Inter-Ethnic/Racial Facial Variations: A Systematic Review and Bayesian Meta-Analysis of Photogrammetric Studies

Background

Numerous facial photogrammetric studies have been published around the world. We aimed to critically review these studies so as to establish population norms for various angular and linear facial measurements; and to determine inter-ethnic/racial facial variations.

Methods and Findings

A comprehensive and systematic search of PubMed, ISI Web of Science, Embase, and Scopus was conducted to identify facial photogrammetric studies published before December, 2014. Subjects of eligible studies were either Africans, Asians or Caucasians. A Bayesian hierarchical random effects model was developed to estimate posterior means and 95% credible intervals (CrI) for each measurement by ethnicity/race. Linear contrasts were constructed to explore inter-ethnic/racial facial variations. We identified 38 eligible studies reporting 11 angular and 18 linear facial measurements. Risk of bias of the studies ranged from 0.06 to 0.66. At the significance level of 0.05, African males were found to have smaller nasofrontal angle (posterior mean difference: 8.1°, 95% CrI: 2.2°–13.5°) compared to Caucasian males and larger nasofacial angle (7.4°, 0.1°–13.2°) compared to Asian males. Nasolabial angle was more obtuse in Caucasian females than in African (17.4°, 0.2°–35.3°) and Asian (9.1°, 0.4°–17.3°) females. Additional inter-ethnic/racial variations were revealed when the level of statistical significance was set at 0.10.

Conclusions

A comprehensive database for angular and linear facial measurements was established from existing studies using the statistical model and inter-ethnic/racial variations of facial features were observed. The results have implications for clinical practice and highlight the need and value for high quality photogrammetric studies.     

Structural basis for apoptosis inhibition by Epstein-Barr virus BHRF1

Epstein-Barr virus (EBV) is associated with human malignancies, especially those affecting the B cell compartment such as Burkitt lymphoma. The virally encoded homolog of the mammalian pro-survival protein Bcl-2, BHRF1 contributes to viral infectivity and lymphomagenesis. In addition to the pro-apoptotic BH3-only protein Bim, its key target in lymphoid cells, BHRF1 also binds a selective sub-set of pro-apoptotic proteins (Bid, Puma, Bak) expressed by host cells. A consequence of BHRF1 expression is marked resistance to a range of cytotoxic agents and in particular, we show that its expression renders a mouse model of Burkitt lymphoma untreatable. As current small organic antagonists of Bcl-2 do not target BHRF1, the structures of it in complex with Bim or Bak shown here will be useful to guide efforts to target BHRF1 in EBV-associated malignancies, which are usually associated with poor clinical outcomes.     

The thorough screening of the MUTYH gene in a large French cohort of sporadic colorectal cancers

The MUTYH gene encodes a key glycosylase of the base-excision repair system that is involved in maintaining genomic DNA stability against oxidative damage. Biallelic germline MUTYH mutations have been proved to greatly predispose to non-familial adenomatous polyposis (FAP) and non-hereditary non-polyposis colorectal cancer (HNPCC) familial recessive forms of colorectal cancer with multiple adenomas. To date, there is still much debate over the impact of monoallelic germline MUTYH mutations on colorectal carcinogenesis. To evaluate their role in the susceptibility to sporadic colon and rectum cancers, we screened 1024 French sporadic colorectal cancer cases and 1121 French healthy controls for Caucasian MUTYH-associated polyposis mutations, including already known mutations p.Gly382Asp and p.Tyr165Cys, and new mutation p.Val479Phe. We observed a nonstatistically significant association between these MUTYH mutations at a heterozygous state and an increase in colorectal cancer risk (odds ratio [OR] 1.26, 95% confidence interval [CI] 0.70-2.27). As a result, we conclude that heterozygous MUTYH mutations do not play a major role in sporadic colorectal carcinogenesis although a modest effect on this process cannot be ruled out.     

