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PubMed2001

Glycogen synthase kinase-3beta regulates presenilin 1 C-terminal fragment levels.

The majority of familial Alzheimer's disease cases have been attributed to mutations in the presenilin 1 (PS1) gene. PS1 is synthesized as an inactive holoprotein that undergoes endoproteolytic processing to generate a functional N- and C-terminal heterodimer (NTF and CTF, respectively). We identified a single residue in PS1, Ser(397), which regulates the CTF levels in a population of dimer that has a rapid turnover. This residue is part of a highly conserved glycogen synthase kinase-3beta (GSK-3beta) consensus phosphorylation site within the loop domain of PS1. Site-directed mutagenesis at the Ser(397) position increased levels of PS1 CTF but not NTF or holoprotein. Similar increases in only CTF levels were seen when cells expressing wild type PS1 were treated with lithium chloride, an inhibitor of GSK-3beta. Both wild type and PS1 S397A CTF displayed a biphasic turnover, reflecting rapidly degraded and stable populations. Rapid turnover was delayed for mutant PS1 S397A, causing increased CTF. These data demonstrate that PS1 NTF.CTF endoproteolytic fragments are generated in excess, that phosphorylation at Ser(397) by GSK-3beta regulates the discard of excess CTF, and that the disposal of surplus NTF is mediated by an independent mechanism. Overall, the results indicate that production of active NTF.CTF dimer is more complex than limited endoproteolysis of PS1 holoprotein and instead involves additional regulatory events.

Amino Acid Motifs↗
PubMed1996

Immunocytochemical and biochemical characterization of glial phenotypes in normal and immortalized cultures derived from 3-day-old chick embryo encephalon.

We examined properties of glia derived from very early neurogenesis in the chick embryo, as well as their behavior in response to extended cell passages and at various periods in culture. Primary cultures derived from the telencephalic region of 3-day-old chick embryo (stage 19) exhibited intense staining for vimentin (Vim; indicative of immature glial phenotypes) throughout the 17-day culture period, transitioning to Vim-positive/glial fibrillary acidic protein (GFAP)-positive astroblasts after a single cell passage at 13 days in vitro (DIV). With subsequent passage (P; through P6), cell continued to coexpress Vim/GFAP with the occasional appearance of fibronectin (Fib). By P11, Vim staining was faint, whereas GFAP staining gained in intensity, indicating the presence of mature astrocytes. These cultures also featured significant activity of glutamine synthetase (GS), which increased slightly with both cell passage and days in culture, correlating well with immunocytochemical findings. The activity of 2'3'-cyclic nucleotide 3'-phosphohydrolase (CNP) remained low, indicating a low percentage of mature oligodendrocytes. Thus, embryonic day (E)3H glia cultures mature into astrocytes given sufficient time in culture. To obtain a stable population of glia at various stages of astrocytic differentiation, we immortalized and subcloned homogenous colonies of E3H glia precursors at specific stages of development. A cell suspension was electroporetically transfected with the pSV40neo gene for large T antigen (E3H.SV5). After 5 passages, the parent colonies consisted of a heterogeneous population of cells, most of which were vim and GFAP positive. Following subcloning, one line (colony 7) displayed the staining pattern of mature astrocytes. However, with advancing age in culture, staining for both vim and GFAP became increasingly faint. Compared with control (normal) cultures, transfected cells exhibited a significantly lower activity of GS that did not fluctuate with days in culture but decreased with advancing cell passage. Furthermore, CNP activity in E3H.SV5 colony 7 was approximately double that observed in normal cultures at the same cell passage. This observation suggests that the phenotype of transfected glia was less stable than that observed in normal glial cultures.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed2001

Impact of herbicides on the abundance and structure of indigenous beta-subgroup ammonia-oxidizer communities in soil microcosms.

