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Biomedical subjects

D J Klein

Publications and source records attributed to D J Klein.

At least 19 recordsLinked to original sources
PubMed2004

The roles of ribosomal proteins in the structure assembly, and evolution of the large ribosomal subunit.

The structures of ribosomal proteins and their interactions with RNA have been examined in the refined crystal structure of the Haloarcula marismortui large ribosomal subunit. The protein structures fall into six groups based on their topology. The 50S subunit proteins function primarily to stabilize inter-domain interactions that are necessary to maintain the subunit's structural integrity. An extraordinary variety of protein-RNA interactions is observed. Electrostatic interactions between numerous arginine and lysine residues, particularly those in tail extensions, and the phosphate groups of the RNA backbone mediate many protein-RNA contacts. Base recognition occurs via both the minor groove and widened major groove of RNA helices, as well as through hydrophobic binding pockets that capture bulged nucleotides and through insertion of amino acid residues into hydrophobic crevices in the RNA. Primary binding sites on contiguous RNA are identified for 20 of the 50S ribosomal proteins, which along with few large protein-protein interfaces, suggest the order of assembly for some proteins and that the protein extensions fold cooperatively with RNA. The structure supports the hypothesis of co-transcriptional assembly, centered around L24 in domain I. Finally, comparing the structures and locations of the 50S ribosomal proteins from H.marismortui and D.radiodurans revealed striking examples of molecular mimicry. These comparisons illustrate that identical RNA structures can be stabilized by unrelated proteins.

Animals↗
PubMed2001

The kink-turn: a new RNA secondary structure motif.

Analysis of the Haloarcula marismortui large ribosomal subunit has revealed a common RNA structure that we call the kink-turn, or K-turn. The six K-turns in H.marismortui 23S rRNA superimpose with an r.m.s.d. of 1.7 A. There are two K-turns in the structure of Thermus thermophilus 16S rRNA, and the structures of U4 snRNA and L30e mRNA fragments form K-turns. The structure has a kink in the phosphodiester backbone that causes a sharp turn in the RNA helix. Its asymmetric internal loop is flanked by C-G base pairs on one side and sheared G-A base pairs on the other, with an A-minor interaction between these two helical stems. A derived consensus secondary structure for the K-turn includes 10 consensus nucleotides out of 15, and predicts its presence in the 5'-UTR of L10 mRNA, helix 78 in Escherichia coli 23S rRNA and human RNase MRP. Five K-turns in 23S rRNA interact with nine proteins. While the observed K-turns interact with proteins of unrelated structures in different ways, they interact with L7Ae and two homologous proteins in the same way.

Amino Acid Sequence↗
PubMed2001

Directed self-avoiding walks in random media.

Two types of directed self-avoiding walks (SAW's), namely, three-choice directed SAW and outwardly directed SAW, have been studied on infinite percolation clusters on the square lattice in two dimensions. The walks on the percolation clusters are generated via a Monte Carlo technique. The longitudinal extension R(N) and the transverse fluctuation W(N) have been measured as a function of the number of steps N. Slight swelling is observed in the longitudinal direction on the random lattices. A crossover from shrinking to swelling of the transverse fluctuations is found at a certain length N(c) of the walks. The exponents related to the transverse fluctuations are seen to be unchanged in the random media even as the percolation threshold is reached. The scaling function form of the extensions are verified.

Journal Article↗
PubMed2001

Structural characterization of quinoxaline homopolymers and quinoxaline/ether sulfone copolymers by matrix-assisted laser desorption ionization mass spectrometry.

