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1. A Porous Crystalline Nitrone‐Linked Covalent Organic Framework**

   https://doi.org/10.1002/anie.202307674  

   Kurandina, Daria; Huang, Banruo; Xu, Wentao; Hanikel, Nikita; Darù, Andrea; Stroscio, Gautam D.; Wang, Kaiyu; Gagliardi, Laura; Toste, F. Dean; Yaghi, Omar M. (July 2023, Angewandte Chemie International Edition)

   Abstract Herein, we report the synthesis of a nitrone‐linked covalent organic framework, COF‐115, by combiningN,N′,N′,N′′′‐(ethene‐1, 1, 2, 2‐tetrayltetrakis(benzene‐4, 1‐diyl))tetrakis(hydroxylamine) and terephthaladehyde via a polycondensation reaction. The formation of the nitrone functionality was confirmed by solid‐state¹³C multi cross‐polarization magic angle spinning NMR spectroscopy of the¹³C‐isotope‐labeled COF‐115 and Fourier‐transform infrared spectroscopy. The permanent porosity of COF‐115 was evaluated through low‐pressure N₂, CO₂, and H₂sorption experiments. Water vapor and carbon dioxide sorption analysis of COF‐115 and the isoreticular imine‐linked COF indicated a superior potential ofN‐oxide‐based porous materials for atmospheric water harvesting and CO₂capture applications. Density functional theory calculations provided valuable insights into the difference between the adsorption properties of these COFs. Lastly, photoinduced rearrangement of COF‐115 to the associated amide‐linked material was successfully demonstrated. 

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2. Engineered occluded apo-intermediate of LacY

   https://doi.org/10.1073/pnas.1816267115  

   Smirnova, Irina; Kasho, Vladimir; Kaback, H. Ronald (November 2018, Proceedings of the National Academy of Sciences)

   The lactose permease ofEscherichia coli(LacY) utilizes an alternating access symport mechanism with multiple conformational intermediates, but only inward (cytoplasmic)- or outward (periplasmic)-open structures have been characterized by X-ray crystallography. It is demonstrated here with sugar-binding studies that cross-linking paired-Cys replacements across the closed cytoplasmic cavity stabilize an occluded conformer with an inaccessible sugar-binding site. In addition, a nanobody (Nb) that stabilizes a periplasmic-open conformer with an easily accessible sugar-binding site in WT LacY fails to cause the cytoplasmic cross-linked mutants to become accessible to galactoside, showing that the periplasmic cavity is closed. These results are consistent with tight association of the periplasmic ends in two pairs of helices containing clusters of small residues in the packing interface between N- and C-terminal six-helix bundles of the symporter. However, after reduction of the disulfide bond, the Nb markedly increases the rate of galactoside binding, indicating unrestricted access to the Nb epitope and the galactoside-binding site from the periplasm. The findings indicate that the cross-linked cytoplasmic double-Cys mutants resemble an occluded apo-intermediate in the transport cycle. 

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3. Fracture, fatigue, and friction of polymers in which entanglements greatly outnumber cross-links

   https://doi.org/10.1126/science.abg6320  

   Kim, Junsoo; Zhang, Guogao; Shi, Meixuanzi; Suo, Zhigang (October 2021, Science)

   Longer and stronger; stiff but not brittle Hydrogels are highly water-swollen, cross-linked polymers. Although they can be highly deformed, they tend to be weak, and methods to strengthen or toughen them tend to reduce stretchability. Two papers now report strategies to create tough but deformable hydrogels (see the Perspective by Bosnjak and Silberstein). Wanget al. introduced a toughening mechanism by storing releasable extra chain length in the stiff part of a double-network hydrogel. A high applied force triggered the opening of cycling strands that were only activated at high chain extension. Kimet al. synthesized acrylamide gels in which dense entanglements could be achieved by using unusually low amounts of water, cross-linker, and initiator during the synthesis. This approach improves the mechanical strength in solid form while also improving the wear resistance once swollen as a hydrogel. —MSL 

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4. KDM6A facilitates Xist upregulation at the onset of X inactivation

   https://doi.org/10.1186/s13293-024-00683-3  

   Lin, Josephine; Zhang, Jinli; Ma, Li; Fang, He; Ma, Rui; Groneck, Camille; Filippova, Galina_N; Deng, Xinxian; Kinoshita, Chizuru; Young, Jessica_E; et al (January 2025, Biology of Sex Differences)

