New directions in craniofacial morphogenesis

The vertebrate head is an extremely complicated structure: development of the head requires tissue-tissue interactions between derivates of all the germ layers and coordinated morphogenetic movements in three dimensions. In this review, we highlight a number of recent embryological studies, using chicken, frog, zebrafish and mouse, which have identified crucial signaling centers in the embryonic face. These studies demonstrate how small variations in growth factor signaling can lead to a diversity of phenotypic outcomes. We also discuss novel genetic studies, in human, mouse and zebrafish, which describe cell biological mechanisms fundamental to the growth and morphogenesis of the craniofacial skeleton. Together, these findings underscore the complex interactions leading to species-specific morphology. These and future studies will improve our understanding of the genetic and environmental influences underlying human craniofacial anomalies.     

Synthesising 30 Years of Mathematical Modelling of Echinococcus Transmission

Background

Echinococcosis is a complex zoonosis that has domestic and sylvatic lifecycles, and a range of different intermediate and definitive host species. The complexities of its transmission and the sparse evidence on the effectiveness of control strategies in diverse settings provide significant challenges for the design of effective public health policy against this disease. Mathematical modelling is a useful tool for simulating control packages under locally specific transmission conditions to inform optimal timing and frequency of phased interventions for cost-effective control of echinococcosis. The aims of this review of 30 years of Echinococcus modelling were to discern the epidemiological mechanisms underpinning models of Echinococcus granulosus and E. multilocularis transmission and to establish the need to include a human transmission component in such models.

Methodology/Principal Findings

A search was conducted of all relevant articles published up until July 2012, identified from the PubMED, Web of Knowledge and Medline databases and review of bibliographies of selected papers. Papers eligible for inclusion were those describing the design of a new model, or modification of an existing mathematical model of E. granulosus or E. multilocularis transmission. A total of 13 eligible papers were identified, five of which described mathematical models of E. granulosus and eight that described E. multilocularis transmission. These models varied primarily on the basis of six key mechanisms that all have the capacity to modulate model dynamics, qualitatively affecting projections. These are: 1) the inclusion of a ‘latent’ class and/or time delay from host exposure to infectiousness; 2) an age structure for animal hosts; 3) the presence of density-dependent constraints; 4) accounting for seasonality; 5) stochastic parameters; and 6) inclusion of spatial and risk structures.

Conclusions/Significance

This review discusses the conditions under which these mechanisms may be important for inclusion in models of Echinococcus transmission and proposes recommendations for the design of dynamic human models of transmission. Accounting for the dynamic behaviour of the Echinococcus parasites in humans will be key to predicting changes in the disease burden over time and to simulate control strategies that optimise public health impact.     

Frontal Bone Insufficiency in Gsk3β Mutant Mice

The development of the mammalian skull is a complex process that requires multiple tissue interactions and a balance of growth and differentiation. Disrupting this balance can lead to changes in the shape and size of skull bones, which can have serious clinical implications. For example, insufficient ossification of the bony elements leads to enlarged anterior fontanelles and reduced mechanical protection of the brain. In this report, we find that loss of Gsk3β leads to a fully penetrant reduction of frontal bone size and subsequent enlarged frontal fontanelle. In the absence of Gsk3β the frontal bone primordium undergoes increased cell death and reduced proliferation with a concomitant increase in Fgfr2-IIIc and Twist1 expression. This leads to a smaller condensation and premature differentiation. This phenotype appears to be Wnt-independent and is not rescued by decreasing the genetic dose of β-catenin/Ctnnb1. Taken together, our work defines a novel role for Gsk3β in skull development.     

