A gene family required for human germ cell development evolved from an ancient meiotic gene conserved in metazoans

The Deleted in AZoospermia (DAZ) genes encode potential RNA-binding proteins that are expressed exclusively in prenatal and postnatal germ cells and are strong candidates for human fertility factors. Here we report the identification of an additional member of the DAZ gene family, which we have called BOULE. With the identification of this gene, it is clear that the human DAZ gene family contains at least three members: DAZ, a Y-chromosome gene cluster that arose 30–40 million years ago and whose deletion is linked to infertility in men; DAZL, the “father” of DAZ, a gene that maps to human chromosome 3 and has homologs required for both female and male germ cell development in other organisms; and BOULE, a gene that we propose is the “grandfather” of DAZ and maps to human chromosome 2. Human and mouse BOULE resemble the invertebrate meiotic regulator Boule, the proposed ortholog of DAZ, in sequence and expression pattern and hence likely perform a similar meiotic function. In contrast, the previously identified human DAZ and DAZL are expressed much earlier than BOULE in prenatal germ stem cells and spermatogonia; DAZL also is expressed in female germ cells. These data suggest that homologs of the DAZ gene family can be grouped into two subfamilies (BOULE and DAZL) and that members of the DAZ family evolved from an ancestral meiotic regulator, Boule, to assume distinct, yet overlapping, functions in germ cell development.

Ullrich scleroatonic muscular dystrophy is caused by recessive mutations in collagen type VI

Ullrich syndrome is a recessive congenital muscular dystrophy affecting connective tissue and muscle. The molecular basis is unknown. Reverse transcription–PCR amplification performed on RNA extracted from fibroblasts or muscle of three Ullrich patients followed by heteroduplex analysis displayed heteroduplexes in one of the three genes coding for collagen type VI (COL6). In patient A, we detected a homozygous insertion of a C leading to a premature termination codon in the triple-helical domain of COL6A2 mRNA. Both healthy consanguineous parents were carriers. In patient B, we found a deletion of 28 nucleotides because of an A → G substitution at nucleotide −2 of intron 17 causing the activation of a cryptic acceptor site inside exon 18. The second mutation was an exon skipping because of a G → A substitution at nucleotide −1 of intron 23. Both mutations are present in an affected brother. The first mutation is also present in the healthy mother, whereas the second mutation is carried by their healthy father. In patient C, we found only one mutation so far—the same deletion of 28 nucleotides found in patient B. In this case, it was a de novo mutation, as it is absent in her parents. mRNA and protein analysis of patient B showed very low amounts of COL6A2 mRNA and of COL6. A near total absence of COL6 was demonstrated by immunofluorescence in fibroblasts and muscle. Our results demonstrate that Ullrich syndrome is caused by recessive mutations leading to a severe reduction of COL6.

Sex ratio adjustment in relation to paternal attractiveness in a wild bird population.

When the relative fitness of sons and daughters differs, sex-allocation theory predicts that it would be adaptive for individuals to adjust their investment in different sexes of offspring. Sex ratio adjustment by females in response to the sexual attractiveness of their mate would be an example of this. In vertebrates the existence of this form of sex ratio adjustment is controversial and may be confounded with sex-biased mortality, particularly in sexually size-dimorphic species. Here we use PCR amplification of a conserved W-chromosome-linked gene to show that the sex ratio within broods of a natural population of sexually size-monomorphic collared flycatchers Ficedula albicollis is related to the size of their father's forehead patch, a heritable secondary sexual character implicated in female choice. Experimental manipulations of paternal investment, which influence the size of his character in future breeding attempts, result in corresponding changes in the sex ratio of offspring born to males in those breeding attempts. In contrast, manipulations of maternal investment have no effect on future sex ratios, and there is no relationship between variables predicting the reproductive value of the brood and nestling sex ratio. Analysis of recruitment of offspring reveals similar patterns of sex ratio bias. The results suggest that female collared flycatchers be able to adjust the sex ratio of eggs ovulated in response to the phenotype of their mate. This finding is most consistent with "genetic quality" models of sexual selection.

Isolation and molecular characterization of a human T-cell lymphotropic virus type II (HTLV-II), subtype B, from a healthy Pygmy living in a remote area of Cameroon: an ancient origin for HTLV-II in Africa.

