The free energy in the Derrida--Retaux recursive model

We are interested in a simple max-type recursive model studied by Derrida and Retaux (2014) in the context of a physics problem, and find a wide range for the exponent in the free energy in the nearly supercritical regime

Thrombus Structural Composition in Cardiovascular Disease

Thrombosis is a major complication of cardiovascular disease, leading to myocardial infarction, acute ischemic stroke (AIS), or venous thromboembolism. Thrombosis occurs when a thrombus forms inside blood vessels disrupting blood flow. Developments in thrombectomy to remove thrombi from vessels have provided new opportunities to study thrombus composition which may help to understand mechanisms of disease and underpin improvements in treatments. We aimed to review thrombus compositions, roles of components in thrombus formation and stability, and methods to investigate thrombi. Also, we summarize studies on thrombus structure obtained from cardiovascular patients and animal models. Thrombi are composed of fibrin, red blood cells, platelets, leukocytes, and neutrophil extracellular traps. These components have been analyzed by several techniques, including scanning electron microscopy, laser scanning confocal microscopy, histochemistry, and immunohistochemistry; however, each technique has advantages and limitations. Thrombi are heterogenous in composition, but overall, thrombi obtained from myocardial infarction are composed of mainly fibrin and other components, including platelets, red blood cells, leukocytes, and cholesterol crystals. Thrombi from patients with acute ischemic stroke are characterized by red blood cell- and platelet-rich regions. Thrombi from patients with venous thromboembolism contain mainly red blood cells and fibrin with some platelets and leukocytes. Thrombus composition from patients with myocardial infarction is influenced by ischemic time. Animal thrombosis models are crucial to gain further mechanistic information about thrombosis and thrombus structure, with thrombi being similar in composition compared with those from patients. Further studies on thrombus composition and function are key to improve treatment and clinical outcome of thrombosis

Mixing of Active and Sterile Neutrinos

We investigate mixing of neutrinos in the $\nu$MSM (neutrino Minimal Standard Model), which is the MSM extended by three right-handed neutrinos. Especially, we study elements of the mixing matrix $\Theta_{\alpha I}$ between three left-handed neutrinos $\nu_\alpha$ ($\alpha = e,\mu,\tau$) and two sterile neutrinos $N_I$ ($I=2,3$) which are responsible to the seesaw mechanism generating the suppressed masses of active neutrinos as well as the generation of the baryon asymmetry of the universe (BAU). It is shown that $\Theta_{eI}$ can be suppressed by many orders of magnitude compared with $\Theta_{\mu I}$ and $\Theta_{\tau I}$, when the Chooz angle $\theta_{13}$ is large in the normal hierarchy of active neutrino masses. We then discuss the neutrinoless double beta decay in this framework by taking into account the contributions not only from active neutrinos but also from all the three sterile neutrinos. It is shown that $N_2$ and $N_3$ give substantial, destructive contributions when their masses are smaller than a few 100 MeV, and as a results $\Theta_{e I}$ receive no stringent constraint from the current bounds on such decay. Finally, we discuss the impacts of the obtained results on the direct searches of $N_{2,3}$ in meson decays for the case when $N_{2,3}$ are lighter than pion mass. We show that there exists the allowed region for $N_{2,3}$ with such small masses in the normal hierarchy case even if the current bound on the lifetimes of $N_{2,3}$ from the big bang nucleosynthesis is imposed. It is also pointed out that the direct search by using $\pi^+ \to e^+ + N_{2,3}$ and $K^+ \to e^+ + N_{2,3}$ might miss such $N_{2,3}$ since the branching ratios can be extremely small due to the cancellation in $\Theta_{eI}$, but the search by $K^+ \to \mu^+ + N_{2,3}$ can cover the whole allowed region by improving the measurement of the branching ratio by a factor of 5.Comment: 30 pages, 32 figure

Small poly-L-lysines improve cationic lipid-mediated gene transfer in vascular cells in vitro and in vivo

