In vivo mRNA expression of a multi-mechanistic mAb combination protects against Staphylococcus aureus infection.

Single monoclonal antibodies (mAbs) can be expressed in vivo through gene delivery of their mRNA formulated with lipid nanoparticles (LNPs). However, delivery of a mAb combination could be challenging due to the risk of heavy and light variable chain mispairing. We evaluated the pharmacokinetics of a three mAb combination against Staphylococcus aureus first in single chain variable fragment scFv-Fc and then in immunoglobulin G 1 (IgG1) format in mice.

Exploring the Chain Release Mechanism from an Atypical Apicomplexan Polyketide Synthase.

Polyketide synthases (PKSs) are megaenzymes that form chemically diverse polyketides and are found within the genomes of nearly all classes of life. We recently discovered the type I PKS from the apicomplexan parasite , PKS2, which contains a unique putative chain release mechanism that includes ketosynthase (KS) and thioester reductase (TR) domains. Our bioinformatic analysis of the thioester reductase of PKS2, TR, suggests differences compared to other systems and hints at a possibly conserved release mechanism within the apicomplexan subclass Coccidia.

Assessment of Epithelial Lining Fluid Partitioning of Systemically Administered Monoclonal Antibodies in Rats.

For systemically administered monoclonal antibodies (mAbs) with pharmacological targets in the epithelial lining fluid (ELF), information on the partitioning of mAb between plasma and ELF is instrumental for dose predictions. Bronchoalveolar lavage (BAL) combined with measurements of urea as indicator of sample dilution is often used to estimate ELF concentrations of a drug. However, unbalanced extraction of mAb and urea could potentially lead to a systematic bias in the back-calculated ELF concentration.

Single-Cell RNA-Seq of Cisplatin-Treated Adult Stria Vascularis Identifies Cell Type-Specific Regulatory Networks and Novel Therapeutic Gene Targets.

The endocochlear potential (EP) generated by the stria vascularis (SV) is necessary for hair cell mechanotransduction in the mammalian cochlea. We sought to create a model of EP dysfunction for the purposes of transcriptional analysis and treatment testing. By administering a single dose of cisplatin, a commonly prescribed cancer treatment drug with ototoxic side effects, to the adult mouse, we acutely disrupt EP generation.

An optimized protocol for retina single-cell RNA sequencing.

Purpose: Single-cell RNA sequencing (scRNA-seq) is a powerful technique used to explore gene expression at the single cell level. However, appropriate preparation of samples is essential to obtain the most information out of this transformative technology. Generating high-quality single-cell suspensions from the retina is critical to preserve the native expression profile that will ensure meaningful transcriptome data analysis.

Single-Cell RNA-Sequencing From Mouse Incisor Reveals Dental Epithelial Cell-Type Specific Genes.

Dental epithelial stem cells give rise to four types of dental epithelial cells: inner enamel epithelium (IEE), outer enamel epithelium (OEE), stratum intermedium (SI), and stellate reticulum (SR). IEE cells further differentiate into enamel-forming ameloblasts, which play distinct roles, and are essential for enamel formation. These are conventionally classified by their shape, although their transcriptome and biological roles are yet to be fully understood.

Cell-Specific Transcriptional Responses to Heat Shock in the Mouse Utricle Epithelium.

Sensory epithelia of the inner ear contain mechanosensory hair cells (HCs) and glia-like supporting cells (SCs), both of which are required for hearing and balance functions. Each of these cell types has unique responses to ototoxic and cytoprotective stimuli. Non-lethal heat stress in the mammalian utricle induces heat shock proteins (HSPs) and protects against ototoxic drug-induced hair cell death.

Single Cell and Single Nucleus RNA-Seq Reveal Cellular Heterogeneity and Homeostatic Regulatory Networks in Adult Mouse Stria Vascularis.

The stria vascularis (SV) generates the endocochlear potential (EP) in the inner ear and is necessary for proper hair cell mechanotransduction and hearing. While channels belonging to SV cell types are known to play crucial roles in EP generation, relatively little is known about gene regulatory networks that underlie the ability of the SV to generate and maintain the EP. Using single cell and single nucleus RNA-sequencing, we identify and validate known and rare cell populations in the SV.

Amplitude Analysis of D_{s}^{+}→π^{+}π^{0}η and First Observation of the W-Annihilation Dominant Decays D_{s}^{+}→a_{0}(980)^{+}π^{0} and D_{s}^{+}→a_{0}(980)^{0}π^{+}.

We present the first amplitude analysis of the decay D_{s}^{+}→π^{+}π^{0}η. We use an e^{+}e^{-} collision data sample corresponding to an integrated luminosity of 3.19  fb^{-1} collected with the BESIII detector at a center-of-mass energy of 4.

Precision Measurement of the Branching Fractions of η^{'} Decays.

Based on a sample of (1310.6±7.0)×10^{6}J/ψ events collected with the BESIII detector, we present measurements of J/ψ and η^{'} absolute branching fractions using the process J/ψ→γη^{'}.

Study of the D^{0}→K^{-}μ^{+}ν_{μ} Dynamics and Test of Lepton Flavor Universality with D^{0}→K^{-}ℓ^{+}ν_{ℓ} Decays.

