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Biomedical subjects

S Fath

Publications and source records attributed to S Fath.

7 recordsLinked to original sources

Differential roles of phosphorylation in the formation of transcriptional active RNA polymerase I.

Regulation of rDNA transcription depends on the formation and dissociation of a functional complex between RNA polymerase I (pol I) and transcription initiation factor Rrn3p. We analyzed whether phosphorylation is involved in this molecular switch. Rrn3p is a phosphoprotein that is predominantly phosphorylated in vivo when it is not bound to pol I. In vitro, Rrn3p is able both to associate with pol I and to enter the transcription cycle in its nonphosphorylated form. By contrast, phosphorylation of pol I is required to form a stable pol I-Rrn3p complex for efficient transcription initiation. Furthermore, association of pol I with Rrn3p correlates with a change in the phosphorylation state of pol I in vivo. We suggest that phosphorylation at specific sites of pol I is a prerequisite for proper transcription initiation and that phosphorylation/dephosphorylation of pol I is one possibility to modulate cellular rDNA transcription activity.

Escherichia coli↗

Neuronal localization of the TNFalpha converting enzyme (TACE) in brain tissue and its correlation to amyloid plaques.

The tumor necrosis factor (TNF)-alpha converting enzyme (TACE) can cleave the cell-surface ectodomain of the amyloid-beta precursor protein (APP), thus decreasing the generation of amyloid-beta (Abeta) by cultured non-neuronal cells. While the amyloidogenic processing of APP in neurons is linked to the pathogenesis of Alzheimer's disease (AD), the expression of TACE in neurons has not yet been examined. Thus, we assessed TACE expression in a series of neuronal and non-neuronal cell types by Western blots. We found that TACE was present in neurons and was only faintly detectable in lysates of astrocytes, oligodendrocytes, and microglial cells. Immunohistochemical analysis was used to determine the cellular localization of TACE in the human brain, and its expression was detected in distinct neuronal populations, including pyramidal neurons of the cerebral cortex and granular cell layer neurons in the hippocampus. Very low levels of TACE were seen in the cerebellum, with Purkinje cells at the granular-molecular boundary staining faintly. Because TACE was localized predominantly in areas of the brain that are affected by amyloid plaques in AD, we examined its expression in a series of AD brains. We found that AD and control brains showed similar levels of TACE staining, as well as similar patterns of TACE expression. By double labeling for Abeta plaques and TACE, we found that TACE-positive neurons often colocalized with amyloid plaques in AD brains. These observations support a neuronal role for TACE and suggest a mechanism for its involvement in AD pathogenesis as an antagonist of Abeta formation.

ADAM Proteins↗

Association of yeast RNA polymerase I with a nucleolar substructure active in rRNA synthesis and processing.

A novel ribonucleoprotein complex enriched in nucleolar proteins was purified from yeast extracts and constituents were identified by mass spectrometry. When isolated from rapidly growing cells, the assembly contained ribonucleic acid (RNA) polymerase (pol) I, and some of its transcription factors like TATA-binding protein (TBP), Rrn3p, Rrn5p, Rrn7p, and Reb1p along with rRNA processing factors, like Nop1p, Cbf5p, Nhp2p, and Rrp5p. The small nucleolar RNAs (snoRNAs) U3, U14, and MRP were also found to be associated with the complex, which supports accurate transcription, termination, and pseudouridylation of rRNA. Formation of the complex did not depend on pol I, and the complex could efficiently recruit exogenous pol I into active ribosomal DNA (rDNA) transcription units. Visualization of the complex by electron microscopy and immunogold labeling revealed a characteristic cluster-forming network of nonuniform size containing nucleolar proteins like Nop1p and Fpr3p and attached pol I. Our results support the idea that a functional nucleolar subdomain formed independently of the state of rDNA transcription may serve as a scaffold for coordinated rRNA synthesis and processing.

Cell Nucleolus↗

The occurrence of treponemes and their spherical bodies on polytetrafluoroethylene membranes.

The occurrence of small (diameter 0.125 micrometers) and large (diameter 0.27 micrometers) treponemal species on expanded polytetrafluoroethylene membranes were demonstrated in vivo. In the apical part of the expanded polytetrafluoroethylene membrane only the smaller treponemes were colonizing, while in other parts a mixed population of different bacterial species including large treponemes was seen. Only the smaller treponemes were able to form spherical bodies in the occlusive part of the membrane. All morphological characteristics of spherical bodies such as common outer sheath, randomly distributed axial flagella, sheathless protoplasmic cylinders and central bodies could be differentiated. Possible causes for the formation of spherical bodies are discussed.

Adult↗

The paperless essay: one way to teach writing and computer skills in medical school.

We designed an assignment for first-year medical students that included instruction in writing and in computer use, two important subjects that are usually neglected in the traditional curriculum. As part of a neuroscience course, students wrote an essay using a word processor and submitted it to the instructor via the campus computer network. If requested by the instructor, the students submitted a revision of their essays without a grade penalty. As a result of completing the assignment, students learned the importance of revision and were stimulated to learn more about computers. With only slight modification of medical school courses, faculty can place more emphasis on writing skills and computer literacy.

Computer Literacy↗

[Intensive studies seminar for dental prophylaxis].

The significant role oral prophylactic measures play in the prevention of caries and periodontal disease and the importance of continuing systematic treatment for patients suffering from periodontitis have been scientifically documented in clinical studies. Practical application of this knowledge on a day-to-day basis in dental offices has thus far been hampered by the shortage of appropriately trained personnel. In September 1989, the Zahnärztekammer Berlin founded the "Intensive Studies Seminar for Dental Prophylaxis". In a one-year, vocational course of study, participants acquire the knowledge and practical skills necessary to establish and maintain a system of prophylactic treatment capable of being integrated into the dental practice. The purpose of the following article is to give information concerning the concept behind the program, as well as to introduce the course of study and its various aspects. The experiences gained in the program's first year were positive, and graduates of the course are in demand. It is therefore to be hoped that the concept underlying this seminar will take hold.

Adolescent↗

Stimulus equivalence and transitive associations: A methodological analysis.

When a number of two-stimulus relations are established through training within a set of stimuli, other two-stimulus relations often emerge in the same set without direct training. These, termed "transitive stimulus relations," have been demonstrated with a variety of visual and auditory stimuli. The phenomenon has served as a behavioral model for explaining the emergence of rudimentary comprehension and reading skills, and the development of generative syntactic repertoires. This article considers the range of relations that can arise between a given number of stimuli in a class, the number of directly established two-stimulus relations necessary for the emergence of transitive relations, the forms that training sets of stimuli can take, and the number of transitive two-stimulus relations that can be induced without direct training. The procedures needed to establish and assess transitive stimulus control, the possible interactions between the training and testing procedures, and the constrainst these interactions place upon the analysis of transitive stimulus control are also examined. The present analysis indicates that in a transitivity test, choice among such stimuli may be controlled by (1) the relation between the sample and the positive comparison stimulus (transitive stimulus control), (2) the relation between the sample and the negative comparison stimulus (S- rule control), and (3) possible discriminative properties that may inadvertently be established in the positive and negative comparison stimuli (valence control). Methods are described for distinguishing these three forms of stimulus control.

Journal Article↗