Search

Tetraspanins regulate key processes in immune cells; however, the function of the leukocyte-restricted tetraspanin CD53 is unknown. Here we show that CD53 is essential for lymphocyte recirculation. Lymph nodes of Cd53-/- mice were smaller than those of wild-type mice due to a marked reduction in B cells and a 50% decrease in T cells. This reduced cellularity reflected an inability of Cd53-/- B and T cells to efficiently home to lymph nodes, due to the near absence of L-selectin from Cd53-/- B cells and reduced stability of L-selectin on Cd53-/- T cells. Further analyses, including on human lymphocytes, showed that CD53 stabilizes L-selectin surface expression and may restrain L-selectin shedding via both ADAM17-dependent and ADAM17-independent mechanisms. The disruption in lymphocyte recirculation in Cd53-/- mice led to impaired immune responses dependent on antigen delivery to lymph nodes. Together these findings demonstrate an essential role for CD53 in lymphocyte trafficking and immunity.

While snake venoms have been the subject of intense study, comparatively little work has been done on lizard venoms. In this study, we have examined the structural and functional diversification of anguimorph lizard venoms and associated toxins, and related these results to dentition and predatory ecology. Venom composition was shown to be highly variable across the 20 species of Heloderma, Lanthanotus, and Varanus included in our study. While kallikrein enzymes were ubiquitous, they were also a particularly multifunctional toxin type, with differential activities on enzyme substrates and also ability to degrade alpha or beta chains of fibrinogen that reflects structural variability. Examination of other toxin types also revealed similar variability in their presence and activity levels. The high level of venom chemistry variation in varanid lizards compared to that of helodermatid lizards suggests that venom may be subject to different selection pressures in these two families. These results not only contribute to our understanding of venom evolution but also reveal anguimorph lizard venoms to be rich sources of novel bioactive molecules with potential as drug design and development lead compounds.

Venom has only been recently discovered to be a basal trait of the Anguimorpha lizards. Consequently, very little is known about the timings of toxin recruitment events, venom protein molecular evolution, or even the relative physical diversifications of the venom system itself. A multidisciplinary approach was used to examine the evolution across the full taxonomical range of this ∼130 million-year-old clade. Analysis of cDNA libraries revealed complex venom transcriptomes. Most notably, three new cardioactive peptide toxin types were discovered (celestoxin, cholecystokinin, and YY peptides). The latter two represent additional examples of convergent use of genes in toxic arsenals, both having previously been documented as components of frog skin defensive chemical secretions. Two other novel venom gland-overexpressed modified versions of other protein frameworks were also recovered from the libraries (epididymal secretory protein and ribonuclease). Lectin, hyaluronidase, and veficolin toxin types were sequenced for the first time from lizard venoms and shown to be homologous to the snake venom forms. In contrast, phylogenetic analyses demonstrated that the lizard natriuretic peptide toxins were recruited independently of the form in snake venoms. The de novo evolution of helokinestatin peptide toxin encoding domains within the lizard venom natriuretic gene was revealed to be exclusive to the helodermatid/anguid subclade. New isoforms were sequenced for cysteine-rich secretory protein, kallikrein, and phospholipase A(2) toxins. Venom gland morphological analysis revealed extensive evolutionary tinkering. Anguid glands are characterized by thin capsules and mixed glands, serous at the bottom of the lobule and mucous toward the apex. Twice, independently this arrangement was segregated into specialized serous protein-secreting glands with thick capsules with the mucous lobules now distinct (Heloderma and the Lanthanotus/Varanus clade). The results obtained highlight

Background: ECG is an important tool in the diagnosis of ischemic heart disease and arrhythmia. Computerized automatic diagnostic tools may help clinicians in diagnosing these diseases and give early warning when the ECG is continuously monitored. Their success depends on the availability of reliable ECG wave identification systems. The conventional algorithms include the use of derivative-based methods and non-linear filtering. In the past decades, the wavelet transform has been advocated. Although investigators have compared the performance of wavelet transform with the conventional algorithms on QRS detection, research is still needed on the performance of these algorithms on P and T wave detection. In this study, we compared the accuracy of a derivative-based method and the wavelet transform in P, R and T wave detection. Methods: ECG signals were downloaded from 48 files of the European ST-T database. We extracted 11 one-minute recordings to cover a variety of ECG morphologies. The signals were filtered by a bandpass filter. The derivative-based method identified the ECG waves by applying rules on the smoothed differentiated signal. For the wavelet transform, the first derivative of a Gaussian was used as the basis function. The number of P, R and T waves correctly identified by the derivative-based method and the wavelet transform were compared. Results: 806 ECG beats were analyzed. 89.4% of the P waves were identified correctly using wavelet (compared to 80.2% for the derivative-based method). The lack of statistical significance (p=0.07) may be due to a lack of power. 99.0% of R waves were identified correctly using wavelet compared to 98.8% for the derivative-based method. 91.8 % of the T waves were correctly identified using wavelet compared to 77.3% for the derivative- based method (p<0.05). Conclusion: The wavelet-based method was shown to be superior to the conventional derivative-based method especially in T wave identification.

Background: ECG is an important tool in the diagnosis of ischemic heart disease and arrhythmia. Computerized automatic diagnostic tools may help clinicians in diagnosing these diseases and give early warning when the ECG is continuously monitored. Their success depends on the availability of reliable ECG wave identification systems. The conventional algorithms include the use of derivative-based methods and non-linear filtering. In the past decades, the wavelet transform has been advocated. Although investigators have compared the performance of wavelet transform with the conventional algorithms on QRS detection, research is still needed on the performance of these algorithms on P and T wave detection. In this study, we compared the accuracy of a derivative-based method and the wavelet transform in P, R and T wave detection. Methods: ECG signals were downloaded from 48 files of the European ST-T database. We extracted 11 one-minute recordings to cover a variety of ECG morphologies. The signals were filtered by a bandpass filter. The derivative-based method identified the ECG waves by applying rules on the smoothed differentiated signal. For the wavelet transform, the first derivative of a Gaussian was used as the basis function. The number of P, R and T waves correctly identified by the derivative-based method and the wavelet transform were compared. Results: 806 ECG beats were analyzed. 89.4% of the P waves were identified correctly using wavelet (compared to 80.2% for the derivative-based method). The lack of statistical significance (p=0.07) may be due to a lack of power. 99.0% of R waves were identified correctly using wavelet compared to 98.8% for the derivative-based method. 91.8 % of the T waves were correctly identified using wavelet compared to 77.3% for the derivative- based method (p<0.05). Conclusion: The wavelet-based method was shown to be superior to the conventional derivative-based method especially in T wave identification.