Mutations in the human PTEN-induced kinase 1 (PINK1) gene are linked to recessive familial Parkinson's disease. Animal models of altered PINK1 function vary greatly in their phenotypic characteristics. Drosophila pink1 mutants exhibit mild dopaminergic neuron degeneration and locomotion defects. Such defects are not observed in mice with targeted null mutations in pink1, although these mice exhibit impaired dopamine release and synaptic plasticity. Here, we report that in zebrafish, morpholino-mediated knockdown of pink1 function did not cause large alterations in the number of dopaminergic neurons in the ventral diencephalon. However, the patterning of these neurons and their projections are perturbed. This is accompanied by locomotor dysfunction, notably impaired response to tactile stimuli and reduced swimming behaviour. All these defects can be rescued by expression of an exogenous pink1 that is not a target of the morpholinos used. These results indicate that normal PINK1 function during development is necessary for the proper positioning of populations of dopaminergic neurons and for the establishment of neuronal circuits in which they are implicated.

Currently, there are no effective treatments to directly repair damaged heart tissue after cardiac injury since existing therapies focus on rescuing or preserving reversibly damaged tissue. Cell-based therapies using cardiomyocytes generated from stem cells present a promising therapeutic approach to directly replace damaged myocardium with new healthy tissue. However, the molecular mechanisms underlying the commitment of stem cells into cardiomyocytes are not fully understood and will be critical to guide this new technology into the clinic. Since GATA4 is a critical regulator of cardiac differentiation, we examined the molecular basis underlying the early activation of GATA4 gene expression during cardiac differentiation of pluripotent stem cells. Our studies demonstrate the direct involvement of histone acetylation and transcriptional coactivator p300 in the regulation of GATA4 gene expression. More importantly, we show that histone acetyltransferase (HAT) activity is important for GATA4 gene expression with the use of curcumin, a HAT inhibitor. In addition, the widely used histone deacetylase inhibitor valproic acid enhances both histone acetylation and cardiac specification.

Environmental effects such as dust mitigation can amplify the spread of viruses via inhaling infected dust particles. Infusion and the spreading rate of human saliva over the dust particles can play a critical role in contiguous virus spread. In the present study, mechanical and chemical interactions of human saliva with environmental dust particles are considered. The saliva droplet impact on dust particles is examined while mimicking saliva droplet spreading during coughing in a dusty ambience. The mechanisms of saliva infusion and cloaking on the dust particles are explored. The characteristics of saliva droplet normal and oblique impacts on a dust particle are examined experimentally and numerically to evaluate the amount of saliva residues on the impacted particle surface. The findings reveal that the saliva liquid infuses and cloaks the dust particle surfaces. The saliva droplet impact on the dust particles leaves a considerable amount of saliva residues on the impacted surfaces, which remain undried for a prolonged period in indoor environments. Weak adhesion of the saliva-infected dust particles on surfaces, such as glass surfaces, enables saliva-infected dust particles to rejoin neighboring ambient air while possessing a high potential for virus spreading.

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