Unique Site Research Articles

The Role of Hydrogen Sulfide in iNOS and APP Localization and Expression in Neurons and Glial Cells Under Traumatic Effects: An Experimental Study with Bioinformatics Analysis and Biomodeling.

Hydrogen sulfide (H2S) donors are emerging as promising candidates for neuroprotective agents. However, H2S-dependent neuroprotective mechanisms are not yet fully understood. We have demonstrated that an H2S donor (sodium sulfide, Na2S) reduces the expression of inducible NO synthase (iNOS) and amyloid-beta precursor protein (APP) in damaged neural tissue at 24 h and 7 days following traumatic brain injury (TBI). The application of aminooxyacetic acid (AOAA), an inhibitor of cystathionine β-synthase (CBS), produced the opposite effect. Seven days after TBI, iNOS expression was observed not only in the cytoplasm but also in some neuronal nuclei, while APP was exclusively localized in the cytoplasm and axons of damaged neurons. It was also shown that iNOS and APP were present in the cytoplasm of mechanoreceptor neurons (MRNs) in the crayfish, in axons, as well as in certain glial cells 8 h after axotomy. Na2S and AOAA had opposing effects on axotomized MRNs and ganglia in the ventral nerve cord (VNC). Multiple sequence alignments revealed a high degree of identity among iNOS and APP amino acid residues in various vertebrate and invertebrate species. In the final stage of this study, biomodeling identified unique binding sites for H2S, hydrosulfide anion (HS-), and thiosulfate (S2O32-) with iNOS and APP.

Constructing Ru-Co2P Lewis Acid-Base Pairs to Prompt Hydrogen Evolution Reaction in Alkaline Seawater Electrolyte.

Seawater electrolysis is an ideal approach to generating green hydrogen. Nevertheless, the sluggish kinetics of water dissociation and the detrimental chlorine chemistry environment are serious obstructions for industrial applications. Herein, constructing unique (Co) Lewis acid and (Ru-P) base pair sites in Ru-Co2P decorated on nitrogen and phosphorus co-doped carbon (Ru-Co2P/NPC) significantly optimizes the energy barrier of water dissociation and enhances the anti-corrosive ability for alkaline seawater splitting. As expected, the optimal Ru-Co2P/NPC-2 exhibits exceptional hydrogen evolution reaction (HER) performances with overpotentials as low as 22.0 and 26.0mV to derive 10 mAcm-2 and operate steadily (@ 50 mAcm-2) over 30 h in alkaline and alkaline seawater electrolytes. The experimental and theoretical results elucidate that Co acting as Lewis acid sites prompts the water adsorption and breakage of the H─O bond, whereas Ru-P as Lewis base sites facilitates the hydrogen desorption in alkaline media. Furthermore, modulated chemical microenvironments can be beneficial to hinder chloride corrosion on the active sites of catalysts. This work sheds light on the rational construction of a highly efficient electrocatalyst for alkaline HER in seawater.

Reversible Multi-Complexation of CO2 to Alkaline Earth Metal Ion-Pair at 400 ppm and 298 K.

The efficient capture of low-pressure CO2 remains a significant challenge due to the lack of established multi-complexation of CO2 to active sites in microporous materials. In this study, we introduce a novel concept of reversible multi-complexation of CO2 to alkaline earth metal (AEM) ion pairs, utilizing a host site in ferrierite-type zeolite (FER). This unique site constrains two AEM ions in proximity, thereby enhancing and isotopically spreading their electrostatic potentials within the zeolite cavity. This electrostatic potential-engineered micropore can trap up to four CO2 molecules, forming M2+-(CO2)n-M2+ (n=0-4, M=Ca, Sr, Ba) complexes, where each CO2 molecule is stabilized by interactions between terminal oxygen (Ot) in CO2 and the AEM ions. Notably, the Ba2+ pair site exhibits higher thermodynamic stability for multiple adsorptions due to the optimal binding mode of Ba2+-Ot-Ba2+. Through high-accuracy energy calculations, we have established the relationship among structure, CO2 uptake, and operating temperature/pressure, demonstrating that the Ba2+ pair site can capture four CO2 molecules even at concentrations as low as 400 ppm and at 298 K. Three of the four molecules of CO2 trapped were removable at room temperature and under vacuum. The findings in the present study provide a new direction for developing efficient CO2 adsorbents.