The potential of two small poly-L-lysines ( sPLLs), low molecular weight sPLL ( LMW-L) containing 7 - 30 lysine residues and L18 with 18 lysine repeats, to enhance the efficiency of liposome-mediated gene transfer ( GT) with cationic lipid DOCSPER {[}1,3- dioleoyloxy- 2-( N-5-carbamoyl-spermine)-propane] in vascular smooth muscle cells ( SMCs) was investigated. Dynamic light scattering was used for determination of particle size. Confocal microscopy was applied for colocalization studies of sPLLs and plasmid DNA inside cells. GT was performed in proliferating and quiescent primary porcine SMCs in vitro and in vivo in porcine femoral arteries. At low ionic strength, sPLLs formed small complexes with DNA ( 50 100 nm). At high ionic strength, large complexes ( 11 mu m) were observed without any significant differences in particle size between lipoplexes ( DOCSPER/ DNA) and lipopolyplexes ( DOCSPER/ sPLL/ DNA). Both sPLLs were colocalized with DNA inside cells 24 h after transfection, protecting DNA against degradation. DOCSPER/ sPLL/ DNA formulations enhanced GT in vitro up to 5- fold, in a porcine model using local periadventitial application up to 1.5- fold. Both sPLLs significantly increased liposome- mediated GT. Poly-L-lysine L18 was superior to LMW-L since it enabled maximal GT at a 10-fold lower concentration. Thus, sPLLs may serve as enhancers for GT applications in SMCs in vitro and in vivo using local delivery. Copyright (c) 2007 S. Karger AG, Basel

Decreasing the use of edible oils in China using WeChat and theories of behavior change: study protocol for a randomized controlled trial.

The consumption of edible oils in China has increased rapidly in recent years, and the total amount of edible-oil intake in the country has ranked first in the world. The choice and intake of edible oils, as a source of fats, are important factors that affect people's health. Many chronic diseases are closely associated with high-calorie and saturated-fat intake. The influence of traditional concepts that promote the use of edible oils among women, particularly housewives, plays a key role in a household's diet and nutrition because the diet-related knowledge, attitude and behaviour of housewives are dominant factors in planning and preparing their family's meals. WeChat, which was developed by Tencent, is a multipurpose messaging, social media and mobile payment application (app) in China. Described by Forbes as one of the world's most powerful apps, WeChat provides considerable convenience in disseminating knowledge. Accordingly, this study aims to design a pilot intervention to decrease the use of edible oils in Chinese households. The intervention, which is based on theories of behaviour change, will be implemented through WeChat. The study design is a randomised controlled trial that adopts knowledge, attitude and practice, social cognitive and stages of change theories as theoretical models. A total of 800 housewives between the ages of 25 and 45 years will be recruited on WeChat and from the communities in four areas (including rural and urban) in Chongqing, China. A self-administered questionnaire will be used to collect information regarding age, educational level, occupation, family members, edible-oil intake habits, knowledge of edible oils and WeChat usage habits. A total of 200 participants will be selected and randomly assigned to two equal-sized groups: group A (the intervention group) and group B (the control group). Group A will receive health education regarding edible oils for four consecutive weeks, whereas group B will be treated as the blank control. Each participant will complete a battery of knowledge, attitude and behaviour tests immediately, 3 months and 6 months after the intervention. In addition, weight, moisture rate, fat rate, visceral fat level and body mass index will be calculated using a multifunctional weighing scale, namely, Tanita BC-601 (Japan). The study is currently in the design stage. This study aims to increase knowledge and awareness of the appropriate use of edible oils, thereby encouraging participants to change behaviour by decreasing the intake of unhealthy levels of edible oils. It will be the first intervention to investigate the use of edible oils in China through WeChat. We predict that receiving health education regarding edible oils through WeChat will substantially improve the knowledge and attitude of the respondents. The members of the intervention group will have increased awareness and will be willing to decrease their use of edible oils to remain healthy. Results of this study may provide scientific evidence for the effect of health education through WeChat on edible oil-intake behaviour, thereby offering a comprehensive intervention to decrease the use of edible oils and promote a healthy lifestyle. Chinese Clinical Trial Registry (primary registry in the World Health Organisation registry network): ChiCTR-IOR-17013472 . Registered on 21 November 2017

