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Disorders of sex development: new genetic factors and impact of medical genomics
Bashamboo, Anu; McElreavey, Ken
Middle East Journal of Medical Genetics: January 2012 - Volume 1 - Issue 1 - p 5–11
doi: 10.1097/01.MXE.0000407742.94579.b1
Article OutlineOutline
Patients and methods Disorders of sex development (DSD) are congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical and covers a wide spectrum of human urogenital anomalies including gonadal dysgenesis, ambiguous genitalia, or testis development in an XX individual.
Results Although there have been major advances in our understanding of the genetic pathway of human gonadal development, progress in the identification of the underlying genetic basis of DSD has been slow. It has been estimated that a molecular diagnosis is made in only around 20% of DSD, except in cases where the biochemical profile indicates a specific steroidogenic block.
Conclusions This review examines recent advances in identifying genetic cause of DSD with an emphasis on the NR5A1 and GATA4 genes. We also discuss new sequencing approaches and their likely impact on the genetic analyses of DSD.
Human Development Genetics, Institut Pasteur, Paris, France
Correspondence to Anu Bashamboo, Human Developmental Genetics Unit, Institut Pasteur, Paris 75724, France Tel: +00 33 1 4568 8920; fax: +00 33 1 4568 8639;e-mail: anu.bashamboo@pasteur.fr
Received January 21, 2011
Accepted February 20, 2011
Genetic model of human gonad development
Recent advances in our understanding of the genetic causes ...
NR5A1, a key player in human gonad development
GATA4
MAP3K1
Genetic causes of 46, XX testicular or ovotesticular disord...
Impact of medical genomics
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Disorder of sex development (DSD) is defined as 'congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical' (Hughes et al., 2006). DSD therefore covers a very wide spectrum of human phenotypes, and it is divided into a series of subgroups. 46, XY DSD includes 46, XY complete or partial gonadal dysgenesis, or undervirilisation or undermasculinization of an XY male, due to defects in androgen synthesis or action. 46, XX DSD includes gonadal dysgenesis, or more commonly overvirilisation or masculinization of an XX female, due to androgen excess. Ovotesticular DSD refers to an individual with both ovarian and testicular material present in the same or different gonads, and 46, XX testicular DSD refers to an XX male with testes. Other forms of DSD include cloacal exstrophy, severe hypospadias, vaginal atresia, and as part of other conditions such as the Mayer–Rokitansky–Kuster–Hauser syndrome, the Smith–Lemli–Opitz syndrome, or the genito–palato–cardiac syndrome (Porter, 2008; Sultan et al., 2009; Greenberg et al., 1987).
There has been a considerable advance in our understanding of the genetic factors involved in gonadal differentiation in the last 20 years since the SRY gene was first identified as the mammalian testis-determining gene (Fig. 1). However, the identification of new genetic causes of human DSD has not improved substantially in recent years. It has been estimated that a molecular diagnosis is made in only around 20% of DSD, except in cases where the biochemical profile indicates a specific steroidogenic block (Hughes et al., 2006). There is clearly an urgent need to identify new genetic factors involved in DSD. This would not only deepen our knowledge on the etiopathology of these conditions, but it will also lead to accurate and comprehensive molecular diagnosis of hitherto untreatable conditions that are difficult to diagnose.
Disorders of sex development also represent a major burden on public health services. They represent a group of both common (hypospadias) and rare (gonadal dysgenesis) disorders, and in many cases, they require costly and long-term surgical treatment options. For the patients and families with DSD, there are additional concerns. A failure to understand the genetic cause or to offer a correct diagnosis can lead to premature and inappropriate clinical decisions that can lead to irreversible surgical interventions. Sex identity can also be a major concern for patients and families. This review will focus on recent genetic advances in one subset of DSD. These are the pathologies that are due to errors in human sex determination, the choice between the gonad developing as a testis or an ovary, that is, 46, XY complete or partial gonadal dysgenesis and 46, XX testicular or ovotesticular DSD.
Our current knowledge of the genes involved in gonadal development has come mainly from rodent studies and the molecular analysis of human cases of DSD. These have shown that several genes, including Lhx9, NR5A1, Wt1, GATA4, and Fog2 are required for the development of the early genital ridge in the mouse (Fig. 1; Sekido and Lovell-Badge, 2009). Absence of these genes leads to a failure of gonadal development in both female and male embryos. Rodent studies indicate that in the male, SRY acts during a restricted window of time during embryonal development to activate the downstream effector Sox9 (Sekido and Lovell-Badge, 2008). Sertoli cells are one of the first somatic cell lineages to differentiate during testis formation and produce anti-Müllerian Hormone (AMH). SRY expression ensures the differentiation of sufficient Sertoli cells to initiate testicular development by positively regulating Sox9 expression. Once formed, the Sertoli cells coordinate the cellular and morphogenetic events leading to sex determination. This includes the development of Leydig cells, which synthesize and produce the male hormone testosterone, and which differentiate after the appearance of Sertoli cells (Sekido and Lovell-Badge, 2008, 2009). In contrast, ovarian somatic sex determination appears to be relatively labile, with a potential to switch to a testis state. Complete or partial XX male sex-reversal is observed in humans and mice with loss-of-function mutations of the genes WNT4, RSPO1, and Foxl2 (Sekido and Lovell-Badge, 2009). In XX Wnt4−/− mutant embryos, the gonads are partially masculinized, with transient expression of male-specific genes (Sox9) and the presence of Leydig-like cells producing testosterone, and a testis-specific vasculature (Vainio et al., 1999). RSPO1 mutations give an almost identical gonadal phenotype (Tomizuka et al., 2008). In the presence of Wnt, RSPO1 binds to LRP6, a coreceptor of the Wnt receptor frizzled, to stabilize β-catenin. RSPO1 therefore amplifies Wnt signaling, indicating that β-catenin may repress the testis pathway (Fig. 1; Schlessinger et al., 2010). SRY may inhibit β-catenin and promote Sox9 transcription. In mice lacking Foxl2, the expression of several early testis-determining genes including Sox9 are dysregulated, suggesting that it acts as an antitestis gene (Schlessinger et al., 2010). In murine XY ovotestes, the somatic cells express either Sox9 or Foxl2 but never both in the same cell, suggesting that Sox9 suppresses the ovarian pathway in Sertoli cell precursors (Uhlenhaut et al., 2009; Wilhelm et al., 2009). Mammalian sex-determination may therefore involve a battle of the sexes with antagonism between the male-promoting Sox9 pathway and the female-promoting (or male-supressing) Wnt4/Foxl2 pathway(s) in the somatic cell lineage (Fig. 1).
Recent advances in our understanding of the genetic causes of 46, XY gonadal dysgenesis
Complete 46, XY gonadal dysgenesis is characterized by the absence of testicular tissue in gonads, which consists of a streak of fibrous tissue. The phenotype is female, with normal appearance of the external genitalia. These individuals are candidates for carrying mutations in genes involved in the early events of gonadal sex determination. Partial 46, XY gonadal dysgenesis is characterized by the presence of some testicular tissue in the gonads. The external genitalia may be partially masculinized depending on the quantity of testicular material present in the gonads. Although these individuals form distinct clinical groups, we argue that some cases of 46, XY ambiguous external genitalia and infertile male with apparently normal testis may be part of the clinical spectrum of gonadal dysgenesis. The reason for this is two-fold: (a) several pedigrees have been described where the phenotype ranges from 46, XY complete gonadal dysgenesis to simple hypospadias. In some pedigrees, the causative genetic mutation is known and the variation in the severity of the phenotype may be due to other genetic modifiers (Jawaheer et al., 2003; Dumic et al., 2008). (b) Mutations in the same gene, or occasionally the same amino acid change, can be associated with each of the following: 46, XY complete or partial gonadal dysgenesis, 46, XY male with hypospadias, and 46, XY infertile male.
