Insertion and Anchoring of the HIV-1 Fusion Peptide into a Complex Membrane Mimicking the Human T-Cell.

A fundamental understanding of how the HIV-1 envelope (Env) protein facilitates fusion is still lacking. The HIV-1 fusion peptide, consisting of 15 to 22 residues, is the N-terminus of the gp41 subunit of the Env protein. Further, this peptide, a promising vaccine candidate, initiates viral entry into target cells by inserting and anchoring into human immune cells.

Observation of the distribution of macro-, micro-, and toxic element contents of almond kernels burned with different digestion methods.

In this study, the elemental contents of almonds burned with four different methods to capture the elemental amount of almond kernels in the best way, to increase the release of obtainable elements by decomposing plant tissues, and to make them more atomized were measured and compared with ICP-AES. Depending on the digestion types, the K and Ca contents of almond varieties were determined as 10,167.35 (microwave) and 13,004.

Insurmountable antagonism of human mu opioid receptors by buprenorphine is due to hemi-equilibrium.

Buprenorphine is an FDA approved drug for the treatment of opioid use disorder and is a long-lasting, low efficacy (partial) agonist of the μ opioid receptor. As a partial agonist, buprenorphine can act as either an agonist or an antagonist depending on the efficiency of the cellular signaling system. Here we investigated the antagonist properties of buprenorphine using a genetically-encoded biosensor to monitor cAMP levels in real time in HEK293 cells expressing a relatively low density of the human μ receptor.

Design, Synthesis and Biological Evaluation of 2-Phenyl Indole Analogues of OXi8006 as Colchicine Site Inhibitors of Tubulin Polymerization and Vascular Disrupting Agents.

Inhibitors of tubulin polymerization represent a promising therapeutic approach for the treatment of solid tumors. Molecules that bind to the colchicine site are of interest as they can function with a dual mechanism of action as both potent antiproliferative agents and tumor-selective vascular disrupting agents (VDAs). One such example is a 2-aryl-3-aroyl-indole molecule (OXi8006) from our laboratory that demonstrates potent inhibition of tubulin polymerization and strong antiproliferative activity (cytotoxicity) against a variety of human cancer cell lines.

Gene family rearrangements and transcriptional priming drive the evolution of vegetative desiccation tolerance in Selaginella.

Extreme dryness is lethal for nearly all plants, excluding the so-called resurrection plants, which evolved vegetative desiccation tolerance (VDT) by recruiting genes common in most plants. To better understand the evolution of VDT, we generated chromosome-level assemblies and improved genome annotations of two Selaginella species with contrasting abilities to survive desiccation. We identified genomic features and critical mechanisms associated with VDT through sister-group comparative genomics integrating multi-omics data.

Stage-specific pharmacodynamic chloroquine and pyronaridine action on artemisinin ring-stage resistant Kelch C580Y mutation correlates to hemozoin inhibition process.

The antimalarial quinolines pyronaridine and chloroquine both inhibit hemozoin crystallization, predominately produced by intra-erythrocytic trophozoite stage parasites. Pyronaridine extends activity to ring-stage chloroquine-sensitive parasites, in contrast to chloroquine. Here, we investigated chloroquine and pyronaridine hemozoin inhibition type correlated to stage-specific activity on chloroquine-resistant ring-stage artemisinin sensitive and resistant CamWT and CamWT-C580Y parasites.

Testing the Antigenic Potential of Transmembrane Proteins To Develop a Thermostable Tuberculosis MOF-Liposomal Vaccine.

Tuberculosis is one of the deadliest infectious diseases and continues to be a major health risk in many parts of the world. Even today, the century-old Bacillus Calmette-Guerin (BCG) vaccine is the only formulation on the market and is ineffective for several sections of the global population responsible for transmission. In the search for antigens that can mount a robust immune response, we have reported the recombinant expression and purification of two novel membrane proteins, the Cation transporter protein V (CtpV) and the Mycobacterial copper transporter B (MctB) present on the membrane surface of .

Antimicrobial Peptides as Broad-Spectrum Therapeutics: Computational Analysis to Identify Universal Physical-Chemical Features Responsible for Multitarget Activity.

Antimicrobial peptides (AMPs) hold significant potential as broad-spectrum therapeutics due to their ability to target a variety of different pathogens, including bacteria, fungi, and viruses. However, the rational design of these peptides requires the molecular understanding of properties that enable such broad-spectrum activity. In this study, we present a computational analysis that utilizes machine-learning methods to distinguish peptides with single-target activity from those with activity against multiple pathogens.

