Nanoscale Characterization of Interaction of Nucleosomes with H1 Linker Histone.

In eukaryotic nuclei, DNA is wrapped around an octamer of core histones to form nucleosomes. H1 binds to the linker DNA of nucleosome to form the chromatosome, the next structural unit of chromatin. Structural features on individual chromatosomes contribute to chromatin structure, but not fully characterized.

The Impact of Cell-Intrinsic STAT6 Protein on Donor T Cell-Mediated Graft-Versus-Tumor Effect.

Bone marrow transplantation (BMT) is mainly performed to restore an anti-tumor immune response, called the graft-versus-tumor (GVT) effect, against leukemia, myeloma and lymphoma. This GVT reactivity is driven by donor T cells, and it can also cause lethal graft-versus-host disease (GVHD). We previously demonstrated that the colonization of mice with helminths preserves the GVT response while suppressing GVHD.

Analyses of the Gene in Triple Negative Breast Cancer: Evidence of Regulation of the Gene and Identification of a Specific Exon Overexpressed in Tumor Cell Lines.

Previous data show that the knockdown of the gene in the MDA-MB-231 cell line leads to the downregulation of gene expression. In addition, and genes are co-expressed and dysregulated in some of the same triple negative breast cancer patient samples. We propose that the co-expression of the two genes is attributed to the MYBL1 transcription factor regulation of the gene.

Long-Term 5-HT Receptor Agonist NLX-112 Treatment Improves Functional Recovery After Spinal Cord Injury.

Spinal cord injury (SCI) results in functional deficits below the injured spinal level. The descending serotonergic system in the spinal cord is critically involved in the control of motor and autonomic functions. Specifically, SCI damages the projections of serotonergic fibers, which leads to reduced serotonin inputs and increased amounts of spinal serotonergic receptors.

Identifying Strong Neoantigen MHC-I/II Binding Candidates for Targeted Immunotherapy with SINE.

The discovery of tumor-derived neoantigens which elicit an immune response through major histocompatibility complex (MHC-I/II) binding has led to significant advancements in immunotherapy. While many neoantigens have been discovered through the identification of non-synonymous mutations, the rate of these is low in some cancers, including head and neck squamous cell carcinoma. Therefore, the identification of neoantigens through additional means, such as aberrant splicing, is necessary.

Identification of Disease-Relevant, Sex-Based Proteomic Differences in iPSC-Derived Vascular Smooth Muscle Cells.

The prevalence of cardiovascular disease varies with sex, and the impact of intrinsic sex-based differences on vasculature is not well understood. Animal models can provide important insights into some aspects of human biology; however, not all discoveries in animal systems translate well to humans. To explore the impact of chromosomal sex on proteomic phenotypes, we used iPSC-derived vascular smooth muscle cells from healthy donors of both sexes to identify sex-based proteomic differences and their possible effects on cardiovascular pathophysiology.

Cochlear Mechanics Are Preserved After Inner Ear Delivery of Gold Nanoparticles.

Novel therapeutic delivery systems and delivery methods to the inner ear are necessary to treat hearing loss and inner ear disorders. However, numerous barriers exist to therapeutic delivery into the bone-encased and immune-privileged environment of the inner ear and cochlea, which makes treating inner ear disorders challenging. Nanoparticles (NPs) are a type of therapeutic delivery system that can be engineered for multiple purposes, and posterior semicircular canal (PSCC) infusion is a method to directly deposit them into the cochlea.

Optimized Prime Editing of Human Induced Pluripotent Stem Cells to Efficiently Generate Isogenic Models of Mendelian Diseases.

Prime editing (PE) is a CRISPR-based tool for genome engineering that can be applied to generate human induced pluripotent stem cell (hiPSC)-based disease models. PE technology safely introduces point mutations, small insertions, and deletions (indels) into the genome. It uses a Cas9-nickase (nCas9) fused to a reverse transcriptase (RT) as an editor and a PE guide RNA (pegRNA), which introduces the desired edit with great precision without creating double-strand breaks (DSBs).

Profiling Genome-Wide Methylation Patterns in Cattle Infected with .

DNA methylation (DNAm) regulates gene expression and genomic imprinting. This study aimed to investigate the effect of gastrointestinal (GI) nematode infection on host DNAm. Helminth-free Holstein steers were either infected with (the brown stomach worm) or given tap water only as a control.

