Yellow Hair Research Articles

Identification of four novel mutations in the phenylalanine hydroxylase gene in patients with PKU

Objective To investigate the distributions of PAH gene mutation and provide guidance for gene diagnosis and prenatal diagnosis of patients with PKU in Xinjiang of China.Methods A total of 15 patients (aged from 2 to 10 years, all with blood Phe concentration over 700 μmol/L) who visited Urumqi general hospital of Lanzhou Command were clinically diagnosed as PKU and were included in this study. PCR followed by DNA sequencing was performed to analyze the promoters, all the 13 exons and their flanking introns of PAH gene in these 15 PKU patients.Results PAH gene of 15 PKU patients was amplified by PCR, and PCR products were subjected to DNA sequencing directly.Four PAH gene mutation types, including 5′- Flanking-626G > A, 5′-Flanking-480DelACT, S196fsX4 and IVS8+1G>C, were identified in each of four PKU patients.Consequently reverse DNA sequencing showed G>A at -626 site, ACT deletion at -480 position in the promoter of PAH gene, an insertion at 584 site in the coding region and G>C at the border between exon 8 and intron 8 of PAH gene, respectively. After inquirying from PAH website and international PAH database (www.pahdb.mcgill.ca), these four PAH gene mutation types were verified as novel PAH gene mutations. Additionally, four patients carrying either of these four PAH gene mutation aged 3-5 years old were characterized by typical clinical phenotypes including blood Phe levels between 1 572-1 782 μmol/L, mental retardation, yellow hair and mousy odor of hair, skin and urine. Conclusions 5′-Flanking-626G>A, 5′-Flanking-480DelACT, S196fsX4 and IVS8+1G > C are identified as four novel PAH gene mutations to cause PKU directly probably either by disrupting the normal 3-D structure and affecting enzymatic activity of PAH or depressing the transcription and translation of PAH gene.Together, our identification of four novel PAH gene mutations will provide important clues for future gene diagnosis and prenatal diagnosis of PKU. Key words: Phenylketonurias; Phenylalanine hydroxylase; Mutation

Love, Beauty, and Yeats's "Anne Gregory"

The speaker of W.B. Yeats's poem, "For Anne Gregory" tells Anne that she is doomed to be loved, not for herself alone, but for her yellow hair. Anne finds this prospect so unappealing that she threatens to dye her hair. Why should Anne be dismayed, and what is it to love someone for herself "alone"? These questions take us to the heart of some crucial philosophical problems of romantic love. Rationality has a place here, but not the place it is usually given. We need to assess the rationality of the beloved, as well as of the lover.

Me and You (review)

Reviewed by: Me and You Deborah Stevenson Browne, Anthony . Me and You; written and illus. by Anthony Browne. Farrar, 2010. 32 p. ISBN 978-0-374-34908-0 $16.99 R 6-9 yrs. Popular wisdom claims that there are two sides to every story, and Browne brings his inimitable style to exploring each side’s view of Goldilocks’ famous excursion into the house of the bears. The narrative begins with the bears, a chipper family that dwells in a butter-yellow house in a sunny, green landscape; the trio is depicted in softly textured colored pencil that conveys innocence through its approximation of coloring-book figures and confidence and roomy ease through the expansive full-page images. Meanwhile, Goldilocks is a contemporary urban girl in a rigidly geometrical, near-monochromatic landscape (her yellow hair just peeps out from under her hoodie) that’s cramped into shrunken panel views. The stylistic difference is particularly marked when the two viewpoints converge: Goldilocks’ view of the suspicious bear trio is structurally parallel to the bears’ take, but the mood is very different indeed. Yet the text, narrated by a Baby Bear somewhat lost and lonely amid the occasionally tense grownup interaction, suggests that there was a bit of an opportunity for connection missed (“I wonder what happened to her?” BB muses as he looks sadly out the window). The result is a work that’s both playfully interpretive and interestingly thought-provoking at a youthful level, raising some easily discussable questions: what would it be like to encounter fairy-tale events in real life? How does point of view affect a narrative? Kids who thought they were well past stories of bear-cottage break-ins will reconsider a story they’ve been taking for granted. [End Page 65] Copyright © 2010 The Board of Trustees of the University of Illinois

