How Black is biracial? Black people's empathy toward Black/White biracial people following racial discrimination in the United States.

OBJECTIVES: Two studies investigate how Black people's empathy toward Black/White Biracial people experiencing racial discrimination relates to Black/White Biracial people's identification in the United States. METHOD: Study 1 (N = 151, Mage = 36.3 years, SD = 11.1, 57% female) examines how Black people's perceptions of whether Black/White Biracial people identify as Black at a group level are related to empathy toward them through correlational methods. In Study 2 (N = 590; Mage = 32.3 years, SD = 11.4, 71% women), we experimentally manipulate Black/White Biracial people's racial identity through vignettes and assess Black participants' perceived similarity, racial identification of the Black/White Biracial target as Black, linked fate, and empathy. We tested Black participants' empathy toward a Black/White Biracial target who self-identified as Black, self-identified as White, or self-identified as Biracial, consistent with common identification patterns among Biracial people. RESULTS: Black participants empathized least with Black/White Biracial people who were perceived as identifying as White, or who explicitly self-identified as White. This association was mediated by perceptions that Black/White Biracial and Black people's fates are linked. Overall, Black people were most likely to empathize with Black/White Biracial people identifying as Black. CONCLUSIONS: For liminal group members, identification confers information regarding similarity, shared identity, and linked fate that relate to procuring empathy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Longitudinal Effects of the "Acting White" Accusation and Racial Identity Development Among Black College Students.

The "acting White" accusation (AWA) is a type of cultural invalidation that undermines the racial authenticity of Black youths. This study examines how the AWA and racial identity (RI) influence one another longitudinally during the transition to college for Black students. Findings were moderated by gender. For Black males, a negative feedback loop emerged for RI centrality where AWA experiences predicted lower centrality, which then predicted more AWA experiences over a 2-year period. Additionally, AWA experiences in high school predicted lower RI private regard for Black males and lower RI public regard for Black females during the first year of college. Implications and policy recommendations to address forms of cultural oppression such as the AWA are further discussed.

Blacks' perception of a Biracial's ingroup membership shapes attributions to discrimination following social rejection.

OBJECTIVES: The present research examined if Blacks differ in how they categorize Blacks, Whites, and Black-White Biracials (Biracials, hereafter) as ingroup members and whether those categorizations predict the degree to which they attribute rejection feedback to discrimination. METHODS: In Study 1 (N = 115), Black participants received rejection feedback from a Black, White, or Biracial online partner and then indicated the extent to which they perceived their partner as part of their racial ingroup and the extent to which they attributed the rejection feedback to discrimination. In Study 2a (N = 92), Black participants viewed the profile of a Biracial who self-identified as Black, White, or Biracial and then indicated the extent to which they perceived them as an ingroup member. Study 2b (N = 183) followed a similar design as Study 1 except that Black participants received rejection feedback from a Biracial online partner who self-identified as Black, White, or Biracial. RESULTS: In Study 1, participants considered Black and Biracial partners to be more of an ingroup member than White partners and, in turn, were less likely to attribute rejection feedback to discrimination. In Study 2, participants perceived Biracials who self-identified as White, versus Black or Biracial, to be less of an ingroup member (Study 2a, 2b) and, in turn, were more likely to attribute rejection feedback to discrimination (Study 2b). CONCLUSIONS: Findings suggest that Blacks' perception of a Biracial's ingroup membership affects their attributions to discrimination following social rejection. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

G-protein-coupled receptor dynamics: dimerization and activation models compared with experiment.

Our previously derived models of the active state of the ß2-adrenergic receptor are compared with recently published X-ray crystallographic structures of activated GPCRs (G-protein-coupled receptors). These molecular dynamics-based models using experimental data derived from biophysical experiments on activation were used to restrain the receptor to an active state that gave high enrichment for agonists in virtual screening. The ß2-adrenergic receptor active model and X-ray structures are in good agreement over both the transmembrane region and the orthosteric binding site, although in some regions the active model is more similar to the active rhodopsin X-ray structures. The general features of the microswitches were well reproduced, but with minor differences, partly because of the unexpected X-ray results for the rotamer toggle switch. In addition, most of the interacting residues between the receptor and the G-protein were identified. This analysis of the modelling has also given important additional insight into GPCR dimerization: re-analysis of results on photoaffinity analogues of rhodopsin provided additional evidence that TM4 (transmembrane helix 4) resides at the dimer interface and that ligands such as bivalent ligands may pass between the mobile helices. A comparison, and discussion, is also carried out between the use of implicit and explicit solvent for active-state modelling.