Administration of AICAR, an AMPK Activator, Prevents and Reverses Diabetic Polyneuropathy (DPN) by Regulating Mitophagy.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes in both Type 1 (T1D) and Type 2 (T2D). While there are no specific medications to prevent or treat DPN, certain strategies can help halt its progression. In T1D, maintaining tight glycemic control through insulin therapy can effectively prevent or delay the onset of DPN.

An Overview of Zika Virus and Zika Virus Induced Neuropathies.

Flaviviruses pose a major public health concern across the globe. Among them, Zika virus (ZIKV) is an emerging and reemerging arthropod-borne flavivirus that has become a major international public health problem following multiple large outbreaks over the past two decades. The majority of infections caused by ZIKV exhibit mild symptoms.

Chloroquine Affects Presynaptic Membrane Retrieval in Diaphragm Neuromuscular Junctions of Old Mice.

Aging disrupts multiple homeostatic processes, including autophagy, a cellular process for the recycling and degradation of defective cytoplasmic structures. Acute treatment with the autophagy inhibitor chloroquine blunts the maximal forces generated by the diaphragm muscle, but the mechanisms underlying neuromuscular dysfunction in old age remain poorly understood. We hypothesized that chloroquine treatment increases the presynaptic retention of the styryl dye FM 4-64 following high-frequency nerve stimulation, consistent with the accumulation of unprocessed bulk endosomes.

, Encoding a Leucine-Rich Repeat Containing Receptor-like Protein, Is a Major Aphid () Resistance Gene in Sorghum.

Greenbug, , is one of the important cereal aphid pests of sorghum in the United States and other parts of the world. variety PI 607900 carries the resistance () gene that underlies plant resistance to greenbug biotype I (GBI). Now, the has been determined as the major gene conferring greenbug resistance based on the strong association of its presence with the resistance phenotype in sorghum.

Quality Investigation of Pultruded Carbon Fiber Panels Subjected to Four-Point Flexure via Fiber Optic Sensing.

Pultruded carbon fiber-reinforced composites are attractive to the wind energy industry due to the rapid production of highly aligned unidirectional composites with enhanced fiber volume fractions and increased specific strength and stiffness. However, high volume carbon fiber manufacturing remains cost-prohibitive. This study investigates the feasibility of a pultruded low-cost textile carbon fiber-reinforced epoxy composite as a promising material in spar cap production was undertaken based on mechanical response to four-point flexure loading.

Comparative Analysis of Temperature and Stress Simulations in Mass Concrete for Sluice Gate Structures Based on Chinese and American Standards.

Temperature-induced cracks during the construction of large concrete structures, such as water gates and bridges, caused by hydration heat, pose a serious threat to structural safety and reliability. To address this, various countries have developed temperature control standards and guidelines for mass concrete structures, providing design direction and evaluation criteria. China and the United States (U.

Variations and Asymmetry in Sacral Ventral Rami Contributions to the Bladder.

We have demonstrated in human cadavers and canines that nerve transfer to bladder vesical nerve branches is technically feasible for bladder reinnervation after nerve injury. We further clarify here that sacral (S) ventral rami contribute to these vesical branches in 36 pelvic sides (in 22 human cadavers). Gross post-mortem visualization and open anterior abdominal approaches were used, as was micro-CT of sacral nerve bundles, for further confirmation when needed.

Investigation of CD47 Expression in Renal Cell Tumors and Evaluation of Its Relationship with Prognostic Parameters.

Renal cell carcinoma is an aggressive form of kidney cancer, contributing to an estimated 138,000 deaths globally in 2017. Traditional treatments like chemotherapy and radiation are generally considered ineffective. Additionally, CD47 has been identified as a crucial tumor antigen involved in the development and progression of various cancers, including renal cell carcinoma.

Representing Structural Isomer Effects in a Coarse-Grain Model of Poly(Ether Ketone Ketone).

Carbon-fiber composites with thermoplastic matrices offer many processing and performance benefits in aerospace applications, but the long relaxation times of polymers make it difficult to predict how the structure of the matrix depends on its chemistry and how it was processed. Coarse-grained models of polymers can enable access to these long-time dynamics, but can have limited applicability outside the systems and state points that they are validated against. Here we develop and validate a minimal coarse-grained model of the aerospace thermoplastic poly(etherketoneketone) (PEKK).

