Harvester ant nest architecture is more strongly affected by intrinsic than extrinsic factors.

Behavior is shaped by genes, environment, and evolutionary history in different ways. Nest architecture is an extended phenotype that results from the interaction between the behavior of animals and their environment. Nests built by ants are extended phenotypes that differ in structure among species and among colonies within a species, but the source of these differences remains an open question. To investigate the impact of colony identity (genetics), evolutionary history (species), and the environment on nest architecture, we compared how two species of harvester ants, Pogonomyrmex californicus and Veromessor andrei, construct their nests under different environmental conditions. For each species, we allowed workers from four colonies to excavate nests in environments that differed in temperature and humidity for seven days. We then created casts of each nest to compare nest structures among colonies, between species, and across environmental conditions. We found differences in nest structure among colonies of the same species and between species. Interestingly, however, environmental conditions did not have a strong influence on nest structure in either species. Our results suggest that extended phenotypes are shaped more strongly by internal factors, such as genes and evolutionary history, and are less plastic in response to the abiotic environment, like many physical and physiological phenotypes.

3D-printed phantoms to quantify accuracy and variability of goniometric and volumetric assessment of Peyronie's disease deformities.

Characterization of Peyronie's disease (PD) involves manual goniometry and penile length measurement. These techniques neglect volume loss or hourglass deformities. Inter-provider variability complicates accuracy. Using 3D-printed models, we aimed to evaluate measurement accuracy and variability and establish computational assessment workflows. Five digital phantoms were created: 13.0 cm cylinder, 13.0 cm hourglass cylinder, 15.0 cm cylinder with 40° angulation, 12.0 cm straight penis, and 12.9 cm PD penis with 68° angulation and hourglass. Lengths, volumes, and angles were determined computationally. Each phantom was 3D-printed. Ten urology providers determined lengths, angles, and volumes with measuring tape, goniometer, and volume calculator. Provider versus computational measurements were compared to determine accuracy using t-tests or Wilcoxon rank-sum tests. No significant differences were observed between manual assessment of length of penile models and designed length in penile models. Average curvature angles from providers for bent cylinder and PD phantoms were 38.3° ± 3.9° (p = 0.25) and 57.5°â€†±â€†7.2° (p = 0.006), respectively. When assessing for volume, hourglass cylinder and bent cylinder showed significant differences between designed volume and provider averages. All assessments of length, angle, and volume showed significant provider variability. Our results suggest manual measurements suffer from inaccuracy and variability. Computational workflows are useful for improved accuracy and volume assessment.

New hypotheses about the structure-function of proprotein convertase subtilisin/kexin type 9: analysis of the epidermal growth factor-like repeat A docking site using WaterMap.

LDL cholesterol (LDL-C) is cleared from plasma via cellular uptake and internalization processes that are largely mediated by the low-density lipoprotein cholesterol receptor (LDL-R). LDL-R is targeted for lysosomal degradation by association with proprotein convertase subtilisin-kexin type 9 (PCSK9). Gain of function mutations in PCSK9 can result in excessive loss of receptors and dyslipidemia. On the other hand, receptor-sparing phenomena, including loss-of-function mutations or inhibition of PCSK9, can lead to enhanced clearance of plasma lipids. We hypothesize that desolvation and resolvation processes, in many cases, constitute rate-determining steps for protein-ligand association and dissociation, respectively. To test this hypothesis, we analyzed and compared the predicted desolvation properties of wild-type versus gain-of-function mutant Asp374Tyr PCSK9 using WaterMap, a new in silico method for predicting the preferred locations and thermodynamic properties of water solvating proteins ("hydration sites"). We compared these results with binding kinetics data for PCSK9, full-length LDL-R ectodomain, and isolated EGF-A repeat. We propose that the fast k(on) and entropically driven thermodynamics observed for PCSK9-EGF-A binding stem from the functional replacement of water occupying stable PCSK9 hydration sites (i.e., exchange of PCSK9 H-bonds from water to polar EGF-A groups). We further propose that the relatively fast k(off) observed for EGF-A unbinding stems from the limited displacement of solvent occupying unstable hydration sites. Conversely, the slower k(off) observed for EGF-A and LDL-R unbinding from Asp374Tyr PCSK9 stems from the destabilizing effects of this mutation on PCSK9 hydration sites, with a concomitant increase in the persistence of the bound complex.

Measurement accuracy of 3-Dimensional mapping technologies versus standard goniometry for angle assessment.

BACKGROUND: A specific aspect of the hypospadias phenotype that may contribute to long-term outcomes is the presence of ventral penile curvature and the adequacy of its surgical correction. The current gold standard to assess this angle is intraoperative goniometry of an erect penis. 3-dimensional (3D) mapping technologies may overcome the limitations of these traditional methods through their combination of digital image and geometric replication to produce consistent 3D digital forms of a physical structure. The aim of this study is to evaluate the measurement accuracy and reliability of handheld 3D mapping technologies versus standard goniometry for angle assessment in a laboratory setting. METHODS: Blocks with specified angles (10-45°) were printed using a Zortrax M200 3D printer (±0.2% accuracy). Following the completion of standardized training, blinded participants measured each block angle using a baseline digit goniometer. Additionally, complete digital models of the blocks were created using 3D mapping technologies. Structured light scanning was completed using an Artec Space Spider and Artec Studio 13. Traditional photogrammetry was completed using a Canon Eos Rebel T5i DSLR camera and Agisoft Metashape Pro. Photogrammetry with a 3D camera was completed using the VECTRA H1 and VECTRA Analysis Module. All 3D models were imported into the software Autodesk Inventor in which automated angle measurements through the central plane were obtained. Statistical analysis was performed to determine the accuracy, precision and reliability of each modality using SAS 9.4 software. The reliability of goniometry and each mapping technology was evaluated using two-way random effect models with absolute agreement. RESULTS: Six 3D printed blocks were evaluated. 5 digital models per block were created using each of the 3 mapping technologies. Inter-rater reliability of goniometry was moderate (ICC 0.76, 95% CI 0.46, 0.92), whereas all mapping technologies demonstrated excellent test-retest reliability: structured light scanning (ICC 0.99; 95% CI 0.999, 0.999); traditional photogrammetry (0.99; 0.99, 0.99); 3D camera (0.99; 0.99, 0.99). Mean angle measurements and standard error for each angle and modality are provided in the table. CONCLUSIONS: This study demonstrated excellent accuracy, precision and reliability of off-the-shelf, handheld 3D mapping technologies and moderate reliability for goniometry when applied to measurements of angulation in a laboratory setting. The described methods developed in the laboratory for optimization of angle analysis from 3D models are an important step toward reliable, reproducible phenotypic analysis of congenital genitourinary conditions in future intraoperative and database development applications.

A Maltose-Binding Protein Fusion Construct Yields a Robust Crystallography Platform for MCL1.

Crystallization of a maltose-binding protein MCL1 fusion has yielded a robust crystallography platform that generated the first apo MCL1 crystal structure, as well as five ligand-bound structures. The ability to obtain fragment-bound structures advances structure-based drug design efforts that, despite considerable effort, had previously been intractable by crystallography. In the ligand-independent crystal form we identify inhibitor binding modes not observed in earlier crystallographic systems. This MBP-MCL1 construct dramatically improves the structural understanding of well-validated MCL1 ligands, and will likely catalyze the structure-based optimization of high affinity MCL1 inhibitors.