Speciation by monobrachial centric fusions: A test of the model using nuclear DNA sequences from the bat genus Rhogeessa

Members of Rhogeessa are hypothesized to have undergone speciation via chromosomal rearrangements in a model termed speciation by monobrachial centric fusions. Recently, mitochondrial cytochrome-b sequence data tentatively supported this hypothesis but could not explicitly test the model’s expectations regarding interbreeding among karyotypic forms. These data showed potential evidence for hybridization or incomplete lineage sorting between the karyotypically distinct R. tumida and R. aeneus and identified multiple lineages of karyotypically identical R. tumida. Here, we present a more comprehensive test of speciation by monobrachial centric fusions in Rhogeessa. Our analysis is based on sequence data from two nuclear loci: paternally inherited ZFY and autosomal MPI genes. These data provide results consistent either with incomplete lineage sorting or ancient hybridization to explain alleles shared at low frequency between R. aeneus and R. tumida. Recent and ongoing hybridization between any species can be ruled out. These data confirm the presence of multiple lineages of the 2n = 34 karyotypic form (“R. tumida”) that are not each other’s closest relatives. These results are generally consistent with speciation by monobrachial centric fusions, although additional modes of speciation have also occurred in Rhogeessa. Phylogeographic analyses indicate habitat differences may be responsible for isolation and divergence between different lineages currently referred to as R. tumida.     

Strongyloides stercoralis and HTLV-1 coinfection in CD34+ cord blood stem cell humanized mice: Alteration of cytokine responses and enhancement of larval growth

Viral and parasitic coinfections are known to lead to both enhanced disease progression and altered disease states. HTLV-1 and Strongyloides stercoralis are co-endemic throughout much of their worldwide ranges resulting in a significant incidence of coinfection. Independently, HTLV-1 induces a Th1 response and S. stercoralis infection induces a Th2 response. However, coinfection with the two pathogens has been associated with the development of S. stercoralis hyperinfection and an alteration of the Th1/Th2 balance. In this study, a model of HTLV-1 and S. stercoralis coinfection in CD34⁺ umbilical cord blood hematopoietic stem cell engrafted humanized mice was established. An increased level of mortality was observed in the HTLV-1 and coinfected animals when compared to the S. stercoralis infected group. The mortality was not correlated with proviral loads or total viral RNA. Analysis of cytokine profiles showed a distinct shift towards Th1 responses in HTLV-1 infected animals, a shift towards Th2 cytokines in S. stercoralis infected animals and elevated TNF-α responses in coinfected animals. HTLV-1 infected and coinfection groups showed a significant, yet non-clonal expansion of the CD4⁺CD25⁺ T-cell population. Numbers of worms in the coinfection group did not differ from those of the S. stercoralis infected group and no autoinfective larvae were found. However, infective larvae recovered from the coinfection group showed an enhancement in growth, as was seen in mice with S. stercoralis hyperinfection caused by treatment with steroids. Humanized mice coinfected with S. stercoralis and HTLV-1 demonstrate features associated with human infection with these pathogens and provide a unique opportunity to study the interaction between these two infections in vivo in the context of human immune cells.     

Pigtailed macaque model refinement: topical microbicide safety in the presence of coitus

Background Inclusion of sexual activity in the macaque model for topical microbicide safety evaluation would more closely mimic human use of topical microbicides and provide a more rigorous safety assessment. Methods Initially, male–female partners were monitored in cohousing arrangements to determine whether macaques would copulate ad libitum. The logistics of performing vaginal examinations before and after coital visits were analyzed and optimized. Findings from cervicovaginal examinations conducted before and after sexual activity were compared. Results Coital activity was reliably observed in the majority of cohousing sessions, representing all phases of the menstrual cycle. Female macaques were trained to be restrained while fully alert for pre‐coital vaginal sampling. Post‐coital examinations occur under general sedation. Post‐coital examinations reveal alterations to tissues, microbiology, and pH compared with pre‐coital visits. Conclusions This work clearly demonstrates that it is feasible to incorporate sexual activity in the macaque model for topical microbicide safety assessment.     

Spotlight on Zebrafish: Translational Impact

In recent years, the zebrafish has emerged as an increasingly prominent model in biomedical research. To showcase the translational impact of the model across multiple disease areas, Disease Models & Mechanisms has compiled a Special Issue that includes thought-provoking reviews, original research reporting new and important insights into disease mechanisms, and novel resources that expand the zebrafish toolkit. This Editorial provides a summary of the issue’s contents, highlighting the diversity of zebrafish disease models and their clinical applications.Open in a separate windowE. Elizabeth PattonOpen in a separate windowJames F. AmatrudaOpen in a separate windowLalita Ramakrishnan     

A conversational program for analytical modelling of action potentials in nerve and muscle.

A conversational program is described which is being used for exploratory modelling of digestive tract electrical activity. The structure of the mathematical model is based on the Hodgkin-Huxley equations for nerve axons and the Noble equations for Purkinje fibres of the heart. The parameters of the models are changed conversationally to investigate the effects of frequency, amplitude and waveshape. In this way it is intended to extend the models to include nervous control. The program is also being used to correlate the behaviour of H-H type equations with the simpler dynamics of Van der Pol's equation which is the basis of an oscillator-array model for the stomach and small intestines.