Polyphenylquinoxalines (PPQs) are prepared from self-polymerizable quinoxaline monomers that carry fluorine, hydroxyaryl (ArOH), and phenyl substituents. In basic media, these monomers self-polymerize via a series of nucleophilic aromatic substitution reactions (SNAr), in which aromatic enolates (ArO- nucleophiles) attack the electrophilic carbons bearing F leaving groups to effect fluoride displacement. Polyphenylquinoxaline/polyether-sulfone (PPQ/PES) copolymers are synthesized similarly by combining self-polymerizable quinoxaline monomers with a 1:1 molar mixture of 4,4'-dichlorodiphenyl sulfone and bisphenol A. The MALDI mass spectra of the polymers reveal that the major products up to approximately 15,000 Da molecular mass are homo- or copolymeric macrocycles. Linear byproducts are also observed, arising from nucleophilic ring opening of already formed macrocycles. Oligomers containing at least one PPQ unit readily protonate upon MALDI, whereas PES homopolymers require alkali metal ion addition to become detectable. Molecular orbital calculations point out that the nucleophilic and electrophilic reactivities of the PPQ monomer and the PPQ growing chains generated during propagation are comparable, allowing for continued condensations via SN-Ar, until cyclization terminates this process. The calculations also predict a significantly lower electrophilic reactivity for carbons substituted by chlorine instead of fluorine, justifying the discrimination against incorporation of PES units observed for the copolymers. The computationally optimized structures of PPQ and PPQ/PES macrocycles show a diverse array of cavity sizes and geometries which depend on the size of the macrocycle, the sequence of the repeat units, and the position of the substituents in the quinoxaline ring; quinoxaline pendants (phenyl groups) are found to favor helical arrangements in the prepared macrocycles.

Journal Article↗
PubMed2001

Predictors of late-onset smoking and cessation over 10 years.

PURPOSE: To identify predictors of smoking onset and cessation between early (age 13 years) and late adolescence (age 18 years) and between late adolescence (age 18 years) and young adulthood (age 23 years). METHODS: We employed logistic regression to predict smoking initiation and cessation for an ethnically diverse sample of 3056 adolescents recruited from 30 West Coast schools in 1985 and observed from age 13 to age 23 years. Fifty-six percent of the sample was female. Predictors tapping sociodemographic characteristics, environmental influences, attitudes and beliefs about smoking, bonds with school, and problem behavior were measured at age 13 years (older teenager models) and at age 18 years (young adult models). RESULTS: Robust predictors of both initiation and cessation across the two developmental periods included doing poorly in middle/high school and prior smoking behavior. Predictors common to three of the four models included being young for one's grade cohort and intending to smoke in the next 6 months. Early deviant behavior and drinking fostered initiation among older teenagers, but problem behavior as an older teenager did not predict young adult initiation. Smokers who had few or no high school friends who smoked and felt able to resist prosmoking pressures at age 18 years were more likely to quit by age 23 years. Being female predicted initiation by age 18 years; being African-American, Hispanic, or Asian inhibited it. CONCLUSIONS: The strong association of prior smoking behavior and intentions with later smoking status among both adolescents and young adults underscores the importance of starting smoking prevention early and continuing it through high school. Such programs might also consider the greater vulnerability of females, youth who are young for their grade cohort, and those who are doing poorly in school.

Adolescent↗
PubMed2001

High-risk behaviors associated with early smoking: results from a 5-year follow-up.

PURPOSE: To compare grade 7 nonsmokers, experimenters, and smokers on the basis of prevalence of other problem behaviors at both grade 7 and grade 12. METHODS: Based on longitudinal self-report data from 4327 California and Oregon students, we used logistic regression to develop weighted estimates of the prevalence of academic difficulties, substance use, and delinquent behavior within the three smoking status groups at grades 7 and 12. Huber variance estimates, which adjust for weighting and clustering of observations, were used to assess the statistical significance of differences across groups. RESULTS: Compared with nonsmokers, early smokers were at least 3 times more likely by grade 12 to regularly use tobacco and marijuana, use hard drugs, sell drugs, have multiple drug problems, drop out of school, and experience early pregnancy and parenthood. These adolescents were also at higher risk for low academic achievement and behavioral problems at school, stealing and other delinquent behaviors, and use of predatory and relational violence. Early experimenters were at significantly greater risk for these problems as well, although to a lesser extent than smokers. Importantly, the higher risk among experimenters and smokers of experiencing many of these problems was evident as early as grade 7. CONCLUSIONS: Early experimenters and smokers are more likely than nonsmokers to experience various problem behaviors by grade 12, with many of these problems evident as early as grade 7. Results suggest that substance use programs that target multiple problems in addition to smoking may be most effective for these high-risk adolescents.

