Pass-back chain extension expands multimodular assembly line biosynthesis.

Modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) enzymatic assembly lines are large and dynamic protein machines that generally effect a linear sequence of catalytic cycles. Here, we report the heterologous reconstitution and comprehensive characterization of two hybrid NRPS-PKS assembly lines that defy many standard rules of assembly line biosynthesis to generate a large combinatorial library of cyclic lipodepsipeptide protease inhibitors called thalassospiramides. We generate a series of precise domain-inactivating mutations in thalassospiramide assembly lines, and present evidence for an unprecedented biosynthetic model that invokes intermodule substrate activation and tailoring, module skipping and pass-back chain extension, whereby the ability to pass the growing chain back to a preceding module is flexible and substrate driven. Expanding bidirectional intermodule domain interactions could represent a viable mechanism for generating chemical diversity without increasing the size of biosynthetic assembly lines and challenges our understanding of the potential elasticity of multimodular megaenzymes

Entangling a series of trapped ions by moving cavity bus

Entangling multiple qubits is one of the central tasks for quantum information processings. Here, we propose an approach to entangle a number of cold ions (individually trapped in a string of microtraps) by a moved cavity. The cavity is pushed to include the ions one by one with an uniform velocity, and thus the information stored in former ions could be transferred to the latter ones by such a moving cavity bus. Since the positions of the trapped ions are precisely located, the strengths and durations of the ion-cavity interactions can be exactly controlled. As a consequence, by properly setting the relevant parameters typical multi-ion entangled states, e.g., $W$ state for 10 ions, could be deterministically generated. The feasibility of the proposal is also discussed.Comment: 8 pages, 2 figures, 1 tabl

Quotient Hopf algebras of the free bialgebra with PBW bases and GK-dimensions

Let $\mathbb{K}$ be a field. We study the free bialgebra $\mathcal{T}$ generated by the coalgebra $C=\mathbb{K} g \oplus \mathbb{K} h$ and its quotient bialgebras (or Hopf algebras) over $\mathbb{K}$. We show that the free noncommutative Fa\`a di Bruno bialgebra is a sub-bialgebra of $\mathcal{T}$, and the quotient bialgebra $\overline{\mathcal{T}}:=\mathcal{T}/(E_{\alpha}|~\alpha(g)\ge 2)$ is an Ore extension of the well-known Fa\`a di Bruno bialgebra. The image of the free noncommutative Fa\`a di Bruno bialgebra in the quotient $\overline{\mathcal{T}}$ gives a more reasonable non-commutative version of the commutative Fa\`a di Bruno bialgebra from the PBW basis point view. If char $\mathbb{K}=p>0$, we obtain a chain of quotient Hopf algebras of $\overline{\mathcal{T}}$: $\overline{\mathcal{T}} \twoheadrightarrow \overline{\mathcal{T}}_{n}\twoheadrightarrow \overline{\mathcal{T}}_{n}'(p)\twoheadrightarrow \overline{\mathcal{T}}_{n}(p)\twoheadrightarrow \overline{\mathcal{T}}_{n}(p;d_{1}) \twoheadrightarrow \ldots \twoheadrightarrow \overline{\mathcal{T}}_{n}(p;d_{j},d_{j-1},\ldots,d_{1}) \twoheadrightarrow \ldots \twoheadrightarrow \overline{\mathcal{T}}_{n}(p;d_{p-2},d_{p-3},\ldots,d_{1})$ with finite GK-dimensions. Furthermore, we study the homological properties and the coradical filtrations of those quotient Hopf algebras.Comment: 27 pages, typos correcte

Effect of zinc on galactose-induced cell apoptosis in human lens epithelial cells

AIM:To study the effect of zinc on galactose-induced cell apoptosis in human lens epithelial cells(HLEC). METHODS:HLEC cell line SRA01/04 cells were cultured in DMEM medium and divided into six groups: control group, galactose treatment group, zinc supplement group, zinc supplementation combined with galactose treatment group, zinc deficiency group, zinc deficiency combined with galactose treatment group. The cell viabilities were assayed by MTT, cell morphology and apoptosis were detected by fluorescence microscope and flow cytometry, respectively. RESULTS:The cell viabilities induced by galactose(0, 25, 50, 75, 100, 125mmol/L)were(100.0±5.4)%,(97.5±3.2)%,(91.3±5.3)%,(93.4±0.6)%,(86.6±1.4)% and(83.5±0.4)%, respectively. When the concentration of galactose was 100 and 125mmol/L, cell viability was significantly decreased, compared with the untreated cells(PPPCONCLUSION:Zinc supplementation protects human lens epithelial cells against apoptosis induced by galactose and may have an inhibition effect on cataract formation

dc-europe bulletin no. 1974.9

Published by Groupe democrate-chrétien du Parlement europée

Towards comprehensive structural motif mining for better fold annotation in the "twilight zone" of sequence dissimilarity

Background: Automatic identification of structure fingerprints from a group of diverse protein structures is challenging, especially for proteins whose divergent amino acid sequences may fall into the “twilight-” or “midnight– ” zones where pair-wise sequence identities to known sequences fall below 25 % and sequence-based functional annotations often fail. Results: Here we report a novel graph database mining method and demonstrate its application to protein structure pattern identification and structure classification. The biologic motivation of our study is to recognize common structure patterns in “immunoevasins”, proteins mediating virus evasion of host immune defense. Our experimental study, using both viral and non-viral proteins, demonstrates the efficiency and efficacy of the proposed method. Conclusions: We present a theoretic framework, offer a practical software implementation for incorporating prior domain knowledge, such as substitution matrices as studied here, and devise an efficient algorithm to identify approximate matched frequent subgraphs. By doing so, we significantly expanded the analytical power of sophisticated data mining algorithms in dealing with large volume of complicated and noisy protein structure data. And without loss of generality, choice of appropriate compatibility matrices allows our method to be easily employed in domains where subgraph labels have some uncertainty