Chemometrics in Protein Formulation: Stability Governed by Repulsion and Protein Unfolding.

Therapeutic proteins can be challenging to develop due to their complexity and the requirement of an acceptable formulation to ensure patient safety and efficacy. To date, there is no universal formulation development strategy that can identify optimal formulation conditions for all types of proteins in a fast and reliable manner. In this work, high-throughput characterization, employing a toolbox of five techniques, was performed on 14 structurally different proteins formulated in 6 different buffer conditions and in the presence of 4 different excipients. Multivariate data analysis and chemometrics were used to analyze the data in an unbiased way. First, observed changes in stability were primarily determined by the individual protein. Second, pH and ionic strength are the two most important factors determining the physical stability of proteins, where there exists a significant statistical interaction between protein and pH/ionic strength. Additionally, we developed prediction methods by partial least-squares regression. Colloidal stability indicators are important for prediction of real-time stability, while conformational stability indicators are important for prediction of stability under accelerated stress conditions at 40 °C. In order to predict real-time storage stability, protein-protein repulsion and the initial monomer fraction are the most important properties to monitor.

Revision of the circumglobal deep-sea genus Leucicorus (Teleostei, Ophidiidae) with two new species.

The rare deepsea ophidiid genus Leucicorus was described by Garman (1899) based on L. lusciosus Garman, 1899 caught in the East Pacific. Until 1973 only three additional specimens were caught of which two from the East Pacific belong to L. lusciosus and one from off Hawaii is an undescribed species here described as L. lentibus n. sp. In 1973 a Soviet expedition to the Caribbean Sea trawled 18 specimens from abyssal and hadal depths and based on this material a second Leucicorus species was described, L. atlanticus Nielsen, 1975. Since then eight Leucicorus specimens from the Indo-Pacific and Atlantic Oceans have been caught of which two from the West Atlantic belong to a new species, L. gerringerae n. sp., herein described, four to L. atlanticus and two remain as Leucicorus sp. About 35 demersal Leucicorus specimens have been observed and photographed by ROV (remotely operated vehicle) at depths of 3804-5768 meters in the Pacific Ocean.

Self-Interactions of Two Monoclonal Antibodies: Small-Angle X-ray Scattering, Light Scattering, and Coarse-Grained Modeling.

Using light scattering (LS), small-angle X-ray scattering (SAXS), and coarse-grained Monte Carlo (MC) simulations, we studied the self-interactions of two monoclonal antibodies (mAbs), PPI03 and PPI13. With LS measurements, we obtained the osmotic second virial coefficient, B22, and the molecular weight, Mw, of the two mAbs, while with SAXS measurements, we studied the mAbs' self-interaction behavior in the high protein concentration regime up to 125 g/L. Through SAXS-derived coarse-grained representations of the mAbs, we performed MC simulations with either a one-protein or a two-protein model to predict B22. By comparing simulation and experimental results, we validated our models and obtained insights into the mAbs' self-interaction properties, highlighting the role of both ion binding and charged patches on the mAb surfaces. Our models provide useful information about mAbs' self-interaction properties and can assist the screening of conditions driving to colloidal stability.

Revision of the 'dragon-head cusk eels of the genus Porogadus (Teleostei: Ophidiidae), with description of eight new species and one new genus.

