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PubMed1984

Dietary regulation of levels of active mRNA coding for amylase and serine protease zymogens in the rat pancreas.

The mechanism by which changes in diet mediate levels of exportable enzymes and proenzymes in pancreatic tissue were studied in rats. The relative levels of mRNA coding for pancreatic amylase, lipase, procarboxypeptidases A and B, and the family of serine protease zymogens have been determined by the ability of isolated RNA to direct the synthesis of these products in a high-fidelity micrococcal nuclease-treated reticulocyte-lysate translation system. Translation products synthesized in vitro correlated directly with products synthesized in vivo in pancreatic lobules. Dietary adaptation was observed when dietary carbohydrate was increased from 0 to 58% at the expense of protein (81-23%). The increase in dietary carbohydrate over this range resulted in a 2-fold increase in amylase synthesis in pancreatic lobules and a 1.8-fold increase in mRNA-directed synthesis of amylase in the translation system in vitro. Concomitant with the decrease in dietary protein, synthesis of serine protease zymogens in pancreatic lobules and in the system in vitro decreased by approximately 50%. Over this range of dietary manipulation, ratios of amylase to serine proteases showed a 3.6-fold change. When dietary carbohydrate was further increased to 81% and protein reduced to 0, non-adaptive changes were observed since there was a decrease in amylase synthesis under conditions both in vivo and in vitro. mRNAs coding for pancreatic lipase and procarboxypeptidases A and B were unaffected by the dietary changes. These findings indicate that nutritional regulation in the tissue levels of pancreatic enzymes and proenzymes is mediated by changes in the content of active cytoplasmic mRNAs.

Amylases↗
PubMed1980

Alterations in translatable ribonucleic acid after heat shock of Saccharomyces cerevisiae.

Changes in populations of translatable messenger ribonucleic acids (mRNA's) after heat shock of Saccharomyces cerevisiae were examined and found to correlate very closely with transient alterations in patterns of in vivo protein synthesis. Initial changes included an increase in translatable species coding for polypeptides synthesized during heat shock; this increase was found to be dependent on transcription but did not require ongoing protein synthesis. A decrease was observed in the level of translatable mRNA's coding for polypeptides whose synthesis was repressed after heat shock. This decrease was much more rapid than can be explained solely by termination of transcription. Requirements for this rapid loss of RNA from the translatable pool included both transcription and an active rna1 gene product but not protein synthesis. After the initial changes in translatable RNA induced by heat shock, the patterns of both in vivo and in vitro translation products began to revert to the preshock levels. This recovery period, unlike the earlier changes, was dependent upon a requisite period of protein synthesis.

Fungal Proteins↗
PubMed1994

A mutation in ribosomal protein L9 affects ribosomal hopping during translation of gene 60 from bacteriophage T4.

Ribosomes hop over a 50-nt coding gap during translation of gene 60 mRNA from bacteriophage T4. This event occurs with near-unitary efficiency when gene 60-lacZ fusions are expressed in Escherichia coli. One of the components necessary for this hop is an RNA hairpin structure containing the 5' junction of the 50-nt coding gap. A mutant E. coli was isolated and found to significantly increase hopping when carrying gene 60-lacZ constructs with altered hairpins. The mutation, hop-1, changed Ser93 to Phe in rplI, the gene coding for ribosomal large-subunit protein L9. Ribosomal hopping on a synthetic sequence in the absence of a hairpin was also increased by this mutation. These data suggest that hop-1 may substitute for the function of the hairpin during ribosomal hopping.

Amino Acid Sequence↗
PubMed2002

Absorbed fraction sensitivity to changes in size of the ICRP nose model.

The Human Respiratory Tract Model of ICRP Publication 66 is used for calculations of dose in the extrathorathic (ET1) airways. Scaling for age and body size is included in determining the mass of the target tissue (basal cells) in ET1 but is not included in deriving the absorbed fraction for particulate radiation. For dose calculations, it has been assumed that all absorbed fractions for particulate radiation published in ICRP Publication 66 are independent of age and body size. Therefore, these absorbed fractions are applied to calculate specific effective energy values not only for the Reference Worker but also for non-adults with noses of different sizes. In this note changes to the size of the cylinder model of the anterior nose in ICRP 66 are made by varying the surface area, the cylinder radius, and the thickness of tissue beyond the target region (basal cell). The energy deposition (absorbed fractions) in the target region (basal cells) is calculated using the MCNP4B (Monte Carlo) code to study the effects of these changes on the predicted absorbed fractions within the cylinder model.