In this study, mixtures of five herbicide-formulated products (atrazine, dicamba, fluometuron, metolachlor, and sulfentrazone) were applied to soil microcosm columns in increasing concentrations. The toxic impact of herbicides on the indigenous beta-subclass Proteobacteria autotrophic ammonia-oxidizer (beta-AAO) community was assessed. The beta-AAO population abundances were estimated by competitive polymerase chain reaction (PCR) targeting the gene amoA, encoding the alpha-subunit of ammonia monooxygenase. Community structure was examined by PCR and denaturing gradient gel electrophoresis targeting 16S rDNA with band excision and sequence analysis, and by analysis of amoA gene fragment clone libraries. The 16S rDNA analyses showed that a single ribotype of Nitrosospira cluster 3 was the dominant beta-AAO in all treatments. At a finer scale, amoA clone library analysis suggested a shift in community structure corresponding to the 100-ppm application. Competitive PCR indicated significant differences between treatments. The control exhibited relatively stable population abundance over the time period examined. The 10-ppm treatment induced a population increase, but a significant decrease was induced by the 100-ppm application. At 1,000 ppm, the ammonia-oxidizer population dropped below the method detection limit by the first sampling point. An impact on ammonia oxidizers resulting from the application of herbicides was observed, both in abundance and community structure.

Ammonia↗
PubMed1998

Impact of the October 1995 pill scare in Grampian.

Over two years have elapsed since the Department of Health issued a press release concerning the safety of some third generation contraceptive pills. Warnings about increased abortion rates followed and recently published national figures for England and Wales have confirmed this. In Grampian we have assessed the impact of the pill scare at a subnational level, which has received much less consideration. Grampian has a stable population with an estimated 116,500 women in the reproductive years. The six month period from November 1995 until April 1996 was chosen to monitor the immediate aftermath of the pill scare. Aberdeen Royal Infirmary provides a regional, dedicated abortion service and has maintained a service specific database since 1994. This is an ideal situation to monitor trends in abortion rates in a specific population. Women attending for abortion counselling were asked to complete a questionnaire regarding their recall of media publicity. Live-births at Aberdeen Maternity Hospital from June to November 1996 were also recorded, reflecting conceptions in the study period. Prescribing patterns for combined pills and emergency contraception for Grampian general practitioners and Grampian Healthcare family planning service were also analysed. There was no increase in the abortion rate in the study period when compared with the same period in the preceding year - a total of 728 women underwent an abortion. Forty six women were identified within the 728 as having conceived as a direct consequence of the scare, but their characteristics were not dissimilar to the other women on the database. Live-birth rates were also stable. Emergency contraception prescribing was slightly increased for the family planning service but not in general practice. Both general practice and the family planning service showed an immediate and sharp fall in prescribing of third generation pills mirrored by an increase in second generation pill prescribing. For family planning particularly, prescriptions for third generation pills have shown an increase again from early 1996, although remaining below original levels. Fifty five per cent of the women who were given the questionnaire about media publicity responded. Seventy nine per cent recalled some publicity, but 17 per cent of these women could not remember any specific details. Unlike national reporting, our figures do not substantiate any increase in abortions or deliveries in the aftermath of the pill scare. The slight increase in emergency contraception prescribing by the family planning service more probably reflects local awareness campaigns rather than any appreciable switch away from regular pill use. On a population level, the scare did not have the predicted negative impact on pill users in Grampian and it would have been incorrect for us to extrapolate from national data in this instance. Failure to demonstrate numerical impact for the population does not deny the devastating effect of a termination for an individual woman. The emotional impact of the scare on women, while more difficult to measure, should not be underestimated. The influence on the next generation of women with regard to their contraceptive choice remains to be seen.

Abortion, Induced↗
PubMed1984

The analysis of linkages in demographic theory.