The ophidiid genus Porogadus occurs between 800 and 5300 m in the tropical and subtropical world oceans. Fifteen nominal species have been described since 1878 and most of them until 1902. The genus has been highlighted as needing revision in recent compilations about ophidiiforms and here we present the first comprehensive review. Twelve of the previously described species are here accepted as valid with two being moved to the newly established genus Tenuicephalus n. gen. that encompasses fishes differing from those of Porogadus in the extremely weak ossification, the stout head, absence of head spines and absence of the triple lateral line system considered typical for Porogadus and a reduced dentition. In addition, eight new species are described: Porogadus caboverdensis, P. dracocephalus, P. lacrimatus, P. mendax, P. solomonensis, P. turgidus, Tenuicephalus multitrabs and T. squamilabrus. The species of Porogadus show a distinctive depth segregation with the majority of species having a demersal bathyal life-style between 800 and 3500 m and other species being more or less exclusively restricted to abyssal depths below 3000 m. The biogeographic distribution pattern of bathyal groups shows putative species pairs in the Atlantic versus the eastern Pacific and a clear separation of eastern Pacific from Indo-West Pacific species. The geographic effects and timing are being discussed that may have led to this speciation events. Generally, we found widely distributed species that are found far away from continental masses and others restrained to continental slopes and sometimes exhibiting regionalism. In abyssal depth, the Cabo Verde and Canary basins off NW-Africa have yielded three exclusive species, but it is uncertain at this stage whether this could represent a sampling bias with this area being extensively sampled by the Discovery research vessel (BMNH) over the years from 19701998. Another instance of a potentially endemic abyssal species is that of Porogadus melanocephalus in the Bay of Bengal. The latter has been caught with 45 specimens in a single trawl, representing the highest number of Porogadus specimens collected in any trawl and indicating that these fishes may actually not be as rare as one might assume from the literature.

A new species of viviparous brotula genus Pseudogilbia (Ophidiiformes: Dinematichthyidae) from Brazilian reefs, with an updated diagnosis of the genus.

In this study, a new species of Pseudogilbia Møller, Schwarzhans & Nielsen 2004 is described based on two male specimens (40-44 mm LS ) from shallow reefs of Bahia, Brazil. Pseudogilbia australis sp. nov. is distinguished from its only congener, Pseudogilbia sanblasensis Møller, Schwarzhans & Nielsen 2004 from Caribbean Panama, by having: two lower preopercular pores (vs. one); dorsal-fin rays 65-67 (vs. 69); anal-fin rays 51-53 (vs. 56); pectoral-fin rays 18 (vs. 20); caudal vertebrae 27-28 (vs. 30); pectoral-fin length 15.0%-15.9% LS (vs. 14.3); pelvic-fin length 13.5% LS (vs. 16.4) and a different morphology of the male copulatory organ. Pseudogilbia australis sp. nov. is the only dinematichthyid so far recorded in the South Atlantic. An updated diagnosis for the genus is also provided.

Personalized treatment selection in routine care: Integrating machine learning and statistical algorithms to recommend cognitive behavioral or psychodynamic therapy.

Objective: This study aims at developing a treatment selection algorithm using a combination of machine learning and statistical inference to recommend patients' optimal treatment based on their pre-treatment characteristics. Methods: A disorder-heterogeneous, naturalistic sample of N = 1,379 outpatients treated with either cognitive behavioral therapy or psychodynamic therapy was analyzed. Based on a combination of random forest and linear regression, differential treatment response was modeled in the training data (n = 966) to indicate each individual's optimal treatment. A separate holdout dataset (n = 413) was used to evaluate personalized recommendations. Results: The difference in outcomes between patients treated with their optimal vs. non-optimal treatment was significant in the training data, but non-significant in the holdout data (b = -0.043, p = .280). However, for the 50% of patients with the largest predicted benefit of receiving their optimal treatment, the average percentage of change on the BSI in the holdout data was 52.6% for their optimal and 38.4% for their non-optimal treatment (p = .017; d = 0.33 [0.06, 0.61]). Conclusion: A treatment selection algorithm based on a combination of ML and statistical inference might improve treatment outcome for some, but not all outpatients and could support therapists' clinical decision-making.

Structural insights into human Arginase-1 pH dependence and its inhibition by the small molecule inhibitor CB-1158.