Chapter 3: Pathophysiology

The hallmark pathophysiologic feature of dilated cardiomyopathy is systolic dysfunction. Several pathogenetic mechanisms appear to be operative. These include increased hemodynamic overload, ventricular remodeling, excessive neurohumoral stimulation, abnormal myocyte calcium cycling, excessive or inadequate proliferation of the extracellular matrix, accelerated apoptosis, and genetic mutations. Although beneficial in the early stages of heart failure, these compensatory mechanisms eventually lead to a vicious cycle of worsening heart failure. Genetic causes account for 30\u201340% of DCM and involve genes that encode a heterogeneous group of molecules that participate in force generation, force transmission, sarcomere integrity, cytoskeletal and nuclear architecture, electrolyte homeostasis, mitochondrial function, and transcription. Additional research will improve our understanding of the complex and longitudinal molecular changes that lead from gene mutation to clinical expressio

A functional variant in promoter region of platelet-derived growth factor-D is probably associated with intracerebral hemorrhage

<p>Abstract</p> <p>Background</p> <p>Platelet-derived growth factor D (PDGF-D) plays an important role in angiogenesis, vessel remodeling, inflammation and repair in response to injury. We hypothesized that genetic variation in <it>PDGFD </it>gene might alter the susceptibility to stroke.</p> <p>Findings</p> <p>We determined the genotypes of a single nucleotide polymorphism (SNP) (-858A/C, rs3809021) in 1484 patients with stroke (654 cerebral thrombosis, 419 lacunar infarction, 411 intracerebral hemorrhage [ICH]) and 1528 control subjects from an unrelated Chinese Han population and followed the stroke patients up for a median of 4.5 years.</p> <p>The -858AA genotype showed significantly increased risk of ICH (dominant model: odds ratio [OR] 1.29, 95% confidence interval [CI] 1.00-1.68, <it>P </it>= 0.05; additive model: OR 1.24, 95% CI 1.01-1.52, <it>P </it>= 0.04) than wild-type genotype. Further analyses showed that -858AA genotype conferred about 2-fold increase in risk of non-hypertensive ICH (dominant model: OR 2.1, 95%CI 1.34-3.29, <it>P </it>= 0.001; additive model: OR 1.75, 95% CI 1.24-2.46, <it>P </it>= 0.001). After a median follow-up of 4.5 years, -858AA genotype was associated with a reduced risk of ICH recurrence (dominant model: adjusted hazard ratio [HR] 0.09, 95%CI 0.01-0.74, P = 0.025; additive model: HR 0.21, 95% CI 0.04-1.16, <it>P </it>= 0.073) in non-hypertensive patients.</p> <p>Conclusions</p> <p>The -858AA genotype is probably associated with risk for non-hypertensive ICH. Further studies should be conducted to reveal the role of PDGF-D at various stages of ICH development--beneficial, or deleterious.</p

Growth Differentiation Factor 9 (GDF9) Suppresses Follistatin and Follistatin-Like 3 Production in Human Granulosa-Lutein Cells