Adolescent↗
PubMed2001

Curvature matching and strain relief in bucky-tori: usage of sp3-hybridization and nonhexagonal rings.

The relief of different types of curvature strain in bucky-tori of elemental carbon is considered in a general formal framework. This theory then is used to aid in the design of several structures, which are treated via molecular mechanics. Novel illustrations of the remnant strain are made, and some modest conclusions as to the nature of the structure of the experimentally observed bucky-tori are suggested.

Carbon↗
PubMed2001

Quantitative structure-retention relationships for gas chromatographic retention indices of alkylbenzenes with molecular graph descriptors.

Quantitative structure-retention relationships (QSRR) represent statistical models that quantify the connection between the molecular structure and the chromatographic retention indices of organic compounds, allowing the prediction of retention indices of novel, not yet synthesized compounds, solely from their structural descriptors. Using multiple linear regression, QSRR models for the gas chromatographic Kováts retention indices of 129 alkylbenzenes are generated using molecular graph descriptors. The correlational ability of structural descriptors computed from 10 molecular matrices is investigated, showing that the novel reciprocal matrices give numerical indices with improved correlational ability. A QSRR equation with 5 graph descriptors gives the best calibration and prediction results, demonstrating the usefulness of the molecular graph descriptors in modeling chromatographic retention parameters. The sequential orthogonalization of descriptors suggests simpler QSRR models by eliminating redundant structural information.

Alkylation↗
PubMed2001

Quantitative structure-property relationships generated with optimizable even/odd Wiener polynomial descriptors.

Chemical structures of organic compounds are characterized numerically by a variety of structural descriptors, one of the earliest and most widely used being the Wiener index W, derived from the interatomic distances in a molecular graph. Extensive use of distance-based structural descriptors or topological indices has been made in QSPR and QSAR models, drug design, toxicology, virtual screening of combinatorial libraries, similarity and diversity assessment. Novel topological indices are introduced representing a partitioning of the Wiener polynomial based on counts of even and odd molecular graph distances. During the QSAR/QSPR modeling process the variables of the even and odd power functions are optimized in order to offer an improved mapping of the investigated property. These novel topological indices are tested in QSPR models for the boiling temperature, molar heat capacity, standard Gibbs energy of formation, vaporization enthalpy, refractive index, and density of alkanes. In many cases, the even/odd Wiener polynomial indices proposed here give notably improved correlations or suggest simpler QSPR models.

Chemical Phenomena↗
PubMed2001

Spectro-temporal response field characterization with dynamic ripples in ferret primary auditory cortex.

To understand the neural representation of broadband, dynamic sounds in primary auditory cortex (AI), we characterize responses using the spectro-temporal response field (STRF). The STRF describes, predicts, and fully characterizes the linear dynamics of neurons in response to sounds with rich spectro-temporal envelopes. It is computed from the responses to elementary "ripples," a family of sounds with drifting sinusoidal spectral envelopes. The collection of responses to all elementary ripples is the spectro-temporal transfer function. The complex spectro-temporal envelope of any broadband, dynamic sound can expressed as the linear sum of individual ripples. Previous experiments using ripples with downward drifting spectra suggested that the transfer function is separable, i.e., it is reducible into a product of purely temporal and purely spectral functions. Here we measure the responses to upward and downward drifting ripples, assuming reparability within each direction, to determine if the total bidirectional transfer function is fully separable. In general, the combined transfer function for two directions is not symmetric, and hence units in AI are not, in general, fully separable. Consequently, many AI units have complex response properties such as sensitivity to direction of motion, though most inseparable units are not strongly directionally selective. We show that for most neurons, the lack of full separability stems from differences between the upward and downward spectral cross-sections but not from the temporal cross-sections; this places strong constraints on the neural inputs of these AI units.

