Population and Single-Cell Analysis of Human Cardiogenesis Reveals Unique LGR5 Ventricular Progenitors in Embryonic Outflow Tract

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Warmest Congratulations to Dr. Yuan-Cheng Fung at His Centennial Celebration

Professor Y.C. Fung has made tremendous impacts on science, engineering and humanity through his research and its applications, by setting the highest standards, through educating many students and their students, and providing his exemplary leadership. He has applied his profound knowledge and elegant analytical methods to the study of biomedical problems with rigor and excellence. He established the foundations of biomechanics in living tissues and organs. Through his vision of the power of “making models” to explain and predict biological phenomena, Dr. Fung opened up new vista for bioengineering, from organs-systems to molecules-genes, and has provided the foundation of research activities in many institutions in the United States and the world. He has made outstanding contributions to education in bioengineering, service to professional organizations, and translation to industry and clinical medicine. He is widely recognized as the Father of Biomechanics and the leading Bioengineer in the world. His extraordinary achievements and commands in science, engineering and the arts make him a Renaissance Man for the world.     

The renewal and differentiation of Isl1+ cardiovascular progenitors are controlled by a Wnt/beta-catenin pathway

Isl1(+) cardiovascular progenitors and their downstream progeny play a pivotal role in cardiogenesis and lineage diversification of the heart. The mechanisms that control their renewal and differentiation are largely unknown. Herein, we show that the Wnt/beta-catenin pathway is a major component by which cardiac mesenchymal cells modulate the prespecification, renewal, and differentiation of isl1(+) cardiovascular progenitors. This microenvironment can be reconstituted by a Wnt3a-secreting feeder layer with ES cell-derived, embryonic, and postnatal isl1(+) cardiovascular progenitors. In vivo activation of beta-catenin signaling in isl1(+) progenitors of the secondary heart field leads to their massive accumulation, inhibition of differentiation, and outflow tract (OFT) morphogenic defects. In addition, the mitosis rate in OFT myocytes is significantly reduced following beta-catenin deletion in isl1(+) precursors. Agents that manipulate Wnt signals can markedly expand isl1(+) progenitors from human neonatal hearts, a key advance toward the cloning of human isl1(+) heart progenitors.     

Rapid enrichment of phosphopeptides and phosphoproteins from complex samples using magnetic particles coated with alumina as the concentrating probes for MALDI MS analysis

In this study, we used nanocomposite magnetic particles coated with alumina as the affinity probes to selectively concentrate phosphorylated peptides and proteins from a low volume of sample solution. Tryptic digest products of phosphoproteins including alpha and beta-caseins, human protein phosphatase inhibitor 1, nonfat milk, egg white, and a cell lysate were used as the samples to demonstrate the feasibility of this approach. In only 30 and 90 s, phosphopeptides and phosphoproteins sufficient for characterization by MALDI-MS were enriched by the particles, respectively. Proteins trapped on the particles could be directly digested on the particles. The same particles in the digest solution were employed for enrichment of phosphopeptides. We estimated the required time for performing the enrichment of phosphopeptides from complex samples and characterization by MALDI MS was within 5 min. A small volume (50 microL) and a low concentration (5 x 10(-10) M) of tryptic digest product of a phosphoprotein sample could be dramatically enriched and characterized using this approach.     

Major acute cardiovascular events after dengue infection–A population-based observational study

