A5054249104- Advanced Chemical Physics Studies
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Spectroscopy and Quantum Chemical Studies
- Mass Spectrometry Techniques and Applications
- RNA Research and Splicing
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Epigenetics and DNA Methylation
- Silicon Nanostructures and Photoluminescence
- Semiconductor materials and devices
- Hepatitis C virus research
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- nanoparticles nucleation surface interactions
- Reproductive System and Pregnancy
- Molecular Spectroscopy and Structure
- Reproductive Biology and Fertility
- Genomics and Rare Diseases
- Magnesium in Health and Disease
- Photochemistry and Electron Transfer Studies
- Neonatal Respiratory Health Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Genomics and Phylogenetic Studies
- Molecular spectroscopy and chirality
National Institute of Environmental Health Sciences
2019-2025
National Institutes of Health
2020-2025
Government of the United States of America
2023
Research Triangle Park Foundation
2023
Triangle
2022
North Carolina State University
2010-2016
North Central State College
2012
University of Georgia
2003-2009
Johns Hopkins University
2008-2009
Sex determination of mammalian gonads hinges upon sex-specific differentiation gonadal supporting cells: Sertoli cells in the testis and granulosa ovary. To gain insights into how acquire their identities, we performed joint single-nucleus transcriptomics chromatin accessibility assays on murine across sex determination. By contrasting gene expression corresponding among progenitor differentiated cells, discovered that regions are established shortly after determination, accompanied by...
Abstract Steroid hormone receptors such as the Glucocorticoid Receptor (GR) mediate transcriptional responses to hormones and are frequently targeted in treatment of human diseases. Experiments using bulk populations cells have provided a detailed picture global response but unable interrogate cell-to-cell heterogeneity. To examine glucocorticoid individual cells, we performed single cell RNA sequencing (scRNAseq) breast cancer line. The was robustly detected scRNAseq additional statistical...
Human skin is continuously exposed to environmental DNA damage leading the accumulation of somatic mutations over lifetime an individual. Mutagenesis in human cells can be also caused by endogenous and replication errors. The contributions these processes mutation load healthy humans has so far not been accurately assessed because low numbers from current sequencing methodologies preclude distinction between errors true genome changes. In this work, we sequenced genomes single cell-derived...
The analysis of N-linked glycans by mass spectrometry (MS) has been characterized low signal-to-noise ratios and high limits detection due to their hydrophilicity lack basic sites able be protonated. As a result, every step in glycan sample preparation must thoroughly optimized order minimize loss, contamination, analytical variability. Importantly, properties derivatized counterparts studied exploit certain characteristics for enhancing MS analysis. Herein, the effectiveness incorporation...
Tissue development entails genetically programmed differentiation of immature cell types to mature, fully differentiated cells. Exposure during non-mutagenic environmental factors can contribute cancer risk, but the underlying mechanisms are not understood. We used a mouse model endometrial adenocarcinoma that results from brief developmental exposure an estrogenic chemical, diethylstilbestrol (DES), determine causative factors. Single-cell RNA sequencing (scRNAseq) and spatial...
A self-consistent procedure for constructing a quasidiabatic Hamiltonian representing N(state) coupled electronic states in the vicinity of an arbitrary point nuclear coordinate space is described. The matrix elements are polynomials order. Employing crude adiabatic basis, coefficients linear terms determined exactly using analytic gradient techniques. remaining polynomial from normal form system pseudolinear equations, which uses energy and derivative coupling information obtained reliable...
Aberrant fibroblast function plays a key role in the pathogenesis of idiopathic pulmonary fibrosis, devastating disease unrelenting extracellular matrix deposition response to lung injury. Platelet-derived growth factor α-positive (Pdgfra+) lipofibroblasts (LipoFBs) are essential for injury and maintenance functional alveolar stem cell niche. Little is known about effects on LipoFB function. Here, we used single-cell RNA-Seq (scRNA-Seq) technology PdgfraGFP lineage tracing generate...
The use of assisted reproductive technologies (ART) has enabled the birth over 9 million babies; but it is associated with increased risks negative metabolic outcomes in offspring. Yet, underlying mechanism remains unknown. Calcium (Ca2+) signals, which initiate embryo development at fertilization, are frequently disrupted human ART. In mice, abnormal Ca2+ signals fertilization impair and adult offspring metabolism. Changes intracellular drive mitochondrial activity production metabolites...
Changes in the poly(A) tail length of Odf1 and other transcripts critical for male fertility have been linked to translational activation during sperm formation 1-3 . The mRNA polymerase TENT5C is required fastening flagellum head, but its role shaping profile spermatid transcriptome remains limited 4,5 Here, we comprehensively document how changes across reflect transcript metabolism spermatids. In absence activity, reduced, local distribution ODF1 proteins spermatids disrupted. We show...
Although the RNA of Hepatitis B virus (HBV) is known to be regulated by epitranscriptomic modification N6-methyladenosine (m6A), it remains controversial whether if m6A beneficial or detrimental for viral replication. Here, we employ Nanopore direct sequencing (DRS) analyze HBV epitranscriptome on a single molecule level and elucidate how regulates replication cycle. We found more than 60% all in cells are methylated, ~3x methylated host mRNAs. Previously unreported sites were pol gene,...