Arginase-1 is a manganese-dependent metalloenzyme that catalyzes the hydrolysis of L-arginine into L-ornithine and urea. Arginase-1 is abundantly expressed by tumor-infiltrating myeloid cells that promote tumor immunosuppression, which is relieved by inhibition of Arginase-1. We have characterized the potencies of the Arginase-1 reference inhibitors (2S)-2-amino-6-boronohexanoic acid (ABH) and N ω-hydroxy-nor-L-arginine (nor-NOHA), and studied their pH-dependence and binding kinetics. To gain a better understanding of the structural changes underlying the high pH optimum of Arginase-1 and its pH-dependent inhibition, we determined the crystal structure of the human Arginase-1/ABH complex at pH 7.0 and 9.0. These structures revealed that at increased pH, the manganese cluster assumes a more symmetrical coordination structure, which presumably contributes to its increase in catalytic activity. Furthermore, we show that binding of ABH involves the presence of a sodium ion close to the manganese cluster. We also studied the investigational new drug CB-1158 (INCB001158). This inhibitor has a low-nanomolar potency at pH 7.4 and increases the thermal stability of Arginase-1 more than ABH and nor-NOHA. Moreover, CB-1158 displays slow association and dissociation kinetics at both pH 9.5 and 7.4, as indicated by surface plasmon resonance. The potent character of CB-1158 is presumably due to its increased rigidity compared to ABH as well as the formation of an additional hydrogen-bond network as observed by resolution of the Arginase-1/CB-1158 crystal structure.

The Effect of Point Mutations on the Biophysical Properties of an Antimicrobial Peptide: Development of a Screening Protocol for Peptide Stability Screening.

Therapeutic peptides and proteins show enormous potential in the pharmaceutical market, but high costs in discovery and development are limiting factors so far. Single or multiple point mutations are commonly introduced in protein drugs to increase their binding affinity or selectivity. They can also induce adverse properties, which might be overlooked in a functional screen, such as a decreased colloidal or thermal stability, leading to problems in later stages of the development. In this study, we address the effect of point mutations on the stability of the 4.4 kDa antimicrobial peptide plectasin, as a case study. We combined a systematic high-throughput biophysical screen of the peptide thermal and colloidal stability using dynamic light scattering and differential scanning calorimetry with structure-based methods including small-angle X-ray scattering, analytical ultracentrifugation, and nuclear magnetic resonance spectroscopy. Additionally, we applied molecular dynamics simulations to link obtained protein stability parameters to the protein's molecular structure. Despite their predicted structural similarities, all four plectasin variants showed substantially different behavior in solution. We observed an increasing propensity of plectasin to aggregate at a higher pH, and the introduced mutations influenced the type of aggregation. Our strategy for systematically assessing the stability and aggregation of protein drugs is generally applicable and is of particular relevance, given the increasing number of protein drugs in development.

Albumin-neprilysin fusion protein: understanding stability using small angle X-ray scattering and molecular dynamic simulations.

Fusion technology is widely used in protein-drug development to increase activity, stability, and bioavailability of protein therapeutics. Fusion proteins, like any other type of biopharmaceuticals, need to remain stable during production and storage. Due to the high complexity and additional intramolecular interactions, it is not possible to predict the behavior of fusion proteins based on the behavior the individual proteins. Therefore, understanding the stability of fusion proteins on the molecular level is crucial for the development of biopharmaceuticals. The current study on the albumin-neprilysin (HSA-NEP) fusion protein uses a combination of thermal and chemical unfolding with small angle X-ray scattering and molecular dynamics simulations to show a correlation between decreasing stability and increasing repulsive interactions, which is unusual for most biopharmaceuticals. It is also seen that HSA-NEP is not fully flexible: it is present in both compact and extended conformations. Additionally, the volume fraction of each conformation changes with pH. Finally, the presence of NaCl and arginine increases stability at pH 6.5, but decreases stability at pH 5.0.

A new species of the genus Verilus (Teleostei, Percomorpha, Acropomatidae) from Brazil.