Many seemingly different questions that arise in the analysis of population change can be phrased as the same technical question: How, within a given demographic model, would variable y change if the age- or time-specific function f were to change arbitrarily in shape and intensity? At present demography lacks the machinery to answer this question in analytical and general form. This paper suggests a method based on modern functional calculus for deriving closed-form expressions for the sensitivity of demographic variables to changes in input functions or schedules. It uses this "linkage method" to obtain closed-form expressions for the response of the intrinsic growth rate, birth rate, and age composition of a stable population to arbitrary marginal changes in its age patterns of fertility and mortality. It uses it also to obtain expressions for the transient response of the age composition of a nonstable population to time-varying changes in the birth sequence, and to age-specific fertility and mortality patterns that change over time. The problem of "bias" in period vital rates is also looked at.

Adult↗
PubMedDate not supplied

Ultrastructural and immunoelectron microscopic study of three unusual plurihormonal pituitary adenomas.

Monomorphous pituitary adenomas expressing several hormones by immunocytochemistry are common, whereas adenomas displaying multiple immunoreactivities and consisting of more than one morphologic cell types are rare. Three such unusual pituitary adenomas, surgically removed from two patients with acromegaly and one patient with hyperprolactinemia, were investigated by histology, immunocytochemistry, transmission electron microscopy, as well as immunoelectron microscopy using double immunogold labeling. Immunocytochemistry revealed variable degrees of immunoreactivities for growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (beta-TSH), and alpha-subunit of glycoprotein hormones in all three tumors. The three adenomas consisted of phenotypically diverse cell populations as documented by transmission electron microscopy. In addition to monohormonal GH cells, immunoelectron microscopy demonstrated numerous cells colocalizing GH and PRL or GH and beta-TSH, and rarely PRL and beta-TSH in tumors of acromegalics. The adenoma causing hyperprolactinemia consisted chiefly of mammosomatotrophs colocalizing PRL and GH, whereas beta-TSH labeling was scant. The three tumors in the study were selected from a cluster of five plurimorphous plurihormonal adenomas received from the same locale where they accounted for an unprecedented 21% of adenomas producing GH and/or PRL. The enhanced susceptibility to develop plurimorphous adenomas of the acidophil cell line may have a genetic basis in the stable population the patients came from.

Acromegaly↗
PubMed1997

Patterns of mitochondrial variation within and between African malaria vectors, Anopheles gambiae and An. arabiensis, suggest extensive gene flow.

Anopheles gambiae and An. arabiensis are mosquito species responsible for most malaria transmission in sub-Saharan Africa. They are also closely related sibling species that share chromosomal and molecular polymorphisms as a consequence of incomplete lineage sorting or introgressive hybridization. To help resolve these processes, this study examined the partitioning of mtDNA sequence variation within and between species across Africa, from both population genetic and phylogeographic perspectives. Based on partial gene sequences from the cytochrome b, ND1 and ND5 genes, haplotype diversity was high but sequences were very closely related. Within species, little or no population subdivision was detected, and there was no evidence for isolation by distance. Between species, there were no fixed nucleotide differences, a high proportion of shared polymorphisms, and eight haplotypes in common over distances as great as 6000 km. Only one of 16 shared polymorphisms led to an amino acid difference, and there was no compelling evidence for nonneutral variation. Parsimony networks constructed of haplotypes from both species revealed no correspondence of haplotype with either geography or taxonomy. This trend of low intraspecific genetic divergence is consistent with evidence from allozyme and microsatellite data and is interpreted in terms of both extensive gene flow and recent range expansion from relatively large, stable populations. We argue that retention of ancestral polymorphisms is a plausible but insufficient explanation for low interspecific genetic divergence, and that extensive hybridization is a contributing factor.

Animals↗
PubMed1991

The effect of positive reinforcement on hourly compliance in nasal continuous positive airway pressure users with obstructive sleep apnea.

