Highly sensitive and selective detection of SARS-CoV-2 spike protein S1 using optically-active nanocomposite-coated melt-blown masks.

Detection of viruses, including coronavirus (SARS-CoV-2), via facile, fast, and optical methods is highly important to control pandemics. In this regard, optically-active nanomaterials and nanoparticles (NPs) are a wise choice due to their long-term stability, ease of functionalization, and modifications. In this work, a nanocomposite based on NiFe layered double hydroxide (LDH) and ZIF-67 metal-organic framework (MOF) was designed and synthesized, and decorated on the surface of the melt-blown mask.

High-throughput determination of exchange rates of unmodified and PTM-containing peptides using HX-MS.

Despite the widespread use of MS for hydrogen/deuterium exchange measurements, no systematic, large-scale study has been conducted to compare the observed exchange rates in protein-derived, unstructured peptides measured by MS to the predicted exchange rates calculated from NMR-derived values and how neighboring residues and post-translational modifications influence those exchange rates. In this study, we sought to test the accuracy of predicted values by performing hydrogen exchange measurements on whole cell digests to generate an unbiased dataset of 563 unique peptides derived from naturally-occurring protein sequences. A remarkable 97% of observed exchange rates of peptides are within two-fold of predicted values.

CryoEM structure of an MHC-I/TAPBPR peptide-bound intermediate reveals the mechanism of antigen proofreading.

Class I major histocompatibility complex (MHC-I) proteins play a pivotal role in adaptive immunity by displaying epitopic peptides to CD8+ T cells. The chaperones tapasin and TAPBPR promote the selection of immunogenic antigens from a large pool of intracellular peptides. Interactions of chaperoned MHC-I molecules with incoming peptides are transient in nature, and as a result, the precise antigen proofreading mechanism remains elusive.

Decreased expression of hsa-miR-142-3p and hsa-miR-155-5p in common variable immunodeficiency and involvement of their target genes and biological pathways.

Common variable immunodeficiency (CVID) is the most common symptomatic and heterogeneous type of inborn errors of immunity (IEI). However, the pathogenesis process of this disease is often unknown. Epigenetic modifications may be involved in unresolved patients.

25-Hydroxycholesterol modulates synaptic vesicle endocytosis at the mouse neuromuscular junction.

Many synaptic vesicles undergo exocytosis in motor nerve terminals during neuromuscular communication. Endocytosis then recovers the synaptic vesicle pool and presynaptic membrane area. The kinetics of endocytosis may shape neuromuscular transmission, determining its long-term reliability.

H3K36 methylation regulates cell plasticity and regeneration in the intestinal epithelium.

Plasticity is needed during development and homeostasis to generate diverse cell types from stem and progenitor cells. Following differentiation, plasticity must be restricted in specialized cells to maintain tissue integrity and function. For this reason, specialized cell identity is stable under homeostatic conditions; however, cells in some tissues regain plasticity during injury-induced regeneration.

Satellite DNA shapes dictate pericentromere packaging in female meiosis.

The abundance and sequence of satellite DNA at and around centromeres is evolving rapidly despite the highly conserved and essential process through which the centromere directs chromosome inheritance. The impact of such rapid evolution is unclear. Here we find that sequence-dependent DNA shape dictates packaging of pericentromeric satellites in female meiosis through a conserved DNA-shape-recognizing chromatin architectural protein, high mobility group AT-hook 1 (HMGA1).

AFM observation of protein translocation mediated by one unit of SecYEG-SecA complex.

Protein translocation across cellular membranes is an essential and nano-scale dynamic process. In the bacterial cytoplasmic membrane, the core proteins in this process are a membrane protein complex, SecYEG, corresponding to the eukaryotic Sec61 complex, and a cytoplasmic protein, SecA ATPase. Despite more than three decades of extensive research on Sec proteins, from genetic experiments to cutting-edge single-molecule analyses, no study has visually demonstrated protein translocation.

Adaptive sampling-based structural prediction reveals opening of a GABA receptor through the αβ interface.