A new species of Acropomatid fish, Verilus costai sp. nov., is described from a single locality off Belmonte, State of Bahia, Brazil. It resembles Verilus pseudomicrolepis (Schultz, 1940) from the Caribbean Sea. The two are considered vicariant and they are interpreted to be separated from other species of the genus Verilus by (amongst other characters) the presence of fangs on the dentary (vs. only villiform teeth), the anal fin formula (II+9 vs. III+7) and the naked occiput (vs. scaled). However, formal establishment of a separate genus is postponed until a complete phylogenetic review of the family has been performed. Verilus costai can be distinguished from V. pseudomicrolepis by its higher number of gill rakers (27-31 vs. 21-25), lower number of pseudobranchial filaments (15-23 vs. 21-28), shorter snout length (8.2-11.3 vs. 11.3-13.4 % of SL), and more compressed otoliths (OL:OH = 1.3-1.35 vs. 1.35-1.5). In addition, the fossil otolith-based species Verilus mutinensis (Bassoli, 1906) from the late Miocene to middle Pleistocene of the Mediterranean is thought to be related and indicates that in the past this group was more widely distributed than nowadays and comprised more vicariant species.

The cell-cell junctions of mammalian testes. III. Absence of an endothelial cell layer covering the peritubular wall of the seminiferous tubules-an immunocytochemical correction of a 50-year-old error in the literature.

In the molecular biological and ultrastructural studies of the peritubular wall cells encasing the seminiferous tubules of mammalian testes, we found it necessary to characterize the outermost cell layer bordering on the interstitial space in detail. For half a century, the extremely thin cells of this monolayer have in the literature been regarded as part of a lymphatic endothelium, in particular in rodents. However, our double-label immunofluorescence microscopical results have shown that in all six mammalian species examined, including three rodent ones (rat, mouse, guinea pig), this classification is not correct: the very attenuated cells of this monolayer are not of lymphatic endothelial nature as they do not contain established endothelial marker molecules. In particular, they do not contain claudin-5-positive tight junctions, VE-cadherin-positive adherens junctions, "lymph vessel endothelium hyaluronan receptor 1" (LYVE-1), podoplanin, protein myozap and "von Willebrand Factor" (vWF). By contrast and as controls, all these established marker molecules for the lymphatic endothelial cell type are found in the endothelia of the lymph and-partly also-blood vessels located nearby in the interstitial space. Thus, our results provide evidence that the monolayer cells covering the peritubular wall do not contain endothelial marker molecules and hence are not endothelial cells. We discuss possible methodological reasons for the maintenance of this incorrect cell type classification in the literature and emphasize the value of molecular analyses using multiple cell type-specific markers, also with respect to physiology and medical sciences.

Advancing Therapeutic Protein Discovery and Development through Comprehensive Computational and Biophysical Characterization.

Therapeutic protein candidates should exhibit favorable properties that render them suitable to become drugs. Nevertheless, there are no well-established guidelines for the efficient selection of proteinaceous molecules with desired features during early stage development. Such guidelines can emerge only from a large body of published research that employs orthogonal techniques to characterize therapeutic proteins in different formulations. In this work, we share a study on a diverse group of proteins, including their primary sequences, purity data, and computational and biophysical characterization at different pH and ionic strength. We report weak linear correlations between many of the biophysical parameters. We suggest that a stability comparison of diverse therapeutic protein candidates should be based on a computational and biophysical characterization in multiple formulation conditions, as the latter can largely determine whether a protein is above or below a certain stability threshold. We use the presented data set to calculate several stability risk scores obtained with an increasing level of analytical effort and show how they correlate with protein aggregation during storage. Our work highlights the importance of developing combined risk scores that can be used for early stage developability assessment. We suggest that such scores can have high prediction accuracy only when they are based on protein stability characterization in different solution conditions.

A general method for the creation of dilational surfaces.

Dilational structures can change in size without changing their shape. Current dilational designs are only suitable for specific shapes or curvatures and often require parts of the structure to move perpendicular to the dilational surface, thereby occupying part of the enclosed volume. Here, we present a general method for creating dilational structures from arbitrary surfaces (2-manifolds with or without boundary), where all motions are tangent to the described surface. The method consists of triangulating the target curved surface and replacing each of the triangular faces by pantograph mechanisms according to a tiling algorithm that avoids collisions between neighboring pantographs. Following this algorithm, any surface can be made to mechanically dilate and could, theoretically, scale from the fully expanded configuration down to a single point. We illustrate the method with three examples of increasing complexity and varying Gaussian curvature.