Both hepatitis B virus (HBV), an hepadnavirus with a DNA genome, and A (HAV), picornavirus, require the TRAMP-like host ZCCHC14-TENT4 complex for efficient replication. However, whereas HBV requires nucleotidyltransferase activity of TENT4 to extend stabilize 3′ poly(A) tails mRNA transcribed from its role played by in HAV replication is uncertain. proteins are synthesized directly genomic RNA, which possesses tail, length composition presumably maintained 3Dpol-catalyzed RNA transcription...
Density-functional theory has been used to determine the ground-state geometries and electronic states for homonuclear transition-metal trimers constrained equilateral triangle geometries. This represents first application of consistent theoretical methods all ten 3d block trimers, from scandium zinc. A search potential surfaces yields following ground bond lengths: Sc3(2A1',2.83 A), Ti3(7E',2.32 V3(2E",2.06 Cr3(17E',2.92 Mn3(16A2',2.73 Fe3(11E",2.24 Co3(6E",2.18 Ni3(3A2",2.23 Cu3(2E',2.37...
Abstract Coronaviruses are positive-strand RNA viruses with 3′ polyadenylated genomes and subgenomic transcripts. The lengths of the viral poly(A) tails change during infection by mechanisms that remain poorly understood. Here, we use a splint-ligation method to measure tail length terminal uridylation guanylation mouse hepatitis virus (MHV) RNAs. Upon 17-CL1 cells MHV, member Betacoronavirus genus, observe two populations terminally uridylated transcripts, one ~44 nucleotides long other...
Recently, it has been proposed that ab initio calculations cannot accurately treat molecules comprised of a benzene ring with pi-conjugated substituent, for example, benzaldehyde. Theoretical predictions the benzaldehyde barrier to internal rotation are typically factor 2 too high in comparison experimental values 4.67 (infared) and 4.90 (microwave) kcal mol(-1). However, both experiments use Pitzer's 1946 model compute reduced moment inertia employ experimentally observed torsional...
TRPM7 (transient receptor potential cation channel subfamily M member 7) is a chanzyme with and kinase domains essential for embryo development. Using gamete-specific Trpm7-null lines, we report that TRPM7-mediated Mg2+ influx indispensable reaching the blastocyst stage. expressed dynamically from gametes to blastocysts; displays stage-specific localization on plasma membrane, cytoplasm, nucleus; undergoes cleavage produces C-terminal fragments. underpins homeostasis, excess but not Zn2+ or...
A theoretical study is presented on the adsorption of sarin molecule, a nerve agent, three model solid surfaces: aliphatic (graphane), aromatic (graphene), and ionic (CaO). Calculations are carried out using accurate electronic structure methods based configuration interaction (CI) as well complementary density functional theory (DFT) time dependent (TD) DFT calculations. The objective to describe surface interactions accurately in order identify factors that affect sarin. Potential energy...
Abstract Ab initio SCF‐CI theory has been used to examine the interactions of a single water molecule with 31‐atom nanocluster palladium. Calculations are performed on singly‐charged cationic and anionic particles in addition neutral system determine effects charging adsorption energy barriers dissociation. Penetration dissociated H through surface layer into an interstitial subsurface site is also examined. Adsorption energies intact fall range 0.2–0.8 eV, while barrier dissociation 1.4–2.1...
Idiopathic pulmonary fibrosis (IPF) is a devastating disease with no curative treatment other than lung transplantation. IPF results from maladaptive responses to epithelial injury, but the underlying mechanisms remain unclear. Here, we show that deficiency in innate immune receptor, toll-like receptor 5 (TLR5), associated humans and increased susceptibility injury experimental mice, while activation of TLR5 through synthetic flagellin analogue protects fibrosis. Mechanistically, induces...
ABSTRACT Across mammalian species, new mothers undergo considerable behavioral changes to nurture their offspring and meet the caloric demands of milk production 1-5 . While many neural circuits underlying feeding parenting behaviors are well characterized 6-9 , it is unclear how these different interact adapt during lactation. Here, we transcriptomic in arcuate nucleus (ARC) medial preoptic area (MPOA) mouse hypothalamus response lactation hunger. Furthermore, showed that heightened...
The troublesome barrier to linearity of the ketenyl radical (HCCO) is precisely determined using state-of-the-art computations within focal point approach, by combining complete basis set extrapolation, utilizing aug-cc-pVXZ (X = D, T, Q, 5, 6) family sets, with electron correlation treatments as extensive coupled cluster theory single, double, triple, and perturbative quadruple excitations [CCSDT(Q)]. Auxiliary terms such diagonal Born-Oppenheimer corrections (DBOCs) relativistic...
The negative ion photoelectron spectrum of 1-propynide is computed by employing the multimode vibronic coupling approach. A three-state quasidiabatic Hamiltonian, H(d), reported, which accurately represents ab initio determined equilibrium geometries and harmonic frequencies ground X (2)A(1) state as well low-lying Jahn-Teller distorted components (2)E excited state. It also reproduces both minimum energy crossing point (MECP) on symmetry-required (2)E(x)-(2)E(y) conical intersection seam...
Electronic structure theory has been applied to the naphthalene-, anthracene-, tetracene-, and pentacene-based radicals their anions. Five different density functional methods were used predict adiabatic electron affinities for these radicals. A consistent trend was found, suggesting that affinity at a site of hydrogen removal is primarily dependent upon steric effects polycyclic aromatic hydrocarbons. The results 1-naphthalenyl 2-naphthalenyl compared experiment, it found B3LYP appears be...