Taste bud form and distribution on lips and in the oropharyngeal cavity of cardinal fish species (Apogonidae, Teleostei), with remarks on their dentition

The oral dentition and type and number of taste buds (TB) on the lips and in the oropharyngeal cavity were compared by means of SEM in 11 species of cardinal fishes (Apogonidae) belonging to five genera. The occurrence of a dense cover of skin papillae on the lips of some species (e.g., Apogon frenatus), as well as differences in structure of vomer, tongue, and palatinum, expose additional morphological characters important for clarification of the taxonomy of this group of fishes. Differences are also revealed in the type of dentition, such as on the vomer and epi-hypopharyngeal bones. Strong and dense dentition of the anterior part of the oral cavity and a high number of TB on this site in species feeding on larger prey (e.g., Cheilodipterus spp) is compared to the relatively feeble jaw armor and richness of TB on the more pharyngeal site in species feeding on smaller prey (e.g., Apogon angustatus, A. frenatus). In addition to the three types of TB (Types I-III) previously described from various teleost fish, a fourth type (Type IV), comprising very small buds, was found in some cardinal fish (Apogon angustatus, A. frenatus). The various TB are distributed from the lips to the pharyngeal bones, on the breathing valves, tongue, palatinum, and pharyngeal bones; their number and type on the various sites differ in the different species. In all species studied the Types I and II TB, elevated above the surrounding epithelium, dominated the lips and anterior part of mouth, while Types III and IV, which end apically at the level with the epithelium, dominated the more posterior pharyngeal region. The highest number of TB, around 24,600, were found in Fowleria variegata, a typical nocturnal species, and the lowest in the diurnal and crepuscular Apogon cyanosoma (1,660) and Cheilodipterus quinquestriatus (2,400). Differences are also revealed in the type of dentition, such as on the vomer and epi-hypopharyngeal bones. The number of TB increased with growth of the fishes. The differences in the total number of TB and their distribution in the oropharyngeal cavity in the various species indicates possible different mechanisms of foraging and food-recognition.     

Mapping the Risk of Soil-Transmitted Helminthic Infections in the Philippines

BackgroundIn order to increase the efficient allocation of soil-transmitted helminth (STH) disease control resources in the Philippines, we aimed to describe for the first time the spatial variation in the prevalence of A. lumbricoides, T. trichiura and hookworm across the country, quantify the association between the physical environment and spatial variation of STH infection and develop predictive risk maps for each infection.Conclusions/SignificanceThis analysis revealed significant spatial variation in STH infection prevalence within provinces of the Philippines. This suggests that a spatially targeted approach to STH interventions, including mass drug administration, is warranted. When financially possible, additional STH surveys should be prioritized to high-risk areas identified by our study in Luzon.     

Modelling parasite aggregation: disentangling statistical and ecological approaches

The overdispersion in macroparasite infection intensity among host populations is commonly simulated using a constant negative binomial aggregation parameter. We describe an alternative to utilising the negative binomial approach and demonstrate important disparities in intervention efficacy projections that can come about from opting for pattern-fitting models that are not process-explicit. We present model output in the context of the epidemiology and control of soil-transmitted helminths due to the significant public health burden imposed by these parasites, but our methods are applicable to other infections with demonstrable aggregation in parasite numbers among hosts.     

Modeling the Effects of Integrating Larval Habitat Source Reduction and Insecticide Treated Nets for Malaria Control

Integrated vector management for malaria control has received a lot of recent interest. Attacking multiple points in the transmission cycle is hoped to act synergistically and improve upon current single-tool interventions based on the use of insecticide-treated bed nets (ITNs). In the present study, we theoretically examined the application of larval habitat source reduction with ITNs in reducing malaria transmission. We selected this type of environmental management to complement ITNs because of a potential secondary mode of action that both control strategies share. In addition to increasing vector mortality, ITNs reduce the rate at which female mosquitoes locate human hosts for blood feeding, thereby extending their gonotrophic cycle. Similarly, while reducing adult vector emergence and abundance, source reduction of larval habitats may prolong the cycle duration by extending delays in locating oviposition sites. We found, however, that source reduction of larval habitats only operates through this secondary mode of action when habitat density is below a critical threshold. Hence, we illustrate how this strategy becomes increasingly effective when larval habitats are limited. We also demonstrate that habitat source reduction is better suited to human populations of higher density and in the presence of insecticide resistance or when the insecticidal properties of ITNs are depleted.     

