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J Blau

Publications and source records attributed to J Blau.

13 recordsLinked to original sources
PubMed2001

The Drosophila circadian clock: what we know and what we don't know.

Circadian rhythms are regulated by endogenous body clocks, which are formed by rhythmic cycles of clock gene expression. Almost all reviews of the Drosophila circadian clock state that the intracellular oscillator is based on a simple negative feedback loop. However, not many 'simple' feedback loops in biology last for 24 h. Instead, the Drosophila clock is a series of precisely timed steps that are deliberately slow. In this paper, I will discuss the current model for how the Drosophila clock is regulated, and ask what questions remain to be answered.

Animals↗
PubMed1999

Cycling vrille expression is required for a functional Drosophila clock.

We identified a novel regulatory loop within Drosophila's circadian clock. A screen for clock-controlled genes recovered vrille (vri), a transcription factor essential for embryonic development. vri is expressed in circadian pacemaker cells in larval and adult brains. vri RNA levels oscillate with a circadian rhythm. Cycling is directly regulated by the transcription factors dCLOCK and CYCLE, which are also required for oscillations of period and timeless RNA. Eliminating the normal vri cycle suppresses period and timeless expression and causes long-period behavioral rhythms and arrhythmicity, indicating that cycling vri is required for a functional Drosophila clock. We also show that dCLOCK and VRI independently regulate levels of a neuropeptide, pigment dispersing factor, which appears to regulate overt behavior.

ARNTL Transcription Factors↗
PubMed1998

double-time is a novel Drosophila clock gene that regulates PERIOD protein accumulation.

We have isolated three alleles of a novel Drosophila clock gene, double-time (dbt). Short- (dbtS) and long-period (dbtL) mutants alter both behavioral rhythmicity and molecular oscillations from previously identified clock genes, period and timeless. A third allele, dbtP, causes pupal lethality and eliminates circadian cycling of per and tim gene products in larvae. In dbtP mutants, PER proteins constitutively accumulate, remain hypophosphorylated, and no longer depend on TIM proteins for their accumulation. We propose that the normal function of DOUBLETIME protein is to reduce the stability and thus the level of accumulation of monomeric PER proteins. This would promote a delay between per/tim transcription and PER/TIM complex function, which is essential for molecular rhythmicity.

Alleles↗
PubMed1998

The Drosophila clock gene double-time encodes a protein closely related to human casein kinase Iepsilon.

The cloning of double-time (dbt) is reported. DOUBLETIME protein (DBT) is most closely related to human casein kinase Iepsilon. dbtS and dbtL mutations, which alter period length of Drosophila circadian rhythms, produce single amino acid changes in conserved regions of the predicted kinase. dbtP mutants, which eliminate rhythms of per and tim expression and constitutively overproduce hypophosphorylated PER proteins, abolish most dbt expression. dbt mRNA appears to be expressed in the same cell types as are per and tim and shows no evident oscillation in wild-type heads. DBT is capable of binding to PER in vitro and in Drosophila cells, suggesting that a physical association of PER and DBT regulates PER phosphorylation and accumulation in vivo.

Amino Acid Sequence↗
PubMed1996

Three functional classes of transcriptional activation domain.

We have studied the abilities of different transactivation domains to stimulate the initiation and elongation (postinitiation) steps of RNA polymerase II transcription in vivo. Nuclear run-on and RNase protection analyses revealed three classes of activation domains: Sp1 and CTF stimulated initiation (type I); human immunodeficiency virus type 1 Tat fused to a DNA binding domain stimulated predominantly elongation (type IIA); and VP16, p53, and E2F1 stimulated both initiation and elongation (type IIB). A quadruple point mutation of VP16 converted it from a type IIB to a type I activator. Type I and type IIA activators synergized with one another but not with type IIB activators. This observation implies that synergy can result from the concerted action of factors stimulating two different steps in transcription: initiation and elongation. The functional differences between activators may be explained by the different contacts they make with general transcription factors. In support of this idea, we found a correlation between the abilities of activators, including Tat, to stimulate elongation and their abilities to bind TFIIH.

Base Sequence↗
PubMed1994

Transcriptional elongation by RNA polymerase II is stimulated by transactivators.

We report that a variety of transactivators stimulate elongation by RNA polymerase II. Activated transcription complexes have high processivity and are able to read through pausing and termination sites efficiently. In contrast, nonactivated and "squelched" transcription mostly arrests prematurely. Activators differ in the extent to which they stimulate processivity; for example, GAL4-VP16 and GAL4-E1a are more effective than GAL4-AH. The stimulation of elongation can be as important as the stimulation of initiation in activating expression of a reporter gene. We suggest that setting the competence of polymerase II to elongate is an integral part of the initiation step that is controlled by activators cooperating with the general transcription factors.

