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PubMed1990

Doe v. Wilson.

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Amyotrophic Lateral Sclerosis↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed2001

Grapes, galls, and geography: the distribution of nuclear and mitochondrial DNA variation across host-plant species and regions in a specialist herbivore.

Studies of patterns of molecular variation in natural populations can provide important insights into a number of evolutionary problems. Among these, the question of whether geographic factors are more important than ecological factors in promoting population differentiation and ultimately speciation has been an important and contentious area in evolutionary biology. Systems involving herbivorous insects have played a leading role in this discussion. This study examined the distribution of molecular variation in a highly specialized gall-forming insect, grape phylloxera (Daktulosphaira vitifoliae Fitch), that is found on both sympatric and allopatric host-plant species of the genus Vitis. In addition, the relationship of insects in the introduced range in the United States to ancestral populations in the native range was examined. Evidence for differentiation along host-plant lines from both nuclear (RAPD) and mitochondrial (COI) DNA was confounded with the effect of geography. Differentiation was found where hosts were allopatric or parapatric, but no evidence was found for such differentiation on two hosts, V. vulpina and V. aestivalis, that are broadly sympatric. The question of population differentiation onto these sympatric hosts can be considered to be resolved--it has not occurred in spite of a long history of association. Evidence was equivocal, but suggestive of a period of divergence in allopatry prior to reestablishment of contact, for insects associated with another host plant species, V. cinerea, found in both sympatric and parapatric populations. A low level of diversity and placement of samples collected from the grape species V. riparia at the tip of a phylogenetic tree supports the hypothesis that this host has been recently colonized from populations from the Mississippi Valley. A polyphyletic origin for biotype B grape phylloxera was supported: Although most samples collected from vineyards in the introduced range in California had similar haplotypes, they were closely related to natives on V. vulpina from the Atlantic Coast-Piedmont region. All samples collected from vineyards in Oregon and Washington were closely related to natives on V. riparia in the northern United States.

Adaptation, Physiological↗
PubMed2000

Lutzomyia whitmani (Diptera: Psychodidae) as vector of Leishmania (V.) braziliensis in Paraná state, southern Brazil.

The phlebotomine sandflies in the northern areas of the state of Paraná, Brazil, particularly those in the '16a' health region, were investigated over a 3-year period. Using CDC light traps (with and without hamster bait) and Shannon traps (with lights and horse or human bait), 16 species were collected from seven municipal districts which were known foci for cutaneous leishmaniasis: Arapongas; Apucarana; Cambira; Marumbi; Faxinal; Florestópolis; and Sabáudia. Although the frequency at which each species was collected varied with the collection site, Lutzomyia whitmani predominated (62.0% of all the sandflies collected), followed by Lu. fischeri (13.3%), Lu. pessoai (10.8%), Lu. migonei (8.2%) and Lu. intermedia (2.8%). Lutzomyia monticola, Lu. shanonni, Lu. firmatoi, Lu. lanei, Lu. alphabetica, Lu. misionensis, Lu. correalimai, Lu. cortellezzii, Lu. longipenis, Brumptomyia brumpti and B. nitzulescui together represented the remaining 3.0% of the collected sandflies. Three of the 1961 female sandflies collected and dissected in the municipal district of Cambira, where a recent case of cutaneous leishmaniasis had been registered, were found to have flagellates in their guts. All three were Lu. whitmani. The parasites from each of these infections were successfully isolated in NNN and 'Tobie and Evans' media and/or by inoculation into a hind foot of a golden hamster. The results of isoenzyme electrophoresis indicated that all three isolates were of Leishmania (Viannia) braziliensis.

Animals↗
PubMed1989

c-myb but not c-myc suppresses the hemin-induced nonterminal expression of hemoglobin by murine erythroleukemia cells.

