On the computation of in vivo transmural mean stress of patient-specific aortic wall

Biomechanics and Modeling in Mechanobiology - It is well known that residual deformations/stresses alter the mechanical behavior of arteries, e.g., the pressure–diameter curves. In an effort...     

Abnormal Whole Blood Thrombi in Humans with Inherited Platelet Receptor Defects

To delineate the critical features of platelets required for formation and stability of thrombi, thromboelastography and platelet aggregation measurements were employed on whole blood of normal patients and of those with Bernard-Soulier Syndrome (BSS) and Glanzmann’s Thrombasthenia (GT). We found that separation of platelet activation, as assessed by platelet aggregation, from that needed to form viscoelastic stable whole blood thrombi, occurred. In normal human blood, ristocetin and collagen aggregated platelets, but did not induce strong viscoelastic thrombi. However, ADP, arachidonic acid, thrombin, and protease-activated-receptor-1 and -4 agonists, stimulated both processes. During this study, we identified the genetic basis of a very rare double heterozygous GP1b deficiency in a BSS patient, along with a new homozygous GP1b inactivating mutation in another BSS patient. In BSS whole blood, ADP responsiveness, as measured by thrombus strength, was diminished, while ADP-induced platelet aggregation was normal. Further, the platelets of 3 additional GT patients showed very weak whole blood platelet aggregation toward the above agonists and provided whole blood thrombi of very low viscoelastic strength. These results indicate that measurements of platelet counts and platelet aggregability do not necessarily correlate with generation of stable thrombi, a potentially significant feature in patient clinical outcomes.     

The Protective Effect of Human Umbilical Cord Blood CD34+ Cells and Estradiol against Focal Cerebral Ischemia in Female Ovariectomized Rat: Cerebral MR Imaging and Immunohistochemical Study

Human umbilical cord blood derived CD34⁺ stem cells are reported to mediate therapeutic effects in stroke animal models. Estrogen was known to protect against ischemic injury. The present study wished to investigate whether the protective effect of CD34⁺ cells against ischemic injury can be reinforced with complemental estradiol treatment in female ovariectomized rat and its possible mechanism. Experiment 1 was to determine the best optimal timing of CD34⁺ cell treatment for the neuroprotective effect after 60-min middle cerebral artery occlusion (MCAO). Experiment 2 was to evaluate the adjuvant effect of 17β-estradiol on CD34⁺ cell neuroprotection after MCAO. Experiment 1 showed intravenous infusion with CD34⁺ cells before MCAO (pre-treatment) caused less infarction size than those infused after MCAO (post-treatment) on 7T magnetic resonance T2-weighted images. Experiment 2 revealed infarction size was most significantly reduced after CD34⁺ + estradiol pre-treatment. When compared with no treatment group, CD34⁺ + estradiol pre-treatment showed significantly less ADC reduction at 2 h and 2 d, less CBF reduction at 2 h and less hyperperfusion at 2 d. The immunoreactivity of c-Fos, c-Jun and GFAP was attenuated, and BDNF showed significant recovery from 2 h to 2 d after MCAO, especially after CD34⁺ + estradiol pre-treatment. The present study suggests pre-treatment with CD34⁺ cells with complemental estradiol can be most protective against ischemic injury, which may act through stabilization of cerebral hemodynamics and normalization of the expressions of immediate early genes and BDNF.     

Tasselseed5 encodes a cytochrome C oxidase that functions in sex determination by affecting jasmonate catabolism in maize

Maize (Zea mays L.) is a monoecious grass plant in which mature male and female florets form the tassel and ear, respectively. Maize is often used as a model plant to study flower development. Several maize tassel seed mutants, such as the recessive mutants tasselseed1 (ts1) and tasselseed2 (ts2), exhibit a reversal in sex determination, which leads to the generation of seeds in tassels. The phenotype of the dominant mutant, Tasselseed5 (Ts5), is similar to that of ts2. Here, we positionally cloned the underlying gene of Ts5 and characterized its function. We show that the GRMZM2G177668 gene is overexpressed in Ts5. This gene encodes a cytochrome C oxidase, which catalyzes the transformation of jasmonoyl‐L‐isoleucine (JA‐Ile) to 12OH‐JA‐Ile during jasmonic acid catabolism. Consistent with this finding, no JA‐Ile peak was detected in Ts5 tassels during the sex determination period, unlike in the wild type. Transgenic maize plants overexpressing GRMZM2G177668 exhibited a tassel‐seed phenotype similar to that of Ts5. These results indicate that the JA‐Ile peak in tassels is critical for sex determination and that the Ts5 mutant phenotype results from the disruption of this peak in tassels during sex determination.     

Intersected functional zone of transcriptional regulators patterns stemness within stem cell niche of root apical meristem

Root stem cell niche (SCN) consists of a quiescent center (QC) and surrounding stem cells. Disrupted symplastic communication leads to loss of stemness in the whole SCN. Several SCN regulators were reported to move between cells for SCN maintenance. However, single mutant of these regulators is insufficient to abolish QC stemness despite the high differentiation rate in surrounding stem cells. To dissect the mechanism behind such distinct stemness in SCN, we combined the mis‐expression strategy with pWOX5:icals3m system in which QC is symplastically isolated. We found the starch accumulation in QC could be synergistically repressed by WUSCHEL‐RELATED HOMEOBOX 5 (WOX5), SHORT‐ROOT (SHR), SCARCROW (SCR), and PLETHORA (PLT). Like PLTs, other core regulators also exhibited dimorphic functions by inhibiting differentiation at a higher dose while promoting cell division at a low protein level. Being located in the center of the intersected expression zones, QC cells receive the highest level of core regulators, forming the most robust stemness within SCN. WUSCHEL‐RELATED HOMEOBOX 5 was sufficient to activate PLT1/2 expression, contributing to the QC‐enriched PLTs. Our results provide experimental evidence supporting the long‐standing hypothesis that the combination of spatial expression, synergistic function and dosage effect of core regulators result in spatially distinct stemness in SCN.     

Exosome derived from CD137‐modified endothelial cells regulates the Th17 responses in atherosclerosis

The role of exosomes derived from endothelial cells (ECs) in the progression of atherosclerosis (AS) and inflammation remains largely unexplored. We aimed to investigate whether exosome derived from CD137‐modified ECs (CD137‐Exo) played a major role in AS and to elucidate the potential mechanism underlying the inflammatory effect. Exosomes derived from mouse brain microvascular ECs treated with agonist anti‐CD137 antibody were used to explore the effect of CD137 signalling in AS and inflammation in vitro and vivo. CD137‐Exo efficiently induced the progression of AS in ApoE^?/? mice. CD137‐Exo increased the proportion of Th17 cells both in vitro and vivo. The IL‐6 contained in CD137‐Exo which is regulated by Akt and NF‐КB pathway was verified to activate Th17 cell differentiation. IL‐17 increased apoptosis, inhibited cell viability and improved lactate dehydrogenase (LDH) release in ECs subjected to inflammation induced by lipopolysaccharide (LPS). The expression of soluble intercellular adhesion molecule1 (sICAM‐1), monocyte chemoattractant protein‐1 (MCP‐1) and E‐selectin in the supernatants of ECs after IL‐17 treatment was dramatically increased. CD137‐Exo promoted the progression of AS and Th17 cell differentiation via NF‐КB pathway mediated IL‐6 expression. This finding provided a potential method to prevent local and peripheral inflammation in AS.