1,451 research outputs found
The CAG repeat at the Huntington disease gene in the Portuguese population : insights into its dynamics and to the origin of the mutation
Huntington disease (HD) is caused by an
expansion of a CAG repeat. This repeat is a dynamic
mutation that tends to undergo intergenerational instability.
We report the analysis of the CAG repeat in a large
population sample (2,000 chromosomes) covering all regions
of Portugal, and a haplotype study of (CAG)n and
(CCG)n repeats in 140 HD Portuguese families. Intermediate
class 2 alleles represented 3.0% of the population;
and two expanded alleles (36 and 40 repeats, 0.11%) were
found. There was no evidence for geographical clustering
of the intermediate or expanded alleles. The Portuguese
families showed three different HD founder haplotypes
associated with 7-, 9- or 10-CCG repeats, suggesting the
possibility of different origins for theHDmutation among
this population. The haplotype carrying the 7-CCG repeat
was the most frequent, both in normal and in expanded
alleles. In general, we propose that three mechanisms,
occurring at different times,may lead to the evolution from
normal CAGs to full expansion: first, a mutation bias towards
larger alleles; then, a stepwise process that could
explain the CAGdistributions observed in themore recent
haplotypes; and, finally, a pool of intermediate (class 2)
alleles more prone to give rise to expanded HD alleles.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/9759/
2003.Instituto de Genética Médica Jacinto Magalhães
The effect of transmucosal 0.2mg/kg Midazolam premedication on dental anxiety, anaesthetic induction and psychological morbidity in children undergoing general anaesthesia for tooth extraction
<b>Background:</b> The project aims were to evaluate the benefit of transmucosal Midazolam 0.2mg/kg pre-medication on anxiety, induction behaviour and psychological morbidity in children undergoing general anaesthesia (GA) extractions. <b>Method:</b> 179 children aged 5-10 years (mean 6.53 years) participated in this randomised, double blind, placebo controlled trial. Ninety children had Midazolam placed in the buccal pouch. Dental anxiety was recorded pre operatively and 48 hours later using a child reported MCDAS-FIS scale. Behaviour at anaesthetic induction was recorded and psychological morbidity was scored by the parent using the Rutter Scale pre-operatively and again one-week later. Subsequent dental attendance was recorded at one, three and six months after GA. <b>Results:</b> Whilst levels of mental anxiety did not reduce overall, the most anxious patients demonstrated a reduction in anxiety after receiving midazolam premedicationmay (p=0.01). Neither induction behaviour nor psychological morbidity improved. Irrespective of group, parents reported less hyperactive (p= 0.002) and more prosocial behaviour (p=0.002) after the procedure:;, older children improved most (p=0.048), Post GA Dental attendance was poor and unrelated to after the procedure and unaffected by premedication. <b>Conclusion:</b> 0.2mg/kg buccal Midazolam provided some evidence for reducing anxiety in the most dentally anxious patients. However, induction behaviour, psychological morbidity and subsequent dental attendance were not found to alter between the premedication groups
PGB pair production at LHC and ILC as a probe of the topcolor-assisted technicolor models
The topcolor-assisted technicolor (TC2) model predicts some light pseudo
goldstone bosons (PGBs), which may be accessible at the LHC or ILC. In this
work we study the pair productions of the charged or neutral PGBs at the LHC
and ILC. For the productions at the LHC we consider the processes proceeding
through gluon-gluon fusion and quark-antiquark annihilation, while for the
productions at the ILC we consider both the electron-positron collision and the
photon-photon collision. We find that in a large part of parameter space the
production cross sections at both colliders can be quite large compared with
the low standard model backgrounds. Therefore, in future experiments these
productions may be detectable and allow for probing TC2 model.Comment: 26 pages, 16 figures. slight changes in the text; notations for
curves changed; references adde
Using honey to heal diabetic foot ulcers
