A combined NMR and deep neural network approach for enhancing the spectral resolution of aromatic side chains in proteins.

Nuclear magnetic resonance (NMR) spectroscopy is an important technique for deriving the dynamics and interactions of macromolecules; however, characterizations of aromatic residues in proteins still pose a challenge. Here, we present a deep neural network (DNN), which transforms NMR spectra recorded on simple uniformly C-labeled samples to yield high-quality H-C correlation maps of aromatic side chains. Key to the success of the DNN is the design of NMR experiments that produce data with unique features to aid the DNN produce high-resolution spectra.

High sensitivity direct magnetic field detection based metrology for ultra-thin magnetic films and Li-ion cells.

Ultra-low magnetic field sensing is emerging as a tool for materials' diagnostics, particularly for the operando studies of electrochemical systems. A magnetic metrology system having the capability of sensing fields as low as ∼1.88 pT has been setup for such studies using a commercial atomic magnetometer.

Tetra-benzimidazoles flanking divinyl-phenothiazine: AIEgens as aza-Michael acceptors in concentration-tuned responses to biogenic amine vapors.

Tetra-benzimidazole rotors flanking a divinyl-phenothiazine stator are realized as red AIEgens and newly identified as efficient aza-Michael acceptors for the identification of biogenic amine vapors. Weakly red-emissive solids display a blue-shifted turn-on emission by rapid aza-Michael addition and simultaneous reverse Knoevenagel reactions. Concentration variation imposes better crystallinity and facilitates radiative decay, offering distinct emissions.

Negative contribution from defects responsible for low Young's modulus of graphene oxide at small defect densities.

Graphene oxide has been extensively employed as an additive in several nanocomposites to enhance their mechanical stability even though its Young's modulus is significantly smaller than that of pristine graphene. In the past decade, various chemical functionalizations have been attempted to enhance the mechanical strength of graphene oxide. In this work, we analyze the atomic contributions to the Young's modulus (YM) of graphene oxide with relevant models to decouple the role of the defects and the oxygen functionalities.

Mapping the FF domain folding pathway via structures of transiently populated folding intermediates.

Despite the tremendous accomplishments of AlpaFold2/3 in predicting biomolecular structure, the protein folding problem remains unsolved in the sense that accurate atomistic models of how protein molecules fold into their native conformations from an unfolded ensemble are still elusive. Here, using chemical exchange saturation transfer (CEST) NMR experiments and a comprehensive four-state kinetic model of the folding trajectory of a 71 residue four-helix bundle FF domain from human HYPA/FBP11 we present an atomic resolution structure of a transiently formed intermediate, I2, that along with the structure of a second intermediate, I1, provides a description of the FF domain folding trajectory. By recording CEST profiles as a function of urea concentration the extent of compaction along the folding pathway is evaluated.

Rational engineering of an antimalarial peptide with enhanced proteolytic stability and preserved parasite invasion inhibitory activity.

We describe rational chemical engineering to enhance the proteolytic stability of a chimeric peptide using a combination of unique strategies that involve the incorporation of a series of d-amino acids into the parent l-peptide sequence and restricting the conformational freedom of the peptide by covalent stitching. We hypothesize that replacing a stretch of sequence of an unstructured peptide motif with d-amino acids would increase its proteolytic stability without significantly affecting its affinity to the target protein. Also, considering the C-C distances, replacing an appropriate pair of residues with cysteine to form an additional disulfide bond in the molecule would provide additional stability to the engineered peptide.

Regulated Charge Transfer in Donor-Acceptor Metal-Organic Frameworks for Highly-Sensitive Photodetectors.

In photo-induced charge separation, organic thin films with donor and acceptor chromophores are vital for uses such as artificial photosynthesis and photodetection. The main challenges include optimizing charge separation efficiency and identifying the ideal acceptor/donor ratio. Achieving this is difficult due to the variability in molecular configurations within these typically amorphous organic aggregates.

Steering diffusion selectivity of chemical isomers within aligned nanochannels of metal-organic framework thin film.

The movement of molecules (i.e. diffusion) within angstrom-scale pores of porous materials such as metal-organic frameworks (MOFs) and zeolites is influenced by multiple complex factors that can be challenging to assess and manipulate.

Excitonic Effects on the Ultrafast Nonlinear Optical Response of MoS and Fluorinated Graphene/MoS Heterostructure Films for Photonic Applications.

