Emergence of antibiotic-specific phenotypes during prolonged treatment of mice.

A major challenge in tuberculosis (TB) therapeutics is that antibiotic exposure leads to changes in the physiologic state of () which may enable the pathogen to withstand treatment. While antibiotic-treated have been evaluated in short-term experiments, it is unclear if and how long-term treatment with diverse antibiotics with varying treatment-shortening activity (sterilizing activity) affect physiologic states differently. Here, we used SEARCH-TB, a pathogen-targeted RNA-sequencing platform, to characterize the transcriptome in the BALB/c high-dose aerosol infection mouse model following 4-week treatment with three sterilizing and three non-sterilizing antibiotics.

Transcriptional adaptation of that survives prolonged multi-drug treatment in mice.

A major reason that curing tuberculosis requires prolonged treatment is that drug exposure changes bacterial phenotypes. The physiologic adaptations of that survive drug exposure have been obscure due to low sensitivity of existing methods in drug-treated animals. Using the novel SEARCH-TB RNA-seq platform, we elucidated phenotypes in mice treated for with the global standard 4-drug regimen and compared them with the effect of the same regimen .

lmerSeq: an R package for analyzing transformed RNA-Seq data with linear mixed effects models.

Background: Studies that utilize RNA Sequencing (RNA-Seq) in conjunction with designs that introduce dependence between observations (e.g. longitudinal sampling) require specialized analysis tools to accommodate this additional complexity.

A comparison of methods for multiple degree of freedom testing in repeated measures RNA-sequencing experiments.

Background: As the cost of RNA-sequencing decreases, complex study designs, including paired, longitudinal, and other correlated designs, become increasingly feasible. These studies often include multiple hypotheses and thus multiple degree of freedom tests, or tests that evaluate multiple hypotheses jointly, are often useful for filtering the gene list to a set of interesting features for further exploration while controlling the false discovery rate. Though there are several methods which have been proposed for analyzing correlated RNA-sequencing data, there has been little research evaluating and comparing the performance of multiple degree of freedom tests across methods.

Refractory neutrophilic asthma and ciliary genes.

Background: Refractory asthma (RA) remains poorly controlled, resulting in high health care utilization despite guideline-based therapies. Patients with RA manifest higher neutrophilia as a result of increased airway inflammation and subclinical infection, the underlying mechanisms of which remain unclear.

Objective: We sought to characterize and clinically correlate gene expression differences between refractory and nonrefractory (NR) asthma to uncover molecular mechanisms driving group distinctions.

Keratometry, biometry, and prediction of intraocular lens power in adult tigers (Panthera tigris).

Objective: To calculate the necessary pseudophakic intraocular lens (IOL) power to approximate emmetropia in adult tigers.

Animals: 17 clinically normal adult tigers.

Procedures: 33 eyes of 17 clinically normal adult tigers underwent routine ophthalmic examination and B-scan ultrasonography while anesthetized for unrelated procedures.

Ensconsin-dependent changes in microtubule organization and LINC complex-dependent changes in nucleus-nucleus interactions result in quantitatively distinct myonuclear positioning defects.

Nuclear movement is a fundamental process of eukaryotic cell biology. Skeletal muscle presents an intriguing model to study nuclear movement because its development requires the precise positioning of multiple nuclei within a single cytoplasm. Furthermore, there is a high correlation between aberrant nuclear positioning and poor muscle function.

Prevalence and type of ocular disease in a population of aged captive nondomestic felids.

Objectives: Report of prevalence and type of ocular disease in a captive population of nondomestic felids.

Methods: Medical records of 202 cats from 1993 to 2018 were reviewed. Species, age at diagnosis, sex, ocular examination abnormalities, systemic/physical examination abnormalities, type of examination (visual, sedated, or anesthetized), ocular structures affected, other diagnostics, therapy, and resolution of ocular disease were recorded.

MCMSeq: Bayesian hierarchical modeling of clustered and repeated measures RNA sequencing experiments.

Background: As the barriers to incorporating RNA sequencing (RNA-Seq) into biomedical studies continue to decrease, the complexity and size of RNA-Seq experiments are rapidly growing. Paired, longitudinal, and other correlated designs are becoming commonplace, and these studies offer immense potential for understanding how transcriptional changes within an individual over time differ depending on treatment or environmental conditions. While several methods have been proposed for dealing with repeated measures within RNA-Seq analyses, they are either restricted to handling only paired measurements, can only test for differences between two groups, and/or have issues with maintaining nominal false positive and false discovery rates.

Pathogenicity and selective constraint on variation near splice sites.

Mutations that perturb normal pre-mRNA splicing are significant contributors to human disease. We used exome sequencing data from 7833 probands with developmental disorders (DDs) and their unaffected parents, as well as more than 60,000 aggregated exomes from the Exome Aggregation Consortium, to investigate selection around the splice sites and quantify the contribution of splicing mutations to DDs. Patterns of purifying selection, a deficit of variants in highly constrained genes in healthy subjects, and excess de novo mutations in patients highlighted particular positions within and around the consensus splice site of greater functional relevance.

is dispensable for normal fat deposition in mice.

Genome-wide association studies (GWAS) have detected association between variants in or near the () locus and metabolic traits, including central obesity, fatty liver and waist-to-hip ratio. is also known to be upregulated in the adipose tissue of obese patients. However, the physiological role of is not understood.

Genomic variation in the vomeronasal receptor gene repertoires of inbred mice.

Background: Vomeronasal receptors (VRs), expressed in sensory neurons of the vomeronasal organ, are thought to bind pheromones and mediate innate behaviours. The mouse reference genome has over 360 functional VRs arranged in highly homologous clusters, but the vast majority are of unknown function. Differences in these receptors within and between closely related species of mice are likely to underpin a range of behavioural responses.

Comparison of single time-point [111-In] pentetreotide SPECT/CT with dual time-point imaging of neuroendocrine tumors.

Purpose: to determine whether single time-point single-photon emission computed tomography-computed tomography (SPECT/CT) somatostatin receptor imaging can replace traditional dual time-point planar and SPECT somatostatin receptor scintigraphy for evaluation of neuroendocrine tumors.

Materials And Methods: twenty-four patients (9 males, 15 females; mean age: 56 years; range: 14-82 years) underwent [111-In] pentetreotide scintigraphy, with planar whole-body images acquired at 24 and 48 hours after injection and abdominal SPECT/CT at 24 hours postinjection. Two blinded readers independently interpreted each study, using single time-point (24 hours planar and SPECT/CT) and separately using dual time-point (24- and 48-hours planar, and 24-hour SPECT without CT) image information.