Previous reports have described compliance with nasal continuous positive airway pressure (nCPAP) for the treatment of obstructive sleep apnea (OSA) only in terms of the number of patients able to use it beyond their initial trial night or those continuing after some home use. Because of a possible difference between the level of compliance (mean number of hours of use per 24 h) needed for symptomatic relief of OSA versus cardiovascular improvement, the level of hourly compliance in chronic nCPAP users may be important. The first part of this study prospectively examines compliance in a stable population of OSA patients already using nCPAP for 6 months to 2 yr. The second part is a prospective randomized, crossover study examining the effect of weekly (three times) then monthly (twice) positive reinforcement on hourly compliance of new nCPAP users for 3 months versus no reinforcement for 3 months. Positive reinforcement consisted of telephone discussions with the patients about the severity or complications of OSA, benefits of nCPAP, and suggestions about minimizing side effects. Using self-assessment scales, each patient reported the perceived level of improvement from the untreated to the treated condition and the prevalence and severity of side effects from the nCPAP therapy. The level of compliance in stable, chronic nCPAP users with OSA was 6.1 +/- 2.2 h/24 h (n = 9). For the new nCPAP users during the nonreinforced period, the mean compliance was 6.0 +/- 2.8 h/24 h; that during the reinforcement period was 6.0 +/- 2.7 h/24 h (NS). There was no significant correlation between perceived improvement in OSA symptoms or between the perceived side effects of nCPAP versus hourly compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed2001

Phylogeography of the asian elephant (Elephas maximus) based on mitochondrial DNA.

Populations of the Asian elephant (Elephas maximus) have been reduced in size and become highly fragmented during the past 3,000 to 4,000 years. Historical records reveal elephant dispersal by humans via trade and war. How have these anthropogenic impacts affected genetic variation and structure of Asian elephant populations? We sequenced mitochondrial DNA (mtDNA) to assay genetic variation and phylogeography across much of the Asian elephant's range. Initially we compare cytochrome b sequences (cyt b) between nine Asian and five African elephants and use the fossil-based age of their separation (approximately 5 million years ago) to obtain a rate of about 0.013 (95% CI = 0.011-0.018) corrected sequence divergence per million years. We also assess variation in part of the mtDNA control region (CR) and adjacent tRNA genes in 57 Asian elephants from seven countries (Sri Lanka, India, Nepal, Myanmar, Thailand, Malaysia, and Indonesia). Asian elephants have typical levels of mtDNA variation, and coalescence analyses suggest their populations were growing in the late Pleistocene. Reconstructed phylogenies reveal two major clades (A and B) differing on average by HKY85/gamma-corrected distances of 0.020 for cyt b and 0.050 for the CR segment (corresponding to a coalescence time based on our cyt b rate of approximately 1.2 million years). Individuals of both major clades exist in all locations but Indonesia and Malaysia. Most elephants from Malaysia and all from Indonesia are in well-supported, basal clades within clade A. thus supporting their status as evolutionarily significant units (ESUs). The proportion of clade A individuals decreases to the north, which could result from retention and subsequent loss of ancient lineages in long-term stable populations or, perhaps more likely, via recent mixing of two expanding populations that were isolated in the mid-Pleistocene. The distribution of clade A individuals appears to have been impacted by human trade in elephants among Myanmar, Sri Lanka, and India, and the subspecies and ESU statuses of Sri Lankan elephants are not supported by molecular data.

Animals↗
PubMed2003

Long-term succession of structure and diversity of a biofilm formed in a model drinking water distribution system.

In this study, we examined the long-term development of the overall structural morphology and community composition of a biofilm formed in a model drinking water distribution system with biofilms from 1 day to 3 years old. Visualization and subsequent quantification showed how the biofilm developed from an initial attachment of single cells through the formation of independent microcolonies reaching 30 micro m in thickness to a final looser structure with an average thickness of 14.1 micro m and covering 76% of the surface. An analysis of the community composition by use of terminal restriction fragment length polymorphisms showed a correlation between the population profile and the age of the sample, separating the samples into young (1 to 94 days) and old (571 to 1,093 days) biofilms, whereas a limited spatial variation in the biofilm was observed. A more detailed analysis with cloning and sequencing of 16S rRNA fragments illustrated how a wide variety of cells recruited from the bulk water initially attached and resulted in a species richness comparable to that in the water phase. This step was followed by the growth of a bacterium which was related to Nitrospira, which constituted 78% of the community by day 256, and which resulted in a reduction in the overall richness. After 500 days, the biofilm entered a stable population state, which was characterized by a greater richness of bacteria, including Nitrospira, Planctomyces, Acidobacterium, and Pseudomonas. The combination of different techniques illustrated the successional formation of a biofilm during a 3-year period in this model drinking water distribution system.