The gene NR5A1, which encodes steroidogenic factor-1, is a pivotal transcriptional regulator of genes involved in the hypothalamic–pituitary–steroidogenic axis (Morohashi et al., 1992; Luo et al., 1994). During early male development, NR5A1 positively regulates the expression of two key genes involved in male sex determination and differentiation: SOX9 (Sry-box 9) and AMH (De Santa Barbara et al., 1998; Sekido and Lovell-Badge, 2008). NR5A1 also modulates the expression of many factors involved in cholesterol mobilization and steroid hormone biosynthesis, including HMG-CoA synthase, steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase, and several cytochrome P450 steroid hydroxylase enzymes (Lin and Achermann, 2008). The NR5A1 protein consists of a DNA-binding domain of two zinc fingers (ZFs), a hinge region, a ligand-binding domain, and two activation function domains (Hoivik et al., 2010). NR5A1 is expressed in the Sertoli and Leydig cells of the developing testis and in Sertoli cells of the prepubertal and adult testis (Morohashi et al., 1994; Hanley et al., 1999). Mice lacking NR5A1 exhibit both gonadal and adrenal agenesis (Luo et al., 1994). Human NR5A1 mutations were first reported in association with 46, XY DSD and adrenal insufficiency, and in a 46, XX girl with adrenal insufficiency (Lin and Achermann, 2008). More recently, the range of phenotypes that are associated with NR5A1 mutations has broadened and includes 46, XY complete and partial gonadal dysgenesis, penoscrotal hypospadias, micropenis with anorchidia, and 46, XX primary ovarian insufficiency (Lin and Achermann, 2008; Köhler et al., 2009; Lourenço et al., 2009).
In a mouse NR5A1 Leydig cell-specific knockout, mice had hypoplastic testes where the lumens of the seminiferous tubules failed to open and spermatogonia never developed into mature sperm (Jeyasuria et al., 2004). These mice also showed reduced expression of two key genes in testosterone biosynthesis: cytochrome P450 steroid hydroxylase 11a and steroidogenic acute regulatory protein (Jeyasuria et al., 2004). We decided to investigate whether NR5A1 mutations could also be associated with some cases of male infertility. Infertility is a major public health burden, with one in seven couples worldwide having problems conceiving (Skakkebaek et al., 2006). In recent years, there has been increasing concern about a possible decline in the reproductive health, and this trend is paralleled by an increasing demand for infertility treatments. In the majority of the cases, the underlying cause of male infertility is unknown although familial clustering of male subfertility and families with multiple infertile or subfertile men, where an autosomal recessive or dominant mutation with sex-limited expression is likely to be present, indicates a substantial genetic contribution (Gianotten et al., 2004). In a mutation screen, we identified mutations in NR5A1 coding sequences in 4% of men with severe spermatogenic failure (azoospermia or severe oligospermia) in otherwise healthy men with normal external genitalia (Bashamboo et al., 2010). In these cases, other known causes of infertility were excluded. This observation is important for several reasons: (a) the data therefore support the hypothesis of Skakkebaek et al. (2006) that a subset of men with spermatogenic failure have a mild form of gonadal dysgenesis (Wohlfahrt-Veje et al., 2009). The gonadal histology in one of our reported case supports this hypothesis (Bashamboo et al., 2010). (b) Our data suggest that this subset of men with severe spermatogenic may also be at risk of endocrine dysfunction and failing testosterone with increasing age. This highlights a need for careful clinical investigation of men presenting with infertility and incongruous testosterone and gonadotropin levels. (c) We demonstrate that approximately 4% of men with otherwise unexplained severe spermatogenic failure carry mutations in the NR5A1 gene, which makes this the most common single gene defect associated with nonobstructive infertility (Bashamboo et al., 2010 and unpublished observations). The data also suggest that some forms of male infertility may be an indicator of mild testicular dysgenesis.
Our data on the role of NR5A1 in a range of gonadal anomalies is particularly informative. We see that the range of phenotypes is large. In the familial cases, we observe normal, apparently healthy men and women carrying mutations that are pathogenic in other individuals (Lourenço et al., 2009). The pathogenic phenotypes range in an XY individual from infertile men with normal appearance of the external genitalia to XY complete gonadal dysgenesis with female external genitalia. In an XX individual, we observed primary amenorrhea and premature ovarian failure. In several patients, the same amino acid change is associated with different phenotypes in different individuals (Lourenço et al., 2009; Bashamboo et al., 2010; unpublished data). This obviously presents a serious challenge in genetic counseling, and it is not yet possible to predict genotype/phenotype correlations. This also highlights the importance of establishing the complete family history in each case of DSD. Other family members with infertility (but apparently normal development of the gonad and external genitalia) may be a sign of a familial case of DSD that warrants further investigation.
GATA4 belongs to the evolutionarily conserved Gata family of sex tissue and organ-specific vertebrate transcriptional regulators, consisting of two ZFs (Patient and McGhee, 2002). The C-terminal ZF is required for recognition and DNA binding, whereas the N-terminal ZF contributes to the stability of this binding.
ZFs are also crucial for protein–protein interactions with other transcription cofactors. In humans, GATA4 is strongly expressed in the somatic cell population of the developing gonad before and during the time of sex determination (Viger et al., 1998). GATA4 cooperatively interacts with several proteins to regulate the expression of the sex-determining genes Sry, Sox9 and Amh, and key steroidogenic factors (Miyamoto et al., 2008; Nishida et al., 2008; Viger et al., 2008). Mice lacking GATA4 die in utero because of profound abnormalities in ventral morphogenesis and heart tube formation (Kuo et al., 1997; Molkentin et al., 1997). In humans, mutations in GATA4 are associated with congenital heart defects (CHD), including atrial septal defects, ventricular septal defects, pulmonary valve thickening, or insufficiency of the cardiac valves (Garg et al., 2003; Hirayama-Yamada et al., 2005; Nemer et al., 2006; Tomita-Mitchell et al., 2007). In all of the cases of CHD associated with mutations in GATA4, other organs were reported as normal.
The critical role of GATA4 in gonadal development is highlighted by Gata4ki mice that have a p.Val217Gly mutation in the N-terminal ZF domain (Bouma et al., 2007). This knock-in mutation abrogates the interaction of GATA4 with the cofactor Fog2, and these animals display severe anomalies in testis development (Crispino et al., 2001; Tevosian et al., 2002). Fog2 may act as a transcriptional repressor or activator, depending on the cellular and promoter context. Mice lacking Fog2 exhibit a block in gonadogenesis, and a translocation involving Fog2 in humans is reported to be associated with male hypergonadotropic hypogonadism (Crispino et al., 2001; Tevosian et al., 2002; Finelli et al., 2007). In vitro, Fog2 represses Gata4-dependent transcription of AMH in primary Sertoli cell cultures (Tremblay et al., 2001). Although the mechanism of Fog2 and GATA4 interaction in the gonad is not well defined, it is essential that a direct physical interaction between GATA4 and Fog2 be maintained, as abrogation of the same results in abnormal testis development in mice (Crispino et al., 2001; Tevosian et al., 2002). We identified a missense mutation in the GATA4 gene (p.Gly221Arg) associated with a familial case of 46, XY DSD and CHD (Fig. 2; Lourenço et al., 2011). The mutation showed altered biological activity. It compromised the ability of the protein to bind to and transactivate the AMH promoter. The mutation did not interfere with the direct protein–protein interaction, but it disrupted synergistic activation of the AMH promoter by GATA4 and NR5A1. The p.Gly221Arg mutant protein also failed to bind to Fog2. Our data demonstrate the key role of GATA4 in human testicular development. This familial case shows that GATA4 mutations may be associated with both syndromic and nonsyndromic forms of 46, XY DSD and that the same GATA4 amino acid change may be associated with more or less severe gonadal phenotypes, suggesting a role of genetic modifiers. However, the overall incidence of GATA4 mutations in 46, XY DSD remains to be determined.