Diabetic ulcers seem to be arrested in the inflammatory/proliferative stage of the healing process, allowing infection and inflammation to preclude healing. Antibiotic-resistant bacteria have become a major cause of infections, including diabetic foot infections. It is proposed here that the modern developments of an ancient and traditional treatment for wounds, dressing them with honey, provide the solution to the problem of getting diabetic ulcers to move on from the arrested state of healing. Honeys selected to have a high level of antibacterial activity have been shown to be very effective against antibiotic-resistant strains of bacteria in laboratory and clinical studies. The potent anti-inflammatory action of honey is also likely to play an important part in overcoming the impediment to healing that inflammation causes in diabetic ulcers, as is the antioxidant activity of honey. The action of honey in promotion of tissue regeneration through stimulation of angiogenesis and the growth of fibroblasts and epithelial cells, and its insulin-mimetic effect, would also be of benefit in stimulating the healing of diabetic ulcers. The availability of honey-impregnated dressings which conveniently hold honey in place on ulcers has provided a means of rapidly debriding ulcers and removing the bacterial burden so that good healing rates can be achieved with neuropathic ulcers. With ischemic ulcers, where healing cannot occur because of lack of tissue viability, these honey dressings keep the ulcers clean and prevent infection occurring
The Multifunctional LigB Adhesin Binds Homeostatic Proteins with Potential Roles in Cutaneous Infection by Pathogenic Leptospira interrogans
Leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as Leptospira interrogans. The mode of transmission is commonly limited to the exposure of mucous membrane or damaged skin to water contaminated by leptospires shed in the urine of carriers, such as rats. Infection occurs during seasonal flooding of impoverished tropical urban habitats with large rat populations, but also during recreational activity in open water, suggesting it is very efficient. LigA and LigB are surface localized proteins in pathogenic Leptospira strains with properties that could facilitate the infection of damaged skin. Their expression is rapidly induced by the increase in osmolarity encountered by leptospires upon transition from water to host. In addition, the immunoglobulin-like repeats of the Lig proteins bind proteins that mediate attachment to host tissue, such as fibronectin, fibrinogen, collagens, laminin, and elastin, some of which are important in cutaneous wound healing and repair. Hemostasis is critical in a fresh injury, where fibrinogen from damaged vasculature mediates coagulation. We show that fibrinogen binding by recombinant LigB inhibits fibrin formation, which could aid leptospiral entry into the circulation, dissemination, and further infection by impairing healing. LigB also binds fibroblast fibronectin and type III collagen, two proteins prevalent in wound repair, thus potentially enhancing leptospiral adhesion to skin openings. LigA or LigB expression by transformation of a nonpathogenic saprophyte, L. biflexa, enhances bacterial adhesion to fibrinogen. Our results suggest that by binding homeostatic proteins found in cutaneous wounds, LigB could facilitate leptospirosis transmission. Both fibronectin and fibrinogen binding have been mapped to an overlapping domain in LigB comprising repeats 9–11, with repeat 11 possibly enhancing binding by a conformational effect. Leptospirosis patient antibodies react with the LigB domain, suggesting applications in diagnosis and vaccines that are currently limited by the strain-specific leptospiral lipopolysaccharide coats
Shot noise in mesoscopic systems
This is a review of shot noise, the time-dependent fluctuations in the
electrical current due to the discreteness of the electron charge, in small
conductors. The shot-noise power can be smaller than that of a Poisson process
as a result of correlations in the electron transmission imposed by the Pauli
principle. This suppression takes on simple universal values in a symmetric
double-barrier junction (suppression factor 1/2), a disordered metal (factor
1/3), and a chaotic cavity (factor 1/4). Loss of phase coherence has no effect
on this shot-noise suppression, while thermalization of the electrons due to
electron-electron scattering increases the shot noise slightly. Sub-Poissonian
shot noise has been observed experimentally. So far unobserved phenomena
involve the interplay of shot noise with the Aharonov-Bohm effect, Andreev
reflection, and the fractional quantum Hall effect.Comment: 37 pages, Latex, 10 figures (eps). To be published in "Mesoscopic
Electron Transport," edited by L. P. Kouwenhoven, G. Schoen, and L. L. Sohn,
NATO ASI Series E (Kluwer Academic Publishing, Dordrecht
Molecular diagnosis of Huntington disease in Portugal : implications for genetic counselling and clinical practice
Huntington disease (HD) is a eurodegenerative, autosomal dominant disorder of late-onset, caused by
