Accuracy of Model Estimation versus Tanaka and Johnston Arch Length Analysis.

OBJECTIVES: This study examines how accurate pediatric dentists are at estimating dental arch lengths by comparing their model estimations (guesstimating the arch length without measuring) to the Tanaka and Johnston mixed dentition arch length analysis. STUDY DESIGN: This study consisted of two parts, a survey of practitioners and a model estimating and measuring component. The survey was designed and given to 44 pediatric dentists to determine how many were practicing orthodontics and using arch length analyses routinely. Then 18 pediatric dentists and 13 pediatric dental residents examined 20 sets of mixed dentition models and estimated how much space was available. These estimations were compared to the calculated gold standard, the Tanaka and Johnston arch length analysis of the same models. RESULTS AND CONCLUSIONS: More than half of the dentists surveyed that practice comprehensive orthodontics use arch length estimates. Pediatric dentists and pediatric dental residents are just as good as each other at estimating arch length. Pediatric dentists and pediatric dental residents underestimated arch length by -3.6 and -3.1 mm, respectively. More research needs to be done to determine if model estimation is a clinically acceptable way to judge arch length.

Single nucleus multiomics identifies ZEB1 and MAFB as candidate regulators of Alzheimer's disease-specific cis-regulatory elements.

Cell type-specific transcriptional differences between brain tissues from donors with Alzheimer's disease (AD) and unaffected controls have been well documented, but few studies have rigorously interrogated the regulatory mechanisms responsible for these alterations. We performed single nucleus multiomics (snRNA-seq plus snATAC-seq) on 105,332 nuclei isolated from cortical tissues from 7 AD and 8 unaffected donors to identify candidate cis-regulatory elements (CREs) involved in AD-associated transcriptional changes. We detected 319,861 significant correlations, or links, between gene expression and cell type-specific transposase accessible regions enriched for active CREs. Among these, 40,831 were unique to AD tissues. Validation experiments confirmed the activity of many regions, including several candidate regulators of APP expression. We identified ZEB1 and MAFB as candidate transcription factors playing important roles in AD-specific gene regulation in neurons and microglia, respectively. Microglia links were globally enriched for heritability of AD risk and previously identified active regulatory regions.

Characterization of iron-phosphate-silicate chemical garden structures.

Chemical gardens form when ferrous chloride hydrate seed crystals are added or concentrated solutions are injected into solutions of sodium silicate and potassium phosphate. Various precipitation morphologies are observed depending on silicate and phosphate concentrations, including hollow plumes, bulbs, and tubes. The growth of precipitates is controlled by the internal osmotic pressure, fluid buoyancy, and membrane strength. Additionally, rapid bubble-led growth is observed when silicate concentrations are high. ESEM/EDX analysis confirms compositional gradients within the membranes, and voltage measurements across the membranes during growth show a final potential of around 150-200 mV, indicating that electrochemical gradients are maintained across the membranes as growth proceeds. The characterization of chemical gardens formed with iron, silicate, and phosphate, three important components of an early earth prebiotic hydrothermal system, can help us understand the properties of analogous structures that likely formed at submarine alkaline hydrothermal vents in the Hadean-structures offering themselves as the hatchery of life.

Insurance claim data trends in pulpal therapy for pediatric patients.

BACKGROUND: The purpose of this study was to identify differences in usage trends for 2 specific pulpal therapy treatments in pediatric patients during an 11-year period from January 1, 2010, through December 31, 2020. METHODS: Insurance data claims for children aged 2 through 12 years undergoing a pulpotomy or a pulpectomy performed by a general dentist (GD) or pediatric dentist (PD) from 2010 through 2020 were extracted from a dental data warehouse. The state where the provider was located was included in the extracted claim. RESULTS: Rates of undergoing a pulpotomy or pulpectomy declined from 2010 through 2020 (odds ratio [OR], 0.978 or 0.946, respectively; P < .001). PDs were more likely to perform pulpotomies than GDs (OR, 1.393; P < .001), but PDs were less likely to perform pulpectomies than GDs (OR, 0.225; P < .001). Younger patient age was a significant predictor for undergoing pulpotomy treatment for both GDs and PDs (ORs, 0.850 and 0.892, respectively; P < .001). With increasing patient age, PDs had increased odds of performing a pulpectomy (OR, 1.030; P < .001) and GDs had decreased odds of performing a pulpectomy (OR, 0.995; P = .04). When examining effects according to American Academy of Pediatric Dentistry national membership districts, the trends remained consistent with those above. CONCLUSIONS: The percentage of children undergoing pulpotomy and pulpectomy therapy declined from 2010 through 2020 among both GDs and PDs. PRACTICAL IMPLICATIONS: These changes in pulpal therapy practice might indicate a teaching change in pulpal therapy guidelines, suggesting that less invasive pulpal therapy can be used rather than pulpotomies or pulpectomies.

Simulating Serpentinization as It Could Apply to the Emergence of Life Using the JPL Hydrothermal Reactor.