Electrons↗
PubMed2000

Development of the gerbil inner ear observed in the hemicochlea.

A frequency-dependent change in hearing sensitivity occurs during maturation in the basal gerbil cochlea. This change takes place during the first week after the onset of hearing. It has been argued that the mass of a given cochlear segment decreases during development and thus increases the best frequency. Changes in mass during cochlear maturation have been estimated previously by measuring the changes in cochlear dimensions. Fixed, dehydrated, embedded, or sputter-coated tissues were used in such work. However, dehydration of the tissue, a part of most histological techniques, results in severe distortion of some aspects of cochlear morphology. The present experiments, using a novel preparation, the hemicochlea, show that hydrated structures, such as the tectorial membrane and the basilar membrane hyaline matrix, are up to 100% larger than estimated previous studies. Therefore, the hemicochlea was used to study the development of cochlear morphology in the gerbil between the day of birth and postnatal day 19. We used no protocols that would have resulted in severe distortion of cochlear elements. Consequently, a detailed study of cochlear morphology yields several measures that differ from previously published data. Our experiments confirm growth patterns of the cochlea that include a period of remarkably rapid change between postnatal day 6 and 8. The accelerated growth starts in the middle of the cochlea and progresses toward the base and the apex. In particular, the increase in height of Deiters' cells dominated the change, "pushing" the tectorial membrane toward scala vestibuli. This resulted in a shape change of the tectorial membrane and the organ of Corti. The tectorial membrane was properly extended above the outer hair cells by postnatal day 12. This time coincides with the onset of hearing. The basilar membrane hyaline matrix increased in thickness, whereas the multilayered tympanic cover layer cells decreased to a single band of cells by postnatal day 19. Before and after the period of rapid growth, the observed gross morphological changes are rather small. It is unlikely that dimensional changes of cochlear structures between postnatal days 12 and 19 contribute significantly in the remapping of the frequency-place code in the base of the cochlea. Instead, structural changes affecting the stiffness of the cochlear partition might be responsible for the shift in best frequency.

Animals↗
PubMed2006

Genetics, development and evolution of adaptive pigmentation in vertebrates.

The study of pigmentation has played an important role in the intersection of evolution, genetics, and developmental biology. Pigmentation's utility as a visible phenotypic marker has resulted in over 100 years of intense study of coat color mutations in laboratory mice, thereby creating an impressive list of candidate genes and an understanding of the developmental mechanisms responsible for the phenotypic effects. Variation in color and pigment patterning has also served as the focus of many classic studies of naturally occurring phenotypic variation in a wide variety of vertebrates, providing some of the most compelling cases for parallel and convergent evolution. Thus, the pigmentation model system holds much promise for understanding the nature of adaptation by linking genetic changes to variation in fitness-related traits. Here, I first discuss the historical role of pigmentation in genetics, development and evolutionary biology. I then discuss recent empirically based studies in vertebrates, which rely on these historical foundations to make connections between genotype and phenotype for ecologically important pigmentation traits. These studies provide insight into the evolutionary process by uncovering the genetic basis of adaptive traits and addressing such long-standing questions in evolutionary biology as (1) are adaptive changes predominantly caused by mutations in regulatory regions or coding regions? (2) is adaptation driven by the fixation of dominant mutations? and (3) to what extent are parallel phenotypic changes caused by similar genetic changes? It is clear that coloration has much to teach us about the molecular basis of organismal diversity, adaptation and the evolutionary process.

Adaptation, Biological↗
PubMed1996

The endosymbiont (Buchnera sp.) of the aphid Diuraphis noxia contains plasmids consisting of trpEG and tandem repeats of trpEG pseudogenes.

