_0,\mathfrak{m}_0)$. Let $R_+= \oplus_{n\in \mathbb{N}}R_n$ denote the irrelevant ideal of $R$ and let $M=\oplus_{n\in \mathbb{Z}}M_n$ be a finitely generated graded $R$-module. When $\dim(R_0)\leq 2$ and $\mathfrak{q}_0$ is an arbitrary ideal of $R_0$, we show that the $j$-multiplicity of the graded local cohomology module $j_0({\mathfrak{q}_0},H_{R_+}^i(M)_n)$ has a polynomial behavior for all $n\ll0$.

Vanishing and Artinianness of graded generalized local cohomology

UDC 512.5 Let be a homogeneous Noetherian ring with semilocal base ring Let be the irrelevant ideal of For two finitely generated graded -modules and several results on the vanishing, Artiniannes and tameness property of the graded -modules will be investigated.

Feats of Clay: Considering the Materiality of Late Bronze Age Cyprus

This paper examines the materiality of the Cypriot Base Ring ware through the lens of the new materialisms. Specifically, it draws upon Bennett’s vibrant matter and thing-power, to explore how cultural and technological knowledges of Late Bronze Age Cyprus were informed through material engagements with clay. This approach highlights the agency of matter and illustrates how the distinct capacities of clay (working with water and fire) provoked, enabled and constrained potters’ behaviour, resulting in a distinctive pottery style that was central to the Late Cypriot social and material world. The aim is to demonstrate how people, materials and objects are all matter in relationship, drawing attention to the fluidity, porosity and relationality of the material world.

Synthesis, Characterization and Docking Study of Novel Pyrimidine Derivatives as Anticancer Agents

New compounds 5 and 9 using DNA bases e.g. Adenine 1 and Guanine 6 derivatives have been synthesized. The use of simple methods to synthesize compounds 5 and 9 were done using pyrimidine as an alternative DNA base ring. Another design to synthesize new simple pyrimidine rings utilizing thiourea and ethylcyano acetate to afford 6-amino-2-thiouracil was adopted. The reaction of thiouracil 10 with chloro cyano or chloro ester and ketone, resulted in the formation of adduct compounds 18-21, rather than the formation of compound 17. All the synthesized compounds were subjected to docking study, in order to gain insights into their binding modes against cyclin-dependent protein kinase 2 (CDK-2) that is involved heavily in cell cycle regulation and receptor protein B-cell lymphoma 2 (BCL-2) which is involved in cell apoptosis. These targets were selected based on their key roles in cancer progression via the regulation of the cell cycle and DNA replication. Molecular-docking analyses showed that compound 14e was the best docked ligand against both targets, as it displayed the lowest binding energy, critical hydrogen bonds and hydrophobic interactions with the targets.

Extending p-divisible Groups and Barsotti–Tate Deformation Ring in the Relative Case

Let $k$ be a perfect field of characteristic $p> 2$, and let $K$ be a finite totally ramified extension of $W(k)\big[\frac{1}{p}\big]$ of ramification degree $e$. We consider an unramified base ring $R_0$ over $W(k)$ satisfying certain conditions, and let $R = R_0\otimes _{W(k)}\mathcal{O}_K$. Examples of such $R$ include $R = \mathcal{O}_K[\![s_1, \ldots , s_d]\!]$ and $R = \mathcal{O}_K\langle t_1^{\pm 1}, \ldots , t_d^{\pm 1}\rangle $. We show that the generalization of Raynaud’s theorem on extending $p$-divisible groups holds over the base ring $R$ when $e < p-1$, whereas it does not hold when $R = \mathcal{O}_K[\![s]\!]$ with $e \geq p$. As an application, we prove that if $R$ has Krull dimension $2$ and $e < p-1$, then the locus of Barsotti–Tate representations of $\textrm{Gal}(\overline{R}\big[\frac{1}{p}\big]/R\big[\frac{1}{p}\big])$ cuts out a closed subscheme of the universal deformation scheme. If $R = \mathcal{O}_K[\![s]\!]$ with $e \geq p$, we prove that such a locus is not $p$-adically closed.