Acoustic Stimulation↗
PubMed2001

Prospective risk factors for alcohol misuse in late adolescence.

OBJECTIVE: This longitudinal study investigated Grade-7 and Grade-10 risk factors for alcohol misuse at Grade 12. Alcohol misuse was conceptualized as problem-related drinking (e.g., missing school), high-risk drinking (e.g., drunk driving) and high consumption. METHOD: Prospective analyses using two-part models predicted any alcohol misuse and the amount of misuse (given that some has occurred) for over 4,200 (52% male) participants in the RAND Adolescent Panel Study. Predictor variables were demographics, substance use and exposure, prodrug attitudes, rebelliousness and deviant behavior, self-esteem, family structure and relations, and grades. RESULTS: Grade-7 predictors of alcohol misuse 5 years later included early drinking onset, parental drinking, future intentions to drink, cigarette offers, difficulty resisting pressures to smoke, being white, being male, having an older sibling, deviant behavior and poor grades. By Grade 10, predictors of alcohol misuse 2 years later included drinking and marijuana use by self and peers, future intentions to drink, difficulty resisting pressures to drink and use marijuana, being male, coming from a disrupted family and deviant behavior. Somewhat different predictors were identified for problem-related, high-risk and high consumption drinking, emphasizing the importance of investigating multiple dimensions of misuse. CONCLUSIONS: The high social acceptability of alcohol use makes prevention difficult. Curbing alcohol misuse may be a more attainable goal than preventing any use. These results indicate that predictors of misuse in late adolescence can be identified by Grade 7 and are generally visible and modifiable. Prevention efforts should begin by early adolescence, address both familial and peer influences to drink and use other substances, and take into account problems that predict alcohol misuse (e.g., poor academic performance and early deviant behavior).

Adolescent↗
PubMed2001

Sex differences in predictors of adolescent smoking cessation.

Sex differences in predictors of smoking cessation were investigated among 337 male and 490 female participants in the RAND adolescent panel study. Participants reported smoking at least 11-20 times during the past year at Grade 10, with cessation defined as not smoking during the past year at Grade 12. Controlling for demographics, sex-specific analyses indicated that girls who quit smoking within 2 years had friends who smoked less frequently, perceived less parental approval of their smoking, had weaker intentions to continue smoking, used marijuana less frequently, attended fewer different schools, were more likely to have an intact nuclear family, experienced greater peer support, and rated themselves as healthier. Similar analyses for boys yielded results that were generally weaker and nonsignificant, with smoking quantity accounting for several associations in the sex-specific models. Despite these differences, interaction tests revealed significant sex differences for only three predictors. Implications of these results for understanding adolescent smoking cessation are discussed.

Adolescent↗
PubMed2000

The NMR structure of the nucleocapsid protein from the mouse mammary tumor virus reveals unusual folding of the C-terminal zinc knuckle.

The nucleocapsid protein (NC) from the mouse mammary tumor virus (MMTV) has been overexpressed in Escherichia coli and purified to homogeneity for structural studies by nuclear magnetic resonance (NMR) spectroscopy. The protein contains two copies of a conserved zinc-coordinating "CCHC array" or "zinc knuckle" motif common to the nucleocapsid proteins of nearly all known retroviruses. The residues comprising and adjacent to the zinc knuckles were assigned by standard two-dimensional (1)H and three-dimensional (1)H-(15)N NMR methods; the rotational dynamic properties of the protein were determined from (15)N relaxation experiments, and distance restraints derived from the nuclear Overhauser effect (NOE) data were used to calculate the three-dimensional structure. The (1)H-(1)H NOE and (15)N relaxation data indicate that the two zinc knuckles do not interact with each other, but instead behave as independently folded domains connected by a flexible 13-residue linker segment. The proximal zinc knuckle folds in a manner that is essentially identical to that observed previously for the two zinc knuckles of the human immunodeficiency virus type 1 nucleocapsid protein and for the moloney murine leukemia virus nucleocapsid zinc knuckle domain. However, the distal zinc knuckle of MMTV NC exhibits a rare three-dimensional fold that includes an additional C-terminal beta-hairpin. A similar C-terminal reverse turn-like structure was observed recently in the distal zinc knuckle of the Mason-Pfizer monkey virus nucleocapsid protein [Gao, Y., et al. (1998) Protein Sci. 7, 2265-2280]. However, despite a high degree of sequence homology, the conformation and orientation of the beta-hairpin in MMTV NC is significantly different from that of the reverse turn in MPMV NC. The results support the conclusion that structural features of NC zinc knuckle domains can vary significantly among the different genera of retroviridae, and are discussed in terms of the recent and surprising discovery that MMTV NC can facilitate packaging of the HIV-1 genome in chimeric MMTV mutants.