γ-Aminobutyric acid type A (GABA) receptors are ligand-gated ion channels in the central nervous system with largely inhibitory function. Despite being a target for drugs including general anesthetics and benzodiazepines, experimental structures have yet to capture an open state of classical synaptic α1β2γ2 GABA receptors. Here, we use a goal-oriented adaptive sampling strategy in molecular dynamics simulations followed by Markov state modeling to capture an energetically stable putative open state of the receptor.

2-Cyanopyrimidine-Containing Molecules for N-Terminal Selective Cyclization of Phage-Displayed Peptides.

Current methods for the macrocyclization of phage-displayed peptides often rely on small molecule linkers that nonspecifically react with targeted amino acid residues. To expand tool kits for more regioselective macrocyclization of phage-displayed peptides, this study explores the unique condensation reaction between an N-terminal cysteine and nitrile along with the reactivity of an internal cysteine. Five 2-cyanopyrimidine derivatives were synthesized for this purpose and evaluated for their selective macrocyclization of a protein-fused model peptide.

Spectroscopic Properties and Biological Activity of Fluphenazine Conjugates with Gold Nanoparticles.

Fluphenazine (FPZ) is a well-known neuroleptic that has attracted considerable scientific interest due to its biocidal, virucidal, and antitumor properties. Although methods for encapsulating and delivering FPZ to enhance its activity and reduce side effects have been developed, there is still limited knowledge about its conjugates with gold nanoparticles (AuNPs). Therefore, the aim of this research was to develop a preparation method for stable FPZ-AuNP conjugates and to investigate their physicochemical and biological properties.

HROB Is Implicated in DNA Replication.

DNA replication represents a series of precisely regulated events performed by a complex protein machinery that guarantees accurate duplication of the genetic information. Since DNA replication is permanently faced by a variety of exogenous and endogenous stressors, DNA damage response, repair and replication must be closely coordinated to maintain genomic integrity. HROB has been identified recently as a binding partner and activator of the Mcm8/9 helicase involved in DNA interstrand crosslink (ICL) repair.

A Novel Pathogenic Sense Variant in Exon 7 of the HK1 Gene in a Patient with Hexokinase Deficiency and Gilbert Syndrome.

Background: Hexokinase (HK) deficiency is a rare autosomal recessively inherited disease manifested by chronic nonspherocytic hemolytic anemia. Most patients present with a mild to severe course of the disease (fetal hydrocephalus, neonatal hyperbilirubinemia, severe anemia). We reviewed 37 cases of patients with hexokinase deficiency described so far, focusing on the severity of the disease, clinical presentation, treatment applied, and genetic test results.

Hotspots for Disease-Causing Mutations in the Mitochondrial TIM23 Import Complex.

The human mitochondrial proteome comprises approximately 1500 proteins, with only 13 being encoded by mitochondrial DNA. The remainder are encoded by the nuclear genome, translated by cytosolic ribosomes, and subsequently imported into and sorted within mitochondria. The process of mitochondria-destined protein import is mediated by several intricate protein complexes distributed among the four mitochondrial compartments.

Structures of ATP-binding cassette transporter ABCC1 reveal the molecular basis of cyclic dinucleotide cGAMP export.

Cyclic nucleotide GMP-AMP (cGAMP) plays a critical role in mediating the innate immune response through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. Recent studies showed that ATP-binding cassette subfamily C member 1 (ABCC1) is a cGAMP exporter. The exported cGAMP can be imported into uninfected cells to stimulate a STING-mediated innate immune response.

The PRMT5-splicing axis is a critical oncogenic vulnerability that regulates detained intron splicing.

Protein arginine methyltransferase 5 (PRMT5) is a promising cancer target, yet it's unclear which PRMT5 roles underlie this vulnerability. Here, we establish that PRMT5 inhibition induces a special class of unspliced introns, called detained introns (DIs). To interrogate the impact of DIs, we depleted CLNS1A, a PRMT5 cofactor that specifically enables Sm protein methylation.