Reversible Multi‐Complexation of CO2 to Alkaline Earth Metal Ion‐Pair at 400 ppm and 298 K

AbstractThe efficient capture of low‐pressure CO2 remains a significant challenge due to the lack of established multi‐complexation of CO2 to active sites in microporous materials. In this study, we introduce a novel concept of reversible multi‐complexation of CO2 to alkaline earth metal (AEM) ion pairs, utilizing a host site in ferrierite‐type zeolite (FER). This unique site constrains two AEM ions in proximity, thereby enhancing and isotopically spreading their electrostatic potentials within the zeolite cavity. This electrostatic potential‐engineered micropore can trap up to four CO2 molecules, forming M2+−(CO2)n−M2+ (n=0–4, M=Ca, Sr, Ba) complexes, where each CO2 molecule is stabilized by interactions between terminal oxygen (Ot) in CO2 and the AEM ions. Notably, the Ba2+ pair site exhibits higher thermodynamic stability for multiple adsorptions due to the optimal binding mode of Ba2+−Ot−Ba2+. Through high‐accuracy energy calculations, we have established the relationship among structure, CO2 uptake, and operating temperature/pressure, demonstrating that the Ba2+ pair site can capture four CO2 molecules even at concentrations as low as 400 ppm and at 298 K. Three of the four molecules of CO2 trapped were removable at room temperature and under vacuum. The findings in the present study provide a new direction for developing efficient CO2 adsorbents.

Comment on Lykova et al. (2024): “Natromelansonite, Na3Zr[Si7AlO19]⋅4–5H2O, a new member of the rhodesite mero-plesiotype series from Mont Saint-Hilaire, Quebec, Canada”

Abstract In this communication, we present a brief response to Lykova et al. (2024) who, in a paper in volume 88 https://doi.org/10.1180/mgm.2024.1 (this journal), describe the occurrence of the new mineral natromelansonite, Na3Zr(Si7AlO19)⋅4–5H2O, and provide commentary on the related species, melansonite (Na,□)□2KZrSi8O19⋅5H2O. The comments in question revolve primarily around the roles and abundances of Al and Na in both minerals, and how their incorporation is best represented in their idealised formulae. Lykova et al. (2024) state that Al is an essential component of both melansonite and natromelansonite and should thus be reflected in the ideal formulae. With respect to Na, they propose that the ideal formula of melansonite contains two Na apfu rather than one, as was presented in our initial definition of the mineral. We reiterate there is no unequivocal evidence that Al is an essential component of melansonite, occupying a unique crystallographic site, but rather, it only substitutes for Si. Secondly, though the true Na content of melansonite is probably higher than were originally reported (this being simply explained by the thin nature of the crystals analysed and the volatility of Na under the electron beam), it cannot reconcile the doubling of the Na apfu for melansonite, as was suggested by Lykova et al. (2024).

Distribution of the Culex pipiens mosquito in mainland Portugal: a geospatial modelling study

Abstract Background The mosquito Culex pipiens is a vector for several pathogens, such as the West Nile virus. As the most abundant mosquito in Portugal, understanding its spatial distribution can support vector-borne diseases control and robust public health planning, given the mainland’s favourable climate for this vector. Information on its spatial distribution at a national level is limited, especially its association with climate variables. Thus we aimed to predict the suitability of Culex pipiens distribution in mainland Portugal, considering climate factors. Methods We used presence records for adult and larvae of Culex pipiens mosquitoes sampled across mainland Portugal from January 2017 to October 2023, as part of the Portuguese Vector Surveillance Network program (REVIVE). Between May-October, in random locations and throughout the year in point-of-entry sites, adult mosquito collection used CDC light traps and BG-Sentinel traps, and larvae collection used dippers in breeding sites. Sampling bias was corrected by filtering presence sites, retaining one record per each cell grid of 1 km2. Climatic data (including temperature, precipitation and elevation) were used as predictors in a maximum entropy (MaxEnt) model of the Culex pipiens geographical distribution. Results From the dataset of 6859 records, 1416 unique sites were obtained after filtering. Suitable habitats seem to be mainly distributed on the coast, particularly in Minho, Porto and Lisbon metropolitan areas, and Tagus Valley, with precipitation as the most important predictor. Conclusions Most West Nile Virus case reports come from the south of Portugal, but the potential distribution of Culex pipiens covers the whole mainland territory, with seemingly higher distribution on the north coast. However, bias due to convenience sampling could be present. West Nile vector surveillance should be a priority across all regions to accurately assess transmission risk and implement effective control measures. Key messages • The suitability of Culex pipiens distribution covers the entire mainland of Portugal, with higher presence in the north. • The distribution of Culex pipiens in the country points towards a need for developing region-specific strategies regarding West Nile Virus prevention and control.

