Expression cloning of a cDNA for human ceramide glucosyltransferase that catalyzes the first glycosylation step of glycosphingolipid synthesis.

We have isolated a cDNA encoding human ceramide glucosyltransferase (glucosylceramide synthase, UDP-glucose:N-acylsphingosine D-glucosyltransferase, EC 2.4.1.80) by expression cloning using as a recipient GM-95 cells lacking the enzyme. The enzyme catalyzes the first glycosylation step of glycosphingolipid synthesis and the product, glucosylceramide, serves as the core of more than 300 glycosphingolipids. The cDNA has a G+C-rich 5' untranslated region of 290 nucleotides and the open reading frame encodes 394 amino acids (44.9 kDa). A hydrophobic segment was found near the N terminus that is the potential signal-anchor sequence. In addition, considerable hydrophobicity was detected in the regions close to the C terminus, which may interact with the membrane. A catalytically active enzyme was produced from Escherichia coli transfected with the cDNA. Northern blot analysis revealed a single transcript of 3.5 kb, and the mRNA was widely expressed in organs. The amino acid sequence of ceramide glucosyltransferase shows no significant homology to ceramide galactosyltransferase, which indicates different evolutionary origins of these enzymes.

How the first biopolymers could have evolved.

In this work, we discuss a possible origin of the first biopolymers with stable unique structures. We suggest that at the prebiotic stage of evolution, long organic polymers had to be compact to avoid hydrolysis and had to be soluble and thus must not be exceedingly hydrophobic. We present an algorithm that generates such sequences for model proteins. The evolved sequences turn out to have a stable unique structure, into which they quickly fold. This result illustrates the idea that the unique three-dimensional native structures of first biopolymers could have evolved as a side effect of nonspecific physicochemical factors acting at the prebiotic stage of evolution.

Adherence to the first-AUG rule when a second AUG codon follows closely upon the first.

The rule that eukaryotic ribosomes initiate translation exclusively at the 5' proximal AUG codon is abrogated under rare conditions. One circumstance that has been suggested to allow dual initiation is close apposition of a second AUG codon. A possible mechanism might be that the scanning 40S ribosomal subunit flutters back and forth instead of stopping cleanly at the first AUG. This hypothesis seems to be ruled out by evidence presented herein that in certain mRNAs, the first of two close AUG codons is recognized uniquely. To achieve this, the 5' proximal AUG has to be provided with the full consensus sequence; even small departures allow a second nearby AUG codon to be reached by leaky scanning. This context-dependent leaky scanning unexpectedly fails when the second AUG codon is moved some distance from the first. A likely explanation, based on analyzing the accessibility of a far-downstream AUG codon under conditions of initiation versus elongation, is that 80S elongating ribosomes advancing from the 5' proximal start site can mask potential downstream start sites.

The first extrasolar planet discovered with a new-generation high-throughput Doppler instrument

We report the detection of the first extrasolar planet, ET-1 (HD 102195b), using the Exoplanet Tracker (ET), a new-generation Doppler instrument. The planet orbits HD 102195, a young star with solar metallicity that may be part of the local association. The planet imparts radial velocity variability to the star with a semiamplitude of 63.4 ± 2.0 m s^-1 and a period of 4.11 days. The planetary minimum mass (m sin i) is 0.488MJ ± 0.015M_J. The planet was initially detected in the spring of 2005 with the Kitt Peak National Observatory (KPNO) 0.9 m coudé feed telescope. The detection was confirmed by radial velocity observations with the ET at the KPNO 2.1 m telescope and also at the 9 m Hobby-Eberly Telescope (HET) with its High Resolution Spectrograph. This planetary discovery with a 0.9 m telescope around a V = 8.05 magnitude star was made possible by the high throughput of the instrument: 49% measured from the fiber output to the detector. The ET's interferometer-based approach is an effective method for planet detection. In addition, the ET concept is adaptable to multiple-object Doppler observations or very high precision observations with a cross-dispersed echelle spectrograph to separate stellar fringes over a broad wavelength band. In addition to spectroscopic observations of HD 102195, we obtained brightness measurements with one of the automated photometric telescopes at Fairborn Observatory. Those observations reveal that HD 102195 is a spotted variable star with an amplitude of ~0.015 mag and a 12.3 ± 0.3 day period. This is consistent with spectroscopically observed Ca II H and K emission levels and line-broadening measurements but inconsistent with rotational modulation of surface activity as the cause of the radial velocity variability. Our photometric observations rule out transits of the planetary companion.

