A shared genetic mechanism for melanotic encapsulation of CM-Sephadex beads and a malaria parasite, Plasmodium cynomolgi B, in the mosquito, Anopheles gambiae

Dialysis dose and malnutrition have a great impact on the clinical out come of chronic hemodialysis patients. The interrelationships between them, however, remain undefined. Thus, we performed a study to determine the effects of increasing the dialysis dose on serum albumin concentrations and mortality in hemodialysis patients. We examined urea kinetic modeling, biochemical nutritional indices, comorbid conditions, patient survival time, and annual mortality rate. Dialysis dose, measured by Kt/V, significantly increased from 1.3 +/- 0.3 in 1987 to 1.5 +/- 0.4 in 1990 and to 1.7 +/- 0.4 in 1993. Serum albumin level also increased from 3.8 +/- 0.4 g/dL in 1987 to 4.0 +/- 0.4 in 1990 and to 1.7 +/- 0.4 in 1993. In 1993, 76% of patients had Kt/V > or = 1.50 compared with 45% in 1990 and 28% in 1987, whereas 82% of patients had a serum albumin level > or 4.0 g/dL in 1993 compared with 58% in 1990 and 29% in 1987. Protein catabolic rate and hematocrit also increased from 1987 to 1993, but not serum cholesterol or triglyceride. The annual mortality rate declined from 16.1% in 1987 to 13.2% in 1990 and to 8.0% in 1993. The decrease in mortality appeared to be unrelated to differences in patient selection or comorbid conditions. Serum albumin levels, hematocrit, Kt/V, and protein catabolic rate were significantly related to patient survival after age, sex, and diabetic status had been adjusted. Furthermore, there was a positive correlation between Kt/Vs and serum albumin concentration (r = 0.216, P < 0.001). Thus it appears that increasing the dose of dialysis improves serum albumin levels and perhaps survival rate in hemodialysis patients as well.     

The malaria parasite, Plasmodium falciparum, increases the frequency of multiple feeding of its mosquito vector, Anopheles gambiae

It has often been suggested that vector-borne parasites alter their vector's feeding behaviour to increase their transmission, but these claims are often based on laboratory studies and lack rigorous testing in a natural situation. We show in this field study that the malaria parasite, Plasmodium falciparum, alters the blood-feeding behaviour of its mosquito vector, Anopheles gambiae s.l., in two ways. First, mosquitoes infected with sporozoited, the parasite stage that is transmitted from the mosquito to a human, took up larger blood meals than uninfected mosquitoes. Whereas 72% of the uninfected mosquitoes had obtained a full blood meal, 82% of the infected ones had engorged fully. Second, mosquitoes harbouring sporozoites were more likely to bite several people per night. Twenty-two per cent of the infected mosquitoes, but only 10% of the uninfected mosquitoes, contained blood from at least two people. We conclude that the observed changes in blood-feeding behaviour allow the parasite to spread more rapidly among human hosts, and thus confirm that the parasite manipulates the mosquito to increase its own transmission.     

Microsatellite polymorphism in Anopheles maculatus, a malaria vector in Thailand

Between January 1993 and February 1993, the left internal thoracic arteries of 40 consecutive patients scheduled for aortocoronary bypass operation were examined by transthoracic B-mode imaging. Perioperative measurements correlated well with preoperative noninvasive measurements (r = 0.914). In the postoperative period, B-mode images could not be obtained in 17 (44.7%) of 38 patients. Adequate Doppler spectra of the internal thoracic artery were obtained in all patients preoperatively and in 36 (94.7%) of 38 patients postoperatively. Preoperatively a triphasic wave form was obtained with a large systolic peak followed by small reversed and diastolic components in all patients. Postoperatively this triphasic wave form had been converted into a combined systolic-diastolic wave form. In all patients peak systolic velocity of the internal thoracic artery decreased (96.4 +/- 15.3 vs 64.2 +/- 18.9 cm/sec., P < 0.05), and peak diastolic velocity increased (21.7 +/- 8.8 vs 28.3 +/- 11.2 cm/sec., P < 0.05) significantly in the postoperative period as compared with the preoperative values. A slight decrease in peak systolic and diastolic velocities was detected at twelve months postoperatively. This study indicates that transthoracic B-mode imaging and Doppler spectrum analysis are reliable techniques in the preoperative and postoperative assessment of the internal thoracic artery in myocardial revascularization.     

Pesticide avoidance behavior in Anopheles albimanus, a malaria vector in the Americas

We show that homothorax (hth) is required for the Hox genes to pattern the body of the fruit fly, Drosophila melanogaster. hth is necessary for the nuclear localization of an essential HOX cofactor, Extradenticle (EXD), and encodes a homeodomain protein that shares extensive identity with the product of Meis1, a murine proto-oncogene. MEIS1 is able to rescue hth mutant phenotypes and can induce the cytoplasmic-to-nuclear translocation of EXD in cell culture and Drosophila embryos. Thus, Meis1 is a murine homolog of hth. MEIS1/HTH also specifically binds to EXD with high affinity in vitro. These data suggest a novel and evolutionarily conserved mechanism for regulating HOX activity in which a direct protein-protein interaction between EXD and HTH results in EXD's nuclear translocation.     

