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C A Wilson

Publications and source records attributed to C A Wilson.

At least 19 recordsLinked to original sources
PubMed2006

Evidence for a stimulatory action of melanin-concentrating hormone on luteinising hormone release involving MCH1 and melanocortin-5 receptors.

The present series of studies aimed to further our understanding of the role of melanin-concentrating hormone (MCH) neurones in the central regulation of luteinising hormone (LH) release in the female rat. LH release was stimulated when MCH was injected bilaterally into the rostral preoptic area (rPOA) or medial preoptic area (mPOA), but not when injected into the zona incerta (ZI), of oestrogen-primed ovariectomised rats. In rats that were steroid-primed to generate a surge-like release of LH, MCH administration into the ZI blocked this rise in LH release: no such effect occurred when MCH was injected into the rPOA or mPOA. In vitro, MCH stimulated gonadotrophin-releasing hormone (GnRH) release from hypothalamic explants. Double-label immunohistochemistry showed GnRH-immunoreactive neurones in the vicinity of and intermingled with immunoreactive MCH processes. MCH is the endogenous ligand of the MCH type 1 receptor (MCH1-R). Previously, we have shown a role for melanocortin-5 receptors (MC5-R) in the stimulatory action of MCH, so we next investigated the involvement of both MCH1-R and/or MC5-R in mediating the actions of MCH on GnRH and hence LH release. The stimulatory action of MCH in the rPOA was inhibited by administration of antagonists for either MCH1-R or MC5-R. However, in the mPOA, the action of MCH was blocked only by the MC5-R antagonist. LH release was stimulated by an agonist for MC5-R injected into the rPOA or mPOA; this was blocked by the MC5-R antagonist but not the MCH1-R antagonist. These results indicate that both MCH1-R and MC5-R are involved in the central control of LH release by MCH.

Animals↗
PubMed2006

Mice transgenic for a human porcine endogenous retrovirus receptor are susceptible to productive viral infection.

Porcine endogenous retrovirus (PERV) is considered one of the major risks in xenotransplantation. No valid animal model has been established to evaluate the risks associated with PERV transmission to human patients by pig tissue xenotransplantation or to study the potential pathogenesis associated with PERV infection. In previous work we isolated two genes encoding functional human PERV receptors and proved that introduction of these into mouse fibroblasts allowed the normally nonpermissive mouse cells to become productively infected (T. A. Ericsson, Y. Takeuchi, C. Templin, G. Quinn, S. F. Farhadian, J. C. Wood, B. A. Oldmixon, K. M. Suling, J. K. Ishii, Y. Kitagawa, T. Miyazawa, D. R. Salomon, R. A. Weiss, and C. Patience, Proc. Natl. Acad. Sci. USA 100:6759-6764, 2003). In the present study we created mice transgenic for human PERV-A receptor 2 (HuPAR-2). After inoculation of transgenic animals with infectious PERV supernatants, viral DNA and RNA were detected at multiple time points, indicating productive replication. This establishes the role of HuPAR-2 in PERV infection in vivo; in addition, these transgenic mice represent a new model for determining the risk of PERV transmission and potential pathogenesis. These mice also create a unique opportunity to study the immune response to PERV infection and test potential therapeutic or preventative modalities.

Animals↗
PubMed2005

Thermal insulation and SIDS-an investigation of selected 'Eastern' and 'Western' infant bedding combinations.