Bacteria↗
PubMed1999

Exponential growth in age-structured two-sex populations.

We consider a continuous age-structured two-sex population model which is given by a semilinear system of partial differential equations with nonlocal boundary conditions and is a simpler case of Fredrickson-Hoppensteadt model. The non-linearity is introduced by a source term, called from its physical meaning, the marriage function. The explicit form of the marriage function is not known; however, there is an understanding among the demographers about the properties it should satisfy. We have shown that the homogeneity property of the non-linearity leads to the fact that the system supports exponentially growing persistent solutions using a general form of the marriage function and its properties. This suggests that the model can be viewed as a possible extension of the one-sex stable population theory to monogamously mating two-sex populations.

Age Factors↗
PubMed2005

Degrees and kinds of selection in spontaneous neoplastic transformation: an operational analysis.

Spontaneous neoplastic transformation develops within days in the NIH 3T3 line of cells through differential inhibition of their proliferation under contact inhibition. A small fraction of the population continues to multiply after saturation density is reached and is selected to progressively increase saturation density in successive rounds of confluence. The degree of selection at confluence depends on the extent of proliferation of some cells in a heterogeneous population. The development of transformed foci is an extension of the same selective process that increases saturation density. The expression of the foci is enhanced with increases in the saturation density of the surrounding cells. Transformation is also induced by moderately reducing the concentration of calf serum in the medium during low-density passages, which allows selection of cells that require less growth factor. Further stepwise reductions in serum increase the degree of transformation. Contact inhibition and reduction in serum concentration select for the same phenotype of cell that increases saturation density and generates transformed foci. There is mounting evidence that selection is a major factor in the development of common epithelial tumors of humans, but it extends over decades rather than days, and the in vivo microenvironment selects from more stable populations of cells than those in culture. The many progressive levels of increased saturation density and transformed focus formation suggest that a very large number of genes participate in neoplastic development. The operational model of variation and selection presented here may aid in understanding chemical carcinogenesis and cancer recurrence after chemotherapy.

Animals↗
PubMed1992

Induction of syngeneic cytotoxic T lymphocytes against a B cell tumor. II. Characterization of anti-idiotypic CTL lines and clones.

In an earlier communication we showed that idiotypic immunoglobulin (Id+ Ig) of a B cell hybrid, 2C3, can induce cytotoxic T lymphocytes (CTL) in the spleens of mice that are hyperimmunized with the irradiated tumor cells. To understand the extent of heterogeneity in the splenic CTL population, stable anti-idiotypic CTL lines and clones were established from 2C3-primed splenocytes. One representative CTL line A102 which exhibited the phenotype of CD3+, CD4-, and CD8+, has been maintained in long-term culture for more than 18 months. Cytotoxic specificity of A102 was determined by cold target inhibition assay using a panel of syngeneic and allogeneic B cell tumors. The CTL line A102 was highly cytotoxic to 2C3, only weakly to other syngeneic tumors, but not at all to allogeneic B cell tumor CH12. Furthermore, CTL-mediated cytolysis was significantly abrogated by blocking 2C3 cells with anti-idiotypic monoclonal and polyclonal antibodies. These results clearly show that 2C3 Id represents the immunodominant epitope(s) recognized by the CTL line A102. To isolate a highly Id-specific effector population, A102 was repeatedly subcloned by limiting dilution. One such clone 102.F5 exhibited considerable specificity toward Id+ 2C3 while another clone 102.E10 showed no such specificity in a competitive cytotoxicity assay. This was further confirmed by the inhibition studies with anti-Id mAb. Thus, hyperimmunization with irradiated 2C3 cells evokes a spectrum of anti-2C3 cytotoxic effector cells, of which a major population is reactive to the idiotypic determinants associated with 2C3 Ig.