In mammalian cells, a variety of extracellular stimuli generate intracellular signals that activate the mitogen-activated protein kinase cascade (Robinson and Cobb, 1997). Recently, XY sex reversal was described in association with a murine Map3k4 mutation, suggesting a conserved MAP kinase pathway for testis formation (Bogani et al., 2009). Several proteins involved in human sex development, including SRY, are known to be phosphorylated by an mitogen-activated protein kinase-dependent pathway, and in the case of NR5A1 and GATA4, phosphorylation increases their transcriptional activation potential (Desclozeaux et al., 1998; Charron et al., 2001; Desclozeaux et al., 2002). We previously reported a large familial case of 46, XY DSD (Jawaheer et al., 2003). The phenotype in this family shows an autosomal-dominant mode of inheritance, and linkage analysis indicated that the mutation responsible for the phenotype is located in the proximal chromosome 5q (Jawaheer et al., 2003). Further analyses revealed that this family carried a splice donor site mutation in MAP3K1, and that other, unrelated cases of 46, XY DSD, one familial and two sporadic, also carried mutations in the gene (Pearlman et al., 2010). Remarkably, for a gene product with multiple functions, the affected XY individuals had no other obvious phenotype and female carriers were normal. The incidence of MAP3K1 mutations in DSD was estimated to be around 18%.
Genetic causes of 46, XX testicular or ovotesticular disorder of sex development
Approximately 80% of XX testicular DSD (formerly termed XX male) and 10% of ovotesticular DSD (formerly XX true hermaphrodite) carry the SRY gene in their genome, usually present on the X chromosome (McElreavey et al., 1992; McElreavey and Cortes, 2001). The presence of SRY is sufficient in these cases to result in the testicular tissue being present in the gonads (McElreavey and Cortes, 2001). Considerable research attention is currently focused on understanding the genetic causes of SRY-negative cases. Loss-of-function mutations have been described in RSPO1 and WNT4 associated with syndromic forms of these phenotypes (RSPO1, XX male, palmoplantar hyperkeratosis, and predisposition to squamous cell carcinoma of the skin; Parma et al., 2006; WNT4, SERKAL syndrome, Mandel et al., 2008). In the nonsyndromic forms, the genetic cause is unclear. Rearrangements involving either a duplication of Sox9 or deletions in the regulatory elements of the related SOX9 gene have been described (Cox et al., 2011; Sutton et al., 2011), but to date, mutations involving coding sequences of a gene have not been reported. A number of familial cases of XX testicular or ovotesticular DSD have been reported from the Middle East, and these represent an important resource for mutation identification in the future (Jarrah et al., 2000).
In our experience, we find pathogenic mutations in approximately 20% of cases of 46, XY DSD by screening a relatively limited number of candidate genes. In the case of Sry negative XX DSD, the incidence of disease-causing mutations is much less. The identification of genes involved in these pathologies has been difficult to achieve by classical approaches in human genetics. As a key developmental process, it is surprising that the genetic factors involved in sex determination are not well conserved in evolution. The study of sex development in model organisms such as Drosophila or Caenorhabditis elegans has, for the most part, not provided major insights into mammalian sex-determination. Sex-determination is not well conserved even in vertebrates. Sequencing of candidate genes has also not been as fruitful as one would have anticipated. The other classical approach is to use familial cases to map the mutation. Familial cases of gonadal dysgenesis or XX testicular DSD are not widely reported in the literature, although in our experience, many sporadic cases may in fact be unrecognized familial forms of DSD. These difficulties can be overcome using next-generation sequencing (NGS) approaches. The advent of NGS technologies has tremendously reduced the sequencing cost and the experimental complexity involved in large-scale sequencing experiments. NGS technologies now offer excellent template coverage, rendering sequencing-based genome analysis more readily available and useful to individual, small laboratories. These sequencing methods use massively parallel approaches to sequence several hundred thousand to millions of reads simultaneously (Ansorge, 2009; Metzker, 2010). For a review of the technologies and strategies used, see Bashamboo et al. (2010).
NGS technologies offer substantial cost reductions when compared with the Sanger method, but sequencing the whole human genome remains expensive for most laboratories, and the data analyses involved can be challenging. An alternative approach involves targeting specific regions of the genome that are enriched for NGS sequencing: for example, sequencing all of the exons in the genome; sequencing specific gene families of interest; or focusing just on large chromosome regions or entire chromosomes that are implicated in disease. Recently, whole-exome sequencing has become a highly efficient and cost-effective strategy to selectively sequence the coding regions of the human genome to identify novel genes associated with rare and common Mendelian disorders. The goal of this approach is to identify the functional variant that is responsible for the disease without the high costs associated with either whole-genome sequencing or time-consuming sequencing of many potential candidate genes. It is estimated that the protein-coding regions of the human genome constitute about 85% of the disease-causing mutations. With this in mind, exome sequencing has becoming the method of choice in medical genetics for identifying pathogenic mutations in medical genetics with no prior knowledge of the genes involved (Bilgüvar et al., 2010; Johnson et al., 2010; Krawitz et al., 2010; Otto et al., 2010; Pierce et al., 2010; Caliskan et al., 2011; Kalay et al., 2011). Exome capture approaches are available for targeting approximately 50 Mb or ∼180 000 coding exons across the human genome. Many platforms also offer the capture of miRNAs and noncoding RNA sequences. Selective genomic enrichment of the human exome offers an attractive option for devising new experimental designs aimed at quick identification of potential disease-associated genetic variants. Human exome capture methods are currently based on either custom-designed oligonucleotide microarrays or solution-based hybridization strategies. In addition to generating vast amounts of sequence information, the recent NGS applications not only have the ability to generate huge amounts of sequence data but they also reveal structural variation, thereby bypassing the need for CGH analyses (McKernan et al., 2009).
NGS approaches will have a major impact on the understanding and diagnosis of DSD. However, even in 46, XY underandrogenized individuals with a testis, who are suspected to have an androgen receptor defect, a pathogenic mutation is found only in less than half of the cases (Audi et al., 2010). In cases of simple hypospadias or cryptorchidism, a genetic cause is rarely detected despite epidemiological evidence, suggesting a major genetic contribution to these phenotypes (Fukami et al., 2006; Köhler et al., 2009).
Large-scale genomic sequencing approaches also offer the opportunity to identify genetic factors that influence the severity or penetrance of the phenotype. Familial cases of both 46, XY and 46, XX DSD often show considerable variation in the expression of the phenotype, including families where the underlying genetic cause has been identified (Temel et al., 2007; Lourenço et al., 2009). In a pedigree with hypogonadotropic hypogonadism, a compound heterozygous GNRHR and a heterozygous FGFR1 mutation were identified (Pitteloud et al., 2007).
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ambiguous genitalia; disorders of sex development; exome sequencing; gonadal dysgenesis; next generation sequencing
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By Andrew Vachss
Read by Phil Gigante
Andrew Vachss Dreamscape 9780307949578
The Cross Series: Book 1
Cross and his strange but multi-talented crew together form one of the most ruthless and efficient hired guns the world has known. In this first appearance in a novel, they take on an elusive serial killer who no one has ever seen. This savage murderer is leaving a trail of eviscerated bodies all over the world. Despite knowing the Cross team as ultimate mercenaries, a shadowy team of government operatives hires them to track and capture, but not kill, this elusive hunter, When a pattern is finally deduced in the seemingly random strikes, the Cross crew devises an elaborate plan that will put their leader directly into the creature's path.