Changes in contaminant mass discharge from DNAPL source mass depletion: evaluation at two field sites.

Changes in contaminant fluxes resulting from aggressive remediation of dense nonaqueous phase liquid (DNAPL) source zone were investigated at two sites, one at Hill Air Force Base (AFB), Utah, and the other at Ft. Lewis Military Reservation, Washington. Passive Flux Meters (PFM) and a variation of the Integral Pumping Test (IPT) were used to measure fluxes in ten wells installed along a transect down-gradient of the trichloroethylene (TCE) source zone, and perpendicular to the mean groundwater flow direction. At both sites, groundwater and contaminant fluxes were measured before and after the source-zone treatment. The measured contaminant fluxes (J; ML(-2)T(-1)) were integrated across the well transect to estimate contaminant mass discharge (M(D); MT(-1)) from the source zone. Estimated M(D) before source treatment, based on both PFM and IPT methods, were approximately 76 g/day for TCE at the Hill AFB site; and approximately 640 g/day for TCE, and approximately 206 g/day for cis-dichloroethylene (DCE) at the Ft. Lewis site. TCE flux measurements made 1 year after source treatment at the Hill AFB site decreased to approximately 5 g/day. On the other hand, increased fluxes of DCE, a degradation byproduct of TCE, in tests subsequent to remediation at the Hill AFB site suggest enhanced microbial degradation after surfactant flooding. At the Ft. Lewis site, TCE mass discharge rates subsequent to remediation decreased to approximately 3 g/day for TCE and approximately 3 g/day for DCE approximately 1.8 years after remediation. At both field sites, PFM and IPT approaches provided comparable results for contaminant mass discharge rates, and show significant reductions (>90%) in TCE mass discharge as a result of DNAPL mass depletion from the source zone.

Andante: reducing side-chain rotamer search space during comparative modeling using environment-specific substitution probabilities.

MOTIVATION: The accurate placement of side chains in computational protein modeling and design involves the searching of vast numbers of rotamer combinations. RESULTS: We have applied the information contained within structurally aligned homologous families, in the form of conserved chi angle conservation rules, to the problem of the comparative modeling. This allows the accurate borrowing of entire side-chain conformations and/or the restriction to high probability rotamer bins. The application of these rules consistently reduces the number of rotamer combinations that need to be searched to trivial values and also reduces the overall side-chain root mean square deviation (rmsd) of the final model. The approach is complementary to current side-chain placement algorithms that use the decomposition of interacting clusters to increase the speed of the placement process.

CHORAL: a differential geometry approach to the prediction of the cores of protein structures.

MOTIVATION: Although the cores of homologous proteins are relatively well conserved, amino acid substitutions lead to significant differences in the structures of divergent superfamilies. Thus, the classification of amino acid sequence patterns and the selection of appropriate fragments of the protein cores of homologues of known structure are important for accurate comparative modelling. RESULTS: CHORAL utilizes a knowledge-based method comprising an amalgam of differential geometry and pattern recognition algorithms to identify conserved structural patterns in homologous protein families. Propensity tables are used to classify and to select patterns that most likely represent the structure of the core for a target protein. In our benchmark, CHORAL demonstrates a performance equivalent to that of MODELLER.

Iron chelation promoted by desazadesferrithiocin analogs: An enantioselective barrier.