In the present work, the ultrafast nonlinear optical (NLO) response of some molybdenum disulfide (MoS), fluorinated graphene (FG), and FG/MoS heterostructure thin films was studied using the -scan and optical Kerr effect techniques employing femtosecond laser pulses at different excitation wavelengths (i.e., 400, 570, 610, 660, 800, and 1200 nm).

Elucidating ATP's role as solubilizer of biomolecular aggregate.

Proteins occurring in significantly high concentrations in cellular environments (over 100 mg/ml) and functioning in crowded cytoplasm, often face the prodigious challenges of aggregation which are the pathological hallmark of aging and are critically responsible for a wide spectrum of rising human diseases. Here, we combine a joint-venture of complementary wet-lab experiment and molecular simulation to discern the potential ability of adenosine triphosphate (ATP) as solubilizer of protein aggregates. We show that ATP prevents both condensation of aggregation-prone intrinsically disordered protein Aβ40 and promotes dissolution of preformed aggregates.

How Salt and Temperature Drive Reentrant Condensation of Aβ40.

Within the framework of liquid-liquid phase separation (LLPS), biomolecular condensation orchestrates vital cellular processes, and its dysregulation is implicated in severe pathological conditions. Recent studies highlight the role of intrinsically disordered proteins (IDPs) in LLPS, yet the influence of microenvironmental factors has remained a puzzling factor. Here, via computational simulation of the impact of solution conditions on LLPS behavior of neurologically pathogenic IDP Aβ40, we chanced upon a salt-driven reentrant condensation phenomenon, wherein Aβ40 aggregation increases with low salt concentrations (25-50 mM), followed by a decline with further salt increments.

Effects of a Serotonergic Psychedelic on the Lipid Bilayer.

Serotonergic psychedelics, known for their hallucinogenic effects, have attracted interest due to their ability to enhance neuronal plasticity and potential therapeutic benefits. Although psychedelic-enhanced neuroplasticity is believed to require activation of 5-hydroxytryptamine (serotonin) 2A receptors (5-HTRs), serotonin itself is less effective in promoting such plasticity. Also, the psychoplastogenic effects of these molecules correlate with their lipophilicity, leading to suggestions that they act by influencing the intracellular receptors.

Regioisomers containing triarylboron-based motifs as multi-functional photoluminescent materials: from dual-mode delayed emission to pH-switchable room-temperature phosphorescence.

Triarylboron compounds have been established as promising candidates in optoelectronic applications. However, realizing multi-functional properties in triaryl boron-based materials remains challenging. Herein, we present two regioisomers, 1 and 2, designed judiciously by connecting a dimethylamino donor and a dimesitylboryl acceptor at 1,4 and 2,6-positions of the naphthalene spacer, respectively.

Cross-Coupling of NHC/CAAC-Based Carbodicarbene: Synthesis of Electron-Deficient Diradicaloids.

Herein, we report nickel(0)-catalyzed cross-coupling reactions of NHC/CAAC-based carbodicarbene (NHC = -heterocyclic carbene and CAAC = cyclic(alkyl)(amino)carbene) with different aryl chlorides, bromides, and iodides. The resulting aryl-substituted cationic carbodicarbene derivatives are prone to one-electron oxidation yielding radical-dications, which, depending on the aryl motif employed, follow different modes of radical-radical dimerization and constitute an entry point to carbon/nitrogen- and nitrogen/nitrogen-centered diradicaloids. Subsequently, this coupling strategy was strategically applied to the synthesis of -phenylene- and ,-biphenylene-bridged carbon/carbon-centered electron-deficient diradicaloids.

Anisotropic Porosity and Interface Synergy Enhanced Gas Permselectivity in Heterolayer Metal-Organic Framework Membrane.

The pursuit of sustainable, carbon-free separation technology hinges on the efficient separation of gas mixtures with high separation factors and flow rates, i. e. high permselectivity.

The challenges, opportunities and future of comparative physiology in the Global South: perspectives of early-career researchers.

Researchers in the Global South (GS, developing countries) make valuable contributions to the field of comparative physiology, but face economic and scientific disparities and several unique challenges compared with colleagues in the Global North (developed countries). This Perspective highlights some of the challenges, knowledge gaps and disparities in opportunity faced by GS researchers, especially those at early-career stages. We propose collaborative solutions to help address these issues, and advocate for promoting investment and cultural and societal change for a more inclusive research community.