Downregulation of SIK2 expression promotes the melanogenic program in mice

cAMP response element-binding protein (CREB) promotes melanogenesis by inducing microphthalmia-associated transcription factor (Mitf ) gene expression. We report here that the CREB-specific coactivator TORC and its repressor, salt-inducible kinase 2 (SIK2), are fundamental determinants of the melanogenic program in mice. Exposure of B16 melanoma cells to ultraviolet (UV) light results in the immediate nuclear translocation of TORC1, which is inhibited by SIK2. Overexpression of dominant-negative TORC1 also inhibits UV-induced Mitf gene expression and melanogenesis. α-MSH signaling regulates hair pigmentation, and the decrease in α-MSH activity in hair follicle melanocytes switches the melanin synthesis from eumelanin (black) to pheomelanin (yellow). Mice with the lethal yellow allele of agouti (A(y)) have yellow hair because of impaired activation of the α-MSH receptor. To examine the involvement of SIK2 in the regulation of the melanogenesis switch in vivo, we prepared SIK2-knockout mice, and the Sik2(-/-) genotype was introduced into A(y)/a mice. The resultant Sik2(-/-); A(y)/a mice had brown hair, indicating that SIK2 represses eumelanogenesis in mice.

Involvement of the Melanocortin-1 Receptor in Acute Pain and Pain of Inflammatory but Not Neuropathic Origin

BackgroundResponse to painful stimuli is susceptible to genetic variation. Numerous loci have been identified which contribute to this variation, one of which, MC1R, is better known as a gene involved in mammalian hair colour. MC1R is a G protein-coupled receptor expressed in melanocytes and elsewhere and mice lacking MC1R have yellow hair, whilst humans with variant MC1R protein have red hair. Previous work has found differences in acute pain perception, and response to analgesia in mice and humans with mutations or variants in MC1R.Methodology and Principal FindingsWe have tested responses to noxious and non-noxious stimuli in mutant mice which lack MC1R, or which overexpress an endogenous antagonist of the receptor, as well as controls. We have also examined the response of these mice to inflammatory pain, assessing the hyperalgesia and allodynia associated with persistent inflammation, and their response to neuropathic pain. Finally we tested by a paired preference paradigm their aversion to oral administration of capsaicin, which activates the noxious heat receptor TRPV1. Female mice lacking MC1R showed increased tolerance to noxious heat and no alteration in their response to non-noxious mechanical stimuli. MC1R mutant females, and females overexpressing the endogenous MC1R antagonist, agouti signalling protein, had a reduced formalin-induced inflammatory pain response, and a delayed development of inflammation-induced hyperalgesia and allodynia. In addition they had a decreased aversion to capsaicin at moderate concentrations. Male mutant mice showed no difference from their respective controls. Mice of either sex did not show any effect of mutant genotype on neuropathic pain.ConclusionsWe demonstrate a sex-specific role for MC1R in acute noxious thermal responses and pain of inflammatory origin.

Measuring cortisol in hair and saliva from dogs: coat color and pigment differences

Cortisol concentrations are frequently measured from a variety of sources including blood, saliva, urine, and feces to quantify stress in dogs. However, a need still exists for less intrusive collection methods in domestic animals and for more efficient means of measuring basal cortisol. The objectives of the present study were to minimize restraint for saliva sampling, to validate hair for basal cortisol measurement in dogs, and to determine concentrations of cortisol within the hair shaft and in relation to hair color. Using food luring, 79% of dogs required no restraint for saliva collection. Salivary and hair cortisol concentrations were positively correlated ( P = 0.001), thus validating hair as a medium for basal cortisol quantification. Black dogs had less cortisol than nonblack dogs ( P = 0.039) in hair, but not saliva. Across dogs, the average amount of cortisol did not differ between proximal and distal hair sections ( P = 0.348). However, for 7 of the 9 dogs, more cortisol was present in the distal portions of the hair. We observed a difference in cortisol concentrations among hairs of different colors from individual dogs ( P = 0.001). From the same 7 × 7 cm ischiatic patch from the same dog, black (eumelanin) hairs were consistently lower in cortisol than yellow (pheomelanin) hairs, and cortisol concentrations of agouti hairs were intermediate. This is the first evidence that hair of different colors might sequester cortisol differently.