   Abstract BackgroundX chromosome inactivation (XCI) is a female-specific process in which one X chromosome is silenced to balance X-linked gene expression between the sexes. XCI is initiated in early development by upregulation of the lncRNAXiston the future inactive X (Xi). A subset of X-linked genes escape silencing and thus have higher expression in females, suggesting female-specific functions. One of these genes is the highly conserved geneKdm6a, which encodes a histone demethylase that removes methyl groups at H3K27 to facilitate gene expression.KDM6Amutations have been implicated in congenital disorders such as Kabuki Syndrome, as well as in sex differences in development and cancer. MethodsKdm6awas knocked out (KO) using CRISPR/Cas9 gene editing in hybrid female mouse embryonic stem (ES) cells derived either from a 129 × Mus castaneus(cast) cross or a BL6 xcastcross. In one of the lines a transcriptional stop signal inserted inTsixresults in completely skewed X silencing upon differentiation. The effects of both homozygous and heterozygousKdm6aKO onXistexpression during the onset of XCI were measured by RT-PCR and RNA-FISH. Changes in gene expression and in H3K27me3 enrichment were investigated using allele-specific RNA-seq and Cut&Run, respectively. KDM6A binding to theXistgene was characterized by Cut&Run. ResultsWe observed impaired upregulation ofXistand reduced coating of the Xi during early stages of differentiation inKdm6aKO cells, both homozygous and heterozygous, suggesting a threshold effect of KDM6A. This was associated with aberrant overexpression of genes from the Xi after differentiation, indicating loss of X inactivation potency. Consistent with KDM6A having a direct role inXistregulation, we found that the histone demethylase binds to theXistpromoter and KO cells show an increase in H3K27me3 atXist, consistent with reduced expression. ConclusionsThese results reveal a novel female-specific role for the X-linked histone demethylase, KDM6A in the initiation of XCI through histone demethylase-dependent activation ofXistduring early differentiation. Plain language summaryX chromosome inactivation is a female-specific mechanism that evolved to balance sex-linked gene dosage between females (XX) and males (XY) by silencing one X chromosome in females. X inactivation begins with the upregulation of the long noncoding RNAXiston the future inactive X chromosome. While most genes become silenced on the inactive X chromosome some genes escape inactivation and thus have higher expression in females compared to males, suggesting that escape genes may have female-specific functions. One such gene encodes the histone demethylase KDM6A which function is to turn on gene expression by removing repressive histone modifications. In this study, we investigated the role of KDM6A in the regulation ofXistexpression during the onset of X inactivation. We found that KDM6A binds to theXistgene to remove repressive histone marks and facilitate its expression in early development. Indeed, depletion of KDM6A prevents upregulation ofXistdue to abnormal persistence of repressive histone modifications. In turn, this results in aberrant overexpression of genes from the inactive X chromosome. Our findings point to a novel mechanism ofXistregulation during the initiation of X inactivation, which may lead to new avenues of treatment to alleviate congenital disorders such as Kabuki syndrome and sex-biased immune disorders where X-linked gene dosage is perturbed. 

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5. Bacterial spores respond to humidity similarly to hydrogels

   https://doi.org/10.1073/pnas.2320763121  

   Gor, Gennady Y; Scherer, George W; Stone, Howard A (March 2024, Proceedings of the National Academy of Sciences)

   Bacterial spores have outstanding properties from the materials science perspective, which allow them to survive extreme environmental conditions. Recent work by [S. G. Harrellsonet al.,Nature619, 500–505 (2023)] studied the mechanical properties ofBacillus subtilisspores and the evolution of these properties with the change of humidity. The experimental measurements were interpreted assuming that the spores behave as water-filled porous solids, subjected to hydration forces. Here, we revisit their experimental data using literature data on vapor sorption on spores and ideas from polymer physics. We demonstrate that upon the change of humidity, the spores behave like rubber with respect to their swelling, elasticity, and relaxation times. This picture is consistent with the knowledge of the materials comprising the bacterial cell walls—cross-linked peptidoglycan. Our results provide an interpretation of the mechanics of bacterial spores and can help in developing synthetic materials mimicking the mechanical properties of the spores. 

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