BioMed Central - Latest articles

Rapid phase-modulated water excitation steady-state free precession for fat-suppressed cine cardiovascular MR

Hung-Yu Lin, Subha V. Raman, Yiu-Cho Chung and Orlando P. Simonetti — 2008-05-13

Background: The purpose of this article is to describe a steady-state free precession (SSFP) sequence for fat-suppressed cine cardiovascular magnetic resonance (CMR). A rapid phase-modulated binomial water excitation (WE) pulse is utilized to minimize repetition time and acquisition time. Methods: Three different water excitation pulses were combined with cine-SSFP for evaluation. The frequency response of each sequence was simulated and examined in phantom imaging studies. The ratio of fat to water signal amplitude was measured in phantoms to evaluate the fat suppression capabilities of each method. Six volunteers underwent CMR of the heart at 1.5T to compare retrospectively-gated cine-SSFP with and without water excitation. The ratio of fat to myocardium signal amplitude was measured for conventional cine-SSFP and phase-modulated WE-SSFP. The proposed WE-SSFP method was tested in one patient referred for CMR to characterize a cardiac mass.Results and discussionThe measured frequency response in a phantom corresponded to the numerical Bloch equation simulation demonstrating the widened stop-band around the fat resonant frequency for all water excitation pulses tested. In vivo measurements demonstrated that a rapid, phase-modulated water excitation pulse significantly reduced the signal amplitude ratio of fat to myocardium from 6.92 +/- 2.9 to 0.8 +/- 0.13 (mean +/- SD) without inducing any perceptible artifacts in SSFP cine CMR. Conclusion: Fat suppression can be achieved in SSFP cine CMR while maintaining steady state equilibrium using rapid, phase-modulated, binomial water excitation pulses.

Refined study of the interaction between HIV-1 p6 late domain and ALIX

2008-05-13

The interaction between the HIV-1 p6 late budding domain and ALIX, a class E vacuolar protein sorting factor, was explored by using the yeast two-hybrid approach. We refined the ALIX binding site of p6 as being the leucine triplet repeat sequence (Lxx)4 (LYPLTSLRSLFG). Intriguingly, the deletion of the C-terminal proline-rich region of ALIX prevented detectable binding to p6. In contrast, a four-amino acid deletion in the central hinge region of p6 increased its association with ALIX as shown by its ability to bind to ALIX lacking the proline rich domain. Finally, by using a random screening approach, the minimal ALIX391-510 fragment was found to specifically interact with this p6 deletion mutant. A parallel analysis of ALIX binding to the late domain p9 from EIAV revealed that p6 and p9, which exhibit distinct ALIX binding motives, likely bind differently to ALIX. Altogether our data support a model where the C-terminal proline-rich domain of ALIX allows the access of its p6 binding site to p6 by alleviating a conformational constraint resulting from the presence of the central p6 hinge.

The transcription factor Nfix is essential for normal brain development

2008-05-13

Background: The Nuclear Factor I (NFI) multi-gene family encodes site-specific transcription factors essential for the development of a number of organ systems. We showed previously that Nfia-deficient mice exhibit agenesis of the corpus callosum and other forebrain defects, Nfib-deficient mice have defects in lung maturation and show callosal agenesis and forebrain defects resembling those seen in Nfia-deficient animals, while Nfic-deficient mice have defects in tooth root formation. Recently the Nfix gene has been disrupted and these studies indicated that there were largely uncharacterized defects in brain and skeletal development in Nfix-deficient mice. Results: Here we show that disruption of Nfix by Cre-recombinase mediated excision of the 2nd exon results in defects in brain development that differ from those seen in Nfia and Nfib KO mice. In particular, complete callosal agenesis is not seen in Nfix-/- mice but rather there appears to be an overabundance of aberrant Pax6- and doublecortin-positive cells in the lateral ventricles of Nfix-/- mice, increased brain weight, expansion of the cingulate cortex and entire brain along the dorsal ventral axis, and aberrant formation of the hippocampus. On standard lab chow Nfix-/- animals show a decreased growth rate from ~P8 to P14, lose weight from ~P14 to P22 and die at ~P22. If their food is supplemented with a soft dough chow from P10, Nfix-/- animals show a lag in weight gain from P8 to P20 but then increase their growth rate. A fraction of the animals survive to adulthood and are fertile. The weight loss correlates with delayed eye and ear canal opening and suggests a delay in the development of several epithelial structures in Nfix-/- animals. Conclusions: These data show that Nfix is essential for normal brain development and may be required for neural stem cell homeostasis. The delays seen in eye and ear opening, and the brain morphology defects appear independent of the nutritional deprivation, as rescue of perinatal lethality with soft dough does not eliminate these defects.

