Cyclin-dependent kinases (Cdks} are positive regulators of cell proliferation, whereas Cdk inhibitors {CKIs) inhibit proliferation. We describe a new CKI, p57 v'w2, which is related to p21 cn'1 and p27 gxP1. p57 gn'2 is a potent, tight-binding inhibitor of several G~ cyclin/Cdk complexes, and its binding is cyclin dependent.Unlike CIP1, KIP2 is not regulated by p53. Overexpression of p57 gn'e arrests cells in G~. p57 me2 proteins have a complex structure. Mouse p57/~n'2 consists of four structurally distinct domains: an amino-terminal Cdk inhibitory domain, a proline-rich domain, an acidic-repeat region, and a carboxy-terminal domain conserved with p27gn'L Human p57 ~2 appears to have conserved the amino-and carboxy-terminal domains but has replaced the internal regions with sequences containing proline-alanine repeats. In situ hybridization during mouse embryogenesis revealed that KIP2 mRNA displays a striking pattern of expression during development, showing high level expression in skeletal muscle, brain, heart, lungs, and eye. Most of the KIP2-expressing cells are terminally differentiated, suggesting that p57 ~n'2 is involved in decisions to exit the cell cycle during development and differentiation. Human KIP2 is located at 11p15.5, a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome, a familial cancer syndrome, marking it as a candidate tumor suppressor. The discovery of a new member of the p21 cn'l inhibitor family with novel structural features and expression patterns suggests a complex role for these proteins in cell cycle control and development.

The rationale underlying factor analysis applies to continuous and categorical variables alike; however, the models and estimation methods for continuous (i.e., interval or ratio scale) data are not appropriate for item-level data that are categorical in nature. The authors provide a targeted review and synthesis of the item factor analysis (IFA) estimation literature for ordered-categorical data (e.g., Likert-type response scales) with specific attention paid to the problems of estimating models with many items and many factors. Popular IFA models and estimation methods found in the structural equation modeling and item response theory literatures are presented. Following this presentation, recent developments in the estimation of IFA parameters (e.g., Markov chain Monte Carlo) are discussed. The authors conclude with considerations for future research on IFA, simulated examples, and advice for applied researchers. Keywordsitem factor analysis; parameter estimation; categorical data; confirmatory factor analysis; item response theory Item-level data within the social and behavioral sciences are often categorical in nature. Dichotomous (e.g., disagree vs. agree) or polytomous (e.g., strongly disagree, disagree, neither, agree, and strongly agree) item response formats may fail to maintain the scale and distributional properties assumed by models such as ordinary least squares regression or common linear factor analysis. Traditional regression techniques describe the outcome variable as an optimal linear function of observed predictors. The proper implementation of these techniques requires assumptions such as independent and normally distributed residuals, a continuous conditionally normal outcome, and that the model is correctly specified (i.e., a linear relationship exists between the outcome and predictors). The common linear factor model, which describes the covariances among observed variables as a function of a smaller number of latent factors, makes many of the same assumptions. It is assumed that the unique factors (those that affect only one measured variable) are normally distributed, the outcomes are continuous and conditionally normally distributed, and a linear relationship exists between the observed and latent variables. Although this list of assumptions is not exhaustive, it does represent assumptions that are easily violated with itemlevel ordered-categorical data. Attempting to estimate model parameters, for example, NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript with dichotomous outcomes within the standard confirmatory factor model (as described by Jöreskog, 1969) results in parameter estimates that are biased and impossible to interpret accurately (Di-Stefano, 2002). However, all is not lost; just as logistic and ordinal regression techniques offer appropriate alternatives to linear regression when modeling dichotomous or polytomous (e.g., ordinal, Likert-type scales) outcomes, item factor analysis (IFA) offers an appropriate alternative to the common line...

