Looking the part: social status cues shape race perception

It is commonly believed that race is perceived through another's facial features, such as skin color. In the present research, we demonstrate that cues to social status that often surround a face systematically change the perception of its race. Participants categorized the race of faces that varied along White-Black morph continua and that were presented with high-status or low-status attire. Low-status attire increased the likelihood of categorization as Black, whereas high-status attire increased the likelihood of categorization as White; and this influence grew stronger as race became more ambiguous (Experiment 1). When faces with high-status attire were categorized as Black or faces with low-status attire were categorized as White, participants' hand movements nevertheless revealed a simultaneous attraction to select the other race-category response (stereotypically tied to the status cue) before arriving at a final categorization. Further, this attraction effect grew as race became more ambiguous (Experiment 2). Computational simulations then demonstrated that these effects may be accounted for by a neurally plausible person categorization system, in which contextual cues come to trigger stereotypes that in turn influence race perception. Together, the findings show how stereotypes interact with physical cues to shape person categorization, and suggest that social and contextual factors guide the perception of race.     

Targeting key transcriptional factor STAT3 in colorectal cancer

Molecular and Cellular Biochemistry - In developed countries, colorectal cancer (CRC) is the fourth most common cancer and the second leading cause of malignant-related deaths. CRC is treatable...     

Safety and Proof-of-Concept Study of Oral QLT091001 in Retinitis Pigmentosa Due to Inherited Deficiencies of Retinal Pigment Epithelial 65 Protein (RPE65) or Lecithin:Retinol Acyltransferase (LRAT)

Restoring vision in inherited retinal degenerations remains an unmet medical need. In mice exhibiting a genetically engineered block of the visual cycle, vision was recently successfully restored by oral administration of 9-cis-retinyl acetate (QLT091001). Safety and visual outcomes of a once-daily oral dose of 40 mg/m²/day QLT091001 for 7 consecutive days was investigated in an international, multi-center, open-label, proof-of-concept study in 18 patients with RPE65- or LRAT-related retinitis pigmentosa. Eight of 18 patients (44%) showed a ≥20% increase and 4 of 18 (22%) showed a ≥40% increase in functional retinal area determined from Goldmann visual fields; 12 (67%) and 5 (28%) of 18 patients showed a ≥5 and ≥10 ETDRS letter score increase of visual acuity, respectively, in one or both eyes at two or more visits within 2 months of treatment. In two patients who underwent fMRI, a significant positive response was measured to stimuli of medium contrast, moving, pattern targets in both left and right hemispheres of the occipital cortex. There were no serious adverse events. Treatment-related adverse events were transient and the most common included headache, photophobia, nausea, vomiting, and minor biochemical abnormalities. Measuring the outer segment length of the photoreceptor layer with high-definition optical coherence tomography was highly predictive of treatment responses with responders having a significantly larger baseline outer segment thickness (11.7 ± 4.8 μm, mean ± 95% CI) than non-responders (3.5 ± 1.2 μm). This structure-function relationship suggests that treatment with QLT091001 is more likely to be efficacious if there is sufficient photoreceptor integrity.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01014052","term_id":"NCT01014052"}}NCT01014052     

Distribution of heavy metals in the water,sediments, and fishes from Damodar river basin at steel city,India: a probabilistic risk assessment

Abstract

The present study, deals with the estimation of degrees of contamination, ecological and human health risk of heavy metals (As, Cd, Cr, Cu, Mn, Ni, Pb, and Zn) in sediments, surface water and fishes, which were collected from middle stretch of Damodar river and ponds at Asansol, which receives outfall of various coal-based industries. Metal content in the premonsoon season was higher than the postmonsoon, due to influx of rainwater. The heavy metal pollution indices (HPI) at some locations was observed up to 1.45 times than recommended value and the cadmium (Cd) was found dominating metal for high HPI value. The Cd concentration in surface water and pore water varied from 2.8 to 14.9?µg/L and 15.3–57.0?µg/L, respectively, which was up to 6 times higher than the permissible limit. Ecological risk assessment for sediments illustrates ‘moderate to considerable ecological risk’, especially because of Cd. Hazard index (HI) calculated to identify potential human health risk by dermal exposure of surface water was <0.1, indicating ‘negligible non-cancer risk’ for all age group of people. However, HI varied from 0.73 to 1.49 for adult and 1.37–2.78 by consumption of fishes indicates children have higher ‘non-cancer risk’ than adult.     