Specialized contact sites regulate the fusion of chlamydial inclusion membranes

The intracellular bacterial pathogen Chlamydia trachomatis replicates within a membrane-bound compartment called the inclusion. Upon infection with several chlamydiae, each bacterium creates its own inclusion, resulting in multiple inclusions within each host cell. Ultimately, these inclusions fuse together in a process that requires the chlamydial protein IncA. Here, we show that inclusions form unique contact sites (inclusion contact sites, ICSs) prior to fusion, that serve as fusogenic platforms in which specific lipids and chlamydial proteins concentrate. Fusion depends on IncA clustering within ICSs and is regulated by PI(3,4)P2 and sphingolipids. As IncA concentrates within ICSs, its C-terminus likely interacts in trans with IncA on the apposing membrane, securing a high concentration of IncA at fusion sites. This regulatory mechanism contrasts with eukaryotic or viral fusion systems that are either composed of multiple proteins or use a change in pH to initiate membrane fusion. Thus, our study demonstrates that Chlamydia-mediated membrane fusion is primarily regulated by specific structural domains in IncA and its local organization on the inclusion membrane, which is affected by the host cell lipid composition.

Covalent Organic Framework Stabilized Single CoN4Cl2 Site Boosts Photocatalytic CO2 Reduction into Tunable Syngas.

Solar carbon dioxide (CO2) reduction provides an attractive alternative to producing sustainable chemicals and fuel. However, the construction of a highly active photocatalyst was challenging because of the rapid charge recombination and sluggish surface CO2 reduction. Herein, a unique Co-N4Cl2 single site was fabricated by loading Co species into the 2,2'-bipyridine and triazine-containing covalent organic framework (COF) for CO2 conversion into syngas under visible light irradiation. The resulting champion catalyst TPy-COF-Co enabled a record-high CO production rate of 426 mmol g-1 h-1, associated with the unprecedented turnover number (TON) and turnover frequency (TOF) of 2095 and 1607 h-1, respectively. The catalyst also exhibited favorable recycling performance and widely adjustable syngas production (CO/H2 ratio: 1.8 : 1-1 : 16). A systematical investigation including operando synchrotron X-ray absorption fine structure (XAFS) spectroscopy, in situ attenuated total reflection surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS), and theoretical calculation indicated that the triazine-based COF framework promoted the charge transfer towards the single Co-N4Cl2 sites that greatly promoted the CO2 activation by lowering the energy barrier of *COOH generation, facilitating the CO2 transformation. This work highlights the great potential of the molecular regulation of COF-derived single-atom catalysts to boost CO2 photoreduction efficiency.

Paenilamicins bind to a unique site on the ribosome to inhibit protein synthesis.

Paenilamicins bind to a unique site on the ribosome to inhibit protein synthesis.

Gravfeltet i Hålandsmarka, Time kommune, SV-Norge

In 2008, a pre-development excavation examined a grave field on the ridge of Hålandsmarka. The burial ground was in use from the Early Bronze Age to the end of the Iron Age, and the excavation provided an opportunity to gain new insights into the long-term use of a grave field. The Hålandsmarka excavation allowed archaeologists to explore not only reuse of the grave field throughout this period, but also variations in burial form, treatment of the corpse, and grave goods over shorter timespans. The aim of the project has been to challenge the normative approach to graves as containers of a single burial event, and call attention to construction processes and other practices demonstrating the repeated use and transformation of the graves and their surroundings. Graves can be viewed as places of recurring engagement between the living and the dead, and as opportunities to explore the importance, duration and entanglement of material culture. Hålandsmarka should not be considered as a unique site: the results presented here are heavily dependent on our choice of archaeological methods, and we have the responsibility to be aware of the potential for complexity in both past and present practices when planning future excavations. The findings from Hålandsmarka call attention to the multi-temporal and gathered nature of grave fields in particular, as well as the archaeological record in general.