The cell-cell junctions of mammalian testes: II. The lamellar smooth muscle monolayer cells of the peritubular wall are laterally connected by vertical adherens junctions-a novel architectonic cell-cell junction system.

The testes of sexually mature males of six mammalian species (men, bulls, boars, rats, mice, guinea pigs) have been studied using biochemical as well as light and electron microscopical techniques, in particular immunolocalizations. In these tissues, the peritubular walls represent lamellar encasement structures wrapped around the seminiferous tubules as a bandage system of extracellular matrix layers, alternating with monolayers of very flat polyhedral "lamellar smooth muscle cells" (LSMCs), the number of which varies in different species from 1 to 5 or 6. These LSMCs are complete SMCs containing smooth muscle α-actin (SMA), myosin light and heavy chains, α-actinin, tropomyosin, smoothelin, intermediate-sized filament proteins desmin and/or vimentin, filamin, talin, dystrophin, caldesmon, calponin, and protein SM22α, often also cytokeratins 8 and 18. In the monolayers, the LSMCs are connected by adherens junctions (AJs) based on cadherin-11, in some species also with P-cadherin and/or E-cadherin, which are anchored in cytoplasmic plaques containing ß-catenin and other armadillo proteins, in some species also striatin family proteins, protein myozap and/or LUMA. The LSMC cytoplasm is rich in myofilament bundles, which in many regions are packed in paracrystalline arrays, as well as in "dense bodies," "focal adhesions," and caveolae. In addition to some AJ-like end-on-end contacts, the LSMCs are laterally connected by numerous vertical AJ-like junctions located in variously sized and variously shaped, overlapping (alter super alterum) lamelliform cell protrusions. Consequently, the LSMCs of the peritubular wall monolayers are SMCs sensu stricto which are laterally connected by a novel architectonic system of arrays of vertical AJs located in overlapping cell protrusions.

Striatin is a novel modulator of cell adhesion.

The adherens junctions (AJs) and tight junctions (TJs) provide critical adhesive contacts between neighboring epithelial cells and are crucial for epithelial adhesion, integrity, and barrier functions in a wide variety of tissues and organisms. The striatin protein family, which are part of the striatin interaction phosphatases and kinases complex, are multidomain scaffolding proteins that play important biologic roles. We have previously shown that striatin colocalizes with the tumor suppressor protein adenomatous polyposis coli in the TJs of epithelial cells. Here we show that striatin affects junction integrity and cell migration, probably through a mechanism that involves the adhesion molecule E-cadherin. Cells engaged in cell-cell adhesion expressed a high MW-modified form of striatin that forms stable associations with detergent-insoluble, membrane-bound cellular fractions. In addition, striatin has recently been suggested to be a target of the poly (ADP-ribose) polymerases Tankyrase 1, and we have found that striatin interacts with Tankyrase 1 and is subsequently poly-ADP-ribosylated. Taken together, our results suggest that striatin is a novel cell-cell junctional protein that functions to maintain correct cell adhesion and may have a role in establishing the relationship between AJs and TJs that is fundamental for epithelial cell-cell adhesion.-Lahav-Ariel, L., Caspi, M., Nadar-Ponniah, P. T., Zelikson, N., Hofmann, I., Hanson, K. K., Franke, W. W., Sklan, E. H., Avraham, K. B., Rosin-Arbesfeld, R. Striatin is a novel modulator of cell adhesion.

Comparisons of Analytical Approaches for Determining Shell Thicknesses of Core-Shell Nanoparticles by X-ray Photoelectron Spectroscopy.

