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1. Condensin I ^DC , H4K20me1, and perinuclear tethering maintain X chromosome repression in C. elegans

   https://doi.org/10.1101/2024.04.05.588224  

   Trombley, Jessica; Rakozy, Audry I; Jash, Eshna; Csankovszki, Györgyi (April 2024, bioRxiv)

   Abstract Dosage compensation inCaenorhabditis elegansequalizes X-linked gene expression between XX hermaphrodites and XO males. The process depends on a condensin- containing dosage compensation complex (DCC), which binds the X chromosomes in hermaphrodites to repress gene expression. Condensin I^DCand an additional five DCC components must be present on the X during early embryogenesis in hermaphrodites to establish dosage compensation. However, whether the DCC’s continued presence is required to maintain the repressed state once established is unknown. Beyond the role of condensin I^DCin X chromosome compaction, additional mechanisms contribute to X- linked gene repression. DPY-21, a non-condensin I^DCDCC component, is an H4K20me2/3 demethylase whose activity enriches the repressive histone mark, H4 lysine 20 monomethylation, on the X chromosomes. In addition, CEC-4 tethers H3K9me3-rich chromosomal regions to the nuclear lamina, which also contributes to X- linked gene repression. To investigate the necessity of condensin I^DCduring the larval and adult stages of hermaphrodites, we used the auxin-inducible degradation system to deplete the condensin I^DCsubunit DPY-27. While DPY-27 depletion in the embryonic stages resulted in lethality, DPY-27 depleted larvae and adults survive. In these DPY-27 depleted strains, condensin I^DCwas no longer associated with the X chromosome, the X became decondensed, and the H4K20me1 mark was gradually lost, leading to X-linked gene derepression. These results suggest that the stable maintenance of dosage compensation requires the continued presence of condensin I^DC. A loss-of-function mutation incec-4, in addition to the depletion of DPY-27 or the genetic mutation ofdpy- 21, led to even more significant increases in X-linked gene expression, suggesting that tethering heterochromatic regions to the nuclear lamina helps stabilize repression mediated by condensin I^DCand H4K20me1. Author SummaryIn some organisms, whether an individual becomes male, female, or hermaphrodite is determined by the number of their sex chromosomes. In the nematodeCaenorhabditis elegans, males have one X chromosome, whereas hermaphrodites have two X chromosomes. This difference in the number of X chromosomes is crucial for deciding whether an individual becomes a hermaphrodite or a male. However, having two X chromosomes can lead to problems because it results in different gene expression levels, resulting in hermaphrodite lethality. To solve this issue, many organisms undergo a process called dosage compensation. Dosage compensation inC. elegansis achieved by a group of proteins known as the dosage compensation complex (DCC), which includes a protein called DPY-27. The function of DPY-27 is essential during early embryonic development. This study shows that in contrast to early embryonic development, larvae and adults can still survive when DPY-27 is missing. In these worms, all known mechanisms involved in dosage compensation are disrupted and the X is no longer repressed. Our results suggest that the maintenance of dosage compensation in nematodes is an active process, and that it is essential for survival when the organism is developing, but once fully developed, the process becomes dispensable. 

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2. Spectroscopic and Crystallographic Characterization of the R ₃ N ⁺ −C−H⋅⋅⋅X Interaction

   https://doi.org/10.1002/chem.202103922  

   Capilato, Joseph_N; Harry, Stefan_A; Siegler, Maxime_A; Lectka, Thomas (January 2022, Chemistry – A European Journal)

   Abstract As appreciation for nonclassical hydrogen bonds has progressively increased, so have efforts to characterize these interesting interactions. Whereas several kinds of C−H hydrogen bonds have been well‐studied, much less is known about the R₃N⁺−C−H⋅⋅⋅X variety. Herein, we present crystallographic and spectroscopic evidence for the existence of these interactions, with special relevance to Selectfluor chemistry. Of particular note is the propensity for Lewis bases to engage in nonclassical hydrogen bonding over halogen bonding with the electrophilic F atom of Selectfluor. Further, the first examples of¹H NMR experiments detailing R₃N⁺−C−H⋅⋅⋅X (X=O, N) hydrogen bonds are described. 

