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Biomedical subjects

P Jorgensen

Publications and source records attributed to P Jorgensen.

At least 19 recordsLinked to original sources
PubMed2001

AFM 4.0: a toolbox for DNA microarray analysis.

We have developed a series of programs, collectively packaged as Array File Maker 4.0 (AFM), that manipulate and manage DNA microarray data. AFM 4.0 is simple to use, applicable to any organism or microarray, and operates within the familiar confines of Microsoft Excel. Given a database of expression ratios, AFM 4.0 generates input files for clustering, helps prepare colored figures and Venn diagrams, and can uncover aneuploidy in yeast microarray data. AFM 4.0 should be especially useful to laboratories that do not have access to specialized commercial or in-house software.

Aneuploidy↗
PubMed2001

Fission yeast Clp1p phosphatase regulates G2/M transition and coordination of cytokinesis with cell cycle progression.

BACKGROUND: In Saccharomyces cerevisiae the mitotic-exit network (MEN) functions in anaphase to promote the release of the Cdc14p phosphatase from the nucleolus. This release causes mitotic exit via inactivation of the cyclin-dependent kinase (Cdk). Cdc14p-like proteins are highly conserved; however, it is unclear if these proteins regulate mitotic exit as in S. cerevisiae. In Schizosaccharomyces pombe a signaling pathway homologous to the MEN and termed the septation initiation network (SIN) is required not for mitotic exit, but for initiation of cytokinesis and for a cytokinesis checkpoint that inhibits further cell cycle progression until cytokinesis is complete. RESULTS: We have identified the S. pombe Cdc14p homolog, Clp1p, and show that it is not required for mitotic exit but rather functions together with the SIN in coordinating cytokinesis with the nuclear-division cycle. As cells enter mitosis, Clp1p relocalizes from the nucleolus to the spindle and site of cell division. Clp1p exit from the nucleolus does not depend on the SIN, but the SIN is required for keeping Clp1p out of the nucleolus until completion of cytokinesis. Clp1p, in turn, may promote the activation of the SIN by antagonizing Cdk activity until cytokinesis is complete and thus ensuring that cytokinesis is completed prior to the initiation of the next cell cycle. In addition to its roles in anaphase, Clp1p regulates the G2/M transition since cells deleted for clp1 enter mitosis precociously and cells overexpressing Clp1p delay mitotic entry. Unlike Cdc14p, Clp1p appears to antagonize Cdk activity by preventing dephosphorylation of Cdc2p on tyrosine. CONCLUSIONS: S. pombe Clp1p affects cell cycle progression in a markedly different manner than its S. cerevisiae homolog, Cdc14p. This finding raises the possibility that related phosphatases in animal cells will prove to have important roles in coordinating the onset of cytokinesis with the events of mitosis.

Cell Cycle Proteins↗
PubMed2000

The fork'ed path to mitosis.

A concurrence of genomic, reverse genetic and biochemical approaches has cracked the decade-long enigma concerning the identity of the transcription factors that control gene expression at the G2/M transition in the budding yeast cell cycle.

Fungal Proteins↗
PubMed2000

Proteolysis and the cell cycle: with this RING I do thee destroy.

The ubiquitin system drives the cell division cycle by the timely destruction of numerous regulatory proteins. Remarkably, the two main activities that catalyze substrate ubiquitination in the cell cycle, the Skp1-Cdc53/cullin-F-box protein (SCF) complexes and the anaphase-promoting complex/cyclosome (APC/C), define a new superfamily of E3 ubiquitin ligases, all based on related cullin and RING-H2 finger protein subunits. The circuits that interconnect the SCF, APC/C and cyclin-dependent kinase activities form a master oscillator that coordinates the replication and segregation of the genome.

Anaphase-Promoting Complex-Cyclosome↗
PubMed1999

Altered states: programmed proteolysis and the budding yeast cell cycle.

The recent identification of an essential RING-H2 finger protein in the SCF E3 ubiquitin ligase complex of budding yeast has uncovered a family of related E3 enzymes, including the other main cell cycle E3 complex, the anaphase promoting complex (APC). Recent insights into APC-dependent proteolysis include a novel protease activity that dissolves cohesion between sister chromatids at anaphase, and a crucial phosphatase, Cdc14, whose release from the nucleolus eliminates cyclin-dependent kinase activity and thereby drives exit from mitosis.

Anaphase-Promoting Complex-Cyclosome↗
PubMed1998

Activation of 2'-5' oligoadenylate synthetase by single-stranded and double-stranded RNA aptamers.

A number of small RNA molecules that are high affinity ligands for the 46-kDa form of human 2'-5' oligoadenylate synthetase have been identified by the SELEX method. Surface plasmon resonance analysis indicates that these RNAs bind to the enzyme with dissociation constants in the nanomolar range. Competition experiments indicate that the binding site for the small RNAs on the 2'-5' oligoadenylate synthetase molecule at least partially overlaps that for the synthetic double-stranded RNA, poly(I).poly(C). Several of the RNAs function as potent activators of 2'-5' oligoadenylate synthetase in vitro, although there is no correlation between binding affinity and ability to activate. The RNA aptamers having the strongest activation potential appear to have few base-paired regions. This suggests that 2'-5' oligoadenylate synthetase, which has previously been believed to be activated only by double-stranded RNA, can also be activated by RNA ligands with little secondary structure. Since 2'-5' oligoadenylate synthetase possesses no homology to other known RNA-binding proteins, the development of small specific ligands by SELEX should facilitate studies of RNA-protein interactions and may reveal novel features of the structure-function relationships involving this enzyme.