BACKGROUND: Differences in the incidence of SIDS between 'Western' and 'Eastern' countries has been attributed to cultural practices, which may affect the infants care and thermal environment. AIM: The purpose of this work was to estimate for selected 'commonly' used bedding, sleep positions and practices in Japan, Korea and New Zealand, the intrinsic 'dry' thermal resistance of bedding. Insulation levels are also discussed in the context of published information about the thermal environment in which the bedding is likely to be used. METHOD: Selected Japanese, Korean and New Zealand bedding was loosely tucked over an infant manikin in the lateral, prone and supine sleep positions. Thickness in use was measured, and intrinsic 'dry' thermal resistance estimated using the Wilson Laing model which accommodates the effect on insulation of the three-dimensional arrangement of bedding combinations during use. RESULTS AND DISCUSSION: Thickness of under- and upper-bedding varied among countries with thickness and estimated 'dry' thermal resistance of the upper-bedding affected by the type/combination of bedding and the infants sleep position. Insulation levels are discussed in relation to environmental conditions within and among countries and between seasons. Further information on thermal environments, bedding combinations used and care practices within both Asian and Western countries is needed. CONCLUSIONS: 'Eastern' infants appear likely to be generally covered in bedding combinations of greater insulation than those used to cover 'Western' infants in comparable seasons. Differences existed between insulation of the Japanese and Korean bedding combinations investigated. Lower rates of SIDS apparent in 'Asian' populations do not appear attributable to use of lower levels of bedding insulation only.

Bedding and Linens↗
PubMed2005

Leptin expression in the fetus and placenta during mouse pregnancy.

During pregnancy, leptin concentrations in the maternal circulation are elevated in both humans and rodents but decrease to pre-pregnancy levels at birth, suggesting a role for leptin in the maintenance of pregnancy. Synthesis of leptin by the human placenta is established but whether the murine placenta synthesizes leptin remains controversial. The aims of this study were to determine (a) if the mouse wild-type placenta expresses the ob gene using Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and (b) whether the mouse fetus and placenta contribute to the significant increase of leptin in the maternal circulation during pregnancy. The mouse placenta did not express the ob gene at a level that could be readily detected using RT-PCR. Moreover, both maternal gain in weight and undetectable concentrations of leptin in sera in leptin-deficient ob/ob mothers bearing heterozygote (ob/+) fetuses suggested that the mouse fetus and placenta do not make a significant contribution to the dramatic increase in maternal plasma concentrations of leptin during late gestation. It is therefore concluded that neither fetal- nor placental-derived leptin modulates maternal weight gain during pregnancy.

Amniotic Fluid↗
PubMed2005

Effects of the cannabinoid CB1 receptor antagonist SR141716 on oxygen consumption and soleus muscle glucose uptake in Lep(ob)/Lep(ob) mice.

OBJECTIVE: To investigate the effect of SR141716, a selective CB1 receptor antagonist, on energy expenditure and on glucose uptake in isolated soleus muscle of Lep(ob)/Lep(ob) mice. DESIGN: Female Lep(ob)/Lep(ob) mice (8-10 weeks old) were treated with SR141716 (10 mg/kg, i.p. once daily) or vehicle for 7 days. MEASUREMENTS: Oxygen consumption, daily food and water intake, body weight and glucose uptake in isolated soleus muscle. RESULTS: SR141716 (10 mg/kg, i.p. once daily) resulted in a significant reduction of daily food intake (P<0.01) and body weight (P<0.05) 5 days after daily treatment. Body weight continued to be lower for the rest of the treatment period (P<0.05). There was no significant difference in body weight between the pair-fed and vehicle-treated animals. A 7-day treatment with SR141716 (10 mg/kg, i.p. once daily) caused 37% increase in basal oxygen consumption compared to that of vehicle-treated (90 min mean; P<0.01), and a significant 68% increase in glucose uptake in isolated soleus muscle preparations. CONCLUSION: It is concluded that SR141716 has a direct effect on energy expenditure suggesting that the antiobesity effect of SR141716 is due to activation of thermogenesis in addition to the initial hypophagia. The increase in soleus muscle glucose uptake with SR141716 treatment may contribute to the improved glycaemia seen in the previous studies.

Animals↗
PubMed2005

Pre-vitamin D effective ultraviolet transmission through clothing during simulated wear.