The First Child In A Chinese Family Who Could Read Prior To Entry Into Elementary School: A Qualitative Intrinsic Case Study

ABSTRACT This study is an account of the literacy-related human environment a Chinese girl experienced as the first person in the history of her family who was able to read prior to entry into elementary school. Temporally speaking, the study spanned more than a decade from the initial, tentative research question to the formal, primary research question. Spatially speaking, it crossed three cultures: the Chinese, Korean, and American cultures. The study was inspired by the Zero Project in China, known as the "Project of Quality Education and Implementation for Children Aged Zero (fetus) to Six." The significance of the content issue in a child's literacy curriculum was explored in an interdisciplinary way. Case study served as a holistic research approach and provided the researcher with free temporal and spatial distance to pursue the indefinably multi-dimensional intricacies of a child's early literacy acquisition among generations in the family. Interpretation of the case was based on the relevant concepts within the scope of the researcher's knowledge of Chinese culture. Major findings revealed that the child's literacy acquisition was inseparably related to her parents' background as well as their awareness of and attitudes towards literacy, and that the foundation of all this was the harmony of the family. Through the lens of generational attitudes towards literacy and especially the lens of the researcher's multicultural life experiences, this study contributes to the field of curriculum studies in general and early literacy curriculum in particular by stimulating people to reconsider what to read to children, besides how to read to them. It calls attention once again to the classic curriculum question, "What knowledge is of most worth?" as well as what is the most essential spiritual food human beings need besides physical needs. This study suggests that Chinese philosophy should be included in a child's early literacy curriculum in China and calls for dialogues on the content issue of curriculum to gain a deeper understanding of human nature so that humans might co-live peacefully with all beings in the universe.

The Importance of the First Psychotherapy Case in the Development of the Therapist's Professional Self as Viewed Through the Lens of Self Psychology

This paper explores the gap in the literature between what is herein referred to as the "first psychotherapy case" and its impact on the development of the trainee psychotherapist's professional self. The self psychology concepts of identity development, selfobject needs and fulfillment, narcissism, shame, countertransference, and structuralization are incorporated into the theoretical framework from which this developmental milestone is viewed. The theory's emphasis on early experiences and the development of self highlight the distinctiveness of the first case for the therapist. The beginning psychotherapy case poses a unique context for selfobject experiences and the developing self, involving both the therapist's presumably mature needs (assuming an existing cohesive nuclear self) and more infantile needs as the professional, peripheral self develops. As a result, the potential and important implications for the psychotherapist, the patient, training implications for the supervisor, and the ensuing treatment through termination are identified. The intent is to shed light on an area that is understudied thus far, and to begin a conversation as to why and how the impact of the first case on the psychotherapist should be examined. Implications, limitations, and ideas for future exploratory and qualitative research are also discussed.

The First Century of Right to Arms Litigation

This Article examines state court cases involving the right to arms, during the first century following ratification of the Amendment in 1791. This is not the first article to survey some of those cases. This Article includes additional cases, and details the procedural postures and facts, not only the holdings. The Article closely examines how the Supreme Court integrated the nineteenth century arms cases into Heller and McDonald to shape modern Second Amendment law. Part I briefly explains two English cases which greatly influenced American legal understandings. Semayne’s Case is the foundation of “castle doctrine” — the right to home security which includes the right of armed self-defense in the home. Sir John Knight’s Case fortified the tradition of the right to bear arms, providing that the person must bear arms in a non-terrifying manner. Part II examines American antebellum cases; these are the cases to which Heller looked for guidance on the meaning of the Second Amendment. Part III looks at cases from Reconstruction and the early years of Jim Crow, through 1891. As with the antebellum cases, the large majority of post-war cases are from the Southeast, which during the nineteenth century was the region most ardent for gun control. The heart of gun control country was Tennessee and Arkansas; courts there resisted some infringements of the right to arms, but eventually gave up. Heller and McDonald did not look to the Jim Crow cases as constructive precedents on the Second Amendment.

Disquieting Discretion: Race, Geography & the Colorado Death Penalty in the First Decade of the Twenty-First Century

This Article demonstrates through original statistical research that prosecutors in Colorado were more likely to seek the death penalty against minority defendants than against white defendants. Moreover, defendants in Colorado’s Eighteenth Judicial District were more likely to face a death prosecution than defendants elsewhere in the state. Our empirical analysis demonstrates that even when one controls for the differential rates at which different groups commit statutorily death-eligible murders, non-white defendants and defendants in the Eighteenth Judicial District were still more likely than others to face a death penalty prosecution. Even when the heinousness of the crime is accounted for, the race of the accused and the place of the crime are statistically significant predictors of whether prosecutors will seek the death penalty. We discuss the implications of this disparate impact on the constitutionality of Colorado’s death penalty regime, concluding that the Colorado statute does not meet the dictates of the Eighth Amendment to the Constitution.