We report characterization of a human T-cell lymphotropic virus type II (HTLV-II) isolated from an interleukin 2-dependent CD8 T-cell line derived from peripheral blood mononuclear cells of a healthy, HTLV-II-seropositive female Bakola Pygmy, aged 59, living in a remote equatorial forest area in south Cameroon. This HTLLV-II isolate, designated PYGCAM-1, reacted in an indirect immunofluorescence assay with HTLV-II and HTLV-I polyclonal antibodies and with an HTLV-I/II gp46 monoclonal antibody but not with HTLV-I gag p19 or p24 monoclonal antibodies. The cell line produced HTLV-I/II p24 core antigen and retroviral particles. The entire env gene (1462 bp) and most of the long terminal repeat (715 bp) of the PYGCAM-1 provirus were amplified by the polymerase chain reaction using HTLV-II-specific primers. Comparison with the long terminal repeat and envelope sequences of prototype HTLV-II strains indicated that PYGCAM-1 belongs to the subtype B group, as it has only 0.5-2% nucleotide divergence from HTLV-II B strains. The finding of antibodies to HTLV-II in sera taken from the father of the woman in 1984 and from three unrelated members of the same population strongly suggests that PYGCAM-1 is a genuine HTLV-II that has been present in this isolated population for a long time. The low genetic divergence of this African isolate from American isolates raises questions about the genetic variability over time and the origin and dissemination of HTLV-II, hitherto considered to be predominantly a New World virus.

Efeitos do consumo materno e/ou paterno de extrato de amora-preta (Rubus spp.) na suscetibilidade da prole feminina à carcinogênese mamária quimicamente induzida

O câncer de mama é o segundo tipo de neoplasia mais prevalente no mundo e o mais comum entre as mulheres. É descrito que o padrão de consumo alimentar materno e paterno está relacionado à suscetibilidade da prole ao desenvolvimento de doenças crônicas não transmissíveis, inclusive o câncer. A amora-preta é uma das frutas com maior conteúdo antioxidante e seus compostos bioativos possuem atividade antioxidante, anticarcinogênica e anti-inflamatória. Sendo assim, o presente trabalho propõe avaliar os efeitos do consumo materno e/ou paterno de extrato de amora-preta (Rubus spp.) na suscetibilidade da prole feminina ao desenvolvimento de neoplasias mamárias quimicamente induzidas. Para tanto, camundongos da linhagem C57BL/6 foram divididos aleatoriamente em 4 grupos: pai amora (PA), mãe amora (MA), pai e mãe amora (PMA) e controle (CTRL). Os pais receberam extrato de amora-preta logo após o desmame durante 8 semanas e as mães receberam o extrato durante a gestação e lactação. O extrato de amora-preta foi administrado na água de beber (0.84g de antocianinas/L) ad libitum. Os pais tratados com extrato de amora apresentaram redução na atividade enzimática da superóxido dismutase (SOD) e da catalase (CAT) no testículo (p<0.05 e p<0.001, respectivamente), aumento na capacidade antioxidante plasmática, na porcentagem de espermatozoides normais e na produção diária de espermatozóides em relação ao grupo controle (p<0.001 para todos). Além disso, os grupos PA, MA e PMA apresentaram aumento na taxa de prenhez (p<0.05) e redução da mortalidade perinatal (p<0.01, p<0.05 e p<0.001, respectivamente). Em relação à prole feminina não submetida à carcinogênese foi observada redução na capacidade antioxidante plasmática nos grupos PA (p<0.001) e MA (p<0.01), enquanto o grupo PMA apresentou aumento nesse parâmetro (p<0.001). No desenvolvimento da glândula mamária, houve aumento do desenvolvimento epitelial nos grupos PA, MA e PMA (p<0.001 para todos), de diferenciação nos grupos MA e PMA (p<0.01 para ambos) e da taxa de apoptose nos grupos MA e PMA (p<0.05), além de redução no número de TEBs nos grupos PA, MA e PMA (p<0.01, p<0.001 e p<0.001, respectivamente). Não foram observadas alterações significativas nas filhas submetidas à indução química da carcinogênese mamária por DMBA. Assim, é possível concluir que apesar de ter alterado o desenvolvimento da glândula mamária, o consumo materno e/ou paterno de extrato de amora-preta não foi capaz de impactar sobre a suscetibilidade da prole feminina à carcinogênese mamária quimicamente induzida.