Cross and his strange but multi-talented crew together form one of the most ruthless and efficient hired guns the world has known. In this first appearance in a novel, they take on an elusive serial killer who no one has ever seen. This savage murderer is leaving a trail of eviscerated bodies all over the world.
Despite knowing the Cross team as ultimate mercenaries, a shadowy team of government operatives hires them to track and capture, but not kill, this elusive hunter, When a pattern is finally deduced in the seemingly random strikes, the Cross crew devises an elaborate plan that will put their leader directly into the creature's path.
Author Bio: Andrew Vachss
Andrew Vachss is a lawyer who represents children and youths exclusively. His many books include the Burke series and two collections of short stories, and his work has appeared in Parade, Antaeus, Esquire, Playboy, and the New York Times, among other publications. A native New Yorker, he divides his time between the city of his birth and the Pacific Northwest.
Category: Fiction/Mystery & Detective
Publisher: Dreamscape

redpajama_set_name: RedPajamaCommonCrawl


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07.09.02 all that's right with our great country
Paul here again, using the shift key and advising everyone to go read Ian McEwan's Atonement pronto. The prose is so good that I cannot quote the prose to demonstrate how good it is. It is far too subtle. Also, I left the book in Reno. But it was a terrible shock to move from that to American Pastoral, 25% of which I read on the Amtrak coming down here. So far I don't know. Very little is happening, and the things that do happen are buried under four stomachs' worth of rumination. (Trenchant and considered rumination, to be sure, but I really dislike essays masquerading as narrative.) It doesn't bother me that Roth feels compelled to put a circle jerk in his idyllic 1950s America—I mean, you expect that sort of thing from the man—but it's a bad sign that said circle jerk, which takes all of two sentences, is actually one of the more memorable events so far. We'll see. Frank Conroy claims it's the best American novel since The Great Gatsby, so maybe Roth's just been clearing his throat so far.
Singing Scrabble: you put down a word, you sing part of a song containing that word. It's harder than you think, and sometimes it leads to inelegancies like "Qat Scratch Fever," and it requires you to drink a lot of red wine so that the next day, when you are in the Middle Eastern restaurant for lunch, your head abruptly folds on itself and your stomach, thrown off balance, tries to reject the tabouleh you've been giving it and for the next three hours you can only lie on the couch and drink tapwater. This requires a change in plans, for I must be a hardy young man to sleep on the beach this weekend.
07.31.02 meu nome e gal i've acquired a lot of poe...
07.26.02 as expected, acquaintances have been kind...
07.20.02 Keep a dream notebook in which, on awaken...
07.10.02 just to watch him die we also commemorate...
07.09.02 all that's right with our great countryPa...


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Parks & Recreation Watch: Season 4 Premiere - I'm Leslie Knope
Published: Sep. 22. 2011 8:07 PM
Parks & Recreation is back and off to quite a start. I was feverishly writing notes and couldn't keep up with the sheer plethora of laughs and tidbits the premiere threw at us.
The plot was simple and straight forward, setting the board for the season, but all the character beats killed from start to finish. Leslie's campaign is thrust forward after our favorite sewage employee sends a picture of his penis to all the women at city hall. Leslie's campaign team sees an opportunity to position herself as a woman, who can't possibly send a picture of her penis to anyone. This forces Leslie's hand with Ben, three months prematurely, and we are treated to possibly the sweetest breakup scene I have ever seen. Adam Scott just nails it and it ends the relationship on as upbeat a note as possible to assure their eventual rekindling. Surely we will see some romantic entanglements along the way though right? It could be interesting to throw a scandal into the race. I am curious, who is Leslie's antagonist going to be and will Tom's company represent them in some capacity?
That's about it for plot though; the rest is all set up. Andy replacing Tom is an interesting choice, don't see him lasting long to be honest, but it will be nice to see Andy do something different (yes I know he has been an assistant for the Parks Department before). I will miss Andy and his antics/interactions at the shoe shine station; who is going to not buy Mouse Rat CD's now.
It takes the whole episode for anything interesting to happen to Ron, besides grow his epic beard in three weeks, but this audit is going to entangle him with the government and Tammy 1 which is basically Ron's worst nightmare. Seeing Ron on the defensive this season is going to allow us to see an interesting side of the character I feel that will allow Nick Offerman to continue to grow one of the funniest characters on TV.
All in all a great start to the season and it really looks like this is the year of, "Leslie 'F***ing' Knope."
Lots of bullets:
-Entertainment 7twenty seems to not do a whole lot in its infancy, but I think the possible Andy/Tom dynamic could be great if Andy ends up working for the upstart.
-Was almost caught off guard by how fast Wiener scandal got used, but they used it to great effect. Anne constantly getting emails and Chris' line, "Your inbox is, literally, filled with penises," took full advantage of the premise. Loved the use of the sound effect on Anne's phone.
-Tom's business card is the best since Patrick Bateman, the magnetism might put him over the top. Oh, and his shoes are something else; leopard print!
-The realization of Ron's emergency pack and the fact that he has apparently never used a vacation day, stocking up over 200, were two more great anecdotes into the legend of Ron Swanson.
-And again, how bout that beard? 3 weeks!
-Of course it is the Sewage Department that started the whole Penis mess, also love how every guy in Pawnee's government is a dirty pervert.
-April taking over for Ron didn't feel like a far stretch, and I especially believe she had complete control over poor Jerry.
-Or maybe not poor Jerry, "biggest penis I have ever seen." Finally a win for Jerry!
-What was up with Rob Lowe's hair?
-Ron hated paperwork already at 12, lost his pinky toe for it, the legend grows further.
-Leslie giving speeches in her sleep is something I hope we get a call back on down the line this season.
And now a landslide of great lines:
-"Too bad, deal with your problems."
-"I really need to shoot a gun." Ron, "Fishing."
-"The whiz palace"
-"Full disclosure, I didn't listen to what you just said."
-"I don't know what you mean, but you had the cadence of a joke."
-"You really know your testes."
-"The testicles are the ears of the genital system, essential but not nice to look at."
-"Go back in times and cut your eyes out."
That is it for this week. Parks & Recreation, arguably the best network comedy, is back and already firing on all cylinders. The episode was fast paced with laugh after laugh coming at you and never letting up. If this is what they have in store for us this year, we are going to be some happy campers.
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gardens, fitness and business centers, and apartments having swimming pools, beauty salons, and a lot more to be enjoyed. All these things you will enjoy when you take an apartment for rent in Raleigh. All the existing apartments of the city are comfortable and in these place as to make visitors love their visit and enjoy in the best perfect manner.
Raleigh apartments that are existed in the hills, in the downtowns, and in the Old Raleigh, are the most beautiful places to reside. Taking an apartment for rent is not only because of the fact that you wishes to live a happy, contented, and satisfied life but also because you can amuse yourself by the neighboring environment when moving around. So you should select this most excellent and top place, full of facilities, to live.
These apartments are excellent for holiday trips. If you like to see historical places, then you must have to take an apartment in Old Raleigh on rent. It comprises of many art galleries and museums. Also, there are entertainment centers, gardens, children museums, and much more that is necessary for holidays. So renting an apartment near all these things is surely a great attraction for the holidays. If you take an apartment there on rent for the whole family, then it will be an expense of 150 to 200 dollars. The apartments here for a family are enough for 5 to 6 people. They can live there easily. In Raleigh, tourists visit in a large amount, so renting apartments have become very common.