Animals↗
PubMed1991

The effects of long term monolayer culture on the proteoglycan phenotype of a clonal population of mature human malignant chondrocytes.

Articular cartilage chondrocytes maintain biosynthetic heterogeneity in cell culture, but undergo irreversible dedifferentiation of their proteoglycan phenotype, as defined by keratan sulfate content. A recently described cell line of malignant human chondrocytes, 105KC, was the first to maintain a differentiated keratan sulfate-proteoglycan phenotype in long-term culture. A clone of 105KC, labeled KC2H3, is currently described and represents a distinct and metabolically more homogeneous population of mature chondrocytes than 105KC. KC2H3 cells universally express keratan sulfate biosynthesis, as defined by indirect immunofluorescence. In addition, KC2H3 expresses a more mature proteoglycan phenotype than 105KC, as demonstrated by the keratan sulfate content: 24% of glycosaminoglycan content of the aggregating proteoglycans of KC2H3 versus 13% for 105KC. Further reported are the effects of long term monolayer culture on the proteoglycan phenotype expressed by KC2H3. After more than 16 months in continuous monolayer, KC2H3 cells remained morphologically indistinguishable from those maintained in suspension alternating with monolayer. In addition, the proteoglycan phenotype remained mature, without a tendency towards dedifferentiation. The flattened morphology adopted by chondrocytes while in monolayer has been considered a stimulus of dedifferentiation; the present study is the first to examine the direct effects of physical state on a homogeneous and stable population of chondrocytes.

Chondroitin Sulfates↗
PubMed2003

Genetic structure and mtDNA diversity of Fundulus heteroclitus populations from polycyclic aromatic hydrocarbon-contaminated sites.

Genetic structure and diversity of mummichog (Fundulus heteroclitus) populations were investigated using mitochondrial DNA (mtDNA) sequences. Forty-six haplotypes were identified among 208 mummichog from the Elizabeth and York Rivers in Virginia, USA. No evidence of decreased gene or nucleotide diversity for mummichog from polycyclic aromatic hydrocarbon (PAH)-contaminated sites was observed. However, based on mtDNA data from 17 sites, a significant correlation (Mantel analysis, p = 0.035) was noted between genetic distance (F(ST)) and PAH concentration but not between genetic distance and geographic distance. Mummichog from the most heavily PAH-contaminated site, Atlantic Wood (AW), were genetically distinct from those of other Elizabeth River sites. At AW, high frequencies of several divergent haplotypes were observed that were more closely allied to the northern mummichog than to the more abundant southern form in the Chesapeake Bay. These data suggested that a locally stable population existed at the AW site. This conclusion is consistent with the observation that mummichog from the AW site display enhanced tolerance to PAH contamination relative to mummichog from noncontaminated sites. Conclusions about gene diversity and the correlation between genetic distance with site differences in PAH concentrations were also consistent with those from tandem genetic analyses based on allozymes.

Animals↗
PubMed2001

Retroviral labeling of Schwann cells: in vitro characterization and in vivo transplantation to improve peripheral nerve regeneration.