A Divine Round Trip: the Literary and Christological Function of the Descent/Ascent Leitmotif in the Gospel of John

The thesis of this dissertation is that the Descent/Ascent Leitmotif, which includes the language of not only descending and ascending, but also going, coming, and being sent, performs a significant literary and christological function in the Gospel of John. The Evangelist's Descent/Ascent Leitmotif becomes the Gospel's organizing principal, drawing together a constellation of verbs and a number of themes, including Jesus-Son's origin, identity, relationship to God, authority, signs and works, life, and glory. In the introductory chapter, after providing a layout of the dissertation, the discussion turns to the spacial dimensions and christological importance of the vertical and horizontal depictions of the descending, ascending, coming, going, and being sent verbs. The focus of chapter two is to explain and illustrate, using a version of the Cinderella story, a method that serves to identify the Leitmotif and the verbs, motifs, and themes the Leitmotif draws within its constellation. This approach, titled a thematic structural method, integrates works from thematic scholars Horst Daemmrich and Eugene Falk with works from literary structural scholars A. J Greimas and Roland Barthes, and is a tool to analyze the influence of the Leitmotif as the Gospel's organizing principal on the relationships between the Leitmotif and numerous themes from which John's Christology emerges. The task of chapter three is to explain the rationale for the selection of the Leitmotif's verbs of descending, ascending, coming, going, and being sent. Chapters four and five investigate how the Evangelist, with the repetition of the Leitmotif, constructs his narrative to tell the story of the historical Jesus and shape the Evangelist's Christology. Additionally, the focus is to analyze the transforming influences of the Descent/Ascent Leitmotif on the themes of Jesus-Son's origin, identity, relationship to the Father, and authority, through his signs and works, life, and glory. The Descent/Ascent Leitmotif depicts a divine round trip, and the emphasis of chapter six is to examine the role of the Leitmotif in Jesus-Son's departure from the world and return to God. The Evangelist's use of the Leitmotif in Jesus' prayer to the Father (John 17) and the promise of the Paraclete are included in this chapter. Due to the Descent/Ascent Leitmotif's inherent spatial overtones, elements related to Jesus' return, including heaven, world, the hour, and his form after his resurrection, are explored from a cosmological and ontological perspective.

Gameland: Escape from Pirate Isle, An Exploration in Sequels

A sequel to another novel can be written as its own stand-alone book. Several authors have accomplished this, most notably J.K. Rowling in the early Harry Potter books. Other writers have failed in their attempts. Following Gameland: Warriors and Wizards, the sequel Escape from Pirate Isle is an attempt at writing a stand-alone book. Similar to the first story, Charles and Cindy, who are brother and sister, are magically transported into a board game to rescue their father. While the story was initially intended to stand on its own, in the end it does not, but not because the first novel needs to be read in order to understand it. Instead, it needs a sequel to be a complete story.

Kikulacho [videorecording] =: The bite within

This documentary shows how Kenyan leaders are to blame for the social injustices suffered by Kenyans since the attainment of independence from the British. The issue of land and land clashes, corruption, irregularities in elections and the constitution are some of the highlights of this documentary.

Wale watu

"Paul and Mary are two people who are from different tribes and deeply in love. Their families share a close relationship and everything looks well for their wedding. However, with the out break of the post-election violence. Dr. Sawega, Paul's father, loses his clinic and his brother through arson. Stoked by politicians and tribalists, things get tense between the two families and the entire nation."--Spaceyangu.com.ar

Photostat copy of Cambridge in New England December ..., undated

Long and narrow six-page photostat copy of a manuscript copy of Father Abbey's Will.

Photostat copy of On the Death of Old Abdy Sweeper at Harvard College in Cambridge, undated

Photostat copy of a three-page poem based on Father Abbey's Will, beginning "Ah mournfull found in Abdy ye small is dead / and with him all our ease and joy is fled." There is no provided information about the author, date, or owner of the original volume.

Photostat copy of Cambridge, December 1731. Some time since..., undated

Goodspeed 3, Ford 611.

Photostat copy of Old Timothy Jobson. TO my dear Wife, my Joy and Life, [ca. 1780]

Goodspeed 4, Ford 618.

"Certificate respecting the Rev. John Seccombe," 1795 August

One leaf (pages 301-302) of the August, 1795 issue of Massachusetts Magazine with an editorial regarding the authorship of Father Abbey's Will. The article identifies John Seccombe as the author based on information provided by "Thaddeus Mason, Esq. of Cambridge, the only surviving classmate, and very intimate friend of the Rev. John Seccombe."

Letter from William Croswell to Thomas H. Perkins, 1823 January 17

Draft of a letter inquiring into money due from a meetinghouse owned by Croswell's father.