Red Hair Research Articles

Black Esophagus From Non-dissected Thoracic Aorta Aneurysm

Acute esophageal necrosis (AEN) also known as black esophagus due to its appearance on endoscopy classically involves the distal esophagus. AEN affecting the mid esophagus with sparing of the distal esophagus is rare and usually occurs in patients with thoracic aortic aneurysmal rupture or aortic dissection. Here we report a case of AEN in a patient with an unruptured and undissected thoracic aorta aneurysm (TAA). A 79-year-old female presented to ER with near syncope. She denied chest pain or gastrointestinal symptoms. She had a history of HTN and TAA, 5.5 cm in size, previously diagnosed and scheduled for repair. Her vital signs were stable with BP of 122/62 mmHg and pulse 81 bpm. Her initial laboratory studies were stable, and only d-dimer was elevated to 2049. Chest CT angiogram revealed an acute bilateral pulmonary embolism (PE) with stable TAA and mural thrombus in descending thoracic aorta. Right heart strain was revealed by echocardiogram and she was started on heparin. On day 2, patient went into acute hypoxemic respiratory failure requiring intubation. As she subsequently developed shock, pressors were initiated. On day 5, melena and bloody gastric residue was found, and hemoglobin declined from 12.2 g/dL to 7.7 g/dL. Heparin was stopped, 2 units of blood were transfused and an IVC filter was placed. Upper endoscopy revealed extensive, circumferential deep ulceration in mid-esophagus with wall irregularity and black discoloration likely esophageal necrosis (figure 1 & 2). Distal esophagus, GE junction, stomach and duodenum appeared normal. Patient was managed supportively with NPO, PPI, fluids and pressors. While her hemoglobin stabilized, patient went into pulseless electrical activity on day 23 and died after unsuccessful resuscitation. We postulate that extrinsic compression of the esophageal wall by the thoracic aortic aneurysm and the intramural thrombus resulted in obstruction of the esophageal blood vessels arising from the descending aorta which supply the mid-esophagus leading to ischemia which was worsened by the hypotension caused by PE.AEN in the setting of a thoracic aortic aneurysm can occur without rupture or dissection.Figure: Endoscopic Images showing extensive circumferential esophageal ulcerations with blackish discoloration.Figure: Endoscopic Image showing friable esophageal mucosa, mucosal separation with out active bleeding.Figure: Sagittal section of CT Angiogram of chest showing thoracic aorta aneurysm of approx. 5.5 cm size causing extrinsic compression at mid esophageal level (green arrow) along with intramural thrombus in thoracic aorta (red arrow head).

Cell signalling: Red alert about lipid's role in skin cancer.

Some versions of the MC1R protein are associated with red hair and an increased risk of developing a skin cancer called melanoma. It emerges that a lipid that binds MC1R might provide a target to reduce this risk. See Letter p.399 People with red hair, fair skin and poor tanning ability have a higher risk of developing melanoma. They often carry variants of the melanocortin-1 receptor (MC1R), which has a reduced capacity to induce pigmentation compared with the more common MCR1 forms. Rutao Cui and colleagues show how a modification called protein palmitoylation increases the ability of variant MCR1 to induce pigmentation in mice, and this is linked to reduced melanoma development. These findings may point to strategies for melanoma prevention, although it remains to be seen whether such an approach is practical.

Palmitoylation-dependent activation of MC1R prevents melanomagenesis.

The melanocortin-1 receptor (MC1R), a G protein-coupled receptor, plays a crucial role in human and mouse pigmentation1–8. Activation of MC1R in melanocytes by α-melanocyte-stimulating hormone (α-MSH)9 stimulates cAMP signaling and melanin production and enhances DNA repair after UV irradiation (UVR)10–16. Individuals carrying MC1R variants, especially those associated with red hair color, fair skin and poor tanning ability (RHC-variants), are associated with higher risk of melanoma5,17,18,19,20. However, how MC1R activity might be modulated by UV irradiation, why redheads are more prone to developing melanoma, and whether the activity of RHC variants might be restored for therapeutic benefit remain unresolved questions. Here we demonstrate a potential MC1R-targeted intervention strategy to rescue loss-of-function MC1R in MC1R RHC-variants for therapeutic benefit based on activating MC1R protein palmitoylation. Specifically, MC1R palmitoylation, primarily mediated by the protein-acyl transferase (PAT) ZDHHC13, is essential for activating MC1R signaling that triggers increased pigmentation, UVB-induced G1-like cell cycle arrest and control of senescence and melanomagenesis in vitro and in vivo. Using C57BL/6J-MC1Re/eJ mice expressing MC1R RHC-variants we show that pharmacological activation of palmitoylation rescues the defects of MC1R RHC-variants and prevents melanomagenesis. The results highlight a central role for MC1R palmitoylation in pigmentation and protection against melanoma.