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3. Tonic extracellular glutamate and ischaemia: glutamate antiporter system x _c ⁻ regulates anoxic depolarization in hippocampus

   https://doi.org/10.1113/JP283880  

   Heit, Bradley S.; Chu, Alex; Sane, Abhay; Featherstone, David E.; Park, Thomas J.; Larson, John (November 2022, The Journal of Physiology)

   AbstractIn stroke, the sudden deprivation of oxygen to neurons triggers a profuse release of glutamate that induces anoxic depolarization (AD) and leads to rapid cell death. Importantly, the latency of the glutamate‐driven AD event largely dictates subsequent tissue damage. Although the contribution of synaptic glutamate during ischaemia is well‐studied, the role of tonic (ambient) glutamate has received far less scrutiny. The majority of tonic, non‐synaptic glutamate in the brain is governed by the cystine/glutamate antiporter, system x_c⁻. Employing hippocampal slice electrophysiology, we showed that transgenic mice lacking a functional system x_c⁻display longer latencies to AD and altered depolarizing waves compared to wild‐type mice after total oxygen deprivation. Experiments which pharmacologically inhibited system x_c⁻, as well as those manipulating tonic glutamate levels and those antagonizing glutamate receptors, revealed that the antiporter's putative effect on ambient glutamate precipitates the ischaemic cascade. As such, the current study yields novel insight into the pathogenesis of acute stroke and may direct future therapeutic interventions.image Key pointsIschaemic stroke remains the leading cause of adult disability in the world, but efforts to reduce stroke severity have been plagued by failed translational attempts to mitigate glutamate excitotoxicity.Elucidating the ischaemic cascade, which within minutes leads to irreversible tissue damage induced by anoxic depolarization, must be a principal focus.Data presented here show that tonic, extrasynaptic glutamate supplied by system x_c⁻synergizes with ischaemia‐induced synaptic glutamate release to propagate AD and exacerbate depolarizing waves.Exploiting the role of system x_c⁻and its obligate release of ambient glutamate could, therefore, be a novel therapeutic direction to attenuate the deleterious effects of acute stroke. 

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4. Revealing Coexisting Cu ⁰ –Cu ⁺ Sites in Cu ₃ N Nanoensembles for Selective CC Coupling of CO ₂ Under Low Overpotential

   https://doi.org/10.1002/cssc.202500003  

   Li, Junrui; Zhong, Hong; Hong_Lee, Soo; Li, Hui; Drisdell, Walter_S; Dun, Chaochao; Burciaga, Rihana; Ingram, Conrad; Beckman, Scott_P; Urban, Jeffrey_J; et al (June 2025, ChemSusChem)

   To address a long‐existing debate on what copper species are responsible for efficient CC coupling, especially ethanol formation, in electrochemical CO₂reduction reaction, herein, a comprehensive study using Cu₃N nanocubes with a uniform size and shape, alongside a single crystalline phase is reported. The Cu₃N nanoensemble electrode has a remarkable Faradaic efficiency (FE) of 64% for ethanol production at a relatively low potential of −0.6 V versus reversible hydrogen electrode. Throughin‐operandoX‐ray absorption spectroscopy study, a dynamic phase evolution that directly correlates with changes in FE across varying applied potentials is observed. Notably, the nanoensemble with a composition of ≈71% Cu⁺and 29% Cu⁰is identified as being selective for ethanol formation at the low overpotential. Conversely, a predominantly metallic Cu phase formed at potentials more negative than −0.6 V favors the hydrogen evolution reaction. Density functional theory calculations at the Cu₃N–Cu interface substantiate that the coexistence of Cu⁰–Cu⁺not only energetically favors the ethanol reaction pathway but also destabilizes the intermediates for ethylene pathway. 

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5. Nickel‐Catalyzed C( sp ² )−C( sp ³ ) Kumada Cross‐Coupling of Aryl Tosylates with Alkyl Grignard Reagents

   https://doi.org/10.1002/adsc.201801586  

   Piontek, Aleksandra; Ochędzan‐Siodłak, Wioletta; Bisz, Elwira; Szostak, Michal (April 2019, Advanced Synthesis & Catalysis)

   Abstract Aryl tosylates are an attractive class of electrophiles for cross‐coupling reactions due to ease of synthesis, low price, and the employment of C−O electrophiles, however, the reactivity of aryl tosylates is low. Herein, we report the Ni‐catalyzed C(sp²)−C(sp³) Kumada cross‐coupling of aryl tosylates with primary and secondary alkyl Grignard reagents. The method delivers valuable alkyl arenes by cross‐coupling with challenging alkyl organometallics possessing β‐hydrogens that are prone to β‐hydride elimination and homo‐coupling. The reaction is catalyzed by an air‐ and moisture stable‐Ni(II) precatalyst. A broad range of electronically‐varied aryl tosylates, including bis‐tosylates, underwent this transformation, and many examples are suitable at mild room temperature conditions. The combination of Ar−X cross‐coupling with the facile Ar−OH activation/cross‐coupling strategy permits for orthogonal cross‐coupling with challenging alkyl organometallics. Furthermore, we demonstrate that the method operates with TON reaching 2000, which is one of the highest turnovers observed to date in Ni‐catalyzed cross‐couplings. magnified image 

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