Variations in the Coding Region of the Agouti Signaling Protein Gene Do Not Explain Agouti/Non-agouti Phenotypes in Macaques

Agouti is a common pigmentation phenotype in mammals including primates. Mutations in the agouti signaling protein gene (ASIP) are known to result in non-agouti black hairs in laboratory mice. It is still unclear whether sequence variation in ASIP is linked with the agouti/non-agouti phenotypes in macaques (Genus Macaca). To address this issue, we have determined and compared nucleotide sequences of protein coding region of ASIP in 18 macaque species and have identified 16 different sequences of the ASIP. Macaca nemestrina, which showed yellow agouti hairs, shared an identical amino acid sequence of ASIP with several non-agouti species. No sequence changes were found in functionally important sites of ASIP in the macaques showing non-agouti dark hair color. These results indicated that the variation in the protein coding region of ASIP did not explain the non-agouti dark coat color in the macaques. Upstream regulatory regions of ASIP and other genes participating in pigmentation system remain to be investigated for the hair color variation in the macaques.

Fluorescence and coloration of grey hair

Grey hair samples were collected from 11 individuals and separated into un-pigmented and pigmented fibres (International Hair Importers). Fluorescence measurements were obtained by using a double-grating fluorescence spectrophotometer and a bifurcated fibre optics accessory to measure the spectra directly from the surface of hair at various distances from the fibre root. Colour measurements were carried out by using a Hunter colorimeter. The fluorescence spectra of un-pigmented hair obtained by the excitation at 290 nm show a peak at 356 nm [tryptophan (Trp)], and multi-peak emissions in the range from 395 to 500 nm. A significant variation in the Trp emission intensity at 356 nm vs. the intensity of emission in the 395-500 nm range was observed for hair collected from various individuals with yellow coloured hair producing stronger relative emission in 395-500 nm range. Quantitative measurements of coloration and the calculation of the Yellowness Index (YI) showed linear correlation between YI and the ratio of fluorescence intensities I(440)/I(356) The spectra obtained by excitation at 320 nm showed the emission peaks at 395 nm (unidentified), 420 nm (N-formylkynurenine), 460 nm (kynurenine), and 495 nm (3-hydroxykynurenine), which are the products of oxidative or metabolic conversion of tryptophan. Un-pigmented, yellow hair showed a build-up of the fluorescence band corresponding to 3-hydroxykynurenine at 495 nm. The data also showed the fluorescence quenching effect of melanin resulting in the lowering of the fluorescence intensity of pigmented hair. The spectra obtained at various positions along the fibres demonstrated gradual photo-decomposition of hair chromophores during their lifetimes. This was indicated by a decrease of Trp fluorescence intensity, which was relatively fast (8.10(-4)-1.5.10(-3) [day(-1)] as calculated for hair obtained from various individuals) for un-pigmented hair and slower for pigmented hair. A decrease in Trp emission was accompanied by an increase in the yellow coloration toward the ends of un-pigmented fibres.

Chemical analysis of late stages of pheomelanogenesis: conversion of dihydrobenzothiazine to a benzothiazole structure

Pheomelanogenesis is a complex pathway that starts with the oxidation of tyrosine (or DOPA, 3,4-dihydroxyphenylalanine) by tyrosinase in the presence of cysteine, which results in the production of 5-S-cysteinyldopa and its isomers. Beyond that step, relatively little has been clarified except for a possible intermediate produced, dihydro-1,4-benzothiazine-3-carboxylic acid (DHBTCA). We therefore carried out a detailed study on the course of pheomelanogenesis using DOPA and cysteine and the physiological enzyme tyrosinase. To elucidate the later stages of pheomelanogenesis, chemical degradative methods of reductive hydrolysis with hydroiodic acid and alkaline peroxide oxidation were applied. The results show that: (1) DHBTCA accumulates after the disappearance of the cysteinyldopa isomers, (2) DHBTCA is then oxidized by a redox exchange with dopaquinone to form ortho-quinonimine, which leads to the production of pheomelanin with a benzothiazine moiety, and (3) the benzothiazine moiety gradually degrades to form a benzothiazole moiety. This latter process is consistent with the much higher ratio of benzothiazole-derived units in human red hair than in mouse yellow hair. These findings may be relevant to the (photo)toxic effects of pheomelanin.

