Biology subjects

Henry, K.

Publications and source records attributed to Henry, K..

4 recordsLinked to original sources

bioRxiv2026

Discovery and Structure Activity Relationship Optimization of a Novel Rv1625c Agonist Chemotype with Antitubercular Activity

Rv1625c/Cya has emerged as a promising target for the development of treatment-shortening therapies for tuberculosis. Screening of an Enamine compound library identified sBQQ004 as an initial hit, and rapid hit optimization led to compound 1, which was subsequently confirmed as an Rv1625c/Cya agonist. Structure activity relationship studies identified lead compound 25 with potent activity against Mycobacterium tuberculosis H37Rv under cholesterol-dependent growth conditions (MIC = 0.27 uM) and strong intramacrophage activity (EC50 = 0.079 uM). Compounds 1 and 25 showed oral bioavailabilities of 84.5% and 51.9% in mice, respectively. Repeat BID dosing of compound 1 resulted in a dose- and time-dependent decrease in systemic exposure. Despite this pharmacokinetic limitation, the potency and overall profile of this chemotype encouraged continued optimization.

microbiology↗

bioRxiv2025

Evolution of crop phenotypic spaces through domestication

O_LIWe used domestication as an in vivo replicated experiment to investigate how divergent selection has shaped the evolution of multivariate phenotypic spaces. C_LIO_LIWe measured 11 to 57 qualitative and quantitative traits in 13 species, either unique or shared between species, and established a framework for cross-species comparisons. C_LIO_LIOur results revealed significant convergence that translated into a cross-species domestication syndrome. Most species exhibited a reduction of the multivariate phenotypic space during domestication. We brought evidence that Near Infrared spectra measured on leaves reflect phenotypic evolution unrelated with domestication, enabling its use as a control for sampling effects across species. Building on this, we developed a multivariate Phenotypic Divergence Index (mPDI) to rank species by the extent of phenotypic divergence under domestication. We found a high disjunction of wild and domestic phenotypic spaces in all species. Neither the mPDI nor the relative size of wild versus domestic multivariate phenotypic spaces was influenced by the domestication timing or mating system. Lastly, we observed a progressive decoupling of trait correlations with increasing time since domestication. C_LIO_LIIn addition to introducing a new index that can be applied for cross-species comparisons, our study uncovers recurring patterns shared among species, pointing to general principles underlying plant domestication. C_LI

evolutionary biology↗

bioRxiv2022

Age and lead configuration matter: A comparative study of RF-induced heating of epicardial and endocardial electronic devices in adult and pediatric anthropomorphic phantoms in 1.5 T MR

BackgroundChildren with congenital heart defects often have life-sustaining indications for a cardiac implantable electronic device (CIED). In children, these devices are typically sewn to the heart epicardium, but the FDA has never licensed an epicardial system as MR-Conditional due to limited data. Childrens hospitals default to either refusing MRI service to a vast majority of pediatric CIED patients or adopting a scan-all strategy based on results from adult studies. We argue that both approaches are flawed, and the risk-benefit decisions should be made on an individual basis. PurposeTo provide evidence-based knowledge on RF-induced heating of CIEDs in children and adults with epicardial and endocardial leads of different lengths. Study TypePhantom Field Strength/Sequence1.5 T. Assessment120 clinically relevant epicardial and endocardial device configurations were implemented in adult and pediatric anthropomorphic phantoms. Temperature rise was recorded during RF exposure at 1.5 T. Statistical TestsMeans comparisons were implemented using two-sample t-tests, reliability analysis using interclass correlation coefficient based on a single rating, absolute-agreement, 2-way mixed-effects model. ResultsThere was significantly higher RF heating of epicardial leads compared to endocardial leads in the pediatric phantom (3.4 {+/-} 3.0 vs. 0.6 {+/-} 0.4 {degrees}C, p<0.001); however, there was no significant difference in the adult phantom (3.0 {+/-} 3.2 vs. 2.0 {+/-} 1.8, p=0.16). Endocardial leads in the pediatric phantom generated significantly less RF heating than in the adult phantom (0.6 {+/-} 0.4 {degrees}C vs. 2.0 {+/-} 1.8 {degrees}C, p<0.001). Data ConclusionBody size and lead length significantly affected RF heating. For models based on younger children with short epicardial leads (e.g., 25cm), RF heating up to 12 {degrees}C was observed, delivering a cumulative thermal dose previously associated with tissue necrosis. In contrast, RF heating in model based on children with endocardial leads was well below the heating expected from physiologic fever (3 {degrees}C).

biophysics↗

bioRxiv2022

Artifacts can be deceiving: The actual location of deep brain stimulation electrodes differs from the artifact seen on magnetic resonance images

IntroductionDeep brain stimulation (DBS) is a common treatment for a variety of neurological and psychiatric disorders. Recent studies have highlighted the role of neuroimaging in localizing the position of electrode contacts relative to target brain areas in order to optimize DBS programming. Among different imaging methods, postoperative magnetic resonance imaging (MRI) has been widely used for DBS electrode localization; however, the geometrical distortion induced by the lead limits its accuracy. In this work, we investigated to what degree the difference between the actual location of the leads tip and the location of the tip estimated from the MRI artifact varies depending on the MRI sequence parameters such as acquisition plane and phase encoding direction, as well as the leads extracranial configuration. Accordingly, an imaging technique to increase the accuracy of lead localization was devised and discussed. MethodsWe designed and constructed an anthropomorphic phantom with an implanted DBS system following 18 clinically relevant configurations. The phantom was scanned at a Siemens 1.5 Tesla Aera scanner using a T1MPRAGE sequence optimized for clinical use and a T1TSE sequence optimized for research purposes. We varied slice acquisition plane and phase encoding direction and calculated the distance between the caudal tip of the DBS lead MRI artifact and the actual tip of the lead, as estimated from MRI reference markers. ResultsImaging parameters and lead configuration substantially altered the difference in the depth of the lead within its MRI artifact on the scale of several millimeters - with a difference as large as 4.99 millimeters. The actual tip of the DBS lead was found to be consistently more rostral than the tip estimated from the MR image artifact. The smallest difference between the tip of the DBS lead and the tip of the MRI artifact using the clinically relevant sequence (i.e., T1MPRAGE) was found with the sagittal acquisition plane and anterior-posterior phase encoding direction. Discussion/ConclusionThe actual tip of an implanted DBS lead is located up to several millimeters rostral to the tip of the leads artifact on postoperative MR images. This distance depends on the MRI sequence parameters and the DBS systems extracranial trajectory. MRI parameters may be altered to improve this localization.

neuroscience↗