Pursuing an apartment is not hard. You just have to find what your requirements are, whether you want to visit alone, or for some business point of view, with family, or just want alone time for u. So if you are there for business point of view, then you must try to pursue an apartment in Downtown. The Old, North, and the West Raleigh all are the top class places for you to reside. So select the locality that you feel is excellent for you and which is replete with facilities. So firstly, choose a price on which you want to take an apartment for rent. This will be easier for you to select the apartment. But mostly, the apartments in Raleigh are inexpensive, so you don't feel any problem for choosing the apartment for rent. You can also see the prices of different apartments on the internet. This will be the most appropriate way for taking an idea for that.
So we can say that the apartments of Raleigh are inexpensive. You can reach them easily and hence they are packed with luxuries that give or offer you a luxurious lifestyle.


NETWORK FINALS: BIG BROTHER and the 8PM rerun of THE GOLDBERGS gained 0.1 in final numbers.
CABLE HIGHLIGHTS: Bravo stayed at the top of a mostly upbeat Wednesday for cable, with REAL HOUSEWIVES OF NYC up a tenth to 0.62, and ODD MOM OUT steady at 0.21. On Discovery, ALASKAN BUSH PEOPLE jumped 0.18 to 0.60, and HOMESTEAD RESCUE ticked up to 0.34. OWN's QUEEN SUGAR gained 0.03 to 0.47. Fox Sports 1's coverage of the CONCACAF GOLD CUP was at 0.47, and Univision's Spanish-language coverage was at 0.31. FX's SNOWFALL had a 0.07 bump to 0.46. On MTV, CATFISH rose 0.09 to 0.46. On VH1, BLACK INK CREW was at 0.45. TBS's FULL FRONTAL returned at 0.42. On HGTV, HOUSE HUNTERS INTL climbed 0.09 to 0.41, HOUSE HUNTERS flew 0.11 to 0.40, and PROPERTY BROS was up 0.03 to 0.36. Lifetime's LITTLE WOMEN LA REUNION was at 0.38, a tick lower than last week. USA's SUITS was steady at 0.36. It was another strong night for MSNBC's RACHEL MADDOW SHOW at 0.36/3M, above Fox News's TUCKER CARLSON TONIGHT at 0.26/2.4M, and CNN's ANDERSON COOPER 360 at 0.20/1.1M. E!'s HOLLYWOOD MEDIUM was up a tenth to 0.30. Spike's LIP SYNC BATTLE ticked down to 0.29. On ID, MURDER BY NUMBERS FELL 0.07 to 0.28, and THE PERFECT MURDER was down 0.08 to 0.24. On TLC, I AM JAZZ held at 0.25, and HAIR GODDESS was down 0.06 to 0.13. Food Network's COOKS VS CONS lost 0.04 to 0.21, and CUTTHROAT KITCHEN ticked up to 0.20. A&E's STORAGE WARS was at 0.20. TV Land's YOUNGER was steady at 0.18. Tru's INSIDE JOKES ticked down to 0.23, then I'M SORRY was at 0.15, after last week's premiere 0.16/0.10. Comedy Central's HOOD ADJACENT rose 0.05 to 0.14. Syfy's BLOOD DRIVE lost a tick to 0.13. In the sub-chart group, BBCAmerica's BROADCHURCH held at 0.04/256K, POP's NIGHTCAP added 0.01 for 0.02/89K, and Sundance's CLEVERMAN was also up 0.01 to 0.02/72K.


text:
Marc Fusion
A concise guide to the world of cinema, tv, and games through the eyes of a sociopath
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Platoon Leader (1988)
Date: February 22, 2018Author: Marc Fusion 0 Comments
Plot: Lt. Jeff Knight (Michael Dudikoff) is fresh out of West Point, but he is thrust into a leadership position in Vietnam, which leads to his men not having much faith in his abilities on the battlefield. The man he assumes control from was not well liked either, as he was determined to do as little as possible and lay low until his tour ended. But Knight is not going to take that approach, as he wants to lead in the field and be a soldier, not someone hiding in the shadows. Even so, he has an uphill climb if he wants to win hearts and minds, especially in this environment. But he tries to bond with the men and prove he is a capable leader, on and off the battlefield, until he is wounded in combat and barely survives. Can he return to his tour and resume command, or is he simply another casualty in this brutal conflict?
Entertainment Value: This one has a lot of potential, as an 80s movie produced by Cannon with Michael Dudikoff in the lead. The movie isn't the b movie action cheese you might expect however, instead Platoon Leader is more of a serious take on war cinema, with some explosive action tossed in. While the action driven elements are fun, the movie is too serious in tone and comes off a little slow at times, so those looking for 80s schlock might be let down. The serious tone isn't an issue itself, but the cast simply isn't up to shouldering a serious premise like this, even Dudikoff struggles with the depth needed for the role. He handles the action scenes, comedic moments, and basic drama well, but stumbles in the more emotional, powerful sequences. The same is true for the rest of the cast, which includes Michael DeLorenzo, Robert F. Lyons, William Smith, and Rick Fitts. When the movie shifts from drama to action, the pace tightens and things pick up, but there's not constant action in this one. I admire the attempt to make an earnest war movie, but given the cast and production values involved, I think Platoon Leader would have been better served as 80s b movie action. But if you're a fan of Dudikoff or Cannon, this is still worth a look.
No nakedness. A little blood, but not much. A few wounds are saturated in the red stuff, but we only see the aftermath, not the kinetic violence. The shoot outs and such are non graphic and have that 80s action feel, so not a grounded, visceral approach to the horrors of war. The action is frequent, with explosions, gun battles, and sieges all on showcase, but as I said above, it is not wall to wall action here. I did appreciate the action scenes, as they liven up the sometimes slow pace and provide some memorable moments. I love how high impact the grenades are, launching people around and we're even treated to a grenade gangbang at one point, which is always fun. The dialogue is fine, but has the serious tone I've mentioned and as such, doesn't give us the kind of wild one liners you might expect from a Dudikoff action flick. I do think it is competent writing, just not overly memorable or quotable. A few fun lines sneak in, just don't count on one liner after one liner here. As for craziness, the serious tone and reeled in action ensures there's little over the top madness here.
Nudity: 0/10
Blood: 1/10
Dialogue: 1/10
Overall Insanity: 0/10
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Aaron NorrisAction MovieKino LorberMichael DeLorenzoMichael DudikoffMoviesPlatoon LeaderRobert F. LyonsThe Cannon GroupWilliam Smith
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text:
Hans Stuck - my heroes
F1 veteran, Nurburgring idol and Le Mans hero Hans Stuck on his personal and racing idols
Formula One veteran, Nurburgring idol and Le Mans hero Hans-Joachim Stuck tells Andrew Frankel who he has admired most in his racing life.
His father, Hans Stuck Sr
"The first has to be my dad," he says, recalling his father's career as a works Auto Union driver, multiple grand prix winner and hillclimb champion. "Racing was in my blood from the day I was born.
"Thanks to him I first drove around the Nürburgring when I was 10 years old, with him sitting next to me in his BMW 700. I think the lap took 40 minutes. He was a wonderful, kind man too."
See pictures from Hans Stuck's career
His mother, Christa Stuck
"She is the most positive person you could ever meet. Her glass is always half full. She came out of the war with not much more than her handbag, but she never looked back.
"She's 88 now, a day hardly ever goes past when I don't speak to her and she's as positive now as she has ever been. It's no exaggeration to say she has been an inspiration to me for my entire life."
"Ronnie Peterson was a fabulous, instinctive driver. When you first drive a new race car you take time to find out what it's like before pushing it.
"Not Ronnie. He'd get in a new car and bam! He'd be quick, really quick on his first lap. We had so much fun together; our driving styles were quite similar and when we were racing against each other it could get really interesting."
"That man could have done anything he wanted. If he had decided to be prime minister, he'd have been prime minister. If I'd paid a bit more attention to the way he went about motor racing, I'd have achieved rather more than I did.