Transgenic analysis of the physiological functions of Mahogunin ring finger‐1 isoforms

Mahogunin Ring Finger-1 (Mgrn1) null mutant mice have a pleiotropic phenotype that includes the absence of yellow hair pigment, abnormal head shape, reduced viability, and adult-onset spongiform neurodegeneration. Mgrn1 encodes a highly conserved E3 ubiquitin ligase with four different isoforms which are differentially expressed and predicted to localize to different subcellular compartments. To test whether loss of specific isoforms causes different aspects of the mutant phenotype, we generated transgenes for each isoform and bred them onto the null mutant background. Mice expressing only isoform I or III appeared completely normal. Isoform II rescued or partially rescued the mutant phenotypes, whereas isoform IV had little or no effect. Our data show that different Mgrn1 isoforms are not functionally equivalent in vivo and that the presence of only isoform I or III is sufficient for normal development, pigmentation, and neuronal integrity.

Winking Through the Chinks: Eros and Ellipsis in Robert Browning's "Love Among the Ruins"

In 1798, and with spooniness of which not many Victorians would ever consider him capable, Thomas Malthus celebrated love at its most pure that culminating glory which scarcely man who has once experienced [it] does not regard as sunny spot in his whole life, where his imagination loves to bask. (1) Over course of nineteenth century, quantity and popularity of lyric verse that seemed to hold out hope of just such basking in sunshine of pure love increased if in geometrical progression. Another type of poem, however, might cast doubtful or disfiguring shadow over Malthus' sunny spot. Which type of poem we are reading may not be made plain until poem's own point of culmination is reached. becomes place which poem starts. Almost century before T. S. Eliot took up theme, The is where we start from became poetic watchword of Edgar Allan Poe. In his essay of 1846 on The Philosophy of Composition, Poe argued that the end was where all works of art should begin. (2) back-to-front bias of Poe's argument was bound to create keen interest in nature and function of final lines of works. It especially encouraged that kind of concluding line which can be perceived growing logically out of title of work--resuming, reaffirming, extending. In 1850, Nathaniel Hawthorne would Scarlet Letter with just such line: 'ON A FIELD, SABLE, THE LETTER A, GULES.' (3) Soon afterward, Robert Browning would Among Ruins (the poem that stood at beginning of his 1855 collection Men and Women) with what looked like another: is (4) Whereas Hawthorne's final line rolls out prepositional phrase through which to re-approach primary subject of work, Browning's final line discards one. In is best, rises proudly sable field to which poem's title, Among Ruins, seemed originally to be consigning it. Browning, it may easily supposed, bent on blazoning through text poem's red-letter word. Ali else might merely be dark background by which love is emphasized and enhanced--among ruins, Love--or nettles out of which love waits to be plucked, like bright casual flower that H. G. Wells in his picture of Among Wreckage imagines starting up amidst debris of catastrophe. (5) conversion of catastrophe indeed appears complete, ruins are triumphantly topped off with something shown to be good gold. Elsewhere in Browning, means love. (6) Here, however, love is gold's antithesis and superseder. For word visibly succeeds to gold on printed page; symmetry about poem's concluding stanza (or stanzas) (7) makes pivot out of word in turn. While first six lines are pitched toward final six lines of poem move powerfully toward because best has to be saved till last: In one year they sent million fighters forth South and North, And they built their gods brazen pillar high As sky, Yet reserved thousand chariots in full force-- Gold, of course. Oh heart! oh blood that freezes, blood that burns! Earth's returns For whole centuries of folly, noise and sin! Shut them in, With their triumphs and their glories and rest! Love is best. (ll. 73-84) This declaration is reinforced scenically when, in turret marking spot where ruined city's ruler stood to view games, rush to Love, thing, is in corresponding succession to historic rush for gold. Now, it is no monarch who stands there but a girl with eager eyes and yellow hair (l. 55). She is only golden prize for which poem's speaker has eyes. expectation of meeting her there whirls him round and he knows it cannot be long Ere we rush, ere we extinguish sight and speech / Each on each (ll. …