Multiple Causes for Delay in Arrival at Hospital in Acute Stroke Patients in Aydin, Turkey

Sakine Memis, Emel Tugrul, Emine Didem Evci and Filiz Ergin — 2008-05-13

This descriptive, hospital-based study, performed in western Turkey, was designed to assess the level of pre-hospital delay and reasons for such delay in acute stroke patients, taking into consideration certain factors such as socioeconomic status, availability of transport options at onset of symptoms. Data were collected from hospital records, and a questionnaire was administered that included questions about socio-demographics, self-reported risk factors and questions related to hospital arrival. The rate of patients arriving at the hospital more than 3 hours after symptom onset was found to be 31.6% for this study. Approximately 1/3 of patients delayed going to the hospital because they were waiting for symptoms to go away while, 1/3 of patients were not aware of the importance of seeking immediate medical help. There was a significant relationship between the use of ambulance transportation and length of time before arrival at the hospitals, though there was no statistically significantly relationship between the existence of stroke risk factors and hospital arrival delay. These results will likely be helpful to health care decision makers as they develop a model for stroke health care and community based training.

A comparison between one- and two-fluoroscopic techniques in percutaneous vertebroplasty

Yen-Yao Li, Tsung-Jen Huang, Chin-Chang Cheng and Robert Wen-Wei Hsu — 2008-05-13

Background: Percutaneous vertebroplasty (PV) is generally performed under fluoroscopic guidance. Technically, single fluoroscope is considered sufficient for effectively monitoring PV. However, single fluoroscopic technique might be time-consuming in rotating the C-arm of the fluoroscope for either antero-posterior (AP) or lateral radiographic view, and causing delay in detecting cement leakage that can occur if the correct sight is not given. The aim of the current investigation was to compare the efficacy and safety of performing PV using one or two sets of fluoroscope. Methods: This retrospective study enrolled 43 patients with painful osteoporotic vertebral fractures and they were treated with one-level PV. A single orthopaedic surgeon operated on all these patients. The patients were divided into two groups on the basis of the method of fluoroscopic control. In Group 1 (15 patients), PV was performed under the assistance of one fluoroscope. In Group 2 (28 patients), PV was performed under the control of two fluoroscopes. The mean follow-up was 19 months (range, 12-30). Results: Neither symptomatic cement leakage nor postoperative infection was found in both groups. The mean operation time in Group 2 was shorter, 37.8 vs. 31.0 minutes for Groups 1 and 2, P=0.03. The incidence of cement leakage for Groups 1 and 2 was 26.7% (4/15) vs. 14.3% (4/28), respectively, P=0.19. Conclusions: We found that the two-fluoroscopic technique can provide simultaneous, real-time AP and lateral radiographic views to monitor entry point and cement delivery for PV and therefore reduce the operation time. The two-fluoroscopic technique did not require a complex manpower organization and has been proved to be a safe and effective technique for PV.

Mathematical modeling and analysis of insulin clearance in vivo

Markus Koschorreck and Ernst Dieter Gilles — 2008-05-13

Background: Analyzing the dynamics of insulin concentration in the blood is necessary for a comprehensive understanding of the effects of insulin in vivo. Insulin removal from the blood has been addressed in many studies. The results are highly variable with respect to insulin clearance and the relative contributions of hepatic and renal insulin degradation. Results: We present a dynamic mathematical model of insulin concentration in the blood and of insulin receptor activation in hepatocytes. The model describes renal and hepatic insulin degradation, pancreatic insulin secretion and nonspecific insulin binding in the liver. Hepatic insulin receptor activation by insulin binding, receptor internalization and autophosphorylation is explicitly included in the model. We present a detailed mathematical analysis of insulin degradation and insulin clearance. Stationary model analysis shows that degradation rates, relative contributions of the different tissues to total insulin degradation and insulin clearance highly depend on the insulin concentration. Conclusions: This study provides a detailed dynamic model of insulin concentration in the blood and of insulin receptor activation in hepatocytes. Experimental data sets from literature are used for the model validation. We show that essential dynamic and stationary characteristics of insulin degradation are nonlinear and depend on the actual insulin concentration.