Abstract 1271: Genetic variants in the 16q24.3 region of melanocortin-1-receptor (MC1R) and prostate cancer risk: A Mendelian randomization analysis of 39,000 cases and 25,000 controls

Abstract We previously reported that men with naturally red hair had a significantly lower risk of prostate cancer (HR=0.46, 95% CI 0.24-0.89) compared with the most prevalent hair color, light brown (Br J Cancer 2013;109(3):747-750). The red hair phenotype is encoded by variants in the melanocortin-1-receptor (MC1R) gene that controls expression of the eumelanin and pheomelanin pigments. In order to re-examine this association through the relatively unbiased Mendelian randomization approach, we examined single nucleotide polymorphisms (SNPs) in and near MC1R in relation to prostate cancer risk using data from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. The analysis includes 38,868 men diagnosed with prostate cancer and 25,210 controls from 35 studies participating in PRACTICAL Consortium (Nat Gen 2014;46(10)1103-1109). Logistic regression modeling was used to estimate the odds ratio (OR) and confidence interval (CI) for the per allele prostate risk associations with 148 genotyped SNPs and 164 imputed SNPs. Variants demonstrating nominal significance (alpha-error p<0.05) as well as those reaching a stringent Bonferroni threshold of p<0.0003 adjustment for multiple comparisons were examined. We identified prostate cancer risk associations with 30 genotyped and 36 imputed polymorphisms that were nominally significant, three of which achieved Bonferroni significance and were in a region of 16q24.3 that includes MC1R, GAS8 (growth arrest specific-8, an alleged tumor suppressor that is deleted in some prostate cancers), and transcription factor-25 (TCF25). These were rs4628973 and rs3743824 that were in high LD (r2=0.931; prostate cancer risk associations p=0.00029 and 0.00023, respectively), as well as rs6500461 that was independently associated with risk (r2=0.20 with rs4628973; p=0.00020). This large-scale Mendelian randomization analysis suggests genetic variants near MC1R, which directs melanocyte melanin synthesis, secretion and human pigmentation, may be associated with risk of prostate cancer. Citation Format: Stephanie J. Weinstein, Tracy M. Layne, Jiaqi Huang, Eric Karlins, Stephen J. Chanock, Demetrius Albanes, the PRACTICAL Consortium. Genetic variants in the 16q24.3 region of melanocortin-1-receptor (MC1R) and prostate cancer risk: A Mendelian randomization analysis of 39,000 cases and 25,000 controls [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1271. doi:10.1158/1538-7445.AM2017-1271

Passionate Love-Letters to a Dead Girl: Elizabeth Siddall in Oscar Wilde's The Picture of Dorian Gray

While Oscar Wilde's attraction to Pre-Raphaelite art has been well documented, surprisingly little attention has been paid to his career-long fascination with Elizabeth Siddall (1829–62). This essay will demonstrate that Wilde's deep and abiding interest in Siddall reverberates across his only novel, The Picture of Dorian Gray (1891), to an extent that has not been considered. I will specifically argue that the suicide of Dorian Gray's lover Sibyl Vane was inspired by Elizabeth Siddall's untimely overdose. The very name Sibyl echoes Siddall, who is best known as the model for John Everett Millais's Ophelia and Dante Gabriel Rossetti's Beata Beatrix. I want to suggest that Siddall, long dead by the 1890s, may have been coded as Celtic across turn-of-the-century Irish literature in ways not hitherto considered. Although Siddall was not born of Irish parents, she served ‘as a model for “a fair Celt with red hair”’ for the Pre-Raphaelite painter William Holman Hunt, perhaps owing to the fact that she was copper-haired, ivory-skinned, Welsh, and working class. As such, Siddall ­– who has not previously been read in a Celtic context – might serve as a signifier of the young, pale, passive, red-haired Irish maiden romanticised across popular culture as a symbol of the Irish nation. Indeed, it is plausible that the Dublin-born Wilde was attracted to Siddall because of her resemblance to the aisling figure derived from the eighteenth-century Gaelic tradition and popular in turn-of-the-century Irish culture. The essay will examine closely the nods to Elizabeth Siddall in The Picture of Dorian Gray and ultimately will propose that the Pre-Raphaelite musings in Wilde – whose engagement with feminism and with his native Ireland have always been complicated – effectively, if not intentionally, silence the figure of the fin-de-siècle New Woman as she appeared across the British and Irish Isles.