Clonal lines of Friend murine erythroleukemia (F-MEL) cells have been generated following transfection with c-myc or c-myb expression plasmids. These clones produce high levels of abnormally regulated proto-oncogene transcripts and fail to terminally differentiate in the presence of dimethyl sulfoxide. To determine the relative levels at which the two proto-oncogenes might exert their inhibitory effects, we asked whether these clones could express differentiated functions in the absence of terminal differentiation. It was found that exposure of c-myc-transfected cells to hemin allows for the induction of hemoglobin, whereas c-myb-transfected cells were refractory to hemin induction. It thus appears that c-myb exerts a more globally suppressive effect on F-MEL-differentiated functions than does c-myc and may prevent the expression of those events that can otherwise be dissociated from the terminally differentiated state.

Animals↗
PubMed1996

Retinoic acid stimulates expression of the functional osteoclast integrin alpha v beta 3: transcriptional activation of the beta 3 but not the alpha v gene.

The capacity of osteoclasts to resorb bone depends, in part, on the surface expression of the integrin alpha v beta 3. We have investigated whether the steroid hormone retinoic acid, known to stimulate bone resorption, regulates the appearance of the alpha v beta 3 complex in avian osteoclast presursors. Using surface labeling, followed by immunoprecipitation with a alpha v beta 3-specific antibody, we show that retinoic acid increases surface expression of the heterodimer in a dose- and time-dependent manner. Northern analysis reveals that the high basal steady-state levels of alpha v mRNA do not change, while those for beta 3 rise significantly from their initially low levels. Nuclear run-on studies confirm that steroid treatment stimulates transcription of the beta 3, but not the alpha v gene. Osteoclast precursors treated with retinoic acid exhibit increased multinucleation and expression of the osteoclast marker enzyme tartrate-resistant acid phosphatase. However, the fused cells do not have an increased capacity to resorb bone. In summary, multinucleated cells generated in this study do not represent fully differentiated bone-resorbing polykaryons. These results suggest that treatment of osteoclast precursors with retinoic acid is necessary, but insufficient, for expression of the mature osteoclast phenotype.

Animals↗
PubMed1985

Medicare program; court ordered regulations regarding prospective payment amount and administrative review--HCFA. Interim rule.

This interim rule is being issued solely in response to an order of the United States District Court for the Northern District of California in Redbud Hospital District v. Heckler, No. C-84-4382 MHP dated June 4, 1985. HCFA disagrees with the court's order and has appealed the decision to the United States Court of Appeals for the Ninth Circuit. These interim rules modify the process for determining the Medicare prospective payment rate for inpatient hospital services to take into account extraordinary and unusual costs incurred after the base year; the special needs of hospitals serving disproportionate numbers of Medicare and low-income patients; and the special needs of sole community hospitals. In addition, they modify the requirements for administrative review of the hospital-specific portion of a hospital's PPS rate. These rules will be null and void in the event that either (a) a stay of the June 14, 1985 order is entered by a higher Court or (b) the June 14, 1985 order is reversed on appeal.

California↗
PubMed1985

Medicare program; court ordered regulations regarding prospective payment amounts and administrative review will not become effective--HCFA. Notice that regulations will not take effect; removal of regulations.

Interim rules providing for certain adjustments to Medicare propective payment rates and modifications to the provider appeal process were published on July 1, 1985 solely in response to an order of the United States District Court for the Northern District of California in Redbud Hospital District v. Heckler, No. C-84-4382 MHP dated June 14, 1985. That portion of the district court order requiring the Secretary to promulgate nationwide regulations was recently stayed by United States to promulgate nationwide regulations was recently stayed by United States Supreme Court Justice Rehnquist, pending the determination of the Secretary's appeal of the case to the United States Court of Appeals for Ninth Circuit. Heckler v. Redbud Hospital District, No. A-32. (Rehnquist, Circuit Justice, July 24, 1985). This document is to notify the public that the interim final rules have, by operation of that decision, been automatically revoked. They will not become effective on August 1, 1985.

California↗
PubMed2000

A preliminary look at source-receptor relationships in the Texas-Mexico border area.