We have demonstrated that growth differentiation factor 9 (GDF9) enhances activin A-induced inhibin β(B)-subunit mRNA levels in human granulosa-lutein (hGL) cells by regulating receptors and key intracellular components of the activin signaling pathway. However, we could not exclude its effects on follistatin (FST) and follistatin-like 3 (FSTL3), well recognized extracellular inhibitors of activin A.hGL cells from women undergoing in vitro fertilization (IVF) treatment were cultured with and without siRNA transfection of FST, FSTL3 or GDF9 and then treated with GDF9, activin A, FST, FSTL3 or combinations. FST, FSTL3 and inhibin β(B)-subunit mRNA, and FST, FSTL3 and inhibin B protein levels were assessed with real-time RT-PCR and ELISA, respectively. Data were log transformed before ANOVA followed by Tukey's test.GDF9 suppressed basal FST and FSTL3 mRNA and protein levels in a time- and dose-dependent manner and inhibited activin A-induced FST and FSTL3 mRNA and protein expression, effects attenuated by BMPR2 extracellular domain (BMPR2 ECD), a GDF9 antagonist. After GDF9 siRNA transfection, basal and activin A-induced FST and FSTL3 mRNA and protein levels increased, but changes were reversed by adding GDF9. Reduced endogenous FST or FSTL3 expression with corresponding siRNA transfection augmented activin A-induced inhibin β(B)-subunit mRNA levels as well as inhibin B levels (P values all <0.05). Furthermore, the enhancing effects of GDF9 in activin A-induced inhibin β(B)-subunit mRNA and inhibin B production were attenuated by adding FST.GDF9 decreases basal and activin A-induced FST and FSTL3 expression, and this explains, in part, its enhancing effects on activin A-induced inhibin β(B)-subunit mRNA expression and inhibin B production in hGL cells

A fresh look at the evolution and diversification of photochemical reaction centers

In this review, I reexamine the origin and diversification of photochemical reaction centers based on the known phylogenetic relations of the core subunits, and with the aid of sequence and structural alignments. I show, for example, that the protein folds at the C-terminus of the D1 and D2 subunits of Photosystem II, which are essential for the coordination of the water-oxidizing complex, were already in place in the most ancestral Type II reaction center subunit. I then evaluate the evolution of reaction centers in the context of the rise and expansion of the different groups of bacteria based on recent large-scale phylogenetic analyses. I find that the Heliobacteriaceae family of Firmicutes appears to be the earliest branching of the known groups of phototrophic bacteria; however, the origin of photochemical reaction centers and chlorophyll synthesis cannot be placed in this group. Moreover, it becomes evident that the Acidobacteria and the Proteobacteria shared a more recent common phototrophic ancestor, and this is also likely for the Chloroflexi and the Cyanobacteria. Finally, I argue that the discrepancies among the phylogenies of the reaction center proteins, chlorophyll synthesis enzymes, and the species tree of bacteria are best explained if both types of photochemical reaction centers evolved before the diversification of the known phyla of phototrophic bacteria. The primordial phototrophic ancestor must have had both Type I and Type II reaction centers

Centrally Administered Pertussis Toxin Inhibits Microglia Migration to the Spinal Cord and Prevents Dissemination of Disease in an EAE Mouse Model

Background: Experimental autoimmune encephalomyelitis (EAE) models are important vehicles for studying the effect of infectious elements such as Pertussis toxin (PTx) on disease processes related to acute demyelinating encephalomyelitis (ADEM) or multiple sclerosis (MS). PTx has pleotropic effects on the immune system. This study was designed to investigate the effects of PTx administered intracerebroventricularly (icv) in preventing downstream immune cell infiltration and demyelination of the spinal cord. Methods and Findings: EAE was induced in C57BL/6 mice with MOG35–55. PTx icv at seven days post MOG immunization resulted in mitigation of clinical motor symptoms, minimal T cell infiltration, and the marked absence of axonal loss and demyelination of the spinal cord. Integrity of the blood brain barrier was compromised in the brain whereas spinal cord BBB integrity remained intact. PTx icv markedly increased microglia numbers in the brain preventing their migration to the spinal cord. An in vitro transwell study demonstrated that PTx inhibited migration of microglia. Conclusion: Centrally administered PTx abrogated migration of microglia in EAE mice, limiting the inflammatory cytokine milieu to the brain and prevented dissemination of demyelination. The effects of PTx icv warrants further investigation and provides an attractive template for further study regarding the pleotropic effects of infectious elements such as PTx in th