Abstract 1561: Gene expression analysis identifies heterogeneity in cutaneous melanoma subjects with disruptive MC1R alleles and BRAF hotspot mutations

Abstract Background: Previous epidemiological and population sequencing studies have established that subjects with melanocortin 1 receptor (MC1R) germline mutations, associated with red hair and light skin phenotypes, have an increased risk of melanoma. However, several conflicting reports about the role of BRAF somatic mutations in MC1R subjects exist in the literature. We hypothesise that this conflict is due to biological process driven heterogeneity within MC1R subjects carrying disruptive alleles. To understand the heterogeneity, we analysed the TCGA cohort at the gene expression level using mRNA sequencing data. Method: From the previously published studies, we identified 68 cutaneous melanoma subjects who were of white ethinicity, had at least one disruptive allele of MC1R, and had BRAF mutations. Associated clinical and mRNA sequencing data were downloaded from the Firebrowse website. An unbiased hierarchical clustering analysis was performed using the preprocessed mRNA data containing 14669 gene expressions. The resultant clusters were then characterised using available clinical variables. A differential expression analysis was performed to identify the genomic signatures of these clusters. The resultant p-values were corrected for false discovery rate (FDR) using the Benjamini-Hochberg approach. Genes with corrected p-values less than 0.01 were further analysed using gene set enrichment analysis (GSEA) preranked lists. Results: An unbiased clustering identified two clear and separable clusters with 40 and 28 subjects respectively. The UV-signature (dipyrimidine C>T load) was correlated with these clusters (p-value = 0.047). However, no significant differences in age at the time of diagnosis, overall survival, and total mutation load between clusters were observed. At the genomic level, 2588 genes were significantly differentially expressed between two clusters (FDR corrected p- value less than 0.05). The top 10 differentially expressed genes included ATF2, MSH6, SP3, MAP3K2, and VEGFB. Further GSEA revealed gene sets playing roles in several pathways and biological processes, including oxidative phosphorylation, UV response in keratinocytes, DNA repair, cell cycle, and cellular response to stress. Conclusion: Cutaneous melanoma subjects with disruptive MC1R alleles and BRAF hotspot mutations have heterogeneous gene expression profiles with several key oncogenes differentially expressed. This suggests potential roles of other pathways, either independently or in cooperation with BRAF mutations, in melanomagenesis in MC1R bearing patients. Citation Format: Piyushkumar A. Mundra, Candelaria Bracalente, Lucas Trucco, Nathalie Dhomen, Richard Marais. Gene expression analysis identifies heterogeneity in cutaneous melanoma subjects with disruptive MC1R alleles and BRAF hotspot mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1561. doi:10.1158/1538-7445.AM2017-1561

Gastro-duodenal protective effect of aqueous leaf extract of Daucuscarota sativus Linn. (Apiaceae) in rats and its possible mechanism of action

Background: Daucuscarota sativus L. (Apiaceae) commonly known as ‘carrot’ is a multipurpose herb cultivated in different parts of the world for its edible roots, juice, oils and leaves. Carrot root as well as its leaves has been credited with many medicinal properties, including cleansing of the intestine and maintenance of acid-alkaline balance in the body. Carrot leaves also known as carrot tops or carrot greens have been used locally as a decoction for healing mouth sores, and in some cases, mixed with honey to clean festering wounds. The present study was therefore designed to evaluate the possible gastro-duodenal protective property of Daucuscarota sativus (DCS) aqueous leaf extract on laboratory-induced ulcers. Aqueous leaf extract prepared by maceration was orally administered one hour before ulcerogens in doses of 50, 100 and 200 mg/kg to groups of randomized adult rats of both sexes. Gastric ulcers were induced using pyloric ligation, methyleneblue, and acetic acid, while cysteamine, and indomethacin-histamine were separately employed for induction of duodenal ulcers in the animals. Positive controls were given standard drugs appropriate for each experimental model. Phytochemical screening of the freshly prepared extract was also carried out, as well as evaluating its antioxidant activity. In each of the models, the aqueous leaf extract of DCS showed a significant (p<0.05-0.001) dose-independent protection against peptic ulcer. The effects produced by the aqueous leaf extract of DCS were comparable to those of the standard drugs (omeprazole; 200 µg/kg, ranitidine; 50 mg/kg, and cimetidine; 50 mg/kg). Phytochemical analysis of the aqueous leaf extract of Daucuscarota sativus revealed the presence of flavonoids, tannins, alkaloids, and saponins, some of which have been reported to elicit cytoprotective effect. Antioxidant analysis showed significant scavenging effect of free radical using nitric oxide, lipid peroxidation and DPPH assay. The findings in this study suggest that the aqueous leaf extract of DCS possesses cytoprotective effect and also reduces secretion of secretagogues, thereby protecting against gastric and duodenal ulcers.