Holoprosencephaly (HPE) is the most common structural defect of the developing forebrain in humans (1 in 250 conceptuses, 1 in 16,000 live-born infants). HPE is aetiologically heterogeneous, with both environmental and genetic causes. So far, three human HPE genes are known: SHH at chromosome region 7q36 (ref. 6); ZIC2 at 13q32 (ref. 7); and SIX3 at 2p21 (ref. 8). In animal models, genes in the Nodal signalling pathway, such as those mutated in the zebrafish mutants cyclops (refs 9,10), squint (ref. 11) and one-eyed pinhead (oep; ref. 12), cause HPE. Mice heterozygous for null alleles of both Nodal and Smad2 have cyclopia. Here we describe the involvement of the TG-interacting factor (TGIF), a homeodomain protein, in human HPE. We mapped TGIF to the HPE minimal critical region in 18p11.3. Heterozygous mutations in individuals with HPE affect the transcriptional repression domain of TGIF, the DNA-binding domain or the domain that interacts with SMAD2. (The latter is an effector in the signalling pathway of the neural axis developmental factor NODAL, a member of the transforming growth factor-beta (TGF-beta) family.) Several of these mutations cause a loss of TGIF function. Thus, TGIF links the NODAL signalling pathway to the bifurcation of the human forebrain and the establishment of ventral midline structures.

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Parental origin-specific alterations of chromosome 11p15 in human cancer suggest the involvement of one or more maternally expressed imprinted genes involved in embryonal tumor suppression and the cancer-predisposing

The gene coding for human cyclin K was isolated as a CPR (cell-cycle progression restoration) gene by virtue of its ability to impart a Far ؊ phenotype to the budding yeast Saccharomyces cerevisiae and to rescue the lethality of a deletion of the G 1 cyclin genes CLN1, CLN2, and CLN3. The cyclin K gene encodes a 357-aminoacid protein most closely related to human cyclins C and H, which have been proposed to play a role in regulating basal transcription through their association with and activation of cyclin-dependent kinases (Cdks) that phosphorylate the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II (RNAP II). Murine and Drosophila melanogaster homologs of cyclin K have also been identified. Cyclin K mRNA is ubiquitously expressed in adult mouse and human tissues, but is most abundant in the developing germ cells of the adult testis and ovaries. Cyclin K is associated with potent CTD kinase and Cdk kinase (CAK) activity in vitro and coimmunoprecipitates with the large subunit of RNAP II. Thus, cyclin K represents a new member of the "transcription" cyclin family which may play a dual role in regulating Cdk and RNAP II activity.

The family Tymoviridae comprises the genus Tymovirus, from which it derives its name, the genus Marafivirus and the newly established genus Maculavirus. Members of the family share the following characteristics: (i) non-enveloped isometric particles c. 30 um in diameter, with a rounded contour and prominent surface structures, and clustering of coat protein subunits in pentamers and hexamers; (ii) the presence in preparations of purified virus particles of two centrifugal components, made up of non-infectious protein shells (T) that may contain small amounts of RNA (primarily subgenomic coat protein mRNA) and of infectious nucleoproteins (B), that contain the virus genome; (iii) possession of a positive-sense, single-stranded RNA genome with an unusually high cytidine content (32 to c. 50%), capped at the 5' terminus and containing a very large ORF encodes replication-related proteins analogous to those of other taxa of the "alpha-like" supergroup of ssRNA viruses; (iv) a replication strategy possibly encompassing posttranslational proteolytic cleavage of the polypeptide encoded by ORF1 by a papain-like virus-encoded protease, and coat protein expression via a subgenomic RNA; (v) the presence in infected cells of cytopathic structures, thought to be the sites of RNA replication, originating from severely altered chloroplasts and/or mitochondria, the periphery of which is lined with vesicles produced by the localized invaginations of the bounding membrane. There are 23, 4, and 2 known species in the genera Tymovirus, Marafivirus and Maculavirus, respectively. The genus Marafivirus also contains one tentative species.

Many constructs developmental scientists study cannot be directly observed. In such cases, scales are created that reflect the construct of interest. Observed behaviors are taken as manifestations of an unobserved common cause. As crucial as measurement is to understanding many psychological phenomenon, it is perhaps even more important when the goal of research is to understand how a construct changes over time. In this article we review several approaches to measurement, note features of latent variable measurement models which are ideally suited to the study of change, describe a hypothetical example, and conclude with a discussion of measurement and development.