BACKGROUND/PURPOSE: Clothing is an important protective layer used to reduce ultraviolet (UV) exposures to the skin surface. However, not all UV exposure is linked to detrimental health effects with some exposure to UVB wavelengths below 316 nm required for the synthesis of pre-vitamin D(3). The aim of the current research was to investigate the effect of fabric type, color, fit, and wetness on the transmission of pre-vitamin D(3) effective UV through garments during simulated wear, in a high UV exposure environment. METHODS: Dosimeters fabricated from polysulfone film were positioned at eight selected body sites on the skin surface and clothing surface of identically designed, loose and fitted, black and white T-shirts made up in two knitted fabric types and tested when both dry and when drying after initial wetting (n=3 replicates). The T-shirts were placed on manikins set to simulate humans in the sun between 09:30 and 12:30 Eastern Standard Time during the Southern Hemisphere summer period. The post-exposure absorbance was measured and the dosimeters were calibrated for biologically effective UV for pre-vitamin D(3) synthesis with a UV spectroradiometer. The effect of fit, fabric type, color, and wetness on pre-vitamin D(3) effective UV transmission during simulated wear was assessed. RESULTS: Irradiances varied among body sites with the highest erythemal exposures to a horizontal plane over the 3 h period reaching approximately 14.5 minimal erythema dose (MED) while the highest exposure under the garment was 0.22 MED which may not be above the threshold for pre-vitamin D(3) synthesis for the time period investigated. Fabric and fit were the main variables affecting transmission of pre-vitamin D(3) effective UV. Some interactions were identified between the fabric color and wetness and between fabric type and color; however, while significantly modifying transmission these effects were small. CONCLUSION: Transmission of pre-vitamin D(3) effective UV occurred through the high UPF knitted fabrics investigated. However, the length of exposure will influence whether the irradiances are sufficient to be above the threshold for pre-vitamin D(3) synthesis. The main effect on transmission of pre-vitamin D(3) effective UV was the fit of the T-shirt and its fabric type (probably structure) rather than color or degree of wetness.

Clothing↗
PubMed2004

Neonatal 5HT activity antagonizes the masculinizing effect of testosterone on the luteinizing hormone release response to gonadal steroids and on brain structures in rats.

Hypothalamic 5HT concentrations are transiently lower in male compared to female Wistar rats in the second week post partum (pp) and our previous findings have shown that pharmacologically potentiating 5HT activity over this period feminizes certain aspects of sexually differentiated behaviours in adult males and androgenized females. In order to investigate whether neonatal testosterone and 5HT interact to influence physiological and morphological brain sexual differences, females, androgenized females and males were treated with the 5HT2 agonist (-) [2,5 dimethoxy-4-iodophenyl]-2-amino propane HCl [(-) DOI], over days 8-16 pp. In androgenized females (250 microg testosterone proprionate, day 2 pp) (-) DOI prevented the delay in vaginal opening, but did not prevent the androgen-induced constant oestrus in females treated with 100 microg TP, day 2 pp. (-) DOI overcame the neonatal androgen effect in suppressing the positive feedback of ovarian steroids in a few males and androgenized females. (-) DOI had a feminizing effect on the volume of the anteroventral periventricular nucleus (normally smaller in males), by significantly increasing its volume in male and androgenized females. It also had a significant antagonistic effect on the testosterone-induced increase in the volume of the sexually dimorphic nucleus of the preoptic area in males and androgenized females. These findings support the view that raised 5HT activity in the second week of life antagonizes the masculinizing effect of neonatal testosterone.

Animals↗
PubMed2003

Central orexin A has site-specific effects on luteinizing hormone release in female rats.

