Extending the honey bee venome with the antimicrobial peptide apidaecin and a protein resembling wasp antigen 5

Honey bee venom is a complex mixture of toxic proteins and peptides. In the present study we tried to extend our knowledge of the venom composition using two different approaches. First, worker venom was analysed by liquid chromatography-mass spectrometry and this revealed the antimicrobial peptide apidaecin for the first time in such samples. Its expression in the venom gland was confirmed by reverse transcription PCR and by a peptidomic analysis of the venom apparatus tissue. Second, genome mining revealed a list of proteins with resemblance to known insect allergens or venom toxins, one of which showed homology to proteins of the antigen 5 (Ag5)/Sol i 3 cluster. It was demonstrated that the honey bee Ag5-like gene is expressed by venom gland tissue of winter bees but not of summer bees. Besides this seasonal variation, it shows an interesting spatial expression pattern with additional production in the hypopharyngeal glands, the brains and the midgut. Finally, our immunoblot study revealed that both synthetic apidaecin and the Ag5-like recombinant from bacteria evoke no humoral activity in beekeepers. Also, no IgG4-based cross-reactivity was detected between the honey bee Ag5-like protein and its yellow jacket paralogue Ves v 5

Dynamic regulation of subcellular calcium handling in the atria:modifying effects of stretch and adrenergic stimulation

Atrial fibrillation is the fast and irregular heart rate that occurs when the upper chambers of the heart experience chaotic electrical activation. Three main factors contribute to the development of this disease: triggers, substrate and modifying factors. An arrhythmia is thus like a fire that needs a spark (Trigger) to ignite a pile of wood (Substrate) and depends on the humidity or accelerants (modifying factors) to burn faster or slower. This body of work takes a closer look at such modifying factors. The major finding of this thesis is that stretching atrial heart muscle cells releases Calcium ions from storage spaces within each cell. If these Calcium release events get frequent enough they can act as triggers for the arrhythmia. The thickness of the atrial muscle is heterogeneous, thus filling the atrium with blood distends thinner parts stronger than ticker portions. The varying degree of stretch might stimulate Calcium release predominantly from myocytes in thinner regions of the atria. This heterogeneity in spontaneous Calcium release can modify also the substrate. A comparable effect of stretch was previously described in the heart’s main chambers. However, it appears that the in the atria it depends on another mechanism, which could serve as a treatment target that mainly acts on the atria without negatively affecting the ventricle

Design and Implementation of a Fluid-Mechanical Dynamic Afterload for Use in an Isolated Heart Apparatus

An isolated heart attached to a fluid-mechanical impedance (afterload) provides a method for study of myocardial processes and pressure and flow mechanics within the heart. Afterloads currently available allow various impedance parameter settings, but they are not automatically or dynamically controlled. A dynamically controlled afterload was constructed and its suitability tested for implementation with an isolated heart apparatus. Initial work was in development of a cardiovascular model to reveal trends for aortic pressure changes with afterload parameter adjustments. The LabVIEWTM model enables simulations with open-loop windkessel-type impedances and simulations with a closed-loop circulatory model. Cataloged trends were used to guide the dynamic afterload controls, and the open-loop impedances provided methods for modeling the fluid-mechanical system. Following this work, a systems analysis tool was developed in LabVIEWTM and Matlab to enable characterization of the fluid-mechanical afterload. The program contains time-domain and spectral analyses that incorporate equal variance algorithms for the correlation analyses and averaging methods for noise reduction in the spectral analyses for stationary signals. Auto- and cross-spectral analyses were used to generate system impedance spectra from dynamic afterload simulations. The culmination of this project was construction of a fluid-mechanical dynamic afterload. The dynamic nature of the afterload involves controlled, automatic adjustment of mechanical resistance, compliance and volume elements. These adjustments in afterload cause input pulsatile pressure to match the mean and range of a reference pressure. Simulations were performed with a pulsatile pressure pump for ten reference pressures with physiologically realistic mean and range values. The dynamic afterload constrained input pressures to within plus or minus 5% of the reference values and typically settled to the targeted values in 45 - 50 cycles. Impedance spectra from the simulations provided consistent and physiologically realistic estimates of afterload parameters fitted to a four-element windkessel-type impedance. Effects of changing impedance on the mean, range and stroke volume followed anticipated trends. These tests demonstrate that the dynamic afterload exhibits the qualities necessary for implementation with an isolated heart apparatus. Furthermore, this system will enable studies both of transient behavior in the isolated heart with changing afterload and of controlled pressure characteristics from a changing input pressure source

Cardiac Arrhythmias

Cardiac arrhythmias are common triggers of emergency admission to cardiology or high-dependency departments. Most cases are easy to diagnose and treat, while others may present a challenge to healthcare professionals. A translational approach to arrhythmias links molecular and cellular scientific research with clinical diagnostics and therapeutic methods, which may include both pharmacological and non-pharmacologic treatments. This book presents a comprehensive overview of specific cardiac arrhythmias and discusses translational approaches to their diagnosis and treatment

Biomedical Signal and Image Processing

Written for senior-level and first year graduate students in biomedical signal and image processing, this book describes fundamental signal and image processing techniques that are used to process biomedical information. The book also discusses application of these techniques in the processing of some of the main biomedical signals and images, such as EEG, ECG, MRI, and CT. New features of this edition include the technical updating of each chapter along with the addition of many more examples, the majority of which are MATLAB based