We assessed two approaches for determining shell thicknesses of core-shell nanoparticles (NPs) by X-ray photoelectron spectroscopy (XPS). These assessments were based on simulations of photoelectron peak intensities for Au-core/C-shell, C-core/Au-shell, Cu-core/Al-shell, and Al-core/Cu-shell NPs with a wide range of core diameters and shell thicknesses. First, we demonstrated the validity of an empirical equation developed by Shard for determinations of shell thicknesses. Values of shell thicknesses from the Shard equation typically agreed with actual shell thicknesses to better than 10 %. Second, we investigated the magnitudes of elastic-scattering effects on photoelectron peak intensities by performing a similar series of simulations with elastic scattering switched off in our simulation software. Our ratios of the C-shell 1s intensity to the Au-core 4f7/2 intensity with elastic scattering switched off were qualitatively similar to those obtained by Torelli et al. from a model that neglected elastic scattering. With elastic scattering switched on, the C 1s/Au 4f7/2 intensity ratios generally changed by less than 10 %, thereby justifying the neglect of elastic scattering in XPS models that are applied to organic ligands on Au-core NPs. Nevertheless, elastic-scattering effects on peak-intensity ratios were generally much stronger for C-core/Au-shell, Al-core/Cu-shell, and Cu-core/Al-shell NPs, and there were second-order dependences on core diameter and shell thickness.

A novel TPR-BEN domain interaction mediates PICH-BEND3 association.

PICH is a DNA translocase required for the maintenance of chromosome stability in human cells. Recent data indicate that PICH co-operates with topoisomerase IIα to suppress pathological chromosome missegregation through promoting the resolution of ultra-fine anaphase bridges (UFBs). Here, we identify the BEN domain-containing protein 3 (BEND3) as an interaction partner of PICH in human cells in mitosis. We have purified full length PICH and BEND3 and shown that they exhibit a functional biochemical interaction in vitro. We demonstrate that the PICH-BEND3 interaction occurs via a novel interface between a TPR domain in PICH and a BEN domain in BEND3, and have determined the crystal structure of this TPR-BEN complex at 2.2 Å resolution. Based on the structure, we identified amino acids important for the TPR-BEN domain interaction, and for the functional interaction of the full-length proteins. Our data reveal a proposed new function for BEND3 in association with PICH, and the first example of a specific protein-protein interaction mediated by a BEN domain.

Long-term pattern and magnitude of soil carbon feedback to the climate system in a warming world.

In a 26-year soil warming experiment in a mid-latitude hardwood forest, we documented changes in soil carbon cycling to investigate the potential consequences for the climate system. We found that soil warming results in a four-phase pattern of soil organic matter decay and carbon dioxide fluxes to the atmosphere, with phases of substantial soil carbon loss alternating with phases of no detectable loss. Several factors combine to affect the timing, magnitude, and thermal acclimation of soil carbon loss. These include depletion of microbially accessible carbon pools, reductions in microbial biomass, a shift in microbial carbon use efficiency, and changes in microbial community composition. Our results support projections of a long-term, self-reinforcing carbon feedback from mid-latitude forests to the climate system as the world warms.

Reappraisal of Synagrops Günther, 1887 with rehabilitation and revision of Parascombrops Alcock, 1889 including description of seven new species and two new genera (Perciformes: Acropomatidae).