Mapping the ranges and relative abundance of the two principal African malaria vectors, Anopheles gambiae sensu stricto and An. arabiensis, using climate data

Members of the Anopheles gambiae complex are major malaria vectors in Africa. We tested the hypothesis that the range and relative abundance of the two major vectors in the complex, An. gambiae sensu stricto and An. arabiensis, could be defined by climate. Climate was characterized at mosquito survey sites by extracting data for each location from climate surfaces using a Geographical Information System. Annual precipitation, together with annual and wet season temperature, defined the ranges of both vectors and were used to map suitable climate zones. Using data from West Africa, we found that where the species were sympatric, An. gambiae s.s. predominated in saturated environments, and An. arabiensis was more common in sites subject to desiccation (r2 = 0.875, p < 0.001). We used the nonlinear equation that best described this relationship to map habitat suitability across Africa. This simple model predicted accurately the relative abundance of both vectors in Tanzania (rs = 0.745, p = 0.002), where species composition is highly variable. The combined maps of species' range and relative abundance showed very good agreement with published maps. This technique represents a new approach to mapping the distribution of malaria vectors over large areas and may facilitate species-specific vector control activities.     

Distribution of genetic diversity in relation to chromosomal inversions in the malaria mosquito Anopheles gambiae

The epidemiology of malaria in Africa is complicated by the fact that its principal vector, the mosquito Anopheles gambiae, constitutes a complex of six sibling species. Each species is characterized by a unique array of paracentric inversions, as deduced by karyotypic analysis. In addition, most of the species carry a number of polymorphic inversions. In order to develop an understanding of the evolutionary histories of different parts of the genome, we compared the genetic variation of areas inside and outside inversions in two distinct inversion karyotypes of A. gambiae. Thirty-five cDNA clones were mapped on the five arms of the A. gambiae chromosomes with divisional probes. Sixteen of these clones, localized both inside and outside inversions of chromosome 2, were used as probes in order to determine the nucleotide diversity of different parts of the genome in the two inversion karyotypes. We observed that the sequence diversity inside the inversion is more than three-fold lower than in areas outside the inversion and that the degree of divergence increases gradually at loci at increasing distance from the inversion. To interpret the data we present a selectionist and a stochastic model, both of which point to a relatively recent origin of the studied inversion and may suggest differences between the evolutionary history of inversions in Anopheles and Drosophila species.     

Mapping quantitative trait loci for immune capacity in the pig

Immune capacity traits show considerable genetic variation in outbred populations. To identify quantitative trait loci (QTLs) for immune capacity in the pig, various measures of immune function (total and differential leukocyte counts, neutrophil phagocytosis, mitogen-induced proliferation, IL-2 production, and virus induced IFN-alpha production in whole blood cultures, and Ab responses to two Escherichia coli antigens) were determined in 200 F2 animals from a wild pig-Swedish Yorkshire intercross. The pedigree has been typed for 236 genetic markers covering all autosomes, the X chromosome and the X/Y pseudoautosomal region. Through interval mapping using a least-squares method, four QTLs with significant effects were identified; one for total leukocyte counts, one for mitogen-induced proliferation, one for prevaccination levels of Abs to E. coli Ag K88, and one for Ab response to the O149 Ag. In addition, several putative QTLs were indicated. The results from the present study conclusively show that it is possible to identify QTLs for immune capacity traits in outbred pig populations by genome analysis.     

Feeding patterns of Anopheles dirus, the major vector of forest malaria in north east India

The feeding behavior of Anopheles dirus, the forest breeding, major malaria vector in northeast India was studied. The analysis of blood meals collected from this mosquito revealed that the species was highly anthropophilic in nature, the anthropophilic index being 90.5. The results of bait collection on human and cattle bait also confirmed its biting preference for human hosts. The species was observed to land on human bait throughout the night, showing prominent biting time at 20.00-21.00, 23.00-24.00 and 02.00-03.00 hours during the study period.     