"People call Alain Prost 'the Professor,' but before him came Lauda; he was the first professor of racing."So I ask him who he admires today, and his answer is not what you might expect.
Andy Priaulx
"The guy who has it all is [BMW WTCC driver] Andy Priaulx. He is the complete racing driver. If I were running a race team, whatever and wherever it was racing, the first person I'd sign would be Andy. He's super-quick, never makes mistakes and great company too.
"I'm asked quite often to show people who've never raced there how to get around the Nürburgring and understandably everyone takes a long time figuring it out. Priaulx just got it straight away."
"Every time you go there, there's a new challenge. The circuit changes so much with the weather that it can be different on every lap."
Re: Hans Stuck - my heroes
An out and out racing God!, no question, a racer who could find that extra percent when needed, don't see to many in F1 nowadays, certainly see them in the tin top racers (BTTC,last Sunday) even the Porsche cup races were exciting, lots of passing on a narrow track and certainly no rattle throwers either!


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H-Town, Our Time Is Now
BOB LEVEY/GETTY IMAGES
Lots of people say the key to our success this year has been all the veteran leadership we're getting. I also hear people talk a lot about the confidence we gained from a great start to the season.
And I can see that. Those things are definitely important. But I want to make a case for the fog machine.
We've got this fog machine in the clubhouse, and it's pretty much the greatest thing ever.
When we get a big win in front of our fans at Minute Maid Park, it's the best feeling in the world for us because everyone on the team knows what's coming next.
We shut off all the lights, and get some music going, and then….
It's fog-machine time!
We'll hit the button on that thing and turn on these club lights we got, and then all of a sudden you look around and see the pitchers are all dancing, and the position players are going nuts.
It gets loud in there. It's mostly hip-hop, and Latin music, and reggaeton, but we throw some country in there, too. I'm always requesting Kendrick Lamar, but there's lots of Migos and Daddy Yankee and Ozuna. It's a good mix.
And people don't hold back. No one is judging you or looking to see if you dance right. It's just a big party.
Here's how I would describe it: Just imagine a nightclub, but without the drinks. (Well, I mean, there are drinks. You can still get something to drink. But it's just Gatorade and water.) And at this club you actually like everyone in there. Everyone is one of your friends.
We all love those fog machine nights. They've brought us closer together as a team, and they've been a big part of why this season has been the most fun I've ever had playing baseball.
Sure, Altuve should be named the league's Most Valuable Player, but Fog Machine might just be the team MVP.
Eric Christian Smith/AP Images
And speaking of Altuve….
Let me take a second here to tell you a story that says all you need to know about that guy.
So it's pretty early in the season, sometime in May, and we're playing in Minnesota. José comes up to me and Marwin González. He wants to talk. I'm hitting like .311 at the time. Marwin's also at .311, and José's sitting at .308. So we're all kind of in the same range.
Well, José's got an idea.
"We should make a bet!"
He says we should all agree that whoever gets to .320 first, the other two will have to buy that person something. Like I don't know, I think he said a nice pair of shoes or a dress shirt.
So he has the whole idea all planned out in his head, and he's selling it to us … like exactly how it will all work.
And the entire time, as he's talking, Marwin and I are just looking back and forth at each other like, What's happening here?
When he finally stops talking, I speak up right away.
"I'm not making any bet like that with you! Are you kidding me?"
Marwin is just shaking his head from side to side at this point.
And Altuve's like, "Come on! Why not? It will be fun. And you guys already have a head start."
So I calmly tell José that I've never hit .320 in the majors, and point out that he's someone who has hit over .330 multiple times in the big leagues.
"I don't like throwing my money away, man."
Marwin agrees, and José just kind of makes a face, and then we all go about our business.
The next day, we all show up at the ballpark and Altuve goes out and gets four hits. One. Two. Three. Four. Four hits. Like it was nothing.
And just like that, his average was at .320! The very next day after he wanted us to make that bet.
It was unreal.
Me and Marwin, we knew what was up, though. We're not suckers. We weren't going for it. After the game we both went up to him and were just like, Do you think we don't know who you are or something?
José just smiled at us and walked off to take some cuts in the cage or something.
Michael Zagaris/Getty Images
In all seriousness, what that fog machine, and the dance parties, and that crazy Altuve story all symbolize for me is the togetherness and closeness of this year's team. I really do believe that one of the big reasons we've been so successful is that we're all so tight. It's not one of those things where everyone kind of stays to themselves, or some guys form little groups off to the side. We all hang out together, and play FIFA on the PS4 in the clubhouse before our games, and joke around, and play pranks, and talk smack. ("The 2017 Astros FIFA champion of the world: Carlos Correa … by a mile!")
Here's the thing, though, and this is super important: We're not all jokes.
We know when it's time to get serious, and we know what it takes to prepare day in and day out to play winning baseball. I truly believe that what makes our team special is that we have the perfect mix of fun times and focused preparation.
There are so many guys providing leadership for us right now, but, for me, everything comes back to Carlos Beltrán. In my opinion, that guy is the most respected player in all of baseball, bar none. He's a 20-year veteran, and he's just filled with wisdom. When he talks to anyone — anyone! — they listen. And it doesn't matter if he goes 0 for 4 or 4 for 4, he's going to find ways to help the team.
Carlos has taught me so many things, not just about baseball, but also just about life. We always go out to eat together when we're on the road, and after every one of those meals, when I'm going to sleep that night, I realize that I've learned like 10 new things. At least.
I love that guy, and he's become the heart and soul of this team.
Then when you can not only add Carlos to your ball club, but also players like Brian McCann — who really is the best teammate you could ever imagine — and Charlie Morton and Josh Reddick, and then to add a Cy Young-type pitcher here recently in Justin Verlander … there's just been a huge increase in terms of veteran leadership as compared to last year.
And, to be honest with you, we've needed some strong guys to lean on this season … especially after Harvey rolled through.
Lachlan Cunningham/Getty Images
We were in awe of how this city responded after the storm, and the strength of this Astros ball club is inspired by that same attitude.
These past six weeks have been such an emotional time.
We were on the road when the storm hit, and I was actually in Fresno doing my rehab when Harvey made landfall. So me and my teammates had to watch everything happen on TV knowing that so many of our friends and family members and wives and children were back home facing down those winds.
It was agonizing.
And for me, sitting there in a hotel room watching all the destruction, and the flooding, and the suffering, and seeing all the posts popping up on Twitter … it was just very difficult to be so far away and to try and wrap my head around what was going on. I was just so very sad. (And for me and Carlos and Juan Centeno, it's unfortunately a deep sadness that we'd experience again when Hurricane Maria devastated our native Puerto Rico.)
I couldn't wait to get back to Houston to meet with people, and to give them hugs, and to help out as best I could. And I'll never forget that first series when we returned home after the storm.
We all got together in the clubhouse beforehand and talked about how we wanted to do everything we possibly could to bring some joy to the people of Houston. And when we got out on the field, we felt the love in return. It really went both ways.
We played some of our best ball during that first series back, and as those games were happening, I can tell you that I noticed so many more little things in the stands — the smiles on people's faces when we got a big hit, how happy little kids were to see us, or people calling out our names and just shouting encouragement. All that stuff touched me even more after the storm, and it really showed me, once again, just how special the people of this city are.
At this point, it really feels like we're all just doing the best we can to lift one another up at the same time.
And now, right in the middle of all of that … it's playoff time.
Stephen Dunn/Getty Images
We all know what these next few weeks are going to mean to this town.
And all of us — José, Marwin, Carlos, McCann, Keuchel, Reddick, Springer … all the guys I beat at FIFA … everyone — we're all ready to make something special happen for the city of Houston.
I can't wait to get going, that's for sure. These playoffs, and coming through for this town, are all I've been thinking about recently.