Detection of Smo, Gli2 and Gli3 Among Basal Cell Carcinoma Patients in Sulaimani Province.

Basal-cell carcinoma (BCC hedgehog (Shh) of BCC. The specific downstream effector in the Shh pathway leading to cancer development is unclear. However in vertebrates, specific downstream effectors in the Shh signaling pathway including zinc-finger transcription factors Gli2 and Gli3 play the Shh pathway. S and controlled cell proliferation. The expression of transducers had not been reported yet in BCC skin of local patients. The aim of this study was to investigate the expression of S BCC biopsies taken from sun Five BCC skin biopsy specimens were taken from the sun which served as material for the study. RNA extracted from the samples, cDNA synthesised carried out and specific primers for each of the S genes were designed. Reverse transcription polymerase chain reaction (RT samples expressed genes for S patients in Sulaimani Province. These findings support the role of S the Shh–receptor complex. These results establish S oncogenes in skin and suggest a pivotal role for these transcription factors in the development of BCC. This method can be used in the diagnosis of BCC and fur study of downstream effectors in the Shh pathway may lead to an effective anti cancer therapy. Key Words: Basal cell carcinoma, Smo, Gli2, Gli3, RT-PCR. JZS (2017) 19 – 2 (Part-A) 1 Detection of Smo, Gli2 and Gli3 Among Basal Cell Carcinoma Patients in Sulaimani Province Department of Biology, College of Science, University of Sulaimani, Sulaimani, Kurdistan Region, Iraq. Basal cell carcinoma is the most common malignancy in humans. Although rarely metasta capable of significant local destruction and disfigurement. Skin cancer is accounting for about half of all cancers occur. BCC constitute approximately 80% of all nonmelanoma skin cancers [ in the world has been reported in Australia [2]. Exposure to ult radiation is generally accepted as the major cause of BCC and the risk of this disease is significantly increased by recreational exposure to the sun during childhood and adolescence cluding fair complexion, red or blond hair, and light eye color, influence responsiveness to but are also independent risk factors [4]; exposures to ionizing radiation, arsenic, and oral methoxsalen ave also been linked to the development of BCC[5,6] Journal homepage www.jzs.univsul.edu.iq Journal of Zankoy Sulaimani Part-A- (Pure and Applied Sciences) Abstract cell carcinoma (BCC) is the most common type of cancer in human. Sonic hedgehog (Shh) signaling pathway impairment plays a key role in the pathogenesis of BCC. The specific downstream effector in the Shh pathway leading to cancer development is unclear. However in vertebrates, specific downstream effectors in e Shh signaling pathway including smoothened, frizzled class receptor (S finger transcription factors Gli2 and Gli3 play an important role in regulating the Shh pathway. SMO, Gli2, and Gli3 family proteins are necessary for adequate and controlled cell proliferation. The expression of SMO, Gli2 and Gli3 signal transducers had not been reported yet in BCC skin of local patients. The aim of this study was to investigate the expression of SMO BCC biopsies taken from sun-exposed skin areas of patients in Sulaimani Provinc Five BCC skin biopsy specimens were taken from the sun which served as material for the study. RNA extracted from the samples, cDNA synthesised carried out and specific primers for each of the S genes were designed. Reverse transcription polymerase chain reaction (RT-PCR) analyses samples expressed genes for SMO, Gli2 and Gli3 in BCC skin biopsies taken from patients in Sulaimani Province. These findings support the role of SMO, Gli2 and Gli3 as a signa receptor complex. These results establish SMO, Gli2 and Gli3 as potent oncogenes in skin and suggest a pivotal role for these transcription factors in the development of BCC. This method can be used in the diagnosis of BCC and fur study of downstream effectors in the Shh pathway may lead to an effective anti cancer therapy.

Variation in male ornaments in two lizard populations with contrasting parasite loads

AbstractIn the context of the immunocompetence handicap hypothesis, we explored how differences in parasite load affect the way in which sexual ornaments codify information about individual quality. We studied variation in sexual signals in two Iberian populations of the lizard Psammodromus algirus, a species in which sexually active males display a red head coloration. In one population, males were free of tick nymphs, whereas in the other one all males were tick‐infested (mean of 12.7 tick nymphs/individual).At the onset of the breeding season, the red‐coloured surface was larger in the non‐parasitized population than in the parasitized one, whereas the opposite was true for colour saturation. We experimentally simulated a bacterial infection (by intraperitoneal injection of lipopolysaccharide) to examine the effects of immune activation on the expression of this sexual ornament. In the non‐parasitized population, our treatment caused a reduction in the red‐coloured surface of experimental males, whereas in the parasitized population it caused a decrease in colour saturation. In the parasitized population, males that displayed sexual coloration were larger, and had fewer parasites, than uncoloured ones, and inflammatory response to lipopolysaccharide injection in the palm of the hind paw was negatively correlated with colour saturation, but not with colour extension. Thus, we suggest parasites not only constrained the expression of sexual ornaments, but they also changed the signal properties that conveyed useful information about the quality of their bearers.