Autosomal recessive retinitis pigmentosa and E150K mutation in the opsin gene

Retinitis pigmentosa (RP) is a heterogeneous group of hereditary disorders of the retina caused by mutation in genes of the photoreceptor proteins with an autosomal dominant (adRP), autosomal recessive (arRP), or X-linked pattern of inheritance. Although there are over 100 identified mutations in the opsin gene associated with RP, only a few of them are inherited with the arRP pattern. E150K is the first reported missense mutation associated with arRP. This opsin mutation is located in the second cytoplasmic loop of this G protein-coupled receptor. E150K opsin expressed in HEK293 cells and reconstituted with 11-cis-retinal displayed an absorption spectrum similar to the wild type (WT) counterpart and activated G protein transducin slightly faster than WT receptor. However, the majority of E150K opsin showed a higher apparent molecular mass in SDS-PAGE and was resistant to endoglycosidase H deglycosidase. Instead of being transported to the plasma membrane, E150K opsin is partially colocalized with the cis/medial Golgi compartment markers such as GM130 and Vti1b but not with the trans-Golgi network. In contrast to the endoplasmic reticulum-retained adRP mutant, P23H opsin, Golgi-retained E150K opsin did not influence the proper transport of the WT opsin when coexpressed in HEK293 cells. This result is consistent with the recessive pattern of inheritance of this mutation. Thus, our study reveals a novel molecular mechanism for retinal degeneration that results from deficient export of opsin from the Golgi apparatus.     

Amino-terminal Cysteine Residues Differentially Influence RGS4 Protein Plasma Membrane Targeting, Intracellular Trafficking, and Function

Regulator of G-protein signaling (RGS) proteins are potent inhibitors of heterotrimeric G-protein signaling. RGS4 attenuates G-protein activity in several tissues. Previous work demonstrated that cysteine palmitoylation on residues in the amino-terminal (Cys-2 and Cys-12) and core domains (Cys-95) of RGS4 is important for protein stability, plasma membrane targeting, and GTPase activating function. To date Cys-2 has been the priority target for RGS4 regulation by palmitoylation based on its putative role in stabilizing the RGS4 protein. Here, we investigate differences in the contribution of Cys-2 and Cys-12 to the intracellular localization and function of RGS4. Inhibition of RGS4 palmitoylation with 2-bromopalmitate dramatically reduced its localization to the plasma membrane. Similarly, mutation of the RGS4 amphipathic helix (L23D) prevented membrane localization and its G(q) inhibitory function. Together, these data suggest that both RGS4 palmitoylation and the amphipathic helix domain are required for optimal plasma membrane targeting and function of RGS4. Mutation of Cys-12 decreased RGS4 membrane targeting to a similar extent as 2-bromopalmitate, resulting in complete loss of its G(q) inhibitory function. Mutation of Cys-2 did not impair plasma membrane targeting but did partially impair its function as a G(q) inhibitor. Comparison of the endosomal distribution pattern of wild type and mutant RGS4 proteins with TGN38 indicated that palmitoylation of these two cysteines contributes differentially to the intracellular trafficking of RGS4. These data show for the first time that Cys-2 and Cys-12 play markedly different roles in the regulation of RGS4 membrane localization, intracellular trafficking, and G(q) inhibitory function via mechanisms that are unrelated to RGS4 protein stabilization.     

Delayed sleep phase disorder and Attention deficit and hyperactivity symptoms in a teenager

JR is an 18-year-old male with five-year history of going to bed late and waking up late. He gives history of poor frustration tolerance, inattention and fidgetiness in school for which he has been unsuccessfully been treated with stimulant medications for last 3 years. There is history of similar sleep problems in his father who works nights as a mechanic. JR's sleep log shows him going to bed early morning and waking up late morning/afternoon. He shows no sleep maintenance problems and sleeps an average of 8 h per night. He shows no symptoms of depression, anxiety, inattention or hyperactivity during his hospital stay. He does not show any learning, cognitive, attention or intellectual deficits. He is currently not taking any medications. He is discharged home after 3-day hospital stay and is reportedly doing well working in a video rental store at night.     