Science Highlights from the Kjell Henriksen Observatory on Svalbard

The Kjell Henriksen Observatory (KHO) is the world's largest optical observatory for auroral and airglow measurements, operated by the University Centre in Svalbard (UNIS). KHO is a unique site that lies underneath the dayside cusp, a funnel-shaped region where particles from the Sun can directly enter the Earth's upper atmosphere, including the ionosphere. Building on the pioneering observations of its predecessor --- the Auroral Station in Adventdalen, Svalbard --- KHO has played a pivotal role in advancing our understanding of phenomena in the polar atmosphere. The Auroral Station and KHO have amassed climatological measurements over Svalbard for an impressive 40-year period. KHO's diverse instrumentation, combined with other co-located optical and radar infrastructure and in-situ measurements from satellites and sounding rockets, has paved the way for impactful multi-instrument studies. Serving as an accessible testbed for instrument development, new types of instruments have recently been installed, both at KHO and on satellites. Beyond its scientific contributions, KHO has become an integral part of the Longyearbyen community, with students, visitors, and locals participating in tours and educational initiatives. This connection underscores KHO's multi-functional role, not only as a centre for excellent research but also as a vital hub for public outreach and engagement.

Paenilamicins are context-specific translocation inhibitors of protein synthesis

The paenilamicins are a group of hybrid nonribosomal peptide–polyketide compounds produced by the honey bee pathogen Paenibacillus larvae that display activity against Gram-positive pathogens, such as Staphylococcus aureus. While paenilamicins have been shown to inhibit protein synthesis, their mechanism of action has remained unclear. Here we determine structures of paenilamicin PamB2-stalled ribosomes, revealing a unique binding site on the small 30S subunit located between the A- and P-site transfer RNAs (tRNAs). In addition to providing a precise description of interactions of PamB2 with the ribosome, the structures also rationalize the resistance mechanisms used by P. larvae. We further demonstrate that PamB2 interferes with the translocation of messenger RNA and tRNAs through the ribosome during translation elongation, and that this inhibitory activity is influenced by the presence of modifications at position 37 of the A-site tRNA. Collectively, our study defines the paenilamicins as a class of context-specific translocation inhibitors.

Selective dealumination of large pore Zeolite Beta for effective Brønsted acid site utilization

Tuning of Al sites through spatial and geometric distribution is a novel pursuit for deterministic catalytic performance. To design an efficient Zeolite Beta for phenol alkylation with optimal physicochemical attributes, we conducted a systematic study with a series of dicarboxylic acids to selectively extract the framework and/or non-framework Aluminium. Herein, the post-synthetic treatment resulted in dealuminated catalysts of silicon-to-aluminum ratio ∼15–53. Extensive Al and Si NMR studies glean the selective extraction of aluminum from the zeolitic framework along with recomposition in T sites. The potency study alludes to the convoluted role of pH, chelating ability, and/or site accessibility for complexation. The differentiated Al extraction results in the emergence of unique super-strong acid sites. The novelty of our approach was established using phenol alkylation with cyclohexanol wherein we observed the highest conversion and desired CC alkylated product formation for the malonic acid-treated Zeolite Beta.

Archetypes of Spatial Concentration Variability of Organic Contaminants in the Atmosphere: Implications for Identifying Sources and Mapping the Gaseous Outdoor Inhalation Exposome.