Orexin A stimulates GnRH release from hypothalamic explants in vitro. The sites of action of orexin A in the regulation of LH release have been investigated in vivo in ovariectomized rats that were given vehicle or estradiol benzoate (EB), with or without an injection of progesterone 48 h later. Orexin A was administered intrahypothalamically under Saffan anesthesia, 50 h after the EB or vehicle; its effects on plasma LH levels were monitored in sequential blood samples. Orexin A (1.0 microg/side) injected into the rostral preoptic area (rPOA) at the level of the organum vasculosum of the lamina terminalis had a stimulatory effect on LH release in EB-treated ovariectomized rats. When orexin A was injected into the medial POA (mPOA) or the arcuate/median eminence, it had an inhibitory effect on the LH surge that occurs in ovariectomized rats primed with EB plus progesterone. Orexin A injected into the mPOA also reduced LH levels in ovariectomized rats untreated with ovarian steroids. Both the stimulatory and inhibitory effects of orexin A were antagonized by SB334867A, a selective orexin 1 receptor antagonist. Furthermore, when given alone into the rPOA, this antagonist attenuated the LH surge induced by EB plus progesterone. Thus, orexin appears to have a dual effect on LH release, being stimulatory in the rPOA and inhibitory in the mPOA or arcuate/median eminence. Both effects may be mediated, at least in part, by the orexin 1 receptor. Double label immunohistochemistry revealed close appositions between orexin A immunoreactive varicosities and a small proportion of GnRH cell bodies in the rPOA. It is suggested that the stimulatory effect of orexin A on LH release may involve direct actions on GnRH neurons.

Animals↗
PubMed2002

Death of HT29 adenocarcinoma cells induced by TNF family receptor activation is caspase-independent and displays features of both apoptosis and necrosis.

The HT29 adenocarcinoma is a common model of epithelial cell differentiation and colorectal cancer and its death is an oft-analyzed response to TNF family receptor signaling. The death event itself remains poorly characterized and here we have examined the involvement of caspases using pan-caspase inhibitors. zVAD-fmk did not block death of HT29 cells in response to activation of the Fas, TRAIL, TNF, TWEAK and LTbeta receptors. The secondary induction of TNF or the other known bona fide death inducing ligands did not account for death following LTbeta receptor activation indicating that TNF family receptors can trigger a caspase-independent death pathway regardless of the presence of canonical death domains in the receptor. To provide a frame of reference, the phenotype of HT29 death was compared to four other TNF family receptor triggered death events; Fas induced Jurkat cell apoptosis, TNF/zVAD induced L929 fibroblast necrosis, TNF induced death of WEHI 164 fibroblastoid cells and TNF/zVAD induced U937 death. The death of HT29 and U937 cells under these conditions is an intermediate form with both necrotic and apoptotic features. The efficient coupling of TNF receptors to a caspase-independent death event in an epithelial cell suggests an alternative approach to cancer therapy.

Active Transport, Cell Nucleus↗
PubMed2001

PartsList: a web-based system for dynamically ranking protein folds based on disparate attributes, including whole-genome expression and interaction information.

As the number of protein folds is quite limited, a mode of analysis that will be increasingly common in the future, especially with the advent of structural genomics, is to survey and re-survey the finite parts list of folds from an expanding number of perspectives. We have developed a new resource, called PartsList, that lets one dynamically perform these comparative fold surveys. It is available on the web at http://bioinfo.mbb.yale.edu/partslist and http://www.partslist.org. The system is based on the existing fold classifications and functions as a form of companion annotation for them, providing 'global views' of many already completed fold surveys. The central idea in the system is that of comparison through ranking; PartsList will rank the approximately 420 folds based on more than 180 attributes. These include: (i) occurrence in a number of completely sequenced genomes (e.g. it will show the most common folds in the worm versus yeast); (ii) occurrence in the structure databank (e.g. most common folds in the PDB); (iii) both absolute and relative gene expression information (e.g. most changing folds in expression over the cell cycle); (iv) protein-protein interactions, based on experimental data in yeast and comprehensive PDB surveys (e.g. most interacting fold); (v) sensitivity to inserted transposons; (vi) the number of functions associated with the fold (e.g. most multi-functional folds); (vii) amino acid composition (e.g. most Cys-rich folds); (viii) protein motions (e.g. most mobile folds); and (ix) the level of similarity based on a comprehensive set of structural alignments (e.g. most structurally variable folds). The integration of whole-genome expression and protein-protein interaction data with structural information is a particularly novel feature of our system. We provide three ways of visualizing the rankings: a profiler emphasizing the progression of high and low ranks across many pre-selected attributes, a dynamic comparer for custom comparisons and a numerical rankings correlator. These allow one to directly compare very different attributes of a fold (e.g. expression level, genome occurrence and maximum motion) in the uniform numerical format of ranks. This uniform framework, in turn, highlights the way that the frequency of many of the attributes falls off with approximate power-law behavior (i.e. according to V(-b), for attribute value V and constant exponent b), with a few folds having large values and most having small values.