2',5'-Oligoadenylate Synthetase↗
PubMed1996

E-box sequence and context-dependent TAL1/SCL modulation of basic helix-loop-helix protein-mediated transcriptional activation.

TAL1/SCL is a basic helix-loop-helix (bHLH) oncoprotein that is expressed in several cell lines including many hematolymphoid cells, but not in T- and B-lineage cells. The TAL1 gene was originally discovered as being transcriptionally activated by chromosomal rearrangements in T-cell acute lymphoblastic leukemia (T-ALL). Here we have shown that TAL1 and the ubiquitously expressed murine bHLH transcription factor ALF1 formed heterodimers that, compared with ALF1 homodimers, had a more restricted E-box specificity and bound preferentially to the glucocorticoid-responsive E-box (Egre) motif (AACAGATGGT). Overexpression of the dominant inhibitory HLH protein Id1 in NIH3T3 cells reduced the transcriptional activity mediated by ALF1 homodimers, whereas the transcriptional activity mediated by TAL1/ALF1 heterodimers was resistant to Id overexpression. Our results show that ALF1 may serve as a dimerization partner for the bHLH oncoprotein TAL1 and form a complex with a distinctive DNA binding property. These findings support the hypothesis that the leukemic characteristics of the TAL1 oncoprotein could be mediated by activation of a set of target genes as heterodimeric complexes with ubiquitously expressed bHLH transcription factors such as ALF1 and that a principal role of TAL1 might be to neutralize an Id-mediated inactivation.

3T3 Cells↗
PubMed1977

On the structure of the deo operon of Escherichia coli.

A characterization of a specialized transducing lambda phage for the deo operon (lambdaddeo), and some composite colE1-deo plasmids is given in this paper. This includes localization of the RSmaI, RHind/III, RBamI, and REcoRI sensitive sites. The deo genes have been localized by construction of composite colE1-deo plasmids. Using the DNA fragments, obtained by digestion with REcoRI and RHindIII, respectively, as templates in an in vitro protein synthesizing system, it has been possible to give the direction of transcription and the exact location of the deo genes, relative to the endonuclease sites. Furthermore, the cytO,P and deoO,P regions have been mapped relative to the structural genes. Supercoiled co1E1-deo DNA has been used as template in the in vitro system; this DNA gives essentially the same results as the endonuclease-fragmented DNA. The use of the different types of templates is discussed.

Coliphages↗
PubMed1976

The mechanism of action of ppGpp on rRNA synthesis in vitro.

We have studied the mechanism of the specific inhibition of ribosomal RNA synthesis by ppGpp in a purified system using as templates E. coli DNA and DNA from lambdad5ilv, which carries a rRNA cistron from E. coli. Ribosomal RNA synthesis, as well as its inhibition by ppGpp, are critically salt-dependent. Of a number of guanosine phosphates tested, only pppGpp (MS II) mimicked the action of ppGpp, establishing the specificity of ppGpp. The two templates gave similar results for rRNA synthesis in all experiments. By using the initiation inhibitor rifampicin, we could show that the specific inhibition of rRNA synthesis by ppGpp is due to its effect on rRNA initiation. The somewhat variable inhibition of RNA synthesis in general by ppGpp is mainly or wholly a consequence of premature chain termination. We propose that ppGpp specifically inhibits rRNA synthesis by acting on the formation of the so-called "closed-promoter complex".

Cell-Free System↗
PubMed1975

Alprenolol in angina pectoris. A comparative study of the tablet form and slow-release formulation.

In a double-blind crossover trial in angina pectoris patients, alprenolol in a slow-release formulation (Aptin Durules) was compared with ordinary Aptin tablets. Four hundred mg per day in tablets given four times a day produced the same increase in exercise tolerance five hours after last intake as did an equivalent dose of slow-release formulation given twice per day nine hours after intake. Aptin Durules in double the dosage had a considerably greater effect. An optimal, sustained and antianginal effect of alprenolol is best achieved by giving 400 to 800 mg per day of slow-release formulation with 10 to 12 hours' dosage interval.

Aged↗
PubMed1975

Patterns of motoneuron dysfunction and recovery.

Electrophysiological studies have been carried out on five patients with neuropathies of different etiologies. In each patient serial estimates were made of the numbers of functioning motor units in various muscles. It was found that the intensity of the neuropathic process and the rate of recovery differed in a consistent way among the motoneuron pools investigated. The lesion was more severe in extensor digitorum brevis neurons than in thenar neurons, while the hypothenar ones were least affected. A stage of partial synaptic failure has been recognized in which a motoneuron appears to be no longer able to excite a muscle fiber, but still capable of maintaining certain trophic activities. By comparing the number of functioning motor units with the size of the maximum evoked muscle response it has been possible to detect the adoption of denervated muscle fibers by axonal sprouts from 'healthy' surviving neurons (collateral reinnervation). Lastly, in some muscles it appears that the adopted muscle fibers may subsequently be recaptured by the original motoneurons following recovery of the latter from the neurotoxic insult.

Adult↗