Most aphids are dependent for their survival on prokaryotic endosymbionts assigned to the genus Buchnera. Among the functions of Buchnera species is the synthesis of tryptophan, which is required by the aphid host. In Buchnera species from the aphid Diuraphis noxia, the genes for anthranilate synthase (trpEG) were found on a plasmid which consisted of seven tandem repeats of a 3.2-kb unit and one 2.6-kb unit which differed in containing a 0.6-kb deletion. One of the 3.2-kb units contained open reading frames corresponding to trpEG; the remaining units contained trpEG pseudogenes (psi). The nucleotide sequence upstream of trpE contained a region that has characteristics of an origin of replication (ori). Relative to trpB (a chromosomal gene), there were about two copies of the trpEG-containing plasmid. Comparisons of the nucleotide sequences of the 3.2-kb units containing trpEG and psi trpEG indicated that most changes occurred in a 700-nucleotide segment that included the region upstream of trpE and the portion of this gene coding for the N terminus. The consequence of these changes was the silencing of trpEG by inactivation of the putative promoter region and premature termination of the TrpE peptide. In contrast, the nucleotide sequence of the segment corresponding to ori was conserved in the units containing trpEG and psi trpEG. We offer a number of speculations on the evolutionary pressure in this lineage which resulted in the silencing of most of trpEG while still retaining the regions resembling ori.

Animals↗
PubMed2006

State-dependent modulation of time-varying gustatory responses.

Sensory processing is modulated by attention, which is a function of network states. Here we show that changes in such states do more than a simple gating of stimuli: they actually re-arrange cortical coding space to emphasize emotional valences. We delivered taste stimuli to rats before and after a spontaneous state change ("disengagement") that is associated with a reduction in attention and a concurrent emergence of cortical mu rhythms. The percentage of cortical neurons that responded to tastes, and the average response across neurons, remained stable with disengagement, but the particulars of the responses changed drastically. The distinctiveness of sucrose and quinine-which represent the high and low ends of the palatability spectrum-increased, the distinctiveness of the two aversive tastes (quinine and citric acid) decreased, and the distinctiveness of sucrose and NaCl, which were almost identically palatable to start with, did not change. Overall, then, the changes appeared to be palatability-specific. Two additional findings were consistent with this conclusion: rats' palatability-related behavioral responses to the tastes changed in similar ways with disengagement and disengagement-related neural changes specifically appeared late in the response, when palatability-specific information emerges in cortical responses. These data suggest that neural state changes can change the content of neural codes.

Action Potentials↗
PubMed1981

Coordinate transcriptional regulation of type I procollagen genes by Rous sarcoma virus.

Chicken embryo fibroblasts infected with a strain of Rous sarcoma virus containing a temperature-sensitive mutation in the gene coding for pp60src, a protein kinase, undergo changes in collagen synthesis within 4 h after a temperature shift. Cells shifted from the restrictive to the permissive temperature for transformation show decreasing levels of collagen synthesis and increasing levels of kinase activity; the reverse occurs when infected cells are shifted from the permissive to the restrictive temperature. Levels of type I procollagen mRNAs coding for pro alpha 1 and pro alpha 2 chains, measured by hybridization to nick-translated cloned alpha 1 and alpha 2 cDNA, decreased simultaneously soon after a reduction in temperature and reached a new steady state at about 50 h after the shift. In order to test for regulation at the transcriptional level, nuclei were isolated from normal and Rous sarcoma virus-transformed chicken embryo fibroblasts and allowed to transcribe in the presence of [alpha-32P]UTP. Procollagen mRNA sequences in newly synthesized and in total RNA from transformed cell preparations were both about 5-fold lower than the levels in normal cell preparations. We conclude that the coordinate decrease in procollagen mRNAs observed in Rous sarcoma virus-transformed chicken embryo fibroblasts is caused primarily by a decrease in the transcription of the type I procollagen genes, a decrease which is directly or indirectly mediated by the pp60src protein kinase.

Animals↗
PubMed2004

Analysis and recognition of 5' UTR intron splice sites in human pre-mRNA.