Carotenoid‐based colour polyphenism in a moth species: search for fitness correlates

AbstractCarotenoid‐based integumental coloration is often associated with individual performance in various animals. This is because the limited amount of the pigment has to be allocated to different vital functions. However, most of the evidence for the carotenoid‐based trade‐off comes from vertebrate studies, and it is unclear if this principle can be applied to insects. This possibility was investigated in Orgyia antiqua L. (Lepidoptera: Lymantriidae). The larvae of this species are polyphenic in their coloration, varying from a highly conspicuous combination of yellow hair tufts on black background to cryptic appearance with brown hair tufts. The conspicuous larvae are aposematic, advertising their aversive hairiness. The maintenance of different colour morphs in O. antiqua requires explanation, as an aposematic signal is expected to evolve towards monomorphism. Chromatographic analysis showed that the yellow coloration of the hair is based on the carotenoid pigment lutein (α‐carotene‐3,3’‐diol). The colour of hair tufts was dependent on their carotenoid content. This justifies an expectation of carotenoid‐based physiological trade‐offs between aposematic coloration and individual performance. To test this hypothesis, we monitored life histories of differently coloured larvae reared on various host plants, recording their body sizes, growth rates, and mortalities in each instar. There was a significant but relatively low heritability of tuft coloration, which allowed us to expect environmental effects. We found no phenotypic associations between hair tuft colour and performance indices in O. antiqua larvae, neither did the quality of host plant affect the frequency of colour morphs. However, the frequency of colour morphs differed between larval instars. Our results suggest that carotenoid‐mediated physiological trade‐offs are not involved in the maintenance of colour morphs in O. antiqua larvae, and factors other than individual condition should be responsible for the observed variability.

Introduction: Popular Entertainment and American Theater Prior to 1900

Although Col. George A. Custer's defeat at Little Big Horn on 25 June 1876 was anything but theatrical event, it certainly became one very soon after. By middle of August, theatergoers in New York City were flocking to Wood's Theatre for Harry Seymour's blood-and-thunder re-enactment Sitting Bull; or, Custer's Last Charge. (1) Meanwhile, out on Plains scout and part-time actor and playwright named William F. Buffalo Bill accidentally found himself on 17 July face to face with Cheyenne warrior named Yellow Hair. The two exchanged single, simultaneous blast of gunfire, which only survived. Taking his opponent's scalp in hand, almost immediately began to weave brief skirmish into larger and more complex battle of deliberately taken revenge for Custer, with as hero. Moreover, according to most reports, fought while decked out in a stage costume of black velvet slashed with scarlet and trimmed with silver buttons (2) Although he was at this particular moment in employ of U.S. Fifth Cavalry, had by this time become something of celebrity on East Coast for his highly stylized (some might say cliche-riddled) touring stage reenactments of his own exploits. Thus, his wearing of stage costume both arises from his ongoing interest in performing frontier persona and inflects event with theatrical note. And in autumn of 1876, further embellished importance of skirmish, and hence his reputation, by starring in New York in play he had commissioned about his killing of Yellow Hair called The Red Right Hand, or The First Scalp for Custer. The printed programs for this show reportedly included poetry and news releases about [the Little Big Horn battle], by which Cody and his managers traded on audience's belief that were transmitting news from front, representing events actually unfolding on plains even as spectators sat watching them in Boston, New York, or Omaha. (3) The transmutation of current events into theater represents but one ingredient in United States' long history of imbuing popular modes of entertainment with matters of cultural or national consideration. As further example of this phenomenon, consider Royall Tyler's The Contrast (1787), where character Jonathan goes out in search of circus-like place he had heard of where a hocus pocus man ... could eat case knife only to find himself in proper playhouse watching Sheridan's School for Scandal The joke is that when they lifted up great green cloth Jonathan naively believed he and rest of audience were merely looking right into next neighbor's house (4) The Contrast is generally credited as the first comedy written by an American to be produced professionally and character of Jonathan as first instance of now-familiar Yankee rube character type. (5) Jonathan's misapprehension of nature of space in which he finds himself one evening once again points to relationship between popular theatrical entertainment and crafting of very frameworks within which knowledge of world could be organized or produced. Which is to say, Jonathan's search for performer of tricks leads him and, by extension, those who have come to theater to watch an actor perform this role to lesson in theatrical verisimilitude. In 1993 Gary A. Richardson observed that Whether out of religious, aesthetic, or ideological bias, nation's cultural arbiters have tradition ally been, at best, ambivalent about America's drama and its functions. This is especially true of drama before O'Neill, about which prevailing opinion seems to be that less said better. (6) Fortunately, this assessment is far less true than it may have been decade ago, for much admirable scholarship has in recent years given serious consideration to American theater prior to advent of literary Modernism. (7) Nevertheless, compelling and important questions still remain, among them questions about extent to which developments in American popular entertainment prior to 1900 contributed contemporaneously to culture's questions about such matters as high- and lowbrow art, popularity versus artistic quality, and representation of political and social events as entertainment. …