Solution biophysics identifies lipid nanoparticle non-sphericity, polydispersity, and dependence on internal ordering for efficacious mRNA delivery.

Lipid nanoparticles (LNPs) are the most advanced delivery system currently available for RNA therapeutics. Their development has accelerated since the success of Patisiran, the first siRNA-LNP therapeutic, and the mRNA vaccines that emerged during the COVID-19 pandemic. Designing LNPs with specific targeting, high potency, and minimal side effects is crucial for their successful clinical use.

Porous Materials for Early Diagnosis of Neurodegenerative Diseases.

Neurodegenerative diseases, particularly Alzheimer's disease and Parkinson's disease, present formidable challenges in modern medicine due to their complex pathologies and the absence of curative treatments. Despite advances in symptomatic management, early diagnosis remains essential for mitigating disease progression and improving patient outcomes. Traditional diagnostic methods, such as MRI, PET, and cerebrospinal fluid biomarker analysis, are often inadequate for the early detection of these diseases.

Fault-Tolerance Study on a Positive-Charged Cleft in 18 rRNA Methyltransferase DIMT1.

Dimethyladenosine transferase 1 (DIMT1) is an RNA -dimethyladenosine (mA) methyltransferase. DIMT1's role in pre-rRNA processing and ribosome biogenesis is critical for cell proliferation. Here, we investigated the minimal number of residues in a positively charged cleft on DIMT1 required for cell proliferation.

Transcription Kinetics in the Coronavirus Life Cycle.

Coronaviruses utilize a positive-sense single-strand RNA, functioning simultaneously as mRNA and the genome. An RNA-dependent RNA polymerase (RdRP) plays a dual role in transcribing genes and replicating the genome, making RdRP a critical target in therapies against coronaviruses. This review explores recent advancements in understanding the coronavirus transcription machinery, discusses it within virus infection context, and incorporates kinetic considerations on RdRP activity.

Proteins with alternative folds reveal blind spots in AlphaFold-based protein structure prediction.

In recent years, advances in artificial intelligence (AI) have transformed structural biology, particularly protein structure prediction. Though AI-based methods, such as AlphaFold (AF), often predict single conformations of proteins with high accuracy and confidence, predictions of alternative folds are often inaccurate, low-confidence, or simply not predicted at all. Here, we review three blind spots that alternative conformations reveal about AF-based protein structure prediction.

Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity.

Identifying cell types and brain regions critical for psychiatric disorders and brain traits is essential for targeted neurobiological research. By integrating genomic insights from genome-wide association studies with a comprehensive single-cell transcriptomic atlas of the adult human brain, we prioritized specific neuronal clusters significantly enriched for the SNP-heritabilities for schizophrenia, bipolar disorder, and major depressive disorder along with intelligence, education, and neuroticism. Extrapolation of cell-type results to brain regions reveals the whole-brain impact of schizophrenia genetic risk, with subregions in the hippocampus and amygdala exhibiting the most significant enrichment of SNP-heritability.

Type 2 Diabetes Mellitus Exacerbates Pathological Processes of Parkinson's Disease: Insights from Signaling Pathways Mediated by Insulin Receptors.

Parkinson's disease (PD), a chronic and common neurodegenerative disease, is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-synuclein. Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by chronic insulin resistance and deficiency in insulin secretion. Extensive evidence has confirmed shared pathogenic mechanisms underlying PD and T2DM, such as oxidative stress caused by insulin resistance, mitochondrial dysfunction, inflammation, and disorders of energy metabolism.

Non-coding RNAs secreted by renal cancer include piR_004153 that promotes migration of mesenchymal stromal cells.

Background: Renal cell cancer (RCC) is the most common and highly malignant subtype of kidney cancer. Mesenchymal stromal cells (MSCs) are components of tumor microenvironment (TME) that influence RCC progression. The impact of RCC-secreted small non-coding RNAs (sncRNAs) on TME is largely underexplored.