Prediction of splice sites in non-coding regions of genes is one of the most challenging aspects of gene structure recognition. We perform a rigorous analysis of such splice sites embedded in human 5' untranslated regions (UTRs), and investigate correlations between this class of splice sites and other features found in the adjacent exons and introns. By restricting the training of neural network algorithms to 'pure' UTRs (not extending partially into protein coding regions), we for the first time investigate the predictive power of the splicing signal proper, in contrast to conventional splice site prediction, which typically relies on the change in sequence at the transition from protein coding to non-coding. By doing so, the algorithms were able to pick up subtler splicing signals that were otherwise masked by 'coding' noise, thus enhancing significantly the prediction of 5' UTR splice sites. For example, the non-coding splice site predicting networks pick up compositional and positional bias in the 3' ends of non-coding exons and 5' non-coding intron ends, where cytosine and guanine are over-represented. This compositional bias at the true UTR donor sites is also visible in the synaptic weights of the neural networks trained to identify UTR donor sites. Conventional splice site prediction methods perform poorly in UTRs because the reading frame pattern is absent. The NetUTR method presented here performs 2-3-fold better compared with NetGene2 and GenScan in 5' UTRs. We also tested the 5' UTR trained method on protein coding regions, and discovered, surprisingly, that it works quite well (although it cannot compete with NetGene2). This indicates that the local splicing pattern in UTRs and coding regions is largely the same. The NetUTR method is made publicly available at www.cbs.dtu.dk/services/NetUTR.

5' Untranslated Regions↗
PubMed1999

Genetic analysis of the guanylate cyclase activator 1B (GUCA1B) gene in patients with autosomal dominant retinal dystrophies.

The guanylate cyclase activator proteins (GCAP1 and GCAP2) are calcium binding proteins which by activating Ret-GC1 play a key role in the recovery phase of phototransduction. Recently a mutation in the GUCA1A gene (coding for GCAP1) mapping to the 6p21.1 region was described as causing cone dystrophy in a British family. In addition mutations in Ret-GC1 have been shown to cause Leber congenital amaurosis and cone-rod dystrophy. To determine whether GCAP2 is involved in dominant retinal degenerative diseases, the GCAP2 gene was screened in 400 unrelated subjects with autosomal dominant central and peripheral retinal dystrophies. A number of changes involving the intronic as well as the coding sequence were observed. In exon 1 a T to C nucleotide change was observed leaving the tyrosine residue 57 unchanged. In exon 3 a 1 bp intronic insertion, a single nucleotide substitution G to A in the intron 3' of this exon, and a GAG to GAT change at codon 155 were observed. This latter change results in a conservative change of glutamic acid to aspartic acid. In exon 4 a 7 bp intronic insertion, a single nucleotide A to G substitution in the intron 5' of this exon, and a single base pair change C to G in the intron 3' of exon 4 were seen. None of these changes would be expected to affect correct splicing of this gene. All these changes were observed in controls. The results of this study do not show any evidence so far that GCAP2 is involved in the pathogenesis of autosomal dominant retinal degeneration in this group of patients. All the changes detected were found to be sequence variations or polymorphisms and not disease causing.

Calcium-Binding Proteins↗
PubMed1999

Hospitalization rates as outcome indicators of national medicinal drug policies: the example of gastrointestinal ulcer.

National medicinal drug policies are employed around the world as a means of maximizing the benefits of medication use. An essential component to the implementation of these policies is their concurrent evaluation, which informs future policy implementation and strategic directions. The overall effect of the policy can be measured by monitoring changes in health outcomes and hospitalization rates for conditions that can be managed with appropriate medication use have been proposed as a potential outcome indicator of national medicinal drug policies. In this paper, a method for establishing the validity of this indicator is described. The method enables suitable conditions to be identified and takes into account potential confounding factors. To demonstrate this a case study of hospitalization rates for gastrointestinal ulcer is presented. The analysis shows that hospitalization rates are suitable as outcome indicators of quality medication use where the hospitalization rate is not confounded by changes in the population profile, disease prevalence and severity, diagnosis, hospital based policies, coding practices, environmental factors or hospital based treatments, but is responsive to changes in the utilization of medication. This method could be used in many countries for determining relevant and valid indicators for monitoring health outcomes.

Journal Article↗
PubMed1992

Disturbance of fluid homeostasis leads to temporally and anatomically distinct responses in neuropeptide and tyrosine hydroxylase mRNA levels in the paraventricular and supraoptic nuclei of the rat.