Unveiling the Genetic Diversity and Demographic History of in Sierra Leone Using Genotyping-By-Sequencing.

is a rare Coffea species boasting a flavor profile comparable to Arabica coffee () and has a good adaptability to lowland tropical climates. This species faces increasing threats from climate change, deforestation, and habitat fragmentation in its West African homeland. Using 1037 novel SNP markers derived from Genotyping-by-Sequencing (GBS), we revealed the presence of three distinct natural populations (mean Fst = 0.

High-Throughput Phenotyping for Agronomic Traits in Cassava Using Aerial Imaging.

Large-scale phenotyping using unmanned aerial vehicles (UAVs) has been considered an important tool for plant selection. This study aimed to estimate the correlations between agronomic data and vegetation indices (VIs) obtained at different flight heights and to select prediction models to evaluate the potential use of aerial imaging in cassava breeding programs. Various VIs were obtained and analyzed using mixed models to derive the best linear unbiased predictors, heritability parameters, and correlations with various agronomic traits.

Dereplication of Natural Product Antifungals via Liquid Chromatography-Tandem Mass Spectrometry and Chemical Genomics.

Recently expanded reports of multidrug-resistant fungal infections underscore the need to develop new and more efficient methods for antifungal drug discovery. A ubiquitous problem in natural product drug discovery campaigns is the rediscovery of known compounds or their relatives; accordingly, we have integrated Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for structural dereplication and Yeast Chemical Genomics for bioprocess evaluation into a screening platform to identify such compounds early in the screening process. We identified 450 fractions inhibiting and the resistant strains of and among more than 40,000 natural product fractions.

Molecular Dynamics Insights into Peptide-Based Tetrodotoxin Delivery Nanostructures.

Tetrodotoxin (TTX), a potent Site-1 sodium channel blocker (S1SCB), offers highly effective local anesthetic properties with minimal addiction potential. To fully leverage TTX's capabilities as a local anesthetic, it is crucial to develop a drug delivery system that balances its systemic toxicity with its therapeutic efficacy. Recent studies have shown that peptide mixtures, derived from fragments of Site-1 sodium channel proteins and enhanced with hydrophobic tails (designated MP1 and MP2), can self-assemble into nanostructures that exhibit remarkable sustained-release capabilities for TTX.

The Expressions of the Immunity- and Muscle Development-Related Genes of 40-Day-Old Broilers Are Promoted in Response to the and Dietary Supplemental Administration of Calcidiol in Conjunction with the Administration of Marek's Disease Vaccine.

Effects of and dietary sources of calcidiol (25(OH)D), combined with Marek's disease vaccine (MDV), on the expression of genes involved with the antioxidant activity, muscle deposition, and immunity in the pectoralis major (P. major) muscle and spleen of 40 d of age (doa) broilers were investigated. The treatments were as follows: (1) non-injected; (2) the injection of 50 μL of commercial MDV, (3) MDV + 1.

Exploring Quantitative MRI Biomarkers of Head and Neck Post-Radiation Lymphedema and Fibrosis: Post Hoc Analysis of a Prospective Trial.

Background: Quantifying head and neck lymphedema and fibrosis (HN-LEF) is crucial in the investigation and management of treatment sequelae in head and neck cancer (HNC).

Methods: The T1- and T2-weighted MRI signal intensity (SI) was examined in relation to HN-LEF categories per physical/tactile examination (No-LEF, A-B = edema, C = edema + fibrosis, D = fibrosis), and MRI structural volumes were examined in relation to a novel 10-point HN-LEF score in the intraoral and submental regions.

Results: We identified differences in ranks among HN-LEF categories in relation to the MRI SI (A-B and C are higher than D and No-LEF for T2 SI, and A-B is the highest for T1).

Cycle Effects Are Not Universal: A Case Study of Urinary C-Reactive Protein Concentrations in Rural Polish and Polish American Samples.

Objectives: We need to better understand how the menstrual cycle interacts with other biological systems, such the inflammation and immune response. One way to study this interaction is through C-reactive protein (CRP). Studies of CRP concentrations across the menstrual cycle have been inconsistent.