The accuracy of the MMSE in detecting cognitive impairment when administered by general practitioners: A prospective observational study

Patrizio Pezzotti, Silvia Scalmana, Antonio Mastromattei and Domenico Di Lallo — 2008-05-13

Background: The Mini-Mental State Examination (MMSE) has contributed to detecting cognitive impairment, yet few studies have evaluated its accuracy when used by general practitioners (GP) in an actual public-health setting. We evaluated the accuracy of MMSE scores obtained by GPs by comparing them to scores obtained by Alzheimer's Evaluation Units (UVA). Methods: The study was observational in design and involved 59 volounter GPs who, after having undergone training, administered the MMSE to patients with symptoms of cognitive disturbances. Individuals who scored [less than or equal to]24 (adjusted by age and educational level) were referred to Alzheimer's Evaluation Units (UVA) for diagnosis (including the MMSE). UVAs were unblinded to the MMSE score of the GP. To measure interrater agreement, the weighted Kappa statistic was calculated. To evaluate factors associated with the magnitude of the difference between paired scores, a linear regression model was applied. To quantify the accuracy in discriminating no cognitive impairment from any cognitive impairment and from Alzheimer's disease (AD), the ROC curves (AUC) were calculated. Results: For the 317 patients, the mean score obtained by GPs was significantly lower (15.8 vs. 17.4 for the UVAs; p<0.01). However, overall concordance was good (Kappa=0.86). Only the diagnosis made by the UVA was associated with the difference between paired scores: the adjusted mean difference was 3.1 for no cognitive impairment and 3.8 for mild cognitive impairment. The AUC of the scores for GPs was 0.80 (95%CI: 0.75-0.86) for discriminating between no impairment and any impairment and 0.89 (95%CI: 0.84-0.94) for distinguishing patients with AD, though the UVA scores discriminated better. Conclusions: In a public-health setting involving patients with symptoms of cognitive disturbances, the MMSE used by the GPs was sufficiently accurate to detect patients with cognitive impairment, particularly those with dementia.

Periodic density functional theory calculations of bulk and the (010) surface of goethite

James D Kubicki, Kristian W Paul and Donald L Sparks — 2008-05-13

Background: Goethite is a common and reactive mineral in the environment. The transport of contaminants and anaerobic respiration of microbes are significantly affected by adsorption and reduction reactions involving goethite. An understanding of the mineral-water interface of goethite is critical for determining the molecular-scale mechanisms of adsorption and reduction reactions. In this study, periodic density functional theory (DFT) calculations were performed on the mineral goethite and its (010) surface, using the Vienna Ab Initio Simulation Package (VASP). Results: Calculations of the bulk mineral structure accurately reproduced the observed crystal structure and vibrational frequencies, suggesting that this computational methodology was suitable for modeling the goethite-water interface. Energy-minimized structures of bare, hydrated (one H2O layer) and solvated (three H2O layers) (010) surfaces were calculated for 1 x 1 and 3 x 3 unit cell slabs. A good correlation between the calculated and observed vibrational frequencies was found for the 1 x 1 solvated surface. However, differences between the 1 x 1 and 3 x 3 slab calculations indicated that larger models may be necessary to simulate the relaxation of water at the interface. Comparison of two hydrated surfaces with molecularly and dissociatively adsorbed H2O showed a significantly lower potential energy for the former. Conclusions: Surface Fe-O and (Fe)O-H bond lengths are reported that may be useful in surface complexation models (SCM) of the goethite (010) surface. These bond lengths were found to change significantly as a function of solvation (i.e., addition of two extra H2O layers above the surface), indicating that this parameter should be carefully considered in future SCM studies of metal oxide-water interfaces.

Review of 'Leishmania - after the Genome' by Peter J. Myler and Nicolas Fasel

Kevin M Tyler — 2008-05-13

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RPS4Y gene family evolution in primates

2008-05-13

Backgound: The RPS4 gene codifies for ribosomal protein S4, a very well-conserved protein present in all kingdoms. In primates, RPS4 is codified by two functional genes located on both sex chromosomes: the RPS4X and RPS4Y genes. In humans, RPS4Y is duplicated and the Y chromosome therefore carries a third functional paralog: RPS4Y2, which presents a testis-specific expression pattern. Results: DNA sequence analysis of the intronic and cDNA regions of RPS4Y genes from species covering the entire primate phylogeny showed that the duplication event leading to the second Y-linked copy occurred after the divergence of New World monkeys, about 35 million years ago. Maximum likelihood analyses of the synonymous and non-synonymous substitutions revealed that positive selection was acting on RPS4Y2 gene in the human lineage, which represents the first evidence of positive selection on a ribosomal protein gene. Putative positive amino acid replacements affected the three domains of the protein: one of these changes is located in the KOW protein domain and affects the unique invariable position of this motif, and might thus have a dramatic effect on the protein function. Conclusions: Here, we shed new light on the evolutionary history of RPS4Y gene family, especially on that of RPS4Y2. The results point that the RPS4Y1 gene might be maintained to compensate gene dosage between sexes, while RPS4Y2 might have acquired a new function, at least in the lineage leading to humans.