Computation of the full likelihood function for estimating variance at a quantitative trait locus

The proportion of alleles identical by descent (IBD) determines the genetic covariance between relatives, and thus is crucial in estimating genetic variances of quantitative trait loci (QTL). However, IBD proportions at QTL are unobservable and must be inferred from marker information. The conventional method of QTL variance analysis maximizes the likelihood function by replacing the missing IBDs by their conditional expectations (the expectation method), while in fact the full likelihood function should take into account the conditional distribution of IBDs (the distribution method). The distribution method for families of more than two sibs has not been obvious because there are n(n - 1)/2 IBD variables in a family of size n, forming an n x n symmetrical matrix. In this paper, I use four binary variables, where each indicates the event that an allele from one of the four grandparents has passed to the individual. The IBD proportion between any two sibs is then expressed as a function of the indicators. Subsequently, the joint distribution of the IBD matrix is derived from the distribution of the indicator variables. Given the joint distribution of the unknown IBDs, a method to compute the full likelihood function is developed for families of arbitrary sizes.     

Enzyme variation at the aspartate aminotransferase locus in members of the Anopheles gambiae complex (Diptera: Culicidae)

The enzyme aspartate aminotransferase (AAT) currently is used to identify Anopheles quadriannulatus Theobald, the animal-biting, nonmalaria vector species of the Anopheles gambiae complex. Samples of An. quadriannulatus from South Africa and An. gambiae Giles s.str. from the island of Grand Comoros and the People's Republic of Congo have shown variation in electromorph frequencies that indicate that AAT has five alleles. The three slowest alleles are found in An. quadriannulatus and the three fastest in An. gambiae, An. arabiensis Patton and An. merus D?nitz. One of these is common to both An. quadriannulatus and An. gambiae. This overlap indicates a potential misidentification of 0.3% of unknown females with a further 2.1% being unidentifiable. However, all of the specimens in the overlap area were classified correctly using octanol dehydrogenase (ODH). Variation at the ODH locus in An. quadriannulatus is recorded for the first time, with four of 157 specimens being heterozygous for the fast allele. The probability of both AAT and ODH giving an incorrect or indecisive identification is 0.0005. The slowest AAT alleles were present in samples from a single locality, indicating the lack of gene flow between subpopulations of An. quadriannulatus in close geographic proximity in the Shingwedzi area, South Africa. A modified method for multiple gel casting is given.     

Congenic strain confirms putative quantitative trait locus for body weight in the rat

Quantitative trait loci (QTLs) affecting body weight were investigated in the backcross population derived from non-diabetic BB/OK and spontaneously hypertensive rat (SHR) strains. The F1 hybrids were backcrossed onto SHR rats, and QTL analysis was performed separately with the resulting backcross populations for each sex on Chromosomes (Chrs) 1, 3, 4, 10, 13, and 18. The body weight was determined at the age of 14 weeks, and the statistical analysis was performed with MAPMAKER/QTL 1.1b computer program. According to the stringent threshold for a lod score of 3.0, markers on Chr 1 were found to be linked with body weight. The QTL with a peak lod score (5.1) on Chr 1 for a male population was located within markers Igf2 and D1Mgh12. In contrast, in the female population the body weight affecting QTL (lod = 5.7) on Chr 1 was located between the D1Mit3 and Lsn markers. The existence of QTLs on Chr 1 affecting body weight in the male population was confirmed by congenic BB.Sa rats, carrying chromosomal region of SHR (Sa-Igf2) on the genetic background of BB rat.     

Response of wild Anopheles funestus to repellent-protected volunteers is unaffected by malaria infection of the vector

A field experiment was conducted to compare the biting behavior of Plasmodium falciparum-infected and uninfected Anopheles on humans using mosquito repellents. Repellent formulations (5% [wt/vol] N,N-diethyl-3-methylbenzamide [deet] or 5% [wt/vol] AI3-37220, a piperidine compound, both in 100% ethanol, or 100% ethanol alone [as a control]) were applied to the lower legs of 3 collectors in each of 4 houses. Collectors caught mosquitoes over 6 collection nights. Mosquitoes were collected into vials after they initiated probing on the leg of a collector. Infected females made up the same proportion of the Anopheles funestus populations biting either repellent-protected or unprotected individuals. We conclude that repellent formulations are equally effective against Plasmodium-infected and uninfected An. funestus.     

Identification of a quantitative trait locus influencing plasma insulin levels after 70% pancreatectomy using the OLETF rat

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type non-insulin-dependent diabetes mellitus (NIDDM) in humans. The OLETF rat has poor capacity for proliferation of pancreatic beta-cells after partial pancreatectomy, which may be the critical pathogenetic event in NIDDM development. The poor pancreatic beta-cell proliferation in this model is characterized by reduction in beta-cell mass and decrease in insulin content in the remnant pancreas. Our investigation was designed to identify quantitative trait loci (QTLs) responsible for beta-cell mass and plasma insulin levels after partial pancreatectomy by performing a genome-wide scan in an F2 intercross obtained by mating the OLETF and the Fischer-344 (F344) rats. We have identified a suggestive QTL for the plasma insulin levels, near D20Mgh5 on rat chromosome 20, with a maximum lod score of 3.75 which accounts for 20% of the total variance, while no QTLs were detected for beta-cell mass. This chromosome 20 QTL, whose OLETF allele is associated with low plasma insulin levels through acting in an incompletely recessive manner, may affect insulin secretion itself rather than beta-cell proliferation.     