Recessive yellow in the Mongolian gerbil ( Meriones unguiculatus)

A new autosomal recessive coat color mutant in the Mongolian gerbil ( Meriones unguiculatus) is described: recessive yellow. On the dorsal side the mutant has a rich yellow to ginger color. Ventrally it shows the typical creamy white belly of a wild-type Mongolian gerbil. The dorsal yellow hairs have short black tips, and a light olive green base. A clear demarcation line between dorsal and ventral color is present. Crosses between recessive yellow animals and multiple homozygous recessive tester animals ( a/a; c chm /c chm ; g/g; p/p) resulted only in animals of an agouti (wild-type) phenotype, showing that the new allele is not allelic with any of the known coat color mutations in the Mongolian gerbil. Molecular studies showed that the new mutant is caused by a missence mutation at the extension ( E) locus. On a non-agouti background ( a/a; e/e) mutant animals look like a dark wild-type agouti. In contrast to wild-type agouti it shows yellow pigmentation and dark ticking at the ventral side, resulting in the absence of a demarcation line. Since black pigment is present in both the agouti and non-agouti variant ( A/A; e/e and a/a; e/e), we conclude that recessive yellow in the Mongolian gerbil is non-epistatic to agouti. Additionally we describe a second mutation at the same locus leading to a similar phenotype, however without black pigment and diminishing yellow pigment during life. Fertility and viability of both new mutants are within normal range. The extension ( E) gene is known to encode the melanocortin 1 receptor (MC1R). Interestingly, this is the only gene that is known to account for substantial variation in skin and hair color in humans. Many different mutations are known of which some are associated with higher skin cancer incidence.

Asociación de albinismo oculocutáneo y distrofia granular en una familia

A 35-year-old female patient with blurred vision since childhood, for which no treatment had been given, presented with poor visual acuity. She had white skin and fair yellow hair. There were several well circumscribed deposits in the central and anterior corneal stroma, and iris transillumination and foveal hypoplasia were evident. The clinical diagnosis was oculo-cutaneous albinism and granular corneal dystrophy. We found oculo-cutaneous albinism in two brothers and granular dystrophy in three brothers, the mother and a son. Corneal dystrophy is an autosomal dominant disorder inherited independently of oculocutaneous albinism, which is inherited as an autosomal recessive condition. This is the first case report of granular dystrophy concurrent with oculocutaneous albinism.