For patients who require lifelong blood transfusions, there is no efficient means, unless chelation therapy is employed, for elimination of excess iron. Alternatives to desferrioxamine, the currently accepted treatment for transfusional iron overload, are being investigated. The current article focuses on an enantiomeric pair of analogs of desferrithiocin, (+)-(S)- and (-)-(R)-2-(2,4-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylic acid (4'-hydroxydesazadesferrithiocin). The crystal structure corroborated the absolute configuration of the two compounds, (+) and (-) for the (S)- and (R)-enantiomers, respectively. Job's plots established the tridentate nature of both analogs and circular dichroism spectra confirmed the ligands' antipodal relationship. (+)-(S)-4'-Hydroxydesazadesferrithiocin is a more efficient deferration agent than is the (-)-(R)-enantiomer in a Cebus apella model of iron overload. Pharmacokinetic analyses and IC(50) measurements in L1210 murine leukemia cells were undertaken in an effort to account for the contrast in efficacy between the two enantiomers. Some differences exist in the plasma pharmacokinetic parameters between the two analogs. However, a more plausible explanation may be the apparent differences in transport across the cell membrane; the IC(50) value in L1210 cells of the (+)-(S)-enantiomer was at least 5-fold lower than that of the (-)-(R)-compound.

Methoxylation of desazadesferrithiocin analogues: enhanced iron clearing efficiency.

The impact of altering the octanol-water partition properties (log P) of analogues of desazadesferrithiocin, (S)-4,5-dihydro-2-(2-hydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid, on the ligands' iron clearing properties is described. Increasing chelator lipophilicity can both substantially augment iron clearing efficiency in Cebus apella primates as well as alter the mode of iron excretion, favoring fecal over urinary output. The complications of iron overload are often associated with the metal's interaction with hydrogen peroxide, generating hydroxyl radicals (Fenton chemistry) and, ultimately, other related deleterious species. In fact, some iron chelators actually promote this chemistry. All of the compounds synthesized and tested in the current study are shown to be both inhibitors of the iron-mediated oxidation of ascorbate, thus removing the metal from the Fenton cycle, and effective radical scavengers.

Desferrithiocin analogue based hexacoordinate iron(III) chelators.

Traditional thinking has been that hexacoordinate Fe(III) ligands are more effective at preventing iron's interactions with reactive oxygen species, most particularly the Fe(II)-mediated reduction of hydrogen peroxide to the hydroxyl radical (i.e., Fenton chemistry), than are ligands of lower denticity. Thus, a hexacoordinate derivative of the well-characterized tricoordinate ligand (S)-2-(2,4-dihydroxyphenyl)-4,5-dihydro-4-thiazolecarboxylic acid [4'-(HO)-DADMDFT], (S,S)-1,11-bis[5-(4-carboxy-4,5-dihydrothiazol-2-yl)-2,4-dihydroxyphenyl]-4,8-dioxaundecane, was designed with the aid of a molecular modeling program and synthesized. Evaluations both in vitro and in vivo were carried out to determine whether there is any advantage, at the level of prevention of Fenton chemistry, radical trapping, or iron clearance, to constructing a desferrithiocin-based hexacoordinate analogue. The hexacoordinate analogue was more effective at preventing the iron-mediated oxidation of ascorbate at low ligand/metal ratios than was its tricoordinate parent and can function as an excellent radical scavenger. At equivalent iron binding doses in the bile duct cannulated rodent, oral administration of the tricoordinate ligand was 3-fold more effective than was po administration of the hexacoordinate derivative. However, sc administration of the hexacoordinate derivative resulted in an efficiency that was 3 times greater than that of the tricoordinate chelator. Unfortunately, the rodent findings were not substantiated in the primates. The hexacoordinate ligand was only about one-half as efficient as its tricoordinate parent when administered sc. Owing to these results, po dosing was not attempted. Thus, there appears to be no overall advantage to coupling two molecules of 4'-(HO)-DADMDFT to afford a hexacoordinate derivative.

Development of a Hypusine Reagent for Peptide Synthesis.

The synthesis of a reagent that enables the incorporation of the unusual amino acid (2S,9R)-hypusine (Hpu) into peptide sequences is described. The reagent, (2S,9R)-11-[(benzyloxycarbonyl)amino]-7-(carbobenzyloxy)-2-[(9-fluorenylmethoxycarbonyl)amino]-9-(tetrahydropyran-2-yloxy)-7-azaundecanoic acid, is utilized in the synthesis of a hexapeptide containing the primary pentapeptide sequence of the eukaryotic initiation factor eIF-5A, L-Cys-L-Thr-Gly-Hpu-L-His-Gly. The reagent is shown to be effective for both solution phase and Merrifield resin synthesis.