Amino Acid Sequence↗
PubMed2000

Anticipatory guidance: what information do parents receive? What information do they want?

OBJECTIVE: To determine whether parents are receiving anticipatory guidance, whether they could use more information on anticipatory guidance topics, and how receipt of anticipatory guidance relates to satisfaction with care. DESIGN AND SAMPLE: Analysis of data from a telephone interview of 2017 respondents between July 1995 and January 1996. A stratified random-digit dialing design was used to obtain a nationally representative sample of parents with children between 0 and 3 years old. MAIN OUTCOME MEASURES: Discussions with a physician or nurse about 6 anticipatory guidance topics and whether parents could use more information on these topics. Willingness of parents to pay extra to discuss these topics and receive additional care. Ratings of how well clinicians provide health care. RESULTS: The percentage of parents who had not discussed each subject with a clinician varied by topic: newborn care (< 3 months old), 38%; crying, 65%; sleep patterns, 59%; encouraging learning, 77%; discipline (ages 6-36 months), 75%; and toilet training (ages 18-36 months), 66%. Thirty-seven percent of parents had not discussed any of these topics. Among parents who had not discussed a particular issue, the percentage who reported that they could use more information ranged from 22% for both newborn care and crying to 55% for encouraging learning; similar percentages who had discussed the topics could also use more information. Parents who had discussed more of these topics with a clinician were more likely to report excellent care. Parents who could use more information on a larger number of topics were much more willing to pay for additional care. CONCLUSIONS: Although anticipatory guidance is considered an important component of well-child care, the majority of parents reported that they had not discussed most standard topics with a clinician. Many parents could use more information on these topics. Effort is required to provide parents with the information they need to take good care of their children. Arch Pediatr Adolesc Med. 2000;154:1191-1198.

Adult↗
PubMed1998

Extrauterine twin-twin transfusion affects renal function and perioperative management of conjoined twins.

This series describes the occurrence of unbalanced circulatory shunting in three consecutively treated pairs of conjoined twins. The impact of renal functional changes and compensatory cardiac physiology on the timing of surgery and perioperative management are illustrated. The craniopagus set of twins presented in renal failure (1A) and cardiac failure (1B) to our hospital at age 2.5 years. Renal transplantation for anuria was performed in 1A before separation of the twins. This did not improve urine output in the hypoperfused twin, and normal renal function was not restored until the twins were separated. Two sets of omphalopagus twins were delivered and transferred to our hospital and separated during the first week of life. In each case a preoperative oliguric state in the underperfused twin reversed after separation, and a postoliguric diuresis ensued. Serum creatinine levels were similar in each pair preoperatively despite the inequality in urine volumes. In conjoined twins, assessment of renal function is necessary and should include serial measurements of urine volumes and urine creatinine clearance. Serum creatinine is not a useful marker of individual twin renal function in this situation. When disparity in renal function exists, early separation is indicated to prevent renal failure and compensatory cardiac failure.

Child, Preschool↗
PubMed1997

The mandibular central incisor, an extraction option.

A case report is presented of a female adolescent with a Class II, division 1 malocclusion that shows a significant mandibular arch length deficiency. Although the facial balance suggested a nonextraction approach, the degree of mandibular anterior dental crowding and preexisting gingival recession indicated extraction in the mandibular arch might be preferable.

Cephalometry↗