Old Woman Magoun

Old Woman Magoun Mary E. Wilkins Freeman The hamlet of Barry's Ford is situated in a sort of high valley among the mountains. Below it the hills lie in moveless curves like a petrified ocean; above it they rise in green-cresting waves which never break. It is Barry's Ford because at one time the Barry family was the most important in the place; and Ford because just at the beginning of the hamlet the little turbulent Barry River is fordable. There is, however, now a rude bridge across the river. Old Woman Magoun was largely instrumental in bringing the bridge to pass. She haunted the miserable little grocery, wherein whiskey and hands of tobacco were the most salient features of the stock in trade, and she talked much. She would elbow herself into the midst of a knot of idlers and talk. "That bridge ought to be built this very summer," said Old Woman Magoun. She spread her strong arms like wings, and sent the loafers, half laughing, half angry, flying in every direction. "Ef I were a man," said she, "I'd go out this very minute and lay the fust log. If I were a passel of lazy men layin' round, I'd start up for once in my life. I would." The men cowered visibly—all except Nelson Barry; he swore under his breath and strode over to the counter. Old Woman Magoun looked after him majestically. "You can cuss all you want to, Nelson Barry," said she; "I ain't afraid of you. I don't expect you to lay ary log of the bridge, but I'm goin' to have it built this very summer." She did. The weakness of the masculine element in Barry's Ford was laid low before such strenuous feminine assertion. Old Woman Magoun and some other women planned a treat—two sucking pigs, and pies, and sweet cake—for a reward after the bridge should be finished. They even viewed leniently the increased consumption of ardent spirits. [End Page 87] "It seems queer to me," Old Woman Magoun said to Sally Jinks, "that men can't do nothin' without havin' to drink and chew to keep their sperits up. Lord! I've worked all my life and never done nuther." "Men is different," said Sally Jinks. "Yes, they be," assented Old Woman Magoun, with open contempt. The two women sat on a bench in front of Old Woman Magoun's house, and little Lily Barry, her granddaughter, sat holding her doll on a small mossy stone near by. From where they sat they could see the men at work on the new bridge. It was the last day of the work. Lily clasped her doll—a poor old rag thing—close to her childish bosom, like a little mother, and her face, round which curled her long yellow hair, was fixed upon the men at work. Little Lily had never been allowed to run with the other children at Barry's Ford. Her grandmother had taught her everything she knew—which was not much, but tending at least to a certain measure of spiritual growth—and she, as it were, poured the goodness of her own soul into this little receptive vase of another. Lily was firmly grounded in her knowledge that it was wrong to lie or steal or disobey her grandmother. She had also learned that one should be very industrious. It was seldom that Lily sat idly holding her doll baby, but this was a holiday because of the bridge. She looked only a child, although she was nearly fourteen; her mother had been married at sixteen. That is, Old Woman Magoun said that her daughter, Lily's mother, had married at sixteen; there had been rumors, but no one had dared openly gainsay the old woman. She said that her daughter had married Nelson Barry and he had deserted her. She had lived in her mother's house, and Lily had been born there, and she had died when the baby was only a week old. Lily's father, Nelson Barry, was the fairly dangerous degenerate of a good old family. Nelson's...

Simulium (Thyrsopelma) duodenicornium, a new black fly species (Diptera: Simuliidae) from the Southeast Region of Brazil

We describe the female, male, pupa, and larva of a new black fly species in the subgenus Thyrsopelma. Males of Simulium duodenicornium n. sp. have a black scutum, without silver bands or patterns, covered with golden yellow hairs. The female scutal pattern is similar to that of most other species in the subgenus Thyrsopelma with a black scutum covered by groups of gray-whitish hairs. Males of the new species can be distinguished by the shape of the ventral plate and females by the shape of the hypogynial valves. The pupa of the new species has 12 short, thick, rigid gill filaments, with highly sclerotized and pointed tips. The pupa is similar to those of Simulium guianense s. l. Wise and Simulium perplexum Shelley, Maia-Herzog, Luna Dias & Couch, but the gill filaments are thicker basally and do not have spicules in an annular arrangement. The larvae are similar to those of most species in the subgenus Thyrsopelma, with ovoid setae covering the body cuticle. The stream in which S. duodenicornium was collected forms part of the headwaters of the Piracicaba River, which is a tributary of the Tietê River. This stream is located in Joanópolis County, São Paulo State, Brazil, in a rainforest area of the Serra da Mantiqueira, in the Atlantic Forest (Mata Atlântica) domain.