Comparative morphology and cytology of the male sperm-transmission organs in viviparous species of clinid fishes (Clinidae: Teleostei, Perciformes)

This work comprises the first comparative study of the morphology and cytology of the sperm transmission organs in males of 14 species of viviparous clinid fishes (Clinidae, Blennioidei, Teleostei). The form and dimensions of these organs differ among the various species studied. The organs are composed of intra-abdominal ampullae, into which the sperm ducts and urinary bladder anchor, and an external protruding intromittent papilla used for insemination. The form of the ampullae differs among the various species, from pear-shaped to horseshoe-shaped. It increases in dimensions with increasing length of the male. In all the species this organ is covered by a connective-tissue tunic that encompasses both circular and longitudinal striated muscle bundles. The lumina of the ampullae harbor the epididymis, a strongly convoluted and plicated duct, which becomes filled with spermatozeugmata during reproduction. From here, the epididymis continues into the protruding intromittent papillae, where its folds gradually straighten at the apical part of the intromittent organ. The form and dimensions of this copulatory organ also differ in the various species. Papillae bearing taste buds are found on the apical parts of the intromittent organ, and it is probable that these, together with the difference in forms of the organ, help to prevent interspecific copulation.     

Low Temperature Tolerance of Pacu, Piaractus mesopotamicus

Pacu, Piaractus mesopotamicus (=Colossoma mitrei), is a South American warm water fish species found in the temperature range of 15–35°C. The culture of a warm water species in temperate regions demands knowledge on its temperature requirements. Pacu introduction into the Israeli fish culture system is being considered. Temperature range in the region is 8–33°C, thus the minimum winter water temperatures might be a limiting factor. To determine what is the minimum temperature pacu would tolerate, and hence which overwintering operations in warm-temperate regions are required for this warm water species, low temperature tolerance tests in the laboratory and observations in the field were carried out. Laboratory experiments reducing temperature by 1–3°C per day were carried out with fish of 150–200g, about the size pacu reach after one culture season. The field observations compared survival of two-year-old pacu of 1.3kg mean weight overwintered in outdoors and in greenhouse ponds. For one-year-old fish 7.5°C was found to be the lower temperature tolerance limit. Two-year-old fish withstand short exposures to this temperature rather well and their lower tolerance limit might be lower. This indicates that in warm-temperate regions pacu should survive in outdoors ponds. In this case some loss of weight should be expected, and suspension of feeding when temperature drops below 16–18°C is recommended to avoid wasting feed that the fish will not consume anyway. To be in the safe side, inflow of the warmest available water into the ponds is recommended if maximum water temperature drops to 10°C or below. Overwintering in greenhouses or other heated facilities would be recommended if an exceptionally cold winter is expected and for regions with lower winter minimum temperatures.     

Epidemiological consequences of a newly discovered cryptic subgroup of Anopheles gambiae

A cryptic subgroup of Anopheles gambiae sensu stricto mosquitoes was recently discovered in West Africa. This 'GOUNDRY' subgroup has increased susceptibility to Plasmodium falciparum, the most deadly form of malaria. Unusual for this major malaria vector, GOUNDRY mosquitoes also seem to bite exclusively outdoors. A mathematical model is developed to assess the epidemiological implications of current vector control tools, bednets and indoor residual spray, preferentially suppressing the more typical indoor biting mosquitoes. It is demonstrated that even if the GOUNDRY mosquitoes have a decreased preference for human blood, vector controls which select for increased GOUNDRY abundance relative to their indoor biting counterparts risks intensifying malaria transmission. Given the widely observed phenomenon of outdoor biting by major malaria vectors, this behaviour should not be ignored in future modelling efforts and warrants serious consideration in control programme strategy.