Antithrombotic activity of kininogen is mediated by inhibitory effects of domain 3 during arterial injury in vivo

High-molecular-weight kininogen (HK) and its domain 3 (D3) exhibit anticoagulant properties and inhibit platelet activation at low thrombin concentration in vitro. We hypothesized that the rapid occlusive thrombosis in HK-deficient (HKd) rats following endothelial injury of the aorta results from enhanced platelet aggregation by thrombin. The effects of D3 (G235-M357) or D3-derived peptides on thrombosis in vivo were tested. D3 and its exon 7C terminal peptide (E7CP, K270-Q292), expressed as glutathione S-transferase (GST) fusion proteins (GST-D3, GST-E7CP), or GST alone, as well as cleaved HK (HKa) or synthetic peptide E7CP, were infused intravenously 10 min before endothelial injury. Blood flow was reduced down to 10% of baseline flow within 28 +/- 5.2 min by a platelet-fibrin thrombus in GST-treated HKd rats compared with >240 min in GST-treated normal HK rats (wild type). GST-D3, GST-E7CP, HKa, or E7CP infusion prolonged the flow time to 233, >240, 223, and >240 min, respectively, in HKd rats. When GST-E7CP was infused 10 min after the injury, blood flow was maintained for >240 min. Thrombin-antithrombin concentrations were elevated by injury in HKd rats receiving GST from 35 to 55 microg/l and decreased with GST-E7CP, HKa, or E7CP reconstitution to 40, 15, and 9 microg/l, respectively. We conclude that HKd rats are prothrombotic and that HKa, kininogen D3, and its fragment E7CP modulate arterial thrombosis after endothelial injury.     

The CNS Synapse Revisited: Gaps,Adhesive Welds,and Borders

Although processes leading up to the point of synapse formation are fairly well understood, the precise sequence of events in which the membranes of two separate cells “lock in” to form a mature synaptic junctional complex is poorly understood. A careful study of the molecules operating at the synapse indicates that their roles are more multifarious than once imagined. In this review we posit that the synapse is a functional organelle with poorly defined boundaries and a complex biochemistry. The role of adhesion molecules, including the integration of their signaling and adhesive properties in the context of synaptic activity is discussed. Special issue dedicated to Anthony Campagnoni     

Inorganic carbon acquisition in the acid‐tolerant alga Chlorella kessleri

The ability of the freshwater alga, Chlorella kessleri, to maintain a carbon concentrating mechanism when grown at acid pH was investigated. The alga grows over the pH range 4.0–9.0 and was found to take up bicarbonate and CO₂ actively when grown at pH 6.0. However, when grown at acid pH (below 5.5), it does not have active CO₂ uptake. The acidotolerant species maintained an internal pH of 6.1–7.5 over the external pH range 4.5–7.5, thus the pH difference between the cell interior and the external medium was large enough to allow for the diffusive uptake of CO₂ at acid external pH. Mass spectrometric monitoring of O₂ and CO₂ fluxes by suspensions of C. kessleri, grown at acid pH, and maintained at pH 7.5 showed that the rates of O₂ evolution did not exceed those of CO₂ uptake. The final CO₂ compensation concentrations of 14.0–17.7 µM reached by photosynthetic cells were above the CO₂ equilibrium concentration in the external medium, indicating a lack of active CO₂ uptake at acid pH. Chlorella kessleri accumulated CO₂ with internal concentrations that were 9.9, 18.7 and 22.7‐fold that of the external medium for cells grown, respectively, at pH 4.5, 5.0 and 5.5. The ability of C. kessleri cells to accumulate high intracellular concentrations of inorganic carbon at acid pH would provide a sufficiently high concentration of CO₂ at the active site of Rubisco thus allowing the alga to maintain growth rates similar to those at alkaline pH.     

RT-qPCR reveals opsin gene upregulation associated with age and sex in guppies (Poecilia reticulata) - a species with color-based sexual selection and 11 visual-opsin genes

Background  

PCR-based surveys have shown that guppies (Poecilia reticulata) have an unusually large visual-opsin gene repertoire. This has led to speculation that opsin duplication and divergence has enhanced the evolution of elaborate male coloration because it improves spectral sensitivity and/or discrimination in females. However, this conjecture on evolutionary connections between opsin repertoire, vision, mate choice, and male coloration was generated with little data on gene expression. Here, we used RT-qPCR to survey visual-opsin gene expression in the eyes of males, females, and juveniles in order to further understand color-based sexual selection from the perspective of the visual system.     