Preservation of Eumelanin Hair Pigmentation in Proopiomelanocortin-Deficient Mice on a Nonagouti (a/a) Genetic Background

The original strain of proopiomelanocortin (POMC)-deficient mice (Pomc-/-) was generated by homologous recombination in 129X1/SvJ (A(w)/A(w))-derived embryonic stem cells using a targeting construct that deleted exon 3, encoding all the known functional POMC-derived peptides including alpha MSH, from the Pomc gene. Although these Pomc-/- mice exhibited adrenal hypoplasia and obesity similar to the syndrome of POMC deficiency in children, their agouti coat color was only subtly altered. To further investigate the mechanism of hair pigmentation in the absence of POMC peptides, we studied wild-type (Pomc+/+), heterozygous (Pomc+/-), and homozygous (Pomc-/-) mice on a nonagouti (a/a) 129;B6 hybrid genetic background. All three genotypes had similar black fur pigmentation with yellow hairs behind the ears, around the nipples, and in the perianal area characteristic of inbred C57BL/6 mice. Histologic and electron paramagnetic resonance spectrometry examination demonstrated that hair follicles in back skin of Pomc-/- mice developed with normal structure and eumelanin pigmentation; corresponding molecular analyses, however, excluded local production of alpha MSH and ACTH because neither Pomc nor putative Pomc pseudogene mRNAs were detected in the skin. Thus, 129;B6 Pomc null mutant mice produce abundant eumelanin hair pigmentation despite their congenital absence of melanocortin ligands. These results suggest that either the mouse melanocortin receptor 1 has sufficient basal activity to trigger and sustain eumelanogenesis in vivo or that redundant nonmelanocortin pathway(s) compensate for the melanocortin deficiency. Whereas the latter implies feedback control of melanogenesis, it is also possible that the two mechanisms operate jointly in hair follicles.

Liver-specific expression of the agouti gene in transgenic mice promotes liver carcinogenesis in the absence of obesity and diabetes

BackgroundThe agouti protein is a paracrine factor that is normally present in the skin of many species of mammals. Agouti regulates the switch between black and yellow hair pigmentation by signalling through the melanocortin 1 receptor (Mc1r) on melanocytes. Lethal yellow (Ay) and viable yellow (Avy) are dominant regulatory mutations in the mouse agouti gene that cause the wild-type protein to be produced at abnormally high levels throughout the body. Mice harboring these mutations exhibit a pleiotropic syndrome characterized by yellow coat color, obesity, hyperglycemia, hyperinsulinemia, and increased susceptibility to hyperplasia and carcinogenesis in numerous tissues, including the liver. The goal of this research was to determine if ectopic expression of the agouti gene in the liver alone is sufficient to recapitulate any aspect of this syndrome. For this purpose, we generated lines of transgenic mice expressing high levels of agouti in the liver under the regulatory control of the albumin promoter. Expression levels of the agouti transgene in the liver were quantified by Northern blot analysis. Functional agouti protein in the liver of transgenic mice was assayed by its ability to inhibit binding of the α-melanocyte stimulating hormone (αMSH) to the Mc1r. Body weight, plasma insulin and blood glucose levels were analyzed in control and transgenic mice. Control and transgenic male mice were given a single intraperitoneal injection (10 mg/kg) of the hepatocellular carcinogen, diethylnitrosamine (DEN), at 15 days of age. Mice were euthanized at 36 or 40 weeks after DEN injection and the number of tumors per liver and total liver weights were recorded.ResultsThe albumin-agouti transgene was expressed at high levels in the livers of mice and produced a functional agouti protein. Albumin-agouti transgenic mice had normal body weights and normal levels of blood glucose and plasma insulin, but responded to chemical initiation of the liver with an increased number of liver tumors compared to non-transgenic control mice.ConclusionsThe data demonstrate that liver-specific expression of the agouti gene is not sufficient to induce obesity or diabetes, but, in the absence of these factors, agouti continues to promote hepatocellular carcinogenesis.

TWO NEW SPECIES OF SAUSSUREA SUBGENUS ERIOCORYNE (ASTERACEAE) FROM THE NEPAL HIMALAYA

Two new species, Saussurea bhutkesh and S. kanaii, belonging to subgenus Eriocoryne (DC.) Hook.f., are described from the Nepal Himalaya. S. bhutkesh differs from S. nishiokae Kitam. in having uniseriate scattered phyllaries and golden yellow hairs on the leaves. S. kanaii differs from S. topkegolensis H. Ohba & S. Akiyama in having conspicuously laciniate leaves with dense white tomentose hairs on the abaxial surface. A key is provided to the Nepalese species of the subgenus.