Whereas inhalation exposure to organic contaminants can negatively impact human health, knowledge of their spatial variability in the ambient atmosphere remains limited. We analyzed the extracts of passive air samplers deployed at 119 unique sites in Southern Canada between 2019 and 2022 for 353 organic vapors. Hierarchical clustering of the obtained data set revealed four archetypes of spatial concentration variability in the outdoor atmosphere, which are indicative of common sources and similar atmospheric dispersion behavior. "Point Source" signatures are characterized by elevated concentration in the vicinity of major release locations. A "Population" signature applies to compounds whose air concentrations are highly correlated with population density, and is associated with emissions from consumer products. The "Water Source" signature applies to substances with elevated levels in the vicinity of water bodies from which they evaporate. Another group of compounds displays a "Uniform" signature, indicative of a lack of major sources within the study area. We illustrate how such a data set, and the derived spatial patterns, can be applied to support the identification of sources, the quantification of atmospheric emissions, the modeling of air quality, and the investigation of potential inequities in inhalation exposure.

Intricate Evolution of Multifunctional Lipoxygenase in Red Algae.

Lipoxygenases (LOXs) from lower organisms have substrate flexibility and function versatility in fatty acid oxidation, but it is not clear how these LOXs acquired the ability to execute multiple functions within only one catalytic domain. This work studied a multifunctional LOX from red alga Pyropia haitanensis (PhLOX) which combined hydroperoxidelyase (HPL) and allene oxide synthase (AOS) activity in its active pocket. Molecular docking and site-directed mutagenesis revealed that Phe642 and Phe826 jointly regulated the double peroxidation of fatty acid, Gln777 and Asn575 were essential to the AOS function, and the HPL activity was improved when Asn575, Gln777, or Phe826 was replaced by leucine. Phylogenetic analysis indicated that Asn575 and Phe826 were unique amino acid sites in the separated clades clustered with PhLOX, whereas Phe642 and Gln777 were conserved in plant or animal LOXs. The N-terminal START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) domain of PhLOX was another key variable, as the absence of this domain disrupted the versatility of PhLOX. Moreover, the functions of two homologous LOXs from marine bacterium Shewanella violacea and red alga Chondrus crispus were examined. The HPL activity of PhLOX appeared to be inherited from a common ancestor, and the AOS function was likely acquired through mutations in some key residues in the active pocket. Taken together, our results suggested that some LOXs from red algae attained their versatility by amalgamating functional domains of ancestral origin and unique amino acid mutations.

A cobalt coordination complex binds on a unique binding site between domain-I and domain-III of serum albumin

Serum albumin binding influences physiological effects and pharmacokinetics of drugs. Major binding sites in serum albumin are sudlow sites I and II, located on domains IIA and IIIA, respectively. However, groove between domain I and III as a binding site is not well studied. In this work, we studied the binding of a cobalt coordination complex (DCoP) with bovine serum albumin (BSA) using multi-spectroscopic methods and molecular docking. DCoP strongly interacts with BSA with association constant of ∼7 × 105M−1. The binding was found to significantly alter protein's conformation and unfolding pathway. Results of this study shows that DCoP binds at the groove formed between domains III and I. We conclude that the groove is a rare binding site for large molecules and coordination complexes. The knowledge of unique binding site of serum albumin enlightens the comprehensive role of protein as a carrier biomacromolecule.

O-GlcNAcylation of ribosome-associated proteins is concomitant with translational reprogramming during proteotoxic stress

Protein O-GlcNAc modification, similar to phosphorylation, supports cell survival by regulating key processes like transcription, cell division, trafficking, signaling, and stress tolerance. However, its role in protein homeostasis, particularly in protein synthesis, folding, and degradation remains poorly understood. Our previous research shows that O-GlcNAc cycling enzymes associate with the translation machinery during protein synthesis and modify ribosomal proteins. Protein translation is closely linked to 26S proteasome activity, which recycles amino acids and clears misfolded proteins during stress, preventing aggregation and cell death. In this study, we demonstrate that pharmacological perturbation of the proteasome—like that used in cancer treatment— leads to the increased abundance of OGT and OGA in a ribosome-rich fraction, concurrent with O-GlcNAc modification of core translational and ribosome-associated proteins. This interaction is synchronous with eIF2α-dependent translational reprogramming. We also found that protein ubiquitination depends partly on O-GlcNAc metabolism in MEFs, as OGT-depleted cells show decreased ubiquitination under stress. Using an O-GlcNAc-peptide enrichment strategy followed by LC-MS/MS, we identified 84 unique O-GlcNAc sites across 55 proteins, including ribosomal proteins, nucleolar factors, and the 70-kDa heat shock protein family. Hsp70 and OGT colocalize with the translational machinery in an RNA-independent manner, aiding in partial protein translation recovery during sustained stress. O-GlcNAc cycling on ribosome-associated proteins collaborates with Hsp70 to restore protein synthesis during proteotoxicity, suggesting a role in tumor resistance to proteasome inhibitors.

