Holocentric Chromosomes of Luzula elegans Are Characterized by a Longitudinal Centromere Groove, Chromosome Bending, and a Terminal Nucleolus Organizer Region

The structure of holocentric chromosomes was analyzed in mitotic cells of Luzula elegans. Light and scanning electron microscopy observations provided evidence for the existence of a longitudinal groove along each sister chromatid. The centromere-specific histone H3 variant, CENH3, colocalized with this groove and with microtubule attachment sites. The terminal chromosomal regions were CENH3-negative. During metaphase to anaphase transition, L. elegans chromosomes typically curved to a sickle-like shape, a process that is likely to be influenced by the pulling forces of microtubules along the holocentric axis towards the corresponding microtubule organizing regions. A single pair of 45S rDNA sites, situated distal to Arabidopsis-telomere repeats, was observed at the terminal region of one chromosome pair. We suggest that the 45S rDNA position in distal centromere-free regions could be required to ensure chromosome stability. Copyright (C) 2011 S. Karger AG, Base

Estimating the malaria risk of African mosquito movement by air travel

BACKGROUND: The expansion of global travel has resulted in the importation of African Anopheles mosquitoes, giving rise to cases of local malaria transmission. Here, cases of 'airport malaria' are used to quantify, using a combination of global climate and air traffic volume, where and when are the greatest risks of a Plasmodium falciparum-carrying mosquito being importated by air. This prioritises areas at risk of further airport malaria and possible importation or reemergence of the disease. METHODS: Monthly data on climate at the World's major airports were combined with air traffic information and African malaria seasonality maps to identify, month-by-month, those existing and future air routes at greatest risk of African malaria-carrying mosquito importation and temporary establishment. RESULTS: The location and timing of recorded airport malaria cases proved predictable using a combination of climate and air traffic data. Extending the analysis beyond the current air network architecture enabled identification of the airports and months with greatest climatic similarity to P. falciparum endemic regions of Africa within their principal transmission seasons, and therefore at risk should new aviation routes become operational. CONCLUSION: With the growth of long haul air travel from Africa, the identification of the seasonality and routes of mosquito importation is important in guiding effective aircraft disinsection and vector control. The recent and continued addition of air routes from Africa to more climatically similar regions than Europe will increase movement risks. The approach outlined here is capable of identifying when and where these risks are greatest

Liver transplantation for type I and type IV glycogen storage disease

Progressive liver failure or hepatic complications of the primary disease led to orthotopic liver transplantation in eight children with glycogen storage disease over a 9-year period. One patient had glycogen storage disease (GSD) type I (von Gierke disease) and seven patients had type IV GSD (Andersen disease). As previously reported [19], a 16.5-year-old-girl with GSD type I was successfully treated in 1982 by orthotopic liver transplantation under cyclosporine and steroid immunosuppression. The metabolic consequences of the disease have been eliminated, the renal function and size have remained normal, and the patient has lived a normal young adult life. A late portal venous thrombosis was treated successfully with a distal splenorenal shunt. Orthotopic liver transplantation was performed in seven children with type N GSD who had progressive hepatic failure. Two patients died early from technical complications. The other five have no evidence of recurrent hepatic amylopectinosis after 1.1–5.8 postoperative years. They have had good physical and intellectual maturation. Amylopectin was found in many extrahepatic tissues prior to surgery, but cardiopathy and skeletal myopathy have not developed after transplantation. Postoperative heart biopsies from patients showed either minimal amylopectin deposits as long as 4.5 years following transplantation or a dramatic reduction in sequential biopsies from one patient who initially had dense myocardial deposits. Serious hepatic derangement is seen most commonly in types T and IV GSD. Liver transplantation cures the hepatic manifestations of both types. The extrahepatic deposition of abnormal glycogen appears not to be problematic in type I disease, and while potentially more threatening in type IV disease, may actually exhibit signs of regression after hepatic allografting

Influence of Clinical Status and Parasite Load on Erythropoiesis and Leucopoiesis in Dogs Naturally Infected with Leishmania (Leishmania) chagasi

Background: The bone marrow is considered to be an important storage of parasites in Leishmania-infected dogs, although little is known about cellular genesis in this organ during canine visceral leishmaniasis (CVL). Methodology/Principal Findings: The aim of the present study was to evaluate changes in erythropoiesis and leucopoiesis in bone marrow aspirates from dogs naturally infected with Leishmania chagasi and presenting different clinical statuses and bone marrow parasite densities. The evolution of CVL from asymptomatic to symptomatic status was accompanied by increasing parasite density in the bone marrow. The impact of bone marrow parasite density on cellularity was similar in dogs at different clinical stages, with animals in the high parasite density group. Erythroid and eosinophilic hypoplasia, proliferation of neutrophilic precursor cells and significant increases in lymphocytes and plasma cell numbers were the major alterations observed. Differential bone marrow cell counts revealed increases in the myeloid:erythroid ratio associated to increased numbers of granulopoietic cells in the different clinical groups compared with non-infected dogs. Conclusions: Analysis of the data obtained indicated that the assessment of bone marrow constitutes an additional and useful tool by which to elaborate a prognosis for CVL

Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.

Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7) results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/-) displayed decreased immobility in the tail suspension test (TST) and an attenuated anhedonia response in the sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF) expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [3H]5-HT and an elevated number of [3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus

The malaria candidate vaccine liver stage antigen-3 is highly conserved in Plasmodium falciparum isolates from diverse geographical areas

<p>Abstract</p> <p>Background</p> <p>A high level of genetic stability has been formerly identified in segments of the gene coding for the liver stage antigen-3 (LSA-3), a subunit vaccine candidate against <it>Plasmodium falciparum</it>. The exploration of <it>lsa-3 </it>polymorphisms was extended to the whole sequence of this large antigen in 20 clinical isolates from four geographical areas; Senegal, Comoro islands, Brazil and Thailand.</p> <p>Methods</p> <p>The whole 4680 bp genomic sequence of <it>lsa-3 </it>was amplified by polymerase chain reaction and sequenced. The clinical isolate sequences were aligned on the sequence of the laboratory reference <it>P. falciparum </it>strain 3D7.</p> <p>Results</p> <p>The non-repeated sequence of <it>lsa-3 </it>was very well conserved with only a few allelic variations scattered along the sequence. Interestingly, a formerly identified immunodominant region, employed for the majority of pre-clinical vaccine development, was totally conserved at the genetic level. The most significant variations observed were in the number and organization of tetrapeptide repeated units, but not in their composition, resulting in different lengths of these repeated regions. The shorter repeated regions were from Brazilian origin. A correlation between the geographical distribution of the parasites with single nucleotide polymorphisms was not detected.</p> <p>Conclusion</p> <p>The lack of correlation between allelic polymorphisms with a specific transmission pressure suggests that LSA-3 is a structurally constrained molecule. The unusual characteristics of the <it>lsa-3 </it>gene make the molecule an interesting candidate for a subunit vaccine against malaria.</p

Effect of an antepartum Pap smear on the coverage of a cervical cancer screening programme: a population-based prospective study

BACKGROUND: Almost one-third of Norwegian women aged 25–69 years invited to have a Pap smear do not attend during the recommended period, and thus constitute a population with high-risk of cervical cancer (CC). Since the incidence of precancerous lesions of the cervix peak with occurrence of pregnancies within the same decade in women aged 25 to 35 years of age, antepartum care presents an opportunity to offer a Pap smear thereby increasing the coverage of the programme. The study objective was to describe the effect of the antepartum Pap smear on the coverage of a cytological CC screening programme. METHODS: Among 2 175 762 women resident in Norway in 31.12.1996, all women who gave birth in 1996–7 were identified from the Medical Birth Registry of Norway. Attendance to the cervical cancer screening was assessed by linkage to the Cytology Registry separately for the pregnant and non-pregnant women cohorts. The results were stratified by age, history of previous Pap smear and history of invitation to the CC screening programme. Logistic regression was used to estimate the relative probabilities of having a Pap smear adjusted for age, screening history, and time since invitation, for pregnant and non-pregnant women, respectively. RESULTS: 69% of the pregnant women had a Pap smear during one year of follow-up since beginning of the pregnancy with the majority taken during the antepartum period. Irrespectively of age or history of having a Pap smear, pregnant women were 4.3 times more likely to have a Pap smear during follow-up compared to non-pregnant women. 63.2% of the pregnant women had a smear as response to the invitation letter compared to 28.7% of the non-pregnant women, OR = 2.1 (95% CI 1.9 to 2.4). As an indication of "over-screening", 5397 pregnant women (57.8%) with a smear shortly before the start of follow-up also had a new Papsmear, compared to 83 023 (32.3%) in non-pregnant. CONCLUSION: Pap smear screening during pregnancy increases the coverage of the CC screening programme. The contribution of the antepartum Pap smear to "over-screening" exists but its effect is modest in countries where women on average become pregnant after the start of recommended age of screening

Higher Expression of CCL2, CCL4, CCL5, CCL21, and CXCL8 Chemokines in the Skin Associated with Parasite Density in Canine Visceral Leishmaniasis

Several previous studies correlated immunopathological aspects of canine visceral leishmaniasis (CVL) with tissue parasite load and/or the clinical status of the disease. Recently, different aspects of the immune response in Leishmania-infected dogs have been studied, particularly the profile of cytokines in distinct compartments. However, the role of chemokines in disease progression or parasite burdens of the visceralising species represents an important approach for understanding immunopathology in CVL. We found an increase in inflammatory infiltrate, which was mainly composed of mononuclear cells, in the skin of animals presenting severe forms of CVL and high parasite density. Our data also demonstrated that enhanced parasite density is positively correlated with the expression of CCL2, CCL4, CCL5, CCL21, and CXCL8. In contrast, there was a negative correlation between parasite density and CCL24 expression. These findings represent an advance in the knowledge of the involvement of skin inflammatory infiltrates in CVL and the systemic consequences and may contribute to developing a rational strategy for the design of new and more efficient prophylactic tools and immunological therapies against CVL

Prevalence, Distribution, and Impact of Mild Cognitive Impairment in Latin America, China, and India: A 10/66 Population-Based Study

A set of cross-sectional surveys carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India reveal the prevalence and between-country variation in mild cognitive impairment at a population level