Transplantation of Schwann cells (SCs) is a promising treatment modality to improve neuronal regeneration. Identification of the transplanted cells is an important step when studying the development of this method. Genetic labeling is the most stable and reliable method of cell identification, but it is still unclear whether it has deleterious effect on SC characteristics. Our aim was to achieve a stable population of SCs transduced with the lacZ gene at a high frequency using a retroviral vector in vitro, and to follow the labeled SC in vitro to assess their viability and phenotypic marker expression. Furthermore, we transplanted lacZ-labeled SCs in a conduit to repair peripheral nerve to investigate their effect on nerve regeneration in vivo. Rat and human SCs were cultured and transduced with an MFG lacZ nls marker gene, achieving a transduction rate of 80% and 70%, respectively. Rat SCs were kept in culture for 27 weeks and examined every 4 weeks for expression of lacZ, viability, and phenotypic marker expression of GFAP, p75, MHC I and II. Throughout this period, transduced rat SCs remained viable and continued to proliferate. The proportion of cells expressing lacZ dropped only by 10% and the expression of phenotypic markers remained stable. Transduced human SCs were followed up for 4 weeks in culture. They proliferated and continued to express the lacZ gene and phenotypic marker expression of GFAP and p75 was preserved. Primary culture of transduced rat SCs were transplanted, syngeneically, in a conduit to bridge a 10 mm gap in sciatic nerve and the grafts were examined after 3 weeks for the presence and participation of labeled SCs and for axonal regeneration distance. Transplanted transduced rat SCs were clearly identified, taking part in the regeneration process and enhancing the axonal regeneration rate by 100% (at the optimal concentration) compared to conduits without SCs. Thus, retroviral introduction of lacZ gene has no deleterious effect on SCs in vitro and these SCs take part and enhance nerve regeneration in vivo.

Animals↗
PubMed2004

Genes, environment, and susceptibility to multiple sclerosis.

Multiple sclerosis (MS) is a chronic disease of the central nervous system affecting young adults and thus representing a major burden also for their families and communities. The etiology of MS is obscure and its pathogenesis is yet incompletely depicted. Increased evidences indicate a strong genetic contribution to MS susceptibility, although others support the view that it is also influenced by environmental factors, possibly related to still unidentified pathogens. MS appears to be more heterogeneous than previously believed at the immunological level, and new pathological studies indicate a series of subset of conditions under the common denominator MS. The use of genetically homogeneous and geographically isolated populations at high MS risk, such as that of Sardinia, insular Italy, becomes in principle a vital requirement to reduce biological variables and the intrinsic complexity of the disease. This review will focus on recent findings on the peculiarity of Sardinian MS concerning epidemiological, genetic, and environmental aspects. Epidemiological studies reveal a clear heterogeneous distribution of MS cases in the Northern province of Sassari which may not be uniquely assigned to genetic variations. Furthermore, a different immunogenetic profile, including the association with other immunomediated diseases, and a progressive change in clinical phenotype, including age at onset, are present in this island which gives us unexpected variations at the level of patients' cohort and territorial distribution, especially when the northern province is compared to the southern one. This renders MS etiopathogenesis more complex than formerly thought even in this selected and genetically stable population.

Disease Susceptibility↗
PubMed2004

Energy reserves and metal-storage granules in the hepatopancreas of Oniscus asellus and Porcellio scaber (Isopoda) from a metal gradient at Avonmouth, UK.

Isopods taken from populations of Onsicus asellus and Porcellio scaber from long-term polluted sites in the vicinity of metal smelting works at Avonmouth, South West England, and from a control site near Tübingen, South Germany, were examined for the frequency and size of metal-containing granules (spherites), lipid droplets and glycogen in their hepatopancreas. The number and size of spherites in the hepatopancreas of O. asellus increased with decreasing distance to the smelter, but such a trend was not found in P. scaber. A trend towards massive reduction in hepatopancreatic energy reserves (lipid, glycogen) with increasing soil metal pollution was observed for O. asellus while, in contrast, the lipid and glycogen content of P. scaber midgut gland cells was independent of the distance to the smelter. In view of previous reports on metal accumulation and biochemical responses to metal pollution, we propose that the two investigated isopod species, which form stable populations in the Avonmouth metal gradient, use different strategies to survive.

Animals↗