Simplified Lipid Nanoparticles for Tissue- And Cell-Targeted mRNA Delivery Facilitate Precision Tumor Therapy in a Lung Metastasis Mouse Model.

mRNA-based applications have achieved remarkable success in the development of next-generation vaccines and the treatment of diverse liver diseases. Overcoming the challenge of delivering mRNA to extrahepatic tissues, especially specific cells within tissues, is crucial for precision therapy. In this study, a platform is developed for selective mRNA delivery to desired cells within tissues by combining lipid nanoparticle (LNP)-based targeted delivery with mRNA sequence-controlled expression. Through systematic optimization, a three-component LNP platform is developed, enabling targeted mRNA delivery to the lung, liver, and spleen. The incorporation of unique microRNA target sites into the mRNA scaffold further enhances control over protein translation in specific cells within the target tissue. This combined strategy, named SELECT (Simplified LNP with Engineered mRNA for Cell-type Targeting), demonstrates its efficacy in distinguishing mRNA expression between tumor and normal cells based on intracellular microRNA abundance. SELECT encapsulating mRNA encoding a tumor-specific cytotoxic protein, human ELANE, exhibits selective mRNA delivery to tumor lesions and significant inhibition of tumor growth in a mouse model of melanoma lung metastasis. Overall, SELECT has great potential as a new precision tumor treatment approach and also offers promising prospects for other mRNA therapies targeting specific cell types.

Structural analysis of the CJ0600 protein from Campylobacter jejuni

The Campylobacter jejuni bacterium, which causes foodborne enteritis in humans, expresses the uncharacterized protein CJ0600. Based on sequence analysis, CJ0600 has been proposed to function as a 1-aminocyclopropane-1-carboxylate (ACC) deaminase (AccDA) or cysteine desulfhydrase (CysDS). However, it has never been investigated whether CJ0600 exerts AccDA or CysDS activity or how CJ0600 mediates its enzymatic activity. To reveal the structural features necessary for the function of CJ0600, we determined the crystal structure of CJ0600 and characterized its enzymatic activity. CJ0600 contains two domains and features an interdomain pocket, which accommodates a pyridoxal 5′-phosphate (PLP) molecule as a Schiff base with its lysine residue (K35), as observed in its structural homologs, including AccDA, CysDS, and serine deaminase (SerDA). However, unlike its structural homologs, CJ0600 exists as a monomer and exhibits unique structural features throughout its structure. Moreover, CJ0600 contains unique active site residues that are not observed in AccDA, CysDS, or SerDA. Consistently, phylogenetic analysis indicates that CJ0600 and its orthologs are evolutionarily distinct from AccDA, CysDS, and SerDA. Indeed, CJ0600 showed no CysDS or SerDA activity and extremely weak AccDA activity. These observations suggest that CJ0600 functions as a unique PLP-dependent enzyme that has not been reported.

An annotated checklist of the lichen biodiversity at two Mars analog sites: The Mars Desert Research Station (Utah, USA) and The Flashline Mars Arctic Research Station (Nunavut, Canada) recorded during the Mars 160 Mission

During the Mars 160 Mission in 2016 and 2017, crews at the Mars Desert Research Station (MDRS) in Utah, USA and the Flashline Mars Arctic Research Station (FMARS) on Tallurutit (Devon Island), Nunavut, Canada, conducted a collections‑based survey of lichen biodiversity at each of these Martian planetary analogs. Here we present the results of these studies as two annotated checklists, including 35 lichen spe‑ cies from MDRS and 13 species from FMARS, alongside details on the distribution of these species, relevant taxonomic notes, and photos of each species as an identification aid. This work adds to our knowledge of the biodiversity of these unique sites and provides an important baseline for future analog research at these stations.