I live here, and so do my parents and many of my closest friends. I love this city with all my heart. Over the past few years, Houston has become my home. And to see this city, our city, go through what it has during the past six weeks has been extremely difficult. To see people — good people, caring people, your neighbors and mine — losing everything, that has been heartbreaking.
But, at the same time, I've also seen the true heart of this place. I've seen the spirit and the kindness and the optimism of this city that I am so proud to call my home. And I'm more convinced than ever that, together, we're going to come back from this tragedy even stronger and more unified.
After the hurricane gave us its best shot, we proved that we are stronger than any storm and that we're at our very best when we all work toward a common goal.
Everyone here joined together to form one big team, and it has been truly amazing. My teammates and I were in awe of how this city responded after the storm, and the strength of this Astros ball club is inspired by that same attitude. We work hard and support one another and overcome any challenges in our path … together.
And, I can tell you this much, if we're able to accomplish what I think we can over these next few weeks, and bring the first World Series title to this great city of ours, the celebration is going to be one for the history books.
Then, years and years later, we'll all be able to tell our grandkids about the incredible playoff run that was part of a year when Houston showed the whole country — the whole world, really — just how tough the people of this city really are.
I am human. Sometimes, in game, I can make it look like I am not. I do things very fast, yes. I work well with my team, yes. I make lots of plays, yes. But I am


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Rexrode: Breaking down MSU's playoff outlook
Joe Rexrode
EAST LANSING – Michigan State is two-thirds through a regular season that will include trips to three of the Big Ten's toughest environments – Ann Arbor, Columbus, Ohio and Lincoln, Neb. – and the memories of a broken-down plane and extra night of makeshift sleep at Rutgers.
It started with a road win over Western Michigan, one of the best teams in the Mid-American Conference. It continued with a home win over Oregon, a top-10 matchup at the time and a score for MSU's scheduling intent if nothing else.
It remains perfect despite more significant, long-term injuries than Mark Dantonio encountered in his first eight MSU seasons combined. It already counts one of the best wins – 27-23 at Michigan on Oct. 17 – achieved among the College Football Playoff hopefuls who will be ranked by the selection committee for the first time Tuesday (7 p.m., ESPN).
And if it finishes with four more wins, followed by a Big Ten championship game victory Dec. 5 in Indianapolis, none of those resume highlights for the No. 6 Spartans (8-0, 4-0 Big Ten) will be needed to make their case for the four-team playoff.
"If Michigan State's unbeaten with a win at Ohio State, they're not just in," said Paul Myerberg, college football writer for USA Today. "That's a No. 1 seed, or close to it."
Rexrode: MSU mailbag gears up for playoff rankings
The posturing comes into play if MSU, which was off Saturday, takes a loss along the way. The last realistic chance to overcome one might be in the Spartans' next game, Saturday at Nebraska.
The idea of MSU losing a competitive game Nov. 21 at No. 1 OSU and sneaking in has faded through the season. But a loss elsewhere and a win in Columbus followed by a Big Ten championship would leave the Spartans with a realistic chance.
"The only loss they could actually afford is a Nebraska loss," said Adam Rittenberg, college football writer for ESPN.com. "It's a late loss but not a super late loss – and the committee won't come out and admit this, but a late loss hurts you more than an early loss."
Though Nebraska is having a rough season, the Cornhuskers had five losses by a combined 13 points entering Saturday, and Lincoln remains one of the league's best environments. MSU's other two games are at home against Maryland (Nov. 14) and Penn State (Nov. 28).
"In this system, quality wins help you way more than bad losses hurt you," Rittenberg said. "In that scenario for Michigan State, you'd be talking about a team with wins over Michigan, Ohio State, Iowa (in the Big Ten title game) and even Oregon. That's a pretty good resume."
And Tuesday will indicate how the committee views MSU's resume to date. The first weekly rankings may not mean much – last season's national champ, Ohio State, was No. 16 initially – but the Spartans will make for an interesting application of the elusive "eyeball test."
Rexrode: Will injuries trip up MSU's title run?
That component of MSU's body of work is why most experts are projecting the Spartans to be outside the top four Tuesday. Entering Saturday's games, the College Football Computer Composite – the old BCS computers – had MSU at No. 5, behind No. 1 LSU, No. 2 Clemson, No. 3 Alabama and No. 4 Ohio State.
Iowa, TCU and Baylor were the next three after MSU. Of those eight teams, only Alabama had a loss entering the weekend. Before Saturday's games, Myerberg projected MSU and Baylor to be just outside the top four, with Ohio State No. 1 and followed in some order by LSU, Clemson and TCU.
Though the preseason loss of star linebacker Ed Davis to a knee injury and multiple hits to MSU's secondary and offensive line have made things more difficult for the Spartans, they've had surprisingly close games with Purdue and Rutgers -- while letting Air Force cut a 28-point lead in half and not putting Central Michigan and Indiana away until the fourth quarter.
Oregon's struggles this season have taken some luster off that win, though the Ducks have consecutive road wins against Washington and Arizona State to improve to 5-3. Oregon has a different look with quarterback Vernon Adams, who was out or ineffective for weeks after making big plays at MSU, and who starred in Thursday's 61-55 triple-overtime win at ASU.
Couch: Sizing up the CFB playoff - Spartans, Big Ten and beyond
Also, scheduling intent is supposed to matter in that committee room.
"You can't penalize Michigan State for the fact that Oregon is not great this season," Rittenberg said. "The committee has said it wants to reward good scheduling, and Michigan State is an example of a team that has tried to do that."
And then there's the win at No. 15 Michigan, which was 5-2 entering Saturday night's game at Minnesota. Of the unbeatens heading into the weekend, Clemson's home win over Notre Dame and LSU's home win over Florida were the most impactful otherwise.
However, some have viewed MSU's win as "fluky," Rittenberg said. The game flipped on the final play, with U-M punter Blake O'Neill dropping the snap, taking a hit and coughing the ball up to MSU's Jalen Watts-Jackson for a 38-yard touchdown return as time expired.
"That's where the human element comes in," Rittenberg said. "It would be fascinating to talk to committee members about how that is viewed. In many ways, Michigan State outplayed Michigan in that game, and it was essentially an even game. But Michigan was in position to win before the last play. Still, it's a win. I would think the coaches on the committee, Barry Alvarez and Tom Osborne, would not under-value a win."
Said Myerberg: "I don't for one second think that win has any less value because of how it ended."
Fox Sports analyst Joel Klatt, though, tweeted that "Michigan State lost in voters' minds," and Big Ten Network analyst Matt Millen called the game an "anomaly."
MSU men's basketball coach Tom Izzo even took a shot at Millen this week for that comment, but Millen is paid to give his opinion. The unpaid College Football Playoff committee of 13 gives the first one that really matters Tuesday.
COLLEGE FOOTBALL PLAYOFF SCHEDULE
Tuesday: The 13-member selection committee will release its first weekly rankings of the top 25 teams in the nation at 7 p.m. on ESPN. The weekly rankings will be released at the same time each week through Dec. 1 (the Nov. 17 rankings will air at 9:30 p.m.)
Dec. 6: The final rankings will be released at noon on ESPN, along with the College Football Playoff semifinal pairings.
Dec. 31: The semifinals, this year at the Orange Bowl and Cotton Bowl, will be played. One will kick off at 4 p.m. and the other at 8 p.m., both airing on ESPN. The Peach Bowl, one of the College Football Bowls that is not a semifinal this year, kicks off at noon on ESPN.
Jan. 1: The other three College Football Playoff bowls not involved in the semifinals this season will be played and air on ESPN – the Fiesta (1 p.m.,) Rose (5 p.m.) and Sugar (8:30 p.m.).