Diverse morphology and motility induced emergent order in bacterial collectives.

Microbial communities exhibit complex behaviors driven by species interactions and individual characteristics. In this study, we delve into the dynamics of a mixed bacterial population comprising two distinct species with different morphology and motility aspects. Employing agent-based modeling and computer simulations, we analyze the impacts of size ratios and packing fractions on dispersal patterns, aggregate formation, clustering, and spatial ordering.

Machine learning unravels inherent structural patterns in Escherichia coli Hi-C matrices and predicts chromosome dynamics.

High dimensional nature of the chromosomal conformation contact map ('Hi-C Map'), even for microscopically small bacterial cell, poses challenges for extracting meaningful information related to its complex organization. Here we first demonstrate that an artificial deep neural network-based machine-learnt (ML) low-dimensional representation of a recently reported Hi-C interaction map of archetypal bacteria Escherichia coli can decode crucial underlying structural pattern. The ML-derived representation of Hi-C map can automatically detect a set of spatially distinct domains across E.

Tailoring solid-state DNP methods to the study of α-synuclein LLPS.

Dynamic Nuclear Polarization (DNP) is a technique that leverages the quantum sensing capability of electron spins to enhance the sensitivity of nuclear magnetic resonance (NMR) signals, especially for insensitive samples. Glassing agents play a crucial role in the DNP process by facilitating the transfer of polarization from the unpaired electron spins to the nuclear spins along with cryoprotection of biomolecules. DNPjuice comprising of glycerol-d/DO/HO has been extensively used for this purpose over the past two decades.

Access to Diverse Glutamic Acid Dendrons and a Janus Peptide Dendrimer Using an Atypical Solid Phase Synthesis.

The negligible cytotoxicity of anion surface-linked dendrons makes glutamic acid-based dendrons a potential candidate for materials and biological applications. Despite the inherent drawbacks of the conventional solution phase synthesis of glutamic acid-based dendrons, there have been no advancements in these protocols. Herein, we demonstrate the first-ever convergent solid phase synthesis of dendrons, up to fourth generation, having glutamic acid branching points produced by preactivation of dicarboxylic acid groups with -hydroxysuccinimide and simultaneous coupling with amine groups of two growing peptide chains, with excellent yields (30-70%).

Probing Short-Range Interactions in Isostructural Hydrate and Perhydrate of Dabrafenib by Magic-Angle Spinning Solid-State NMR.

Dabrafenib (), an anticancer drug, exhibits isostructural properties in its hydrate () and perhydrate () forms, as revealed by single-crystal X-ray diffraction. Despite the HO and HO solvent molecules occupying identical locations, the two polymorphs have different thermal behaviors. In general, determination of stoichiometry of HO in the perhydrate crystals is difficult due to the presence of both HO and HO in the same crystal voids.

hydrolysis of a carbophosphazene ligand leads to one-dimensional lanthanide coordination polymers. Synthesis, structure and dynamic magnetic studies.

An hydrolysis of the P-Cl bonds of the carbophosphazene [{NC(NMe)}{NPCl}] (L) in the presence of hydrated lanthanide(III) nitrates in a dichloromethane and methanol (2 : 1) solvent mixture afforded a series of novel 1D coordination polymers: [{Ln(L)(NO)(CHOH)(HO)} (Cl)] {where Ln(III) = Gd (1), Tb (2), Dy (3), or Er (4) and L is the hydrolyzed carbophosphazene (L) ligand}. X-ray crystallographic analysis revealed that complexes 1-4 are isostructural and crystallized in the monoclinic crystal system having 2/ space group. The coordination polymers are formed because of the involvement of the geminal P(O)(OH) moieties of the carbophosphazene ligand.

Conformational flexibility driving charge-selective substrate translocation across a bacterial transporter.

Bacterial membrane porins facilitate the translocation of small molecules while restricting large molecules, and this mechanism remains elusive at the molecular level. Here, we investigate the selective uptake of large cyclic sugars across an unusual passive membrane transporter, CymA, comprising a charged zone and a constricting N terminus segment. Using a combination of electrical recordings, protein mutagenesis and molecular dynamics simulations, we establish substrate translocation across CymA governed by the electrostatic pore properties and conformational dynamics of the constriction segment.