Cysteine↗
PubMed2001

The effect of partial vitrectomy on blood-ocular barrier function in the rabbit.

PURPOSE: To compare ocular vascular permeability in the rabbit after vitrectomy as assessed by contrast-enhanced magnetic imaging (CE-MRI) and measurements of aqueous and vitreous humor protein concentration. METHODS: Partial vitrectomies were performed, irrigating with BSS or BSS PLUS. Post-operative vascular leakage was determined by CE-MRI following intravenous administration of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Aqueous and vitreous protein concentrations were quantified by standard biochemical assay. ERG evaluations were performed on postoperative days 1, 3, and 7. RESULTS: Using BSS as irrigant, breakdown of the inner blood-retinal barrier (BRB) occurred in 4/7 eyes on post-operative day 1. The rate of Gd-DTPA leakage was significantly greater on postoperative day 1 than that in unoperated, control eyes, but declined approximately 50% by day 3. At both time points, outer BRB breakdown was restricted to the sclerotomy wounds. No BRB leakage was detectable in control eyes. Blood-aqueous barrier (BAB) leakage was bilateral on day 1. Significantly greater Gd-DTPA leakage occurred in the operated eye than in the nonsurgical contralateral eye. On day 3, approximately 40% bilateral reduction in leakage indicated resolution of BAB leakage. Notably, Gd-DTPA leakage of the BAB and BRB was significantly reduced in the BSS PLUS treated group. In contrast to MRI assessments, protein concentrations of the aqueous and vitreous in the surgical eye showed no detectable differences between BSS and BSS PLUS. Concurrent with the transient loss of ocular barrier function, ERG responses also declined. However, by day 7 greater than 90% recovery was noted in BSS PLUS treated animals but not in the BSS treatment group. CONCLUSIONS: CE-MRI is capable of detecting subtle changes in vascular permeability following ocular surgery. Advantages of using BSS PLUS compared to BSS as the irrigating solution can be detected using this technique. BSS PLUS's protection of barrier function is consistent with a rapid recovery in retinal function not observed in BSS treated eyes.

Animals↗
PubMed2001

Detection and characterization of porcine endogenous retrovirus in porcine plasma and porcine factor VIII.

The pig genome contains porcine endogenous retroviruses (PERVs) capable of infecting human cells. Detection of infectious retrovirus in porcine peripheral blood mononuclear cells and endothelial cells suggested to us that pig plasma is likely to contain PERV. Both PERV env sequences and viral reverse transcriptase (RT) activity were detected in all plasma samples isolated from four NIH minipigs. To detect infectious virus from plasma, we performed a culture assay using three cell lines of feline, swine, and human origin that had previously been shown to be permissive for PERV. Infectious virus was successfully cultured from all four NIH minipig plasmas on the swine cell line ST-IOWA. Using RT-PCR with env-specific primers, we could detect expression of PERV class C envelope in the supernatant of ST-IOWA cells that had been exposed to each pig plasma. We next examined a pig plasma derivative, Hyate:C (porcine factor VIII), and found evidence of PERV particles, since all six lots examined were positive for PERV RNA and RT activity. However, infectious virus could not be detected in clinical lots of Hyate:C, suggesting that the manufacturing process might reduce the load of infectious virus to levels below detectable limits of the assay. Detection of infectious virus in porcine plasma confirms and extends the previous findings that certain porcine cells express PERV when manipulated in vitro and clearly demonstrates that there are porcine cells that express infectious PERV constitutively in vivo.

Animals↗
PubMed2001

Age related changes in the tunica media of the vertebral artery: implications for the assessment of vessels injured by trauma.