The response of six mRNAs (for prepro-corticotropin-releasing hormone, prepro-enkephalin, prepro-vasoactive intestinal polypeptide/peptide histidine isoleucine, prepro-neurotensin/neuromedin N, prepro-cholecystokinin, and prepro-tyrosine hydroxylase) was measured in the hypothalamic paraventricular and supraoptic nuclei after increasing periods of osmotic stimulation caused by the replacement of regular drinking water with hypertonic saline (up to five days) or by forced dehydration (up to three days). In addition, hematocrits and concentrations of corticosterone were determined after the different periods of osmotic stimulation and correlated with the effects on the content of the various mRNAs. The temporal response of the mRNAs within the paraventricular and supraoptic nuclei to osmotic stimulation was different within the three compartments of these nuclei. First, in response to overnight osmotic stimulation, magnocellular neurosecretory neurons increased their mRNA content for two molecules (prepro-corticotropin-releasing hormone and tyrosine hydroxylase). As the stimulus was maintained over the next two to four days, these cells accumulated the mRNAs for at least three other peptides (cholecystokinin, vasoactive intestinal polypeptide/peptide histidine isoleucine and enkephalin). Second, the response of peptide-coding mRNAs in parvicellular neurosecretory neurons of the paraventricular nucleus appeared to be slower; no changes could be measured after overnight stimulation. However, after a further two- to four-days of continued osmotic stimulation, the content of the mRNA coding for corticotropin-releasing hormone markedly decreased while that for cholecystokinin increased. No change in the content of the mRNAs coding for prepro-vasoactive intestinal polypeptide/peptide histidine isoleucine, enkephalin, and prepro-neurotensin/neuromedin N could be seen at any time after osmotic stimulation in parvicellular neurosecretory neurons. Third, increases in the content of mRNA coding for corticotropin-releasing hormone in the parvicellular neurons that provide descending projections from the paraventricular nucleus could only be detected after longer periods of osmotic stimulation. The effect of osmotic stimulation on plasma corticosterone concentrations was quickly apparent; plasma corticosterone concentrations were significantly elevated on the first morning after the beginning of salt-loading, and demonstrated the rapid effects of osmotic stimulation on the mechanisms controlling corticosterone release. These results show that the synthetic capability of cells in all three compartments of the paraventricular and supraoptic nuclei are modified by osmotic stimulation over different time scales, thereby allowing differential modulation of the neuroendocrine, autonomic, and behavioral components of the animal's response to disturbances in fluid homeostasis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2006

[Histone variants and histone exchange].

Histones, as the basic components of nucleosome, are essential to chromatin structure and function. To adapt to various states of chromatin, corresponding histone variants are incorporated in nucleosome, and certain modifications also occur on the variants' tails. These variants change the conformation and stability of nucleosome to facilitate transcriptional activation or deactivation, DNA repairing, heterochromatin formation, and others. During histone exchange, chromatin remodeling complex facilitates histone variant deposition into nucleosome, and different variants have diverse deposition pathways. Recently, research on histone variants is not only a new hotspot in epigenetics, but also a new annotation of "histone code". In addition, histone exchange reveals new changing mechanism of DNA-histone interaction.

Animals↗
PubMed2003

Plastic cortical changes induced by learning to communicate with non-speech sounds.

With Morse code, an acoustic message is transmitted using combinations of tone patterns rather than the spectrally and temporally complex speech sounds that constitute the spoken language. Using MEG recordings of the mismatch negativity (MMN, an index of permanent auditory cortical representations of native language speech sounds), we probed the dominant hemisphere for the developing Morse code representations in adult Morse code learners. Initially, the MMN to the Morse coded syllables was, on average, stronger in the hemisphere opposite to the one dominant for the MMN to native language speech sounds. After a training period of 3 months, the pattern reversed, however: the mean Morse code MMN became lateralized to the hemisphere that was predominant for the speech-sound MMN. This suggests that memory traces for the Morse coded acoustic language units develop within the hemisphere that already accommodates the permanent traces for natural speech sounds. These plastic changes manifest, presumably, the close associations formed between the neural representations of the tone patterns and phonemes.

Acoustic Stimulation↗
PubMed1995

The effects of changes in the law concerning mentally disordered offenders: the Alberta experience with Bill C-30.