A human iPSC model of Hutchinson Gilford Progeria reveals vascular smooth muscle and mesenchymal stem cell defects

The segmental premature aging disease Hutchinson-Gilford Progeria syndrome (HGPS) is caused by a truncated and farnesylated form of Lamin A called progerin. HGPS affects mesenchymal lineages, including the skeletal system, dermis, and vascular smooth muscle (VSMC). To understand the underlying molecular pathology of HGPS, we derived induced pluripotent stem cells (iPSCs) from HGPS dermal fibroblasts. The iPSCs were differentiated into neural progenitors, endothelial cells, fibroblasts, VSMCs, and mesenchymal stem cells (MSCs). Progerin levels were highest in MSCs, VSMCs, and fibroblasts, in that order, with these lineages displaying increased DNA damage, nuclear abnormalities, and HGPS-VSMC accumulating numerous calponin-staining inclusion bodies. Both HGPS-MSC and -VSMC viability was compromised by stress and hypoxia in vitro and in vivo (MSC). Because MSCs reside in low oxygen niches in vivo, we propose that, in HGPS, this causes additional depletion of the MSC pool responsible for replacing differentiated cells lost to progerin toxicity.     

Rapid environmental change over the past decade revealed by isotopic analysis of the California mussel in the northeast Pacific

The anthropogenic input of fossil fuel carbon into the atmosphere results in increased carbon dioxide (CO(2)) into the oceans, a process that lowers seawater pH, decreases alkalinity and can inhibit the production of shell material. Corrosive water has recently been documented in the northeast Pacific, along with a rapid decline in seawater pH over the past decade. A lack of instrumentation prior to the 1990s means that we have no indication whether these carbon cycle changes have precedence or are a response to recent anthropogenic CO(2) inputs. We analyzed stable carbon and oxygen isotopes (δ(13)C, δ(18)O) of decade-old California mussel shells (Mytilus californianus) in the context of an instrumental seawater record of the same length. We further compared modern shells to shells from 1000 to 1340 years BP and from the 1960s to the present and show declines in the δ(13)C of modern shells that have no historical precedent. Our finding of decline in another shelled mollusk (limpet) and our extensive environmental data show that these δ(13)C declines are unexplained by changes to the coastal food web, upwelling regime, or local circulation. Our observed decline in shell δ(13)C parallels other signs of rapid changes to the nearshore carbon cycle in the Pacific, including a decline in pH that is an order of magnitude greater than predicted by an equilibrium response to rising atmospheric CO(2), the presence of low pH water throughout the region, and a record of a similarly steep decline in δ(13)C in algae in the Gulf of Alaska. These unprecedented changes and the lack of a clear causal variable underscores the need for better quantifying carbon dynamics in nearshore environments.     

Delineation of xenobiotic substrate sites in rat glutathione S-transferase M1-1

Glutathione S-transferases catalyze the conjugation of glutathione with endogenous and exogenous xenobiotics. Hu and Colman (1995) proposed that there are two distinct substrate sites in rat GST M1-1, a 1-chloro-2,4-dintrobenzene (CDNB) substrate site located in the vicinity of tyrosine-115, and a monobromobimane (mBBr) substrate site. To determine whether the mBBr substrate site is distinguishable from the CDNB substrate site, we tested S-(hydroxyethyl)bimane, a nonreactive derivative of mBBr, for its ability to compete kinetically with the substrates. We find that S-(hydroxyethyl)bimane is a competitive inhibitor (K(I) = 0.36 microM) when mBBr is used as substrate, but not when CDNB is used as substrate, demonstrating that these two sites are distinct. Using site-directed mutagenesis, we have localized the mBBr substrate site to an area midway through alpha-helix 4 (residues 90-114) and have identified residues that are important in the enzymatic reaction. Substitution of alanine at positions along alpha-helix 4 reveals that mutations at positions 103, 104, and 109 exhibit a greater perturbation of the enzymatic reaction with mBBr than with CDNB as substrate. Various other substitutions at positions 103 and 104 reveal that a hydrophobic residue is necessary at each of these positions to maintain optimal affinity of the enzyme for mBBr and preserve the secondary structure of the enzyme. Substitutions at position 109 indicate that this residue is important in the enzyme's affinity for mBBr but has a minimal effect on Vmax. These results demonstrate that the promiscuity of rat GST M1-1 is in part due to at least two distinct substrate sites.