Eumelanin and pheomelanin are predominant pigments in bumblebee (Apidae: Bombus) pubescence.

BackgroundBumblebees (Hymenoptera: Apidae: Bombus) are well known for their important inter- and intra-specific variation in hair (or pubescence) color patterns, but the chemical nature of the pigments associated with these patterns is not fully understood. For example, though melanization is believed to provide darker colors, it still unknown which types of melanin are responsible for each color, and no conclusive data are available for the lighter colors, including white.MethodsBy using dispersive Raman spectroscopy analysis on 12 species/subspecies of bumblebees from seven subgenera, we tested the hypothesis that eumelanin and pheomelanin, the two main melanin types occurring in animals, are largely responsible for bumblebee pubescence coloration.ResultsEumelanin and pheomelanin occur in bumblebee pubescence. Black pigmentation is due to prevalent eumelanin, with visible signals of additional pheomelanin, while the yellow, orange, red and brown hairs clearly include pheomelanin. On the other hand, white hairs reward very weak Raman signals, suggesting that they are depigmented. Additional non-melanic pigments in yellow hair cannot be excluded but need other techniques to be detected. Raman spectra were more similar across similarly colored hairs, with no apparent effect of phylogeny and both melanin types appeared to be already used at the beginning of bumblebee radiation.DiscussionWe suggest that the two main melanin forms, at variable amounts and/or vibrational states, are sufficient in giving almost the whole color range of bumblebee pubescence, allowing these insects to use a single precursor instead of synthesizing a variety of chemically different pigments. This would agree with commonly seen color interchanges between body segments across Bombus species.

Genome-Wide Association Shows that Pigmentation Genes Play a Role in Skin Aging

Loss of fine skin patterning is a sign of both aging and photoaging. Studies investigating the genetic contribution to skin patterning offer an opportunity to better understand a trait that influences both physical appearance and risk of keratinocyte skin cancer. We undertook a meta-analysis of genome-wide association studies of a measure of skin pattern (microtopography score) damage in 1,671 twin pairs and 1,745 singletons (N= 5,087) drawn from three independent cohorts. We identified that rs185146 near SLC45A2 is associated with a skin aging trait at genome-wide significance (P= 4.1× 10-9); to our knowledge this is previously unreported. We also confirm previously identified loci, rs12203592 near IRF4 (P= 8.8× 10-13) and rs4268748 near MC1R (P= 1.2× 10-15). At all three loci we highlight putative functionally relevant SNPs. There are a number of red hair/low pigmentation alleles of MC1R; we found that together these MC1R alleles explained 4.1% of variance in skin pattern damage. We also show that skin aging and reported experience of sunburns was proportional to the degree of penetrance for red hair of alleles of MC1R. Our work has uncovered genetic contributions to skin aging and confirmed previous findings, showing that pigmentation is a critical determinant of skin aging.

The Patriotism of Gentlemen with Red Hair: European Jews and the Liberal State, 1789\u20131939

European Jewish history from 1789–1939 supports the view that construction of national identities even in secular liberal states was determined not only by modern considerations alone but also by ancient patterns of thought, behaviour and prejudice. Emancipation stimulated unprecedented patriotism, especially in wartime, as Jews strove to prove loyalty to their countries of citizenship. During World War I, even Zionists split along national lines, as did families and friends. Jewish patriotism was interchangeable with nationalism inasmuch as Jews identified themselves with national cultures. Although emancipation implied acceptance and an end to anti-Jewish prejudice in the modern liberal state, the kaleidoscopic variety of Jewish patriotism throughout Europe inadvertently undermined the idea of national identity and often provoked anti-Semitism. Even as loyal citizens of separate states, the Jews, however scattered, disunited and diverse, were made to feel, often unwillingly, that they were one people in exile.

Skin disorders in Parkinson's disease: potential biomarkers and risk factors.