Mapping quantitative trait loci for carcass and meat quality traits in a wild boar x Large White intercross

An intercross between wild boar and a domestic Large White pig population was used to map quantitative trait loci (QTL) for body proportions, weight of internal organs, carcass composition, and meat quality. The results concerning growth traits and fat deposition traits have been reported elsewhere. In the present study, all 200 F2 animals, their parents, and their grandparents were genotyped for 236 markers. The marker genotypes were used to calculate the additive and dominance coefficients at fixed positions in the genome of each F2 animal, and the trait values were regressed onto these coefficients in intervals of 1 cM. In addition, the effect of proportion of wild boar alleles was tested for each chromosome. Significant QTL effects were found for percentage lean meat and percentage lean meat plus bone in various cuts, proportion of bone in relation to lean meat in ham, muscle area, and carcass length. The significant QTL were located on chromosomes 2, 3, 4, and 8. Each QTL explained 9 to 16% of the residual variance of the traits. Gene action for most QTL was largely additive. For meat quality traits, there were no QTL that reached the significance threshold. However, the average proportion of wild boar alleles across the genome had highly significant effects on reflectance and drip loss. The results show that there are several chromosome regions with a considerable effect on carcass traits in pigs.     

HOS1, a genetic locus involved in cold-responsive gene expression in arabidopsis

Low-temperature stress induces the expression of a variety of genes in plants. However, the signal transduction pathway(s) that activates gene expression under cold stress is poorly understood. Mutants defective in cold signaling should facilitate molecular analysis of plant responses to low temperature and eventually lead to the identification and cloning of a cold stress receptor(s) and intracellular signaling components. In this study, we characterize a plant mutant affected in its response to low temperatures. The Arabidopsis hos1-1 mutation identified by luciferase imaging causes superinduction of cold-responsive genes, such as RD29A, COR47, COR15A, KIN1, and ADH. Although these genes are also induced by abscisic acid, high salt, or polyethylene glycol in addition to cold, the hos1-1 mutation only enhances their expression under cold stress. Genetic analysis revealed that hos1-1 is a single recessive mutation in a nuclear gene. Our studies using the firefly luciferase reporter gene under the control of the cold-responsive RD29A promoter have indicated that cold-responsive genes can be induced by temperatures as high as 19 degrees C in hos1-1 plants. In contrast, wild-type plants do not express the luciferase reporter at 10 degrees C or higher. Compared with the wild type, hos1-1 plants are l ess cold hardy. Nonetheless, after 2 days of cold acclimation, hos1-1 plants acquired the same degree of freezing tolerance as did the wild type. The hos1-1 plants flowered earlier than did the wild-type plants and appeared constitutively vernalized. Taken together, our findings show that the HOS1 locus is an important negative regulator of cold signal transduction in plant cells and that it plays critical roles in controlling gene expression under cold stress, freezing tolerance, and flowering time.     

Distribution of T1, Q, Pegasus and mariner transposable elements on the polytene chromosomes of PEST, a standard strain of Anopheles gambiae

The chromosomal locations of four families of transposable elements, T1, Q, Pegasus and mariner, have been determined by in situ hybridization to polytene chromosomes of ovarian nurse cells of the mosquito Anopheles gambiae. As part of this effort, we have developed a vigorous pink-eyed laboratory strain of A. gambiae (PEST), rendered homozygous standard for chromosomal inversions on all autosomes. Ten different individuals of this strain were studied with each transposable element probe. The average number of hybridization sites per genome was 83.9 for T1, 63.4 for Q, 31.5 for Pegasus and 64.7 for mariner, excluding pericentric and centromeric regions. However, some degree of polymorphism was observed within each family such that, considering all ten individuals, 94 different sites were detected for T1, 82 sites for Q, 45 sites for Pegasus and 71 sites for mariner. The mean occupancy per site varied from 0.70 (Pegasus) to 0.91 (mariner), which, while significantly higher than that seen for transposable elements in natural populations of Drosophila melanogaster, is comparable to that seen in established laboratory stocks. In addition, these element families were not randomly distributed. All but Pegasus were concentrated in centromeric heterochromatin and centromere-proximal euchromatin, most showed a deficit of hybridization sites in the distal section of chromosomes, and a significant proportion of sites were coincident between families. These results provide the first detailed examination of the cytogenetic location of transposable elements in a nondrosophilid insect, and, through comparison with the behavior of transposable elements in Drosophila, may provide insight into the interaction between elements and host. The mapped elements are also expected to serve as landmarks useful in integrating the developing physical map of the PEST strain with the chromosomal banding pattern.