AIMS: To provide an illustrated, detailed semiquantitative analysis of the important degenerative changes along the length of the vertebral artery so that pathologists faced with investigating a fatal arterial injury can identify important pre-existing wall abnormalities. METHODS: Ten transverse annuli were taken along 34 vertebral arteries from 17 subjects and stained sections were prepared using haematoxylin and eosin and the picro-sirius red method. After routine microscopy, the elastic fibres, collagen, and smooth muscle nuclei in the tunica media were quantified using an eyepiece graticule. An estimate of the severity and extent of elastic tissue fragmentation, collagenous scarring, and intimal thickening/atheroma was then undertaken. RESULTS: Smooth muscle counts remained constant along the artery but collagen counts were higher and elastic counts substantially lower within the intracranial segment. Elastic fibre fragmentation was recognised in infancy and was moderately advanced by early adulthood but considerable collagenous scarring developed later in life. Some individuals demonstrated severe fragmentation and scarring before the age of 35 years. The degenerative changes were often focal and spared the intracranial segment almost completely. Atheroma increased with age but was rarely severe and appeared not to worsen appreciably beyond the age of 40 years. An unusual arrangement of the collagenous tissue was described within the upper cervical loops. CONCLUSION: Damaged vertebral arteries need to be sampled extensively to allow a proper histological assessment. The picro-sirius red method was successful in delineating the fine connective tissue structure of the wall and early degenerative changes. An understanding of the age and site specific changes should allow the pathologist to recognise important pre-existing abnormalities more easily.

Adolescent↗
PubMed2001

Leptin requirement for conception, implantation, and gestation in the mouse.

The ob/ob mouse has a complete absence of circulating leptin, resulting in obesity and infertility. Using the minimum daily dose of leptin required to maintain normal body weight and sexual maturation (5 mg/kg, ip), leptin-treated ob/ob females were mated with either wild-type (+/+) or leptin-treated ob/ob males. The leptin treatment continued throughout pregnancy until weaning or was withdrawn at 0.5, 3.5, 6.5, or 14.5 d post coitum (dpc). Normal pregnancy and parturition with pups of normal weight resulted when ob/ob females were mated with +/+ males and leptin treatment was continued throughout pregnancy (6 of 8 pregnancies), to 14.5 dpc (6 of 8 pregnancies), or to 6.5 dpc (9 of 12 pregnancies). Pregnancy did not result when treatment was stopped at 3.5 dpc (1 of 7 pregnancies) or 0.5 dpc (0 of 6 pregnancies). Similar results were obtained when leptin-treated ob/ob females were mated with leptin-treated ob/ob males. The newborn pups failed to survive after birth in groups treated with leptin up to 14.5 and 6.5 dpc despite reinstating leptin at birth. This appeared to be due to a lack of development of the mammary glands. In conclusion, we have shown that leptin is essential for normal preimplantation and/or implantation processes. It is also essential for normal development of the mammary glands, but is not required for pregnancy and parturition once implantation is established.

Animals↗
PubMed2000

Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice.

Animal donors such as pigs could provide an alternative source of organs for transplantation. However, the promise of xenotransplantation is offset by the possible public health risk of a cross-species infection. All pigs contain several copies of porcine endogenous retroviruses (PERV), and at least three variants of PERV can infect human cell lines in vitro in co-culture, infectivity and pseudotyping experiments. Thus, if xenotransplantation of pig tissues results in PERV viral replication, there is a risk of spreading and adaptation of this retrovirus to the human host. C-type retroviruses related to PERV are associated with malignancies of haematopoietic lineage cells in their natural hosts. Here we show that pig pancreatic islets produce PERV and can infect human cells in culture. After transplantation into NOD/SCID (non-obese diabetic, severe combined immunodeficiency) mice, we detect ongoing viral expression and several tissue compartments become infected. This is the first evidence that PERV is transcriptionally active and infectious cross-species in vivo after transplantation of pig tissues. These results show that a concern for PERV infection risk associated with pig islet xenotransplantation in immunosuppressed human patients may be justified.