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, characterized by a symptom triad comprising resting tremor, rigidity, and akinesia. In addition, non-motor symptoms of PD are well recognized and often precede the overt motor manifestations. Cutaneous manifestations as markers of PD have long been discussed, and cumulative evidence shows an increased prevalence of certain dermatological disorders in PD. Seborrheic dermatitis is considered to occur as a premotor feature of PD referable to dysregulation of the autonomic nervous system. Also, an increased risk of melanoma has been observed in PD. Light hair color is a known risk factor for melanoma, and interestingly the risk of PD is found to be significantly higher in individuals with light hair color and particularly with red hair. Furthermore, several studies have reported a high prevalence of PD in patients with bullous pemphigoid. Moreover, a 2-fold increase in risk of new-onset PD has been observed in patients with rosacea. Besides the association between PD and various dermatological disorders, the skin may be useful in the diagnosis of PD. Early PD pathology is found not only in the brain but also in extra-neuronal tissues. Thus, the protein α-synuclein, which is genetically associated with PD, is present not only in the CNS but also in the skin. Hence, higher values of α-synuclein have been observed in the skin of patients with PD. Furthermore, an increased risk of PD has been found in the Cys/Cys genotype, which is associated with red hair color. In this review, we summarize the current evidence of the association between PD and dermatological disorders, the cutaneous adverse effects of neurological medications, and describe the potential of skin protein expression and biomarkers in identification of risk and diagnosis of PD.

Why are red haired individuals so prone to developing melanoma?

Why are red haired individuals so prone to developing melanoma?

Red hair, MC1R variants, and risk for Parkinson's disease - a meta-analysis.

Several studies have been conducted with mixed results since our initial report of increased Parkinson's disease risk in individuals with red hair and/or red hair‐associated p.R151C variant of the MC1R gene, both of which confer high melanoma risk. We performed a meta‐analysis of six publications on red hair, MC1R, and Parkinson's disease. We found that red hair (pooled odds ratios = 1.68, 95% confidence intervals: 1.07, 2.64) and p.R151C (pooled odds ratios = 1.10, 95% confidence intervals: 1.00, 1.21), but not p.R160W, were associated with greater risk for Parkinson's disease. Our results support potential roles of pigmentation and its key regulator MC1R in the pathogenesis of Parkinson's disease.

The Mole Mapper Study, mobile phone skin imaging and melanoma risk data collected using ResearchKit

Sensor-embedded phones are an emerging facilitator for participant-driven research studies. Skin cancer research is particularly amenable to this approach, as phone cameras enable self-examination and documentation of mole abnormalities that may signal a progression towards melanoma. Aggregation and open sharing of this participant-collected data can be foundational for research and the development of early cancer detection tools. Here we describe data from Mole Mapper, an iPhone-based observational study built using the Apple ResearchKit framework. The Mole Mapper app was designed to collect participant-provided images and measurements of moles, together with demographic and behavioral information relating to melanoma risk. The study cohort includes 2,069 participants who contributed 1,920 demographic surveys, 3,274 mole measurements, and 2,422 curated mole images. Survey data recapitulates associations between melanoma and known demographic risks, with red hair as the most significant factor in this cohort. Participant-provided mole measurements indicate an average mole size of 3.95 mm. These data have been made available to engage researchers in a collaborative, multidisciplinary effort to better understand and prevent melanoma.

Association of five SNPs with human hair colour in the Polish population

Twenty-two variants (single nucleotide polymorphisms – SNPs) of the genes involved in hair pigmentation (OCA2, HERC2, MC1R, SLC24A5, SLC45A2, TPCN2, TYR, TYRP1) were genotyped in a group of 186 Polish participants, representing a range of hair colours (45 red, 64 blond, 77 dark). A genotype-phenotype association analysis was performed.Using z-statistics we identified three variants highly associated with different hair colour categories (rs12913832:A>G in HERC2, rs1805007:T>C and rs1805008:C>T in MC1R). Two variants: rs1800401:C>T in OCA2 and rs16891982:C>G in SLC45A2 showed a high probability of a relation with hair colour, although that probability did not exceed the threshold of statistical significance after applying the Bonferroni correction. We created and validated mathematical logistic regression models in order to test the usefulness of the sets of polymorphisms for hair colour prediction in the Polish population. We subjected four models to stratified cross-validation. The first model consisted of three polymorphisms that proved to be important in the associative analysis. The second model included, apart from the mentioned polymorphisms, additionally rs16891982:C>G in SLC45A. The third model included, apart from the variants relevant in the associating analysis, rs1800401:C>T in OCA. The fourth model consisted of the set of polymorphisms from the first model supplemented with rs16891982:C>G in SLC45A and rs1800401:C>T in OCA. The validation of our models has shown that the inclusion of rs16891982:C>G in SLC45A and rs1800401:C>T in OCA increases the prediction of red hair in comparison with the algorithm including only rs12913832:A>G in HERC2, rs1805007:T>C and rs1805008:C>T in MC1R. The model consisting of all the five above-mentioned genetic variants has shown good prediction accuracies, expressed by the area under the curve (AUC) of the receiver operating characteristics: 0.84 for the red-haired, 0.82 for the dark-haired and 0.71 for the blond-haired.A genotype-phenotype association analysis brought results similar to those in other studies and confirmed the role of rs16891982:C>G, rs12913832:A>G, rs1805007:T>C and rs1805008:C>T in hair colour determination in the Polish population. Our study demonstrated for the first time the possibility of a share of the rs1800401:C>T SNP in the OCA2 gene in hair colour determination. Including this single nucleotide polymorphism in the actual hair colour predicting models would improve their predictive accuracy.