Electrochemical imaging of neurotransmitter release with fast-scan voltammetric ion conductance microscopy.

Understanding the dynamic spatial and temporal release of neurotransmitters can help resolve long-standing questions related to chemical modulation of neurological circuits. Dopamine modulates function in a range of physiological processes and is key to transmission in addiction and neurological disorders. Studies at subcellular scales promise to help develop a broader understanding of dopamine release, diffusion, and receptor activation and how these processes lead to functional outcomes.

An orbital-overlap complement to σ-hole electrostatic potentials.

A σ-hole is an electron-deficient region of positive electrostatic potential (ESP) opposite from a half-filled p orbital involved in forming a covalent bond. The σ-hole concept helps rationalize directional noncovalent interactions, known as σ-hole bonds, between covalently bonded group V-VII atoms and electron-pair donors. The magnitude and orientation of σ-holes are correlated with the strength and geometry of halogen bonds.

Structural dynamics and binding of Caenorhabditis elegans lifespan-extending lipid binding protein-3 to polyunsaturated fatty acids.

Intracellular lipid binding proteins (iLBPs) play crucial roles in lipid transport and cellular metabolism across the animal kingdom. Recently, a fat-to-neuron axis was described in Caenorhabditis elegans, in which lysosomal activity in the fat liberates polyunsaturated fatty acids (PUFAs) that signal to neurons and extend lifespan with durable fecundity. In this study, we investigate the structure and binding mechanisms of a lifespan-extending lipid chaperone, lipid binding protein-3 (LBP-3), which shuttles dihomo-γ-linolenic (DGLA) acid from intestinal fat to neurons.

Internally diketopyrrolopyrrole-bridged bis-anthracene macrocycle: a multifunctional fluorescent platform.

A covalently bridged macrocycle (5) comprising two anthracene strands connected at the lactam positions of a diketopyrrolopyrrole (DPP) chromophore has been constructed. The crystal structure reveals that the central DPP chromophore is wrapped with the externally twisted bis-anthracene macrocycle. The internally bridged macrocycle architecture endows 5 with multifunctional properties.

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver.

Hepatic steatosis is a central phenotype in multi-system metabolic dysfunction and is increasing in parallel with the obesity pandemic. We use a translational approach integrating clinical phenotyping and outcomes, circulating proteomics, and tissue transcriptomics to identify dynamic, functional biomarkers of hepatic steatosis. Using multi-modality imaging and broad proteomic profiling, we identify proteins implicated in the progression of hepatic steatosis that are largely encoded by genes enriched at the transcriptional level in the human liver.

Illuminating anions in biology with genetically encoded fluorescent biosensors.

Anions are critical to all life forms. Anions can be absorbed as nutrients or biosynthesized. Anions shape a spectrum of fundamental biological processes at the organismal, cellular, and subcellular scales.

Potential role of meiofauna in bioremediation: results from a microcosm experiment.

Meiofauna can act as remediation organisms by stimulating microphytobenthos, sequestering carbon dioxide, and degrading organic debris. Sediments from two basins in Lake Mariut, Egypt, which had undergone multiple rounds of restoration, were used in microcosm experiments to assess the role of meiofauna in organic matter degradation. Treatments included sediments with and without fauna, and four chlorophyll-a additions (0.

Directly Fused Porphyrin-Tetracyanopentacenequinone Conjugates: Role of the Cross-Conjugated, Powerful Electron Acceptor in Promoting Highly Efficient Charge Separation.

Tetracyanopentacenequinone, a powerful electron acceptor, is fused directly to the porphyrin π-system to create a new class of donor-acceptor conjugates. Owing to the direct fusion and electron-deficient property of tetracyanopentacenequinone, strong intramolecular charge transfer both in the ground and excited states was witnessed. As a control, porphyrin fused with pentacenequinone was also investigated.

Comprehensive determination of highly symmetric transition metal dichalcogenide multilayers.

This study expands the JAM notation to systematically explore stacking configurations of transition metal dichalcogenide (TMDC) multilayers, covering both conventional and Janus structures. We extended JAM to represent four TMDC types: 1H, 1T, Janus 1H, and Janus 1T, adding characters to describe these structures. Additionally, we updated the JAM algorithm to generate stacking configurations and produce VASP-compatible POSCAR files.