Animals↗
PubMed2000

Assessing annotation transfer for genomics: quantifying the relations between protein sequence, structure and function through traditional and probabilistic scores.

Measuring in a quantitative, statistical sense the degree to which structural and functional information can be "transferred" between pairs of related protein sequences at various levels of similarity is an essential prerequisite for robust genome annotation. To this end, we performed pairwise sequence, structure and function comparisons on approximately 30,000 pairs of protein domains with known structure and function. Our domain pairs, which are constructed according to the SCOP fold classification, range in similarity from just sharing a fold, to being nearly identical. Our results show that traditional scores for sequence and structure similarity have the same basic exponential relationship as observed previously, with structural divergence, measured in RMS, being exponentially related to sequence divergence, measured in percent identity. However, as the scale of our survey is much larger than any previous investigations, our results have greater statistical weight and precision. We have been able to express the relationship of sequence and structure similarity using more "modern scores," such as Smith-Waterman alignment scores and probabilistic P-values for both sequence and structure comparison. These modern scores address some of the problems with traditional scores, such as determining a conserved core and correcting for length dependency; they enable us to phrase the sequence-structure relationship in more precise and accurate terms. We found that the basic exponential sequence-structure relationship is very general: the same essential relationship is found in the different secondary-structure classes and is evident in all the scoring schemes. To relate function to sequence and structure we assigned various levels of functional similarity to the domain pairs, based on a simple functional classification scheme. This scheme was constructed by combining and augmenting annotations in the enzyme and fly functional classifications and comparing subsets of these to the Escherichia coli and yeast classifications. We found sigmoidal relationships between similarity in function and sequence, with clear thresholds for different levels of functional conservation. For pairs of domains that share the same fold, precise function appears to be conserved down to approximately 40 % sequence identity, whereas broad functional class is conserved to approximately 25 %. Interestingly, percent identity is more effective at quantifying functional conservation than the more modern scores (e.g. P-values). Results of all the pairwise comparisons and our combined functional classification scheme for protein structures can be accessed from a web database at http://bioinfo.mbb.yale.edu/alignCopyright 2000 Academic Press.

Animals↗
PubMed2000

The influence of gonadal steroids on pre-pro melanin-concentrating hormone mRNA in female rats.

Melanin-concentrating hormone (MCH) may have a regulatory role in the control of luteinizing hormone (LH) release. We have investigated if gonadal steroids induce changes in the expression of pre-pro MCH (ppMCH) that are associated with changes in the pattern of LH release. Using quantitative in-situ hybridization histochemistry we have determined the effect of administration of either oestradiol benzoate (5 microg/rat) or oestradiol benzoate followed 44 or 48 h later by progesterone (0.5 mg/rat) to ovariectomized rats on the expression of ppMCH in the medial and lateral zona incerta and the lateral hypothalamus. The prevalence of ppMCH transcripts in the intact female rat at 12.00 and 19.00 h on proestrus and the first day of dioestrus was also examined. Oestrogen reduced the intensity of hybridization signal for ppMCH mRNA and this was associated with both a decrease in the number of cells in which the message was detected in the medial zona incerta and a negative feedback effect on LH release in ovariectomized rats. Progesterone administration to oestradiol benzoate-primed rats did not alter the reduced expression in the medial zona incerta in spite of its positive feedback effect on LH release. We suggest that progesterone may act only on post-translational events. Expression in the MCH cell bodies of the lateral zona incerta were not affected but there was a transient decrease 4 h after progesterone treatment in the oestradiol benzoate-primed rats in expression in the lateral hypothalamus. No changes in ppMCH mRNA were seen in intact animals on proestrus or the first day of dioestrus indicating that gonadal steroids are not important in the modulation of ppMCH gene expression during the oestrous cycle. In other steroid-dependent physiological situations, however, oestrogen may influence the expression of ppMCH in a subpopulation of cell bodies in the medial zona incerta.

Animals↗