Impact of point-mutations on the hybridization affinity of surface-bound DNA/DNA and RNA/DNA oligonucleotide-duplexes: comparison of single base mismatches and base bulges

2008-05-13

Background: The high binding specificity of short 10 to 30mer oligonucleotide probes enables single base mismatch (MM) discrimination and thus provides the basis for genotyping and resequencing microarray applications. Recent experiments indicate that the underlying principles governing DNA microarray hybridization - and in particular MM discrimination - are not completely understood. Microarrays usually address complex mixtures of DNA targets. In order to reduce the level of complexity and to study the problem of surface-based hybridization with point defects in more detail, we performed array based hybridization experiments in well controlled and simple situations. Results: We performed microarray hybridization experiments with short 16 to 40mer target and probe lengths (in situations without competitive hybridization) in order to systematically investigate the impact of point-mutations - varying defect type and position - on the oligonucleotide duplex binding affinity. The influence of single base bulges and single base MMs depends predominantly on position - it is largest in the middle of the strand. The position-dependent influence of base bulges is very similar to that of single base MMs, however certain bulges give rise to an unexpectedly high binding affinity. Besides the defect (MM or bulge) type, which is the second contribution in importance to hybridization affinity, there is also a sequence dependence, which extends beyond the defect next-neighbor and which is difficult to quantify. Direct comparison between binding affinities of DNA/DNA and RNA/DNA duplexes shows, that RNA/DNA purine-purine MMs are more discriminating than corresponding DNA/DNA MMs. In DNA/DNA MM discrimination the affected base pair (CG vs. AT) is the pertinent parameter. We attribute these differences to the different structures of the duplexes (A vs. B form). Conclusions: We have shown that DNA microarrays can resolve even subtle changes in hybridization affinity for simple target mixtures. We have further shown that the impact of point defects on oligonucleotide stability can be broken down to a hierarchy of effects. In order to explain our observations we propose DNA molecular dynamics - in form of zipping of the oligonucleotide duplex - to play an important role.

Biocomputational prediction of small non-coding RNAs in Streptomyces

Josef Panek, Jan Bobek, Karel Mikulik, Marek Basler and Jiri Vohradsky — 2008-05-13

Background: The first systematic study of small non-coding RNAs (sRNA, ncRNA) in Streptomyces is presented. Except for a few exceptions, the Streptomyces sRNAs, as well as the sRNAs in other genera of the Actinomyces group, have remained unstudied. This study was based on sequence conservation in intergenic regions of Streptomyces, localization of transcription termination factors, and genomic arrangement of genes flanking the predicted sRNAs. Results: Thirty-two potential sRNAs in Streptomyces were predicted. Of these, expression of 20 was detected by microarrays and RT-PCR. The prediction was validated by a structure based computational approach. Two predicted sRNAs were found to be terminated by transcription termination factors different from the Rho-independent terminators. One predicted sRNA was identified computationally with high probability as a Streptomyces 6S RNA. Out of the 32 predicted sRNAs, 24 were found to be structurally dissimilar from known sRNAs. Conclusions: Streptomyces is the largest genus of Actinomyces, whose sRNAs have not been studied. The Actinomyces is a group of bacterial species with unique genomes and phenotypes. Therefore, in Actinomyces, new unique bacterial sRNAs may be identified. The sequence and structural dissimilarity of the predicted Streptomyces sRNAs demonstrated by this study serve as the first evidence of the uniqueness of Actinomyces sRNAs.

Does transition from an unstable labour market position to permanent employment protect mental health? Results from a 14-year follow-up of school-leavers.