Histone modifications dictate specific biological readouts

The basic unit of chromatin is the nucleosomal core particle, containing 147 bp of DNA that wraps twice around an octamer of core histones. The core histones bear a highly dynamic N-terminal amino acid tail around 20-35 residues in length and rich in basic amino acids. These tails extending from the surface of nucleosome play an important role in folding of nucleosomal arrays into higher order chromatin structure, which plays an important role in eukaryotic gene regulation. The amino terminal tails protruding from the nuclesomes get modified by the addition of small groups such as methyl, acetyl and phosphoryl groups. In this review, we focus on these complex modi- fication patterns and their biological functions. Moreover, these modifications seem to be part of a complex scheme where distinct histone modifications act in a sequential manner or in combination to form a ＂histone code＂ read by other proteins to control the structure and/or function of the chromatin fiber. Errors in this histone code may be involved in many human diseases especially cancer, the nature of which could be therapeutically exploited. Increasing evidence suggests that many proteins bear multiple, distinct modifications, and the ability of one modification to antagonize or synergize the deposition of another can have significant biological consequences.     

Three distinct peptides from the N domain of translation termination factor eRF1 surround stop codon in the ribosome

To study positioning of the polypeptide release factor eRF1 toward a stop signal in the ribosomal decoding site, we applied photoactivatable mRNA analogs, derivatives of oligoribonucleotides. The human eRF1 peptides cross-linked to these short mRNAs were identified. Cross-linkers on the guanines at the second, third, and fourth stop signal positions modified fragment 31–33, and to lesser extent amino acids within region 121–131 (the “YxCxxxF loop”) in the N domain. Hence, both regions are involved in the recognition of the purines. A cross-linker at the first uridine of the stop codon modifies Val66 near the NIKS loop (positions 61–64), and this region is important for recognition of the first uridine of stop codons. Since the N domain distinct regions of eRF1 are involved in a stop-codon decoding, the eRF1 decoding site is discontinuous and is not of “protein anticodon” type. By molecular modeling, the eRF1 molecule can be fitted to the A site proximal to the P-site-bound tRNA and to a stop codon in mRNA via a large conformational change to one of its three domains. In the simulated eRF1 conformation, the YxCxxxF motif and positions 31–33 are very close to a stop codon, which becomes also proximal to several parts of the C domain. Thus, in the A-site-bound state, the eRF1 conformation significantly differs from those in crystals and solution. The model suggested for eRF1 conformation in the ribosomal A site and cross-linking data are compatible.     

Gene-environment interactions in a mutant mouse kindred with native airway constrictor hyperresponsiveness

We mutagenized male BTBR mice with N-ethyl-N-nitrosourea and screened 1315 of their G3 offspring for airway hyperresponsiveness. A phenovariant G3 mouse with exaggerated methacholine bronchoconstrictor response was identified and his progeny bred in a nonspecific-pathogen-free (SPF) facility where sentinels tested positive for minute virus of mice and mouse parvovirus and where softwood bedding was used. The mutant phenotype was inherited through G11 as a single autosomal semidominant mutation with marked gender restriction, with males exhibiting almost full penetrance and very few females phenotypically abnormal. Between G11 and G12, facility infection eradication was undertaken and bedding was changed to hardwood. We could no longer detect airway hyperresponsiveness in more than 37 G12 offspring of 26 hyperresponsive G11 males. Also, we could not identify the mutant phenotype among offspring of hyperresponsive G8–G10 sires rederived into an SPF facility despite 21 attempts. These two observations suggest that both genetic and environmental factors were needed for phenotype expression. We suspect that rederivation into an SPF facility or altered exposure to pathogens or other unidentified substances modified environmental interactions with the mutant allele, and so resulted in disappearance of the hyperresponsive phenotype. Our experience suggests that future searches for genes that confer susceptibility for airway hyperresponsiveness might not be able to identify some genes that confer susceptibility if the searches are performed in SPF facilities. Experimenters are advised to arrange for multigeneration constancy of mouse care in order to clone mutant genes. Indeed, we were not able to map the mutation before losing the phenotype.