the expansion of a CAG repeat in the coding region of the gene. Ours is the reference laboratory for genetic testing in HD, in Portugal, since 1998; 90.1% of all 158 families known were identified for the first time, including patients with unusual presentation or without family history. A total of 338 genetic tests were performed: 234 for diagnosis, 96 for presymptomatic and four for prenatal testing (four were done for family studies). Most referring physicians were neurologists (90.6%); 82.8% of all clinical diagnosis were confirmed, while 83.1% of those sent for exclusion were in fact excluded. In presymptomatic testing,
an excess of female subjects (59.4%) was again verified; 37.5% of the consultands were found to be carriers. None of the foetuses, in four prenatal tests, were mutation carriers. One juvenile case was
inherited from her mother. Our patient population is very similar to others described so far, namely in terms of mean age at onset and (CAG)n distribution, except perhaps for a higher frequency of large normal (class 2) alleles (3.7%). We also identify cases posing particular problems for genetic counselling, such as, ‘homozygosity’ that can pose a serious ethical dilemma, carriers of large normal alleles, and ‘homoallelism’ for a normal gene, which will demand further procedures and may delay results in presymptomatic and prenatal testing
Orientation and dynamics of transmembrane peptides: the power of simple models
In this review we discuss recent insights obtained from well-characterized model systems into the factors that determine the orientation and tilt angles of transmembrane peptides in lipid bilayers. We will compare tilt angles of synthetic peptides with those of natural peptides and proteins, and we will discuss how tilt can be modulated by hydrophobic mismatch between the thickness of the bilayer and the length of the membrane spanning part of the peptide or protein. In particular, we will focus on results obtained on tryptophan-flanked model peptides (WALP peptides) as a case study to illustrate possible consequences of hydrophobic mismatch in molecular detail and to highlight the importance of peptide dynamics for the experimental determination of tilt angles. We will conclude with discussing some future prospects and challenges concerning the use of simple peptide/lipid model systems as a tool to understand membrane structure and function
A study of 54 cases of left displacement of the abomasum: February to July 2005
Fifty-four cows with left displacement of the abomasum (LDA) submitted to the hospital facility at Riverview Veterinary Clinic from February to July 2005 were treated by right flank laparotomy and omentopexy. Five cows died (a survival rate 90.7%) and one cow (1.8%) was culled due to recurrence of the LDA post-operatively. Forty-one cows (76%) returned to good production post-operatively. Thirty-nine cows (72%) were pregnant six months after corrective surgery
The role of γδ T cells in airway epithelial injury and bronchial responsiveness after chlorine gas exposure in mice
BACKGROUND: Acute exposure to chlorine (Cl(2)) gas causes epithelial injury and airway dysfunction. γδ T cells are present in the mucosal surface of the airways and may contribute to the injury/repair response of the epithelium. METHODS: C57Bl/6J (wild type) and TCR-δ(-/- )mice exposed to Cl(2 )(400 ppm) for 5 minutes underwent measurements of airway responses to i.v. methacholine (MCh) at 1, 3, and 5 days after exposure. Bronchoalveolar lavage was performed to determine epithelial and leukocyte counts, and protein content. Tissue repair was assessed by proliferating cell nuclear antigen (PCNA) immunoreactivity and by expression of keratinocyte growth factor (KGF) mRNA by real-time PCR. RESULTS: Wild type mice developed a greater degree of airway hyperresponsiveness to MCh at 1 day post exposure to Cl(2 )compared with TCR-δ(-/- )mice. Epithelial cell counts in BAL after Cl(2 )exposure were greater in TCR-δ(-/- )mice, but macrophages showed a later peak and granulocyte numbers were lower in TCR-δ(-/- )than in wild type mice. Both groups had increased levels of total protein content in BAL after Cl(2 )exposure that resolved after 3 and 5 days, respectively. Epithelial proliferating cell nuclear antigen staining was increased at 1 and 3 days post exposure and was similar in the two groups. KGF mRNA was constitutively expressed in both groups and did not increase significantly after Cl(2 )but expression was lower in TCR-δ(-/- )mice. CONCLUSION: The severity of airway epithelial injury after Cl(2 )is greater in TCR-δ(-/- )mice but the inflammatory response and the change in airway responsiveness to methacholine are reduced. The rates of epithelial regeneration are comparable in both groups
- …