Ieva Reine, Mehmed Novo and Anne Hammarstrom — 2008-05-13

Background: Having secure employment, in contrast to being unemployed, is regarded as an important determinant of health. Research and theories about the negative health consequences of unemployment indicated that transition from unemployment to a paid job could lead to improved health. The objective of this study was to test the hypothesis that obtaining permanent employment after being in an unstable labour market position protects mental health. Methods: A 14-year follow-up of all graduates from compulsory school in an industrial town in northern Sweden was performed at ages 16, 18, 21 and 30 years. Complete data on the cohort were collected for 1044 individuals with the aid of a comprehensive questionnaire. The response rate was 96.4%. The health measurement used in this study was the psychological symptoms analysed by multivariate logistic regression. Those who obtained permanent employment were the focus of the analysis. This group consisted of people who were in an unstable labour market position for a year or more between the ages of 25 and 29, and who had acquired a permanent job one year before and at the time of the investigation. Results: After controlling for gender as well as for an indicator of health-related selection, possible confounders and mediators, an association was found between the lower probability of psychological symptoms and obtaining permanent employment (OR=0.35, 95% CI 0.19-0.63) as well as having permanent employment (OR=0.22, 95% CI 0.10-0.51). Conclusions: Our findings suggest that transition from an unstable labour market position to permanent employment could be health-promoting, even after controlling for possible confounders and mediators, as well as for an indicator of health-related selection. However, as there are few studies in the field, there is a need for more longitudinal studies in order to further analyse the relationship and to examine possible explanations. The policy implication of our study is that the transformation of unstable labour market positions into permanent employment could contribute to better public health.

The diagnostic work up of growth failure in secondary health care; an evaluation of consensus guidelines

2008-05-13

Background: As abnormal growth might be the first manifestation of undetected diseases, it is important to have accurate referral criteria and a proper diagnostic work-up. In the present paper we assess how many children are correctly referred to secondary health care according to existing consensus guidelines, evaluate the diagnostic work-up in secondary health care and study the frequency of underlying medical disorders. Methods: Data on growth and additional diagnostic procedures were collected from medical records of new patients referred for short stature to the outpatient clinics of the general paediatric departments of two hospitals (Erasmus MC - Sophia Children's Hospital, Rotterdam and Spaarne Hospital, Haarlem) between January 1998 and December 2002. As the Dutch Consensus Guideline (DCG) is the only guideline addressing referral criteria as well as diagnostic work-up, the analyses were based on its seven auxological referral criteria to determine whether children were correctly referred or not and on all elements of the diagnostic work up. Results: Of children older than 3 years 76% was correctly referred (CR). 74-88% of these children were short corrected for parental height, 40-61% had a height SDS <-2.5 and 21% showed height deflection ([increment] HSDS < -0.25/ yr or [increment] HSDS < -1). In none of the children a complete detailed routine diagnostic work up was performed and in more than 30% no routine laboratory examination was done at all. Pathologic causes of short stature were found in 27 children (5%). Conclusions: Although the DCG was poorly put into practice, it detects at least 5 % pathologic causes of growth failure in children referred for short stature. New guidelines for referral are required with a better sensitivity and specificity, wherein distance to target height should get more attention. The general diagnostic work up for short stature should include testing for celiac disease in all children and for Turner syndrome in girls.

Skp2 expression is associated with high risk and Elevated Ki67 expression in gastrointestinal stromal tumours

2008-05-13

Background: Gastrointestinal stromal tumors (GIST) exhibit an unpredictable clinical course and can rapidly progress to lethality. Predictions about the biological behavior of GIST are based on a number of canonical clinical and pathologic parameters whose validity in distinguishing between a benign and a malignant tumour is still imperfect. Aim of our study was to investigate the role of morphologic parameters and expression of cells cycle regulators as prognosticators in GIST. Methods: We performed an immunohistochemical analysis for Ki67, p27Kip1, Jab1, and Skp2, on a Tissue Microarray (TMA) containing 94 GIST. Expression of the above proteins was correlated to classically used prognosticators, as well as to risk groups. Clinical significance of histologic and immunohistochemical features were evaluated in 59 patients for whom follow-up information was available. Results: Overexpression of Ki67 and Skp2, and p27Kip1 loss directly correlated with the high risk group (p=0.03, for Ki67 and Skp2, p=0.05, for p27Kip1). Jab1 expression did not exhibit correlation with risk. In 59 cases provided with clinical follow-up, high cellularity, presence of necrosis, and Ki67 overexpression were predictive of a reduced overall survival in a univariate model. The same parameters, as well as mitotic rate, tumour size, and p27Kip1 loss were indicative of a shortened relapse free survival interval. High cellularity, and high mitotic rate retained their prognostic significance by multivariate analysis. Conclusions: Our data suggest that a number of histologic parameters in combination with immunohistochemical expression of cell cycle regulators can facilitate risk categorization and predict biologic behavior in GIST. Importantly this study demonstrates, for the first time, that Skp2 expression correlates with Ki67 expression and high risk in GIST.