BackgroundDengue virus (DENV) infection may be associated with increased risks of major adverse cardiovascular effect (MACE), but a large-scale study evaluating the association between DENV infection and MACEs is still lacking.Methods and findingsAll laboratory confirmed dengue cases in Taiwan during 2009 and 2015 were included by CDC notifiable database. The self-controlled case-series design was used to evaluate the association between DENV infection and MACE (including acute myocardial infarction [AMI], heart failure and stroke). The "risk interval" was defined as the first 7 days after the diagnosis of DENV infection and the "control interval" as 1 year before and 1 year after the risk interval. The incidence rate ratio (IRR) and 95% confidence interval (CI) for MACE were estimated by conditional Poisson regression. Finally, the primary outcome of the incidence of MACEs within one year of dengue was observed in 1,247 patients. The IRR of MACEs was 17.9 (95% CI 15.80–20.37) during the first week after the onset of DENV infection observed from 1,244 eligible patients. IRR were significantly higher for hemorrhagic stroke (10.9, 95% CI 6.80–17.49), ischemic stroke (15.56, 95% CI 12.44–19.47), AMI (13.53, 95% CI 10.13–18.06), and heart failure (27.24, 95% CI 22.67–32.73). No increased IRR was observed after day 14.ConclusionsThe risks for MACEs are significantly higher in the immediate time period after dengue infection. Since dengue infection is potentially preventable by early recognition and vaccination, the dengue-associated MACE should be taken into consideration when making public health management policies.     

Enhanced polyhydroxybutyrate (PHB) production via the coexpressed phaCAB and vgb genes controlled by arabinose PBAD promoter in Escherichia coli

Aim: To develop an approach to enhance polyhydroxybutyrate (PHB) production via the coexpressed phaCAB and vgb genes controlled by arabinose P_BAD promoter in Escherichia coli. Method and Results: The polyhydroxyalkanoates (PHAs) synthesis operon, (phaCAB), from Ralstonia eutropha was overexpressed under the regulation of the arabinose P_BAD promoter in Escherichia coli, and the vgb gene encoding bacterial haemoglobin from Vitreoscilla stercoraria (VHb) was further cloned at downstream of phaCAB to form an artificial operon. The cell dry weight (CDW), PHB content and PHB concentration were enhanced around 1·23‐, 1·57‐, and 1·93‐fold in the engineered cell harbouring phaCAB–vgb (SY‐2) upon 1% arabinose induction compared with noninduction (0% arabinose). Furthermore, by using a recombinant strain harbouring P_BAD promoter‐vgb along with native promoter‐phaCAB construction, the effect of vgb expression level on PHB biosynthesis was positive correlation. Conclusions: The results exploit the possibility to improve the PHB production by fusing the genes phaCAB–vgb from different species under the arabinose regulation system in E. coli. It also demonstrates that increase in VHb level enhances the PHB production. Significance and Impact of the Study: We were successful in providing a new coexpressed system for PHB synthesis in E. coli. This coexpressed system could be regulated by arabinose inducer, and is more stable and cheaper than other induced systems (e.g. IPTG). Furthermore, it could be applied in many biotechnology or fermentation processes.     

Role of tensile stress and strain in the induction of cell death in experimental vein grafts

Tensile stress and strain are known to induce vascular cell proliferation, a process that is physiologically counterbalanced by cell death. Here we investigate whether tensile stress and strain regulate vascular-cell death by using an end-to-end anastomosed rat vein graft model. In such a model, the circumferential tensile stress in the graft wall was increased by approximately 140 times immediately after surgery compared with that in the venous wall. This change was associated with an increase in the percentage of TUNEL-positive cells at 1, 6, 24, 120, 240, and 720h with two distinct peaks at 1 and 24h (10.1+/-3.5 and 14.4+/-3.2%, respectively) compared with that in control jugular veins (0.4+/-0.5 and 0.5+/-0.5% at 1 and 24h, respectively). When tensile stress and strain in the vein graft wall were reduced by using a biomechanical engineering approach, the rate of cell death was reduced significantly (3.6+/-1.1 and 1.6+/-0.5% at 1 and 24h, respectively). Furthermore, DEVD-CHO, a tetrapeptide aldehyde that inhibits the activity of caspase 3, significantly suppressed this event. These results suggest that a step increase in tensile stress and strain in experimental vein grafts induces rapid cell death, which is possibly mediated by cell death signaling mechanisms.