Animals↗
PubMed1991

Human T cell recognition of influenza A nucleoprotein. Specificity and genetic restriction of immunodominant T helper cell epitopes.

The characterization of human T cell antigenic sites on influenza A nucleoprotein (NP) is important for subunit vaccine development for either antibody boosting during infection or to stimulate T cell-mediated immunity. To identify such sites, 31 synthetic peptides that cover more than 95% of the amino acid sequence from NP of influenza A/NT/60/68 virus were tested for their ability to stimulate PBL from 42 adult donors. The most frequently recognized region was covered by a peptide corresponding to residues 206-229 of NP, with 20/42 (48%) of responders. In many individuals this was also one of the peptides that stimulated the strongest T cell responses. Other regions that were also frequently recognized were 341-362 by 13/42 (30%), 297-318 by 10/42 (23%), and 182-205 by 9/42 (21%) of individuals. These peptides covered highly conserved regions in NP of influenza A viruses, suggesting that they could be useful in boosting cross-reactive immunity against the known type A virus strains. In order to define the class II restriction molecules used to present particular T cell epitopes, 22 persons from the donor panel were HLA-typed. The majority of persons who expressed DR2, and proliferated to NP also responded to the major immunodominant region 206-229. In addition, this peptide was also immunodominant in the one person expressing DRw13. The observation that recognition of this peptide is associated with DR2 was confirmed by using short term T cell lines and APC from a panel of typed donors. Further results with virus-specific T cell lines and clones and transfected L cells expressing DR molecules showed that DR1 could also present this peptide. Therefore the results suggest that recognition of 206-229 is associated with at least three different DR haplotypes and this may explain the high frequency with which this peptide is recognized in the population. The fine specificity of the response to peptide 206-229 was distinct when presented by DR1- or DR2-expressing APC. The DR1 response was dependent on the N terminus, and the DR2 response was directed to the C terminus of the peptide.

Adult↗
PubMed1988

Prevalence of diabetes in Israel. Epidemiologic survey.

A survey of 4660 Israeli adults aged 30-65 yr revealed an overall diabetes prevalence of 4.1%. Prevalence was slightly lower in women (3.5%) than in men (4.3%), rose with age, and was highest in the group greater than 60 yr old (10.3%). In approximately 40% of the diabetic subjects, the diagnosis of diabetes was made as a result of the screening program. Association with a family history of diabetes, obesity, and the presence of other diseases was greater in diabetic than in nondiabetic subjects. The prevalence of diabetes differed among different segments of the survey population when classified according to country of origin, being lowest in African and Asian (1.2%), intermediate in American and European (4.9%), and highest in Israeli born (5.5%); this order of prevalence is the reverse of that reported in earlier surveys. The results indicate that the overall diabetes prevalence in Israel, and that within the European- and American-born segment, is comparable to that reported in other westernized societies. The findings also suggest that environmental factors contribute to the phenotypic expression of the non-insulin-dependent genotype(s) but that the influence of such factors varies with different genetic backgrounds.

Adult↗
PubMed1981

Polar types of reported drug involvement among Israeli youth.

The predisposing factors lined to drug involvement may be different for various types of youth, although the outcome is the same. In this sense a bimodal curve of drug involvement would indicate two types of highly involved youth: on the one hand, those from high social status families where low parental control implies a tendency to seek involvement with their peers and solve their personal adjustment problems within the peer group. On the other hand, those from the lower social strata for whom low parental control also implies association with outside peer groups as an alternative to shaky and diffuse families and lack of involvement in school life. This study on the cannabis involvement of 776 boys and girls (aged 14-18), drawn from eight schools, is an attempt to identify and describe these polar types of drug-involved youth in more detail.

Adolescent↗
PubMedDate not supplied

Differential patterns of drug involvement among Israeli youth.

The present study tries to link some demographic, social, psycholoogical and attitudinal variables of drug abuse. The findings were centred around the readiness of secondary school youth in Israel to be involved in drugs and their active searching for drug involvement. A dependent variable based on five indices of drug involvement was constructed. It was then related to parental control, peer involvement in drugs, sex differentiation and membership in youth movements. A bi-modal high involvement curve was found, the first mode consisting of youth of low socio-economic strata who are drop-outs, who associate with outside peer groups as an alternative to their shaky and diffused families and lack of involvement in school life. The other mode consists of youth with a higher socio-economic background who are involved with drugs due to their desire for new hedonistic and emotional experiences. Their openness to experiment with drugs is a corollary to their involvement within a peer group which condones and legitimizes narcotics as well as any experiences which irrespective of their source, provide "a good high". There is a sub-group within this group which would be involved with drugs as a partial escape from personal problems.

Adolescent↗