Jan. 11: The College Football Playoff National Championship will be played in Glendale, Ariz. (8:30 p.m., ESPN).


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6 times Jim Carrey was freaking weird (but we loved it anyway)
April 12, 2019 April 11, 2019 J. Belsino 0 Comments jim carrey, list
Jim Carrey—love him or hate him, his career is full of amazing work. Carrey inspired a generation of comedy lovers over the years with incredible on-camera moments. That being said, he's got a bit of a weird streak. He is an actor, and actors aren't actors if they're not at least kinda weird. It almost seems to be part of the gig. Whether it's moments from the Man on the Moon Netflix documentary or tweeting his political paintings, the In Living Color alum fills the role of 'weird actor guy' well, and he does it with such a lovable panache that his fans gobble it up and stick around for more.
Here are six times Carrey was an utter wackadoo, and the world watched with awe and adoration anyway.
When he wrote himself a check for $10 million
In this interview with Oprah Winfrey, Carrey explains how he would park up in the Hollywood Hills and fantasize about being a success, an idea he admitted getting from reading many self-help books. As part of his desire to be successful and manifest a robust career, he wrote himself a check for $10 million for "Acting Services Rendered" that he carried in his wallet until it deteriorated. Slightly odd? Yah. Charming anyway? You're damn right.
When he surprised us with his painting skills
This is the portrait of a so-called Christian whose only purpose in life is to lie for the wicked. Monstrous! pic.twitter.com/MeYLTy1pqb
— Jim Carrey (@JimCarrey) March 17, 2018
It can be confusing when actors decide to change up their careers and try something new. The public has a certain image of the performer in their minds, and then—voila! Now he or she is doing something different like running a restaurant or farming alpacas.
So when Carrey started painting and sharing his work on social media, his fans reacted with understandable praise and criticism of the pieces. One particular painting of Sarah Huckabee Sanders won him extra ire for its depiction of her as a witch-like hag. The Guardian called his work "proof that Hollywood stars should avoid the canvas." The Telegraph called them "terrible satirical portraits". Meanwhile, The Onion's A.V. Club showed him some love and called him "actually really good", another example of Carrey's uncanny ability to skirt disapproval, even following weird behavior.
Though, if his political satire continues in this direction, he might start an international incident.
When Carrey wouldn't stop being Andy Kaufman
Carrey terrorized the cast and crew of the movie Man On The Moon in which he played Andy Kaufman. Carrey committed fully to the role, playing Kaufman-style pranks on actors. He put Danny Devito's car up on blocks. The Ace Ventura star pretty much tormented all involved by "being Andy" every day, whether cameras rolled or not. The antics were so epic that Netflix released a documentary in 2017 called Jim and Andy using real video footage shot by his girlfriend at the time.
When he pissed everyone off at Fashion Week
He pretty much opened with "fuck" in this chin-droppingly awesome interview with E! News during 2017's Fashion Week. His out-of-the-gate comment was, "I wanted to find the most meaningless thing that I could fucking come to", a win for anyone who walks out of an annoying conversation thinking, "I should've said…", because he did, in fact, say exactly what was on his mind. Then, he does a brief James Brown impression and explains that we are just clusters of tetrahedrons moving around together. Some called it a breakdown, but the cool kids screamed with delight through it all.
When he played a big, unfunny sad sack in Kidding
Carrey started his career as a comedic actor but went on to display incredible acting chops through more serious roles, such as Joel Barish in Eternal Sunshine Of The Spotless Mind and Truman Burbank in The Truman Show. So seeing him go back to the small screen where it all started in a role that is depressing and stressful to watch in Kidding felt downright weird to many of his fans. Variety called the series, "Caught between too many tones and ideas" and an Atlantic review stated, "Jim Carrey is wasted on a bleak TV show".
Though the show is indeed well-written and Carrey, as usual, gives an incredible performance as Jeff Pickles—an iconic Mr. Rogers-esque fellow— many watched hoping for more laughter. Still, the 76% rating it earned on Rotten Tomatoes proves that most of the show's audience was not mad, and the audience forgave him for making us sit through such an emotional gut-punch of a show.
When he dated Jenny McCarthy and supported her anti-vaccine crusade
Was Carrey committed to the anti-vax beliefs he spouted during his relationship with Jenny McCarthy, who went on repeated public tirades against them? Or was he simply whipped?
Either way, the comedy icon was forgiven, as he went on to star in dozens of hit films and win the hearts and minds of many—even after using his celebrity power to wax poetic on something as polarizing as the (debunked) evils of vaccinations. Perhaps his apology helped, but one might surmise that he would have sailed through it all, regardless, because he certainly seems to have a get out of jail free card at the ready when he needs one.
Tags: jim carrey, list
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#tiggesanatomy Day 5: Click/tap below to access a "Click on Target" quiz for Aortic arch/neck anatomy.
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Dr. Forrest's Cheeze Factory: Got Dat E-Vil Mikelj Over A Barrel!
Here we see the E-Vil Mikelj's latest business endeavor!
Seems quite pleased with himself, eh?
You, the consumer, have foiled him again!
Not so pleased with himself now, eh?


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Our Pool Access Deluxe rooms include: 1-bedroom, 1-bath with a rain shower. These 21 generously-sized rooms (50 sqm) allow you direct access to the lap pool. With the open of your door the cool refreshing water beckons you for a morning, afternoon, or night swim.
Our Ocean Sunset Villas include: 1-bedroom, 1-bath, and living area. Our 8 sunset villas (110 sqm) are surrounded by green gardens and breathtaking ocean and sunset views.
Our Ocean Private Pool Villas include: 1-bedroom, 1-bath with bathtub, rain shower, and living area. Our 4 villas (110 sqm) offer a private swimming pool and breathtaking panoramic views of the Andaman Sea and Phi Phi Island.
Our Grand Villa Residence (235 sqm) includes: 2-bedrooms, 2-baths, 2 living areas, kitchenette, private swimming pool, and outdoor deck area. Ideally perched atop the peak of the island, this suite offers views of both the sunrise and sunset. A unique wedding venue or a memorable honeymoon destination with romantic views of the Andaman Sea, coastline, and neighboring islands.
Massages, Body Scrubs, Facials, Manicures, Pedicures, Milk Baths, and Saunas � we have what you need to unwind, relax, and rejuvenate your body. All treatments are expertly administered amid a relaxing, tranquil private suite.
Plan your next company retreat, conference, or meeting with Crown Lanta. Our state-of-the-art meeting room (150 sqm) can accommodate up to 100 people.
*Prices shown are standard prices, may be negotiable depending on the party size and menu. The full day meeting package is inclusive of two coffee/tea breaks and lunch, as well as the room with the standard A/V equipment. The half day meeting package includes one coffee/tea break, lunch, and the room with the standard A/V equipment.
Koh Lanta, located off the western coast of Krabi, is a popular island for tourists. This once backpacker heaven in the 80s, has now evolved into a more up-market destination with the four and five-star resorts attracted to the island�s beautiful, sandy beaches, natural forests, and the crystal clear water.
Koh Lanta is actually a national park, with 81% of its boundary being marine, both with deep and shallow corals. The entire archipelago is made up of more than 50 small islands, while only three are inhabited: Lanta Yai, Lanta Noi, and Koh Ngai. Koh Lanta Yai is most attractive to visitors due to its impressieve beaches and myriad of activities available. If you�re looking for a relaxing, tropical island holiday, Koh Lanta is the answer.
The island, with its 9 beaches and National Park, offers many activities, some of which include: snorkeling, sea cave and/or mangrove kayaking, fishing, elephant trekking, hiking, sightseeing, and shopping in Lanta Old Town & Saladan.
Half-day and full-day tours are available at the hotel tour desk and may be booked upon arrival.