Using e^{+}e^{-} annihilation data of 2.93  fb^{-1} collected at center-of-mass energy sqrt[s]=3.773  GeV with the BESIII detector, we measure the absolute branching fraction of D^{0}→K^{-}μ^{+}ν_{μ} with significantly improved precision: B_{D^{0}→K^{-}μ^{+}ν_{μ}}=(3.

Measurement of the Dynamics of the Decays D_{s}^{+}→η^{(')}e^{+}ν_{e}.

Using e^{+}e^{-} annihilation data corresponding to an integrated luminosity of 3.19  fb^{-1} collected at a center-of-mass energy of 4.178 GeV with the BESIII detector, we measure the absolute branching fractions B_{D_{s}^{+}→ηe^{+}ν_{e}}=(2.

Evidence of a Resonant Structure in the e^{+}e^{-}→π^{+}D^{0}D^{*-} Cross Section between 4.05 and 4.60 GeV.

The cross section of the process e^{+}e^{-}→π^{+}D^{0}D^{*-} for center-of-mass energies from 4.05 to 4.60 GeV is measured precisely using data samples collected with the BESIII detector operating at the BEPCII storage ring.

First Measurement of the Form Factors in D_{s}^{+}→K^{0}e^{+}ν_{e} and D_{s}^{+}→K^{*0}e^{+}ν_{e} Decays.

We report on new measurements of Cabibbo-suppressed semileptonic D_{s}^{+} decays using 3.19  fb^{-1} of e^{+}e^{-} annihilation data sample collected at a center-of-mass energy of 4.178 GeV with the BESIII detector at the BEPCII collider.

Observation of D^{+}→f_{0}(500)e^{+}ν_{e} and Improved Measurements of D→ρe^{+}ν_{e}.

Using a data sample corresponding to an integrated luminosity of 2.93  fb^{-1} recorded by the BESIII detector at a center-of-mass energy of 3.773 GeV, we present an analysis of the decays D^{0}→π^{-}π^{0}e^{+}ν_{e} and D^{+}→π^{-}π^{+}e^{+}ν_{e}.

Measurement of the Absolute Branching Fraction of the Inclusive Semileptonic Λ_{c}^{+} Decay.

Using a data sample of e^{+}e^{-} collisions corresponding to an integrated luminosity of 567  pb^{-1} collected at a center-of-mass energy of sqrt[s]=4.6  GeV with the BESIII detector, we measure the absolute branching fraction of the inclusive semileptonic Λ_{c}^{+} decay with a double-tag method. We obtain B(Λ_{c}^{+}→Xe^{+}ν_{e})=(3.

Measurement of the Branching Fraction For the Semileptonic Decay D^{0(+)}→π^{-(0)}μ^{+}ν_{μ} and Test of Lepton Flavor Universality.

Using a data sample corresponding to an integrated luminosity of 2.93  fb^{-1} taken at a center-of-mass energy of 3.773 GeV with the BESIII detector operated at the BEPCII collider, we perform an analysis of the semileptonic decays D^{0(+)}→π^{-(0)}μ^{+}ν_{μ}.

A comparative analysis of library prep approaches for sequencing low input translatome samples.

Background: Cell type-specific ribosome-pulldown has become an increasingly popular method for analysis of gene expression. It allows for expression analysis from intact tissues and monitoring of protein synthesis in vivo. However, while its utility has been assessed, technical aspects related to sequencing of these samples, often starting with a smaller amount of RNA, have not been reported.

Observation of the Semileptonic Decay D^{0}→a_{0}(980)^{-}e^{+}ν_{e} and Evidence for D^{+}→a_{0}(980)^{0}e^{+}ν_{e}.

Using an e^{+}e^{-} collision data sample of 2.93  fb^{-1} collected at a center-of-mass energy of 3.773 GeV by the BESIII detector at BEPCII, we report the observation of D^{0}→a_{0}(980)^{-}e^{+}ν_{e} and evidence for D^{+}→a_{0}(980)^{0}e^{+}ν_{e} with significances of 6.

Measurement of the Absolute Branching Fraction of the Inclusive Decay Λ_{c}^{+}→Λ+X.

Based on an e^{+}e^{-} collision data sample corresponding to an integrated luminosity of 567  pb^{-1} taken at the center-of-mass energy of sqrt[s]=4.6  GeV with the BESIII detector, we measure the absolute branching fraction of the inclusive decay Λ_{c}^{+}→Λ+X to be B(Λ_{c}^{+}→Λ+X)=(38.2_{-2.

Observation of a_{0}^{0}(980)-f_{0}(980) Mixing.

We report the first observation of a_{0}^{0}(980)-f_{0}(980) mixing in the decays of J/ψ→ϕf_{0}(980)→ϕa_{0}^{0}(980)→ϕηπ^{0} and χ_{c1}→a_{0}^{0}(980)π^{0}→f_{0}(980)π^{0}→π^{+}π^{-}π^{0}, using data samples of 1.31×10^{9}  J/ψ events and 4.48×10^{8}  ψ(3686) events accumulated with the BESIII detector.

A Partial Differential Equation Approach to Inhalation Physiologically Based Pharmacokinetic Modeling.

The heterogeneous nature of the lungs and the range of processes affecting pulmonary drug disposition make prediction of inhaled drugs challenging. These predictions are critical, as the local exposure cannot be measured and current inhalation physiologically based pharmacokinetic (PBPK) models do not capture all necessary features. Utilizing partial differential equations, we present an inhalation PBPK model to describe the heterogeneity in both lung physiology and particle size.