OBJECTIVE: Until recently, the Criminal Code of Canada, enacted in 1892, stood stalwart to social, political and technological changes, particularly with respect to the regulations pertaining to the management of the mentally ill offender. This became more definitely so with the enactment of the Canadian Charter of Rights and Freedoms (1984) as many regulations in the Code about mentally ill offenders contravened the mandates contained in the Charter. The Supreme Court of Canada's decision on Regina v. Swain spurred the Federal Government to bring the regulations on the mentally ill offender into line with the Charter. The result was the enactment of Bill C-30 which was intended to dramatically change the way in which forensic psychiatry was practised in Canada. This paper presents the Alberta findings from a multi-site evaluation commissioned by the Federal Department of Justice to judge the effects of Bill C-30 on forensic health care practices. METHODS: Health records data were used to compare utilization patterns from the year prior to the enactment of Bill C-30 with the year following. In addition, qualitative data were obtained from key clinical and legal informants outlining implementation difficulties that they had experienced. RESULTS: Results support the judgement that Bill C-30 has not achieved its desired effects with respect to the length of the remand, and has resulted in an increased burden on hospitals and health care providers. In addition, an unanticipated finding was the increased use of the Mental Health Act which was considered to place forensic patients in a position of double jeopardy.

Adult↗
PubMedDate not supplied

Cloning and molecular analysis of two different ILV5 genes from a brewing strain of Saccharomyces cerevisiae.

Two different ILV5 genes encoding acetohydroxy-acid isomeroreductases, and named ILV5G and ILV5X, were cloned and sequenced from a Saccharomyces cerevisiae brewing strain. The coding sequence of ILV5X shows a single nucleotide change with respect to that from the ILV5 gene of a S. cerevisiae laboratory strain. In addition, all promoter motifs which are, or are presumed to be, implicated in transcription regulatory functions are identical in ILV5 and ILV5X. In contrast, the coding sequence of ILV5G differs in 5.6% of its nucleotides from that of ILV5 and most of its promoter regulatory motifs show a single nucleotide change with respect to those from ILV5.

2-Acetolactate Mutase↗
PubMed2001

Medicare program; revisions to payment policies and five-year review of and adjustments to the relative value units under the physician fee schedule for calendar year 2002. Final rule with comment period.

This final rule with comment period makes several changes affecting Medicare Part B payment. The changes affect: refinement of resource-based practice expense relative value units (RVUs); services and supplies incident to a physician's professional service;anesthesia base unit variations;recognition of CPT tracking codes; and nurse practitioners, physician assistants, and clinical nurse specialists performing screening sigmoidoscopies. It also addresses comments received on the June 8, 2001 proposed notice for the 5-year review of work RVUs and finalizes these work RVUs. In addition,we acknowledge comments received on our request for information on our policy for CPT modifier 62 that is used to report the work of co-surgeons. The rule also updates the list of certain services subject to the physician self-referral prohibitions to reflect changes to CPT codes and Healthcare Common Procedure Coding System codes effective January 1, 2002. These refinements and changes will ensure that our payment systems are updated to reflect changes in medical practice and the relative value of services. The Medicare, Medicaid, and SCHIP Benefits Improvement and Protection Act of 2000 modernizes the mammography screening benefit and authorizes payment under the physician fee schedule effective January 1, 2002; provides for biennial screening pelvic examinations for certain beneficiaries effective July 1, 2001; provides for annual glaucoma screenings for high-risk beneficiaries effective January 1,2002; expands coverage for screening colonoscopies to all beneficiaries effective July 1, 2001; establishes coverage for medical nutrition therapy services for certain beneficiaries effective January 1, 2002; expands payment for telehealth services effective October 1, 2001; requires certain Indian Health Service providers to be paid for some services under the physician fee schedule effective July 1, 2001; and revises the payment for certain physician pathology services effective January 1, 2001. This final rule will conform our regulations to reflect these statutory provisions. In addition, we are finalizing the calendar year (CY) 2001 interim RVUs and are issuing interim RVUs for new and revised procedure codes for calendar year (CY) 2002. As required by the statute, we are announcing that the physician fee schedule update for CY2002 is -4.8 percent, the initial estimate of the Sustainable Growth Rate (SGR) for CY 2002 is 5.6 percent, and the conversion factor for CY 2002 is $36.1992.

Fee Schedules↗