Scleroderma with crescentic glomerulonephritis: a case report

2008-05-13

IntroductionSystemic sclerosis or scleroderma is an autoimmune rheumatic disease characterized by organ-based fibrosis. Renal involvement in scleroderma occurs mainly in the form of scleroderma renal crisis, affecting 5 to 10% of patients. It remains one of the most important and immediately life-threatening complications of scleroderma, but the prognosis improves considerably after treatment with angiotensin-converting enzyme inhibitors. Other renal pathologies can occur in scleroderma. These include scleroderma overlap syndromes with associated features of lupus nephritis, myeloperoxidase anti-neutrophil cytoplasmic antibodies (ANCA) or proteinase 3 ANCA-associated glomerulonephritis, or crescentic glomerulonephritis. These alternative pathologies should be suspected in any individual patient with a differing clinical picture and the patient should be appropriately investigated. Crescentic glomerulonephritis occurs very rarely in scleroderma. This report describes a patient with scleroderma and crescentic glomerulonephritis.Case presentationA 52-year-old woman with a known history of scleroderma and hypertension on angiotensin-converting enzyme inhibitors was referred to the nephrologist because of a rapid decline in renal function. Kidney biopsy was performed which revealed immune complex-type crescentic glomerulonephritis. Cytoplasmic-staining ANCA was negative. Despite immunosuppressive treatment the patient rapidly went into end-stage renal failure and is still on hemodialysis. Conclusions: Scleroderma is a complex disease, and the best characterized renal involvement in scleroderma is scleroderma renal crisis. However, other renal pathologies can occur in scleroderma. These alternative pathologies should be suspected in any patient with a differing clinical picture and the patient should be appropriately investigated, as the clinical course and treatment are different from the more common scleroderma renal crisis.

Discovery and assembly of repeat family pseudomolecules from sparse genomic sequence data using the Assisted Automated Assembler of Repeat Families (AAARF) algorithm

Jeremy D DeBarry, Renyi Liu and Jeffrey L Bennetzen — 2008-05-13

Background: Higher eukaryotic genomes are typically large, complex and filled with both genes and multiple classes of repetitive DNA. The repetitive DNAs, primarily transposable elements, are a rapidly evolving genome component that can provide the raw material for novel selected functions and also indicate the mechanisms and history of genome evolution in any ancestral lineage. Despite their abundance, universality and significance, studies of genomic repeat content have been largely limited to analyses of the repeats in fully sequenced genomes. Results: In order to facilitate a broader range of repeat analyses, the Assisted Automated Assembler of Repeat Families algorithm has been developed. This program, written in PERL and with numerous adjustable parameters, identifies sequence overlaps in small shotgun sequence datasets and walks them out to create long pseudomolecules representing the most abundant repeats in any genome. Testing of this program in maize indicated that it found and assembled all of the major repeats in one or more pseudomolecules, including coverage of the major Long Terminal Repeat retrotransposon families. Both Sanger sequence and 454 datasets were appropriate. Conclusions: These results now indicate that hundreds of higher eukaryotic genomes can be efficiently characterized for the nature, abundance and evolution of their major repetitive DNA components.

Multilocus analysis of introgression between two sand fly vectors of leishmaniasis.

2008-05-12

Background: The phlebotomine sand flies (Diptera:Psychodidae) Lutzomyia (Nyssomyia) intermedia Lutz & Neiva 1912 and Lutzomyia (Nyssomyia) whitmani Antunes & Coutinho 1932 are two very closely related species and important vectors of American cutaneous leishmaniasis. Two single-locus studies have revealed evidence for introgression between the two species in both mitochondrial and nuclear genomes. These findings have prompted the development of a multilocus approach to investigate in more detail the genetic exchanges between the two species. Results: We analyzed ten nuclear loci using the "isolation with migration" model implemented in the IM program, finding evidence for introgression from L. intermedia towards L. whitmani in three loci. These results confirm that introgression is occurring between the two species and suggest variation in the effects of gene flow among the different regions of the genome. Conclusions: The demonstration that these two vectors are not fully reproductively isolated might have important epidemiological consequences as these species could be exchanging genes controlling aspects of their vectorial capacity.