The molecules feeding life's emergence are thought to have been provided through the hydrothermal interactions of convecting carbonic ocean waters with minerals comprising the early Hadean oceanic crust. Few laboratory experiments have simulated ancient hydrothermal conditions to test this conjecture. We used the JPL hydrothermal flow reactor to investigate CO2 reduction in simulated ancient alkaline convective systems over 3 days (T = 120°C, P = 100 bar, pH = 11). H2-rich hydrothermal simulant and CO2-rich ocean simulant solutions were periodically driven in 4-h cycles through synthetic mafic and ultramafic substrates and Fe>Ni sulfides. The resulting reductants included micromoles of HS- and formate accompanied possibly by micromoles of acetate and intermittent minor bursts of methane as ascertained by isotopic labeling. The formate concentrations directly correlated with the CO2 input as well as with millimoles of Mg2+ ions, whereas the acetate did not. Also, tens of micromoles of methane were drawn continuously from the reactor materials during what appeared to be the onset of serpentinization. These results support the hypothesis that formate may have been delivered directly to a branch of an emerging acetyl coenzyme-A pathway, thus obviating the need for the very first hydrogenation of CO2 to be made in a hydrothermal mound. Another feed to early metabolism could have been methane, likely mostly leached from primary CH4 present in the original Hadean crust or emanating from the mantle. That a small volume of methane was produced sporadically from the 13CO2-feed, perhaps from transient occlusions, echoes the mixed results and interpretations from other laboratories. As serpentinization and hydrothermal leaching can occur wherever an ocean convects within anhydrous olivine- and sulfide-rich crust, these results may be generalized to other wet rocky planets and moons in our solar system and beyond.

Experimentally Testing Hydrothermal Vent Origin of Life on Enceladus and Other Icy/Ocean Worlds.

We review various laboratory strategies and methods that can be utilized to simulate prebiotic processes and origin of life in hydrothermal vent systems on icy/ocean worlds. Crucial steps that could be simulated in the laboratory include simulations of water-rock chemistry (e.g., serpentinization) to produce hydrothermal fluids, the types of mineral catalysts and energy gradients produced in vent interfaces where hydrothermal fluids interface with the surrounding seawater, and simulations of biologically relevant chemistry in flow-through gradient systems (i.e., far-from-equilibrium experiments). We describe some examples of experimental designs in detail, which are adaptable and could be used to test particular hypotheses about ocean world energetics or mineral/organic chemistry. Enceladus among the ocean worlds provides an ideal test case, since the pressure at the ocean floor is more easily simulated in the lab. Results for Enceladus could be extrapolated with further experiments and modeling to understand other ocean worlds. Key Words: Enceladus-Ocean worlds-Icy worlds-Hydrothermal vent-Iron sulfide-Gradient. Astrobiology 17, 820-833.

Cancer-associated fibroblasts promote directional cancer cell migration by aligning fibronectin.

Cancer-associated fibroblasts (CAFs) are major components of the carcinoma microenvironment that promote tumor progression. However, the mechanisms by which CAFs regulate cancer cell migration are poorly understood. In this study, we show that fibronectin (Fn) assembled by CAFs mediates CAF-cancer cell association and directional migration. Compared with normal fibroblasts, CAFs produce an Fn-rich extracellular matrix with anisotropic fiber orientation, which guides the cancer cells to migrate directionally. CAFs align the Fn matrix by increasing nonmuscle myosin II- and platelet-derived growth factor receptor α-mediated contractility and traction forces, which are transduced to Fn through α5ß1 integrin. We further show that prostate cancer cells use αv integrin to migrate efficiently and directionally on CAF-derived matrices. We demonstrate that aligned Fn is a prominent feature of invasion sites in human prostatic and pancreatic carcinoma samples. Collectively, we present a new mechanism by which CAFs organize the Fn matrix and promote directional cancer cell migration.

Putative indigenous carbon-bearing alteration features in martian meteorite Yamato 000593.

We report the first observation of indigenous carbonaceous matter in the martian meteorite Yamato 000593. The carbonaceous phases are heterogeneously distributed within secondary iddingsite alteration veins and present in a range of morphologies including areas composed of carbon-rich spheroidal assemblages encased in multiple layers of iddingsite. We also observed microtubular features emanating from iddingsite veins penetrating into the host olivine comparable in shape to those interpreted to have formed by bioerosion in terrestrial basalts.

Iron-sulfide-bearing chimneys as potential catalytic energy traps at life's emergence.

The concept that life emerged where alkaline hydrogen-bearing submarine hot springs exhaled into the most ancient acidulous ocean was used as a working hypothesis to investigate the nature of precipitate membranes. Alkaline solutions at 25-70°C and pH between 8 and 12, bearing HS(-)±silicate, were injected slowly into visi-jars containing ferrous chloride to partially simulate the early ocean on this or any other wet and icy, geologically active rocky world. Dependent on pH and sulfide content, fine tubular chimneys and geodal bubbles were generated with semipermeable walls 4-100 µm thick that comprised radial platelets of nanometric mackinawite [FeS]±ferrous hydroxide [∼Fe(OH)(2)], accompanied by silica and, at the higher temperature, greigite [Fe(3)S(4)]. Within the chimney walls, these platelets define a myriad of micropores. The interior walls of the chimneys host iron sulfide framboids, while, in cases where the alkaline solution has a pH>11 or relatively low sulfide content, their exteriors exhibit radial flanges with a spacing of ∼4 µm that comprise microdendrites of ferrous hydroxide. We speculate that this pattern results from outward and inward radial flow through the chimney walls. The outer Fe(OH)(2) flanges perhaps precipitate where the highly alkaline flow meets the ambient ferrous iron-bearing fluid, while the intervening troughs signal where the acidulous iron-bearing solutions could gain access to the sulfidic and alkaline interior of the chimneys, thereby leading to the precipitation of the framboids. Addition of soluble pentameric peptides enhances membrane durability and accentuates the crenulations on the chimney exteriors. These dynamic patterns may have implications for acid-base catalysis and the natural proton motive force acting through the matrix of the porous inorganic membrane. Thus, within such membranes, steep redox and pH gradients would bear across the nanometric platelets and separate the two counter-flowing solutions, a condition that may have led to the onset of an autotrophic metabolism through the reduction of carbon dioxide.