Relationship between the melanocortin-1 receptor (MC1R) variant R306ter and physiological responses to mechanical or thermal stimuli in Labrador Retriever dogs

ObjectiveVariants in the MC1R gene have been associated with red hair color and sensitivity to pain in humans. The study objective was to determine if a relationship exists between MC1R genotype and physiological thermal or mechanical nociceptive thresholds in Labrador Retriever dogs. Study designProspective experimental study. AnimalsThirty-four Labrador Retriever dogs were included in the study following public requests for volunteers. Owner consent was obtained and owners verified that their dog was apparently not experiencing pain and had not been treated for pain during the previous 14 days. The study was approved by the Institutional Animal Care and Use Committee. MethodsNociceptive thresholds were determined from a mean of three thermal and five mechanical replications using commercially available algometers. Each dog was genotyped for the previously described MC1R variant (R306ter). Data were analyzed using one-way anova with post hoc comparisons using Tukey’s test (p < 0.05). ResultsThirteen dogs were homozygous wild-type (WT/WT), nine were heterozygous (WT/R306ter), and eight were homozygous variant (R306ter/R306ter) genotype. Four dogs could not be genotyped. A significant difference (p = 0.04) in mechanical nociceptive thresholds was identified between dogs with the WT/WT genotype (12.1±2.1 N) and those with the WT/R306ter genotype (9.2±2.4 N). ConclusionA difference in mechanical, but not thermal, nociceptive threshold was observed between wild-type and heterozygous MC1R variants. Differences in nociceptive thresholds between homozygous R306ter variants and other genotypes for MC1R were not observed. Clinical relevanceCompared with the wild-type MC1R genotype, nociceptive sensitivity to mechanical force in dogs with a single variant R306ter allele may be greater. However, in contrast to the reported association between homozygous MC1R variants (associated with red hair color) and nociception in humans, we found no evidence of a similar relationship in dogs with the homozygous variant genotype.

View from the Lactataion Room at the White House

View from the Lactataion Room at the White House E.A. Farro (bio) We make fast friends—we’re both lost in front of our destination, but it’s so giant we don’t know how or where to enter. The Eisenhower Executive Office Building, housing the executive offices of the White House, takes up four city blocks. It looks like a cross between a castle and a spaceship, a style called Second Empire architecture. “Women’s Energy Summit?” I ask, taking a guess. We fall into step together, both anxious not to be late. In DC, I talk to strangers everywhere: to find out why the train is delayed, because I like their scarf, without reason. This is a city of transients and compulsive networkers; people are as open to meeting as if we were all on a study abroad program. A colleague told me that every conversation should be treated as a job interview, but for me it’s curiosity—I talk to strangers because I can. My new friend, Jessie, is ten years older than me, and far more elegant. She is shy; smiles flicker across her face and disappear. Her suit has a metallic sheen; it fits perfectly over her thin frame. Runner’s legs float inches off the ground on snakeskin heels. Her perfection is made human only by wild red curly hair moving in all directions. [End Page 47] My hair is similarly wild, but in contrast to her feminine sleekness, I still look pregnant. My suit is too tight on the bottom and too big on top—my breasts are oversized canteens of milk. I wear black flats, and my shoulders tilt with the unequal weight of the purse with notebook and business cards on one side and on the other a weekend travel bag with breast pump and all its paraphernalia smashed in. I treat every conference like the apocalypse has happened and I’m forging a new life. Whether it’s a day or a week long, I build a social network as if this event will last forever and I need a posse to survive. It’s as if I can’t conceive of the ephemeral nature of the folding chairs and scheduled keynote. Like Dorothy, I have three key characters in my post-apocalyptic conference world. First, a confidant, the person to sneak out with and go sit in the sun. Second, a Madonna/mother figure, someone who will save me a seat and look out for me (and vice versa). Third, a homeland connection, someone with a tie to the outside world who offers a reality check. For this one-day event, my confidant will be Joe, a twenty-four-year old man interning at the White House who I was told would have the key to the lactation room. My Madonna, Jessie with the red hair, will be the one to bring me into conversations with her large smile. My homeland connection will be another female scientist, new to DC, who like me has no idea how we were invited to this. While I’ll never see the first two again, I will stay in touch with the last; we’ll share a Passover Seder and swap emails over the next several years as we navigate ourselves out of DC and into more permanent lives. The invitation to the White House is a needed beacon of hope. A signal that I’m going in the right direction. Up until eight months ago I was on a different path. For the last decade I’ve been a field scientist. I’m now a staffer in the US Senate. This was the third way, not going into oil in the face of climate change and not crossing my fingers for the next academic gig that wouldn’t pay enough to bridge any future gap in funding. The parting words of congratulations from my postdoctoral mentor were “You know if you leave, you can never come back.” [End Page 48] In field science, dressing up was wearing yoga clothes, or outdoor clothes—pretty much anything from REI. I never owned a purse and felt like a child who’d stolen...