An ongoing review of the fishes of the basal percoid family Acropomatidae has revealed that the genus Synagrops Günther, 1887 as it is currently understood is not a natural group. Species with a serrated pelvic-fin spine are here placed in the resurrected genus Parascombrops Alcock, 1889 (type-species: Parascombrops pellucidus Alcock, 1889), and the new, monospecific genus Caraibops n. gen. (type-species: Synagrops trispinosus Mochizuki & Sano, 1984). Parascombrops is unique amongst Acropomatidae in the combination of the presence of vacant 8th interneural space, a predorsal formula /0+0/0+2/ and an epaxialis attachment type 1. Caraibops n. gen. shares none of these characters and further differs from Parascombrops by an anal-fin formula of III + 9 (vs II + 7 or III + 6), and the absence of denticles on the ectopterygoid. Parascombrops is revised and now contains a total of 13 species, including 7 new: P. analis (Katayama, 1957), P. argyreus (Gilbert & Cramer, 1897), P. glossodon n. sp., P. madagascariensis n. sp., P. mochizukii n. sp., P. nakayamai n. sp., P. ohei n. sp., P. parvidens n. sp., P. pellucidus Alcock, 1889, P. philippinensis (Günther, 1880), P. serratospinosus (Smith & Radcliffe, 1912), P. spinosus (Schultz, 1940) and P. yamanouei n. sp. Synagrops adeni Kotthaus, 1970 and S. malayanus Weber, 1913 are treated as synonyms of P. pellucidus and P. philippinensis, respectively. Lectotypes are designated for P. philippinensis and S. malayanus. The main characters used to distinguish between the species of Parascombrops are: serration of other fin spines, number of gill rakers and pseudobranchial filaments, head profile, presence or absence of ridges on the preopercle, shape of 1st anal-fin pterygiophore, dentition on vomer, palatines and ectopterygoids, orbit diameter, pectoral-fin length, maximal body depth and otolith morphology. The genus Synagrops is here confined to two species, S. japonicus (Döderlein, 1883) and S. bellus (Goode & Bean, 1896), characterized by the apomorphic character of an otic capsule with a posteriorly open myodome, a basioccipital fossa and a very specialized otolith morphology. Synagrops is also characterized by the absence of pelvic-fin spine serrations. Two other species without a serrated pelvic-fin spine, originally described in Synagrops, are removed from this genus. Synagrops microlepis Norman, 1935 is separated into the monotypic Kaperangus n. gen., the only genus in the family with two supraneurals (cf. three in all other taxa). The second, Synagrops pseudomicrolepis Schultz, 1940 is re-assigned to the genus Verilus.        The geographic distribution of Parascombrops as currently composed is discussed, and is shown to be primarily of West Pacific nature, with few species in the Indian Ocean and one in the tropical West-Atlantic (P. spinosus). The West Atlantic species Parascombrops spinosus is very closely related to P. mochizukii from the tropical northwestern Pacific, and the implications of this disjunct distribution are discussed. The high degree of speciation now recognized in Parascombrops species of the West-Pacific indicates that a diverse ecological adaptation within an overall pseudoceanic habitat may have played a major role in speciation, which would have remained obscured without adequate taxonomic resolution.        Fossil, otolith-based records are also briefly discussed in the context. The extant Parascombrops argyreus and P. ohei are reported from the Pliocene of Japan, and Caraibops trispinosus has been recorded from the Pliocene of Venezuela.

The Success of Linear Bootstrapping Models: Decision Domain-, Expertise-, and Criterion-Specific Meta-Analysis.

The success of bootstrapping or replacing a human judge with a model (e.g., an equation) has been demonstrated in Paul Meehl's (1954) seminal work and bolstered by the results of several meta-analyses. To date, however, analyses considering different types of meta-analyses as well as the potential dependence of bootstrapping success on the decision domain, the level of expertise of the human judge, and the criterion for what constitutes an accurate decision have been missing from the literature. In this study, we addressed these research gaps by conducting a meta-analysis of lens model studies. We compared the results of a traditional (bare-bones) meta-analysis with findings of a meta-analysis of the success of bootstrap models corrected for various methodological artifacts. In line with previous studies, we found that bootstrapping was more successful than human judgment. Furthermore, bootstrapping was more successful in studies with an objective decision criterion than in studies with subjective or test score criteria. We did not find clear evidence that the success of bootstrapping depended on the decision domain (e.g., education or medicine) or on the judge's level of expertise (novice or expert). Correction of methodological artifacts increased the estimated success of bootstrapping, suggesting that previous analyses without artifact correction (i.e., traditional meta-analyses) may have underestimated the value of bootstrapping models.