Several factors have recently caused visibility impairment at Big Bend National Park, TX, to be of interest. Analyses of historical data collected there have shown that visibility is poorer and fine particle concentrations are higher at Big Bend than at other monitored Class I areas in the western United States. In addition, air masses frequently arrive there after crossing Mexico, where emissions are not well known. During September and October 1996, a field study was undertaken to begin examining the aerosol, visibility, and meteorology on both sides of the border. Results indicate that, during the study, the largest fractions of fine mass and light extinction at Big Bend were due to sulfates and the trace elements most closely associated with sulfate particles were Na and Se. Based on back trajectory modeling and the spatial, temporal, and inter-species relationships in the fine particle concentrations measured during the study, sulfates arrived at the park from both Mexico and the United States. Se was higher in Texas than in Northern Mexico, while V, Pb, Zn, Ni, and Mn were on average much higher in Mexico.

Aerosols↗
PubMed1992

The virulence gene activator ToxT from Vibrio cholerae is a member of the AraC family of transcriptional activators.

Virulence gene expression in Vibrio cholerae is postulated to involve ToxR-dependent activation of the toxT gene followed by ToxT activation of virulence genes, including several of those involved in biogenesis of the toxin-coregulated pilus. ToxR is a transmembrane, DNA-binding protein which is a member of the OmpR subclass of two-component activator systems in bacteria. Data presented in this report demonstrate that ToxT is similar to the AraC family of transcriptional activators identified in a variety of gram-negative bacteria. The toxT open reading frame begins approximately 200 nucleotides from the end of the tcpF gene, which is part of a cluster of genes responsible for production of the toxin-coregulated pilus. Accumulation of toxT specific mRNA is ToxR dependent and is modulated by environmental conditions that modulate expression of the regulon. Within the intergenic region between tcpF and toxT is a potential stem-loop structure of an unusual nature which may play a role in regulating expression of toxT mRNA. Experiments with tcpF and toxT cloned behind a strong, constitutive promoter suggest that the two genes can be cotranscribed, but Northern (RNA) blot analysis of V. cholerae suggests that if they are, steady-state levels of their messages may be controlled by a posttranscriptional mechanism. Possible mechanisms for ToxR-dependent expression of toxT are discussed.

Amino Acid Sequence↗
PubMed1996

Expression of adenylyl cyclase and G-protein beta subunit in end-stage human heart failure.

BACKGROUND: One of the abnormalities in end-stage human heart failure is desensitization of the beta-adrenergic signaling pathway, resulting in decreased adenylyl cyclase activity and cyclic adenosine 3',5'-monophosphate formation. This process includes changes in expression of receptors and G-protein alpha subunits. It was hypothesized that changes in the gene expression of G-protein beta subunits (Gbeta) and of adenylyl cyclase itself may contribute to the attenuation of activation of adenylyl cyclase. METHODS AND RESULTS: The hypothesis was tested by determining messenger RNA steady-state levels (Northern and slot-blot analyses) of adenylyl cyclase type V (a major isoform in adult myocardium) and Gbeta in the left ventricles of patients with terminal heart failure because of idiopathic dilated cardiomyopathy (n = 10) or ischemic heart disease (n = 7) and in the left ventricles of nonfailing donors (n = 5). Adenylyl cyclase type V messenger RNA was elevated by 85 +/- 25% in dilated cardiomyopathy and by 113 +/- 35% in ischemic heart disease (P < .05 vs nonfailing hearts). In contrast, Gbeta messenger RNA was unchanged in cardiomyopathy (3.48 +/- 0.18 pg/microgram total RNA vs nonfailing hearts 3.99 +/- 0.46) and decreased in ischemic heart disease (2.43 +/- 0.26, P < .01). CONCLUSION: The data indicate that gene expression of the major cardiac isoform of adenylyl cyclase (type V) seems increased in human end-stage heart failure. Therefore, attenuated adenylyl cyclase activity in this condition may not be the result of adenylyl cyclase messenger RNA downregulation. Similarly, the unchanged or decreased expression of Gbeta argues against changes in Gbeta contributing to this process.

Adenylyl Cyclases↗