The Minstrel’s Death, and: The Execution, and: Hats Off, and: Epistle to Friends

The Minstrel’s Death, and: The Execution, and: Hats Off, and: Epistle to Friends Vintilă Ivănceanu (bio) Translated by Victor Pambuccian (bio) The Minstrel’s Death My love, I’m thinking of youThe way a prowler longs for an earl’s pocket watch!While in my flesh handcars collide head onAnd horses suffer heart attacks. Do you get to see in mirrors one of your breastsWith that white flag stuck in its flesh?It had been bitten by a vicious dogAnd kissed by William Tell. And your golden hair like a golden coin,Your blue hair, your red hair—Oh! Your hair and your own dead loved ones and AmenAnd when, my love, did you slaughter that rooster of yours? And your hand kissed by lay parishioners,Your stockings with their gracious smellCaught with a lasso like some aged reindeer… And me turned on the third side,The way the dead turns in his graveAnd watches in the earth his wifeMaking love with two men of water. And me, my love, poor me,A coin flipped in the air against bets by a finger,The dead the moment he takes the coin in his mouthTo cross the waters in a one-horse shay. translated from the Romanian by Victor Pambuccian [End Page 58] The Execution IThe pendulum clock ticks inside my bones.So what? I’ll throw my bones to the dogs.My love, don’t water your breasts with rat poisonI’ll grow again teeth and lips.The pendulum clock ticks inside my only suit,Impeccably ironed and brushed.It was raining onRose Street Nr 6With that funeral wheat porridge turned blueAnd with white poet meat.Whoever cries is dumb.Do you pity gramophones?Don’t cry.Don’t bury me,Leave me naked in the middle of the street,This dead body deserves to be hit by passing cars. IIPendulum clock, beware of the poet!For he will tie you to a horseAnd will tie you to himself.He will beat the horse with the hairOf his dead lover.The poet will beat the poetWith the family deadIn alphabetical order.The horse will run to the king of dog catchers,The poet will run to the laboratory dog,And you, pendulum clock, willBreak apart, leaving two pieces,One of which will be pulled by the horseThe other by the poet,To be lead to the king of dog catchers,To be lead astray to the laboratory dog [End Page 59] And the king of dog catchers will judge youFor the birth of the dog catchersAnd the laboratory dog will judge youFor the death of laboratory dogs.And they will sentence youTo be finely ground in the poet’s hat,And the poet will grind you with his elbows,He will squeeze your juice with his teethUntil you will be like dust on furnitureUntil you will become like dust on bootsUntil you will be like dust on the dead. translated from the Romanian by Victor Pambuccian [End Page 60] Hats Off We attach so many wings to our heelsAnd so many dogs commit suicide for us.The jockey alone ends up mutilated,Hallowed, lynched,Like a Madonna caught in bedWith an old weightlifter.Yet we are smiling.Our hunchback fallsInto the garden of a pharmacist…Dogs that took their own lives, winged heels,And the pharmacist is burying the jar with rat poisonUnder the male and female soldier pair.And everything is well-balancedLike the extrapolated, long-time dead.So that’s how things are?Hats off,Hats off to myself,For I was born out of the adultery ofThe Madonna with a weightlifter.Hats off, hats off to myself,For I was born to cure leprosyBy spitting on it poem after poem.I was born to say thatThe dead man is dead that the boil is a boilThat the piano is butcheryThe way the sea is my mother,The way the clocks areThe tip of a cast iron...