Dynamics of vascular branching morphogenesis: the effect of blood and tissue flow

Vascularization of embryonic organs or tumors starts from a primitive lattice of capillaries. Upon perfusion, this lattice is remodeled into branched arteries and veins. Adaptation to mechanical forces is implied to play a major role in arterial patterning. However, numerical simulations of vessel adaptation to haemodynamics has so far failed to predict any realistic vascular pattern. We present in this article a theoretical modeling of vascular development in the yolk sac based on three features of vascular morphogenesis: the disconnection of side branches from main branches, the reconnection of dangling sprouts ('dead ends'), and the plastic extension of interstitial tissue, which we have observed in vascular morphogenesis. We show that the effect of Poiseuille flow in the vessels can be modeled by aggregation of random walkers. Solid tissue expansion can be modeled by a Poiseuille (parabolic) deformation, hence by deformation under hits of random walkers. Incorporation of these features, which are of a mechanical nature, leads to realistic modeling of vessels, with important biological consequences. The model also predicts the outcome of simple mechanical actions, such as clamping of vessels or deformation of tissue by the presence of obstacles. This study offers an explanation for flow-driven control of vascular branching morphogenesis

Root rot pathogens of Cinnamomum cassia in Vietnam

A study was conducted to determine the pathogens causing root rot, wilt and dieback disease of Cinnamomum cassia (Chinese cinnamon or cassia) in Vietnam, in nurseries and plantations in the Yen Bai, Quang Ninh, Thanh Hoa and Quang Nam provinces, and streams in the Yen Bai province. Pathogens were identified using morphology and internal transcribed spacer (ITS) sequence analysis. The 204 isolates obtained included 125 Phytophthora isolates and 79 from other oomycete genera. There were 112 isolates of P. cinnamomi, four P. heveae, two P. virginiana, three P. multibullata and four P. × vanyenensis. The pathogenicity and virulence of 16 P. cinnamomi, two P. heveae, two P. multibullata and four P. × vanyenensis isolates were assessed using lesion size after under-bark inoculation of C. cassia stems, and root damage following inoculation of 4-month-old C. cassia seedlings. The most virulent isolate from both assessments was a P. cinnamomi from the Quang Nam plantation. Isolates of P. cinnamomi showed a wide range of virulence, with isolates from healthy trees or seedlings showing the lowest virulence. Isolates of P. × vanyenensis, P. multibullata and P. heveae showed moderate or low pathogenicity. This study showed that although P. cinnamomi is the most common pathogen associated with dieback disease in Vietnamese C. cassia plantations, other Phytophthora species may also cause this disease. Knowledge of the presence of these soil- and waterborne pathogens will encourage improved soil and water hygiene in nurseries and implement measures to prevent the spread of the pathogens in plantations

Isoscalar-isovector mass splittings in excited mesons

Mass splittings between the isovector and isoscalar members of meson nonets arise in part from hadronic loop diagrams which violate the Okubo-Zweig-Iizuka rule. Using a model for these loop processes which works qualitatively well in the established nonets, I tabulate predictions for the splittings and associated isoscalar mixing angles in the remaining nonets below about 2.5 GeV, and explain some of their systematic features. The results for excited vector mesons compare favorably with experiment.Comment: 8 RevTeX pages, including 1 LaTeX figure. CMU-HEP93-23/DOE-ER-40682-4

One Health ethics: The need for policy before research and action

One Health implies a strong emphasis on ethics, recognising the interdependent relationships of humans, animals and the environment. We argue that the universal ethical principles for human-subject research, presented in the Belmont report as Respect for Persons, Beneficence and Justice, should be applied to custodians of animals and the environment. Drawing on published and unpublished research, we highlight the challenges and opportunities of this approach in practice and policy. Respect for Persons is demonstrated through informed consent. We describe the high rate of consent received in livestock research projects, raising questions around legitimacy, and outline a study to improve comprehension and engagement in the informed consent process for livestock keepers. Beneficence dictates that benefits to research participants are maximized. We outline how a long-term impact assessment was designed with intrinsic value for farmers, using participatory photography. Additionally, we describe efforts towards non-maleficence through providing participants with research board contacts. We provide new data on low contact-rates and discuss possible causes. Justice requires that research risks and benefits are distributed equally. We show how the requirement to sign written consent forms may preclude those working in informal livestock markets from participating in, and therefore sharing risks and benefits of research projects

Hypertension and albuminuria in chronic kidney disease mapped to a mouse chromosome 11 locus

Chronic kidney disease (CKD) is a key cause of hypertension and a potent independent risk for cardiovascular disease. Epidemiological studies suggest a strong genetic component determining susceptibility for renal disease and, by inference, the associated cardiovascular risk. With a subtotal nephrectomy model of kidney disease, we found the 129S6 mouse strain to be very susceptible to the development of hypertension, albuminuria, and kidney injury, whereas the C57BL/6 strain is relatively resistant. Accordingly, we set out to map quantitative trait loci conferring susceptibility to hypertension and albuminuria using this model with F2 mice. We found significant linkage of the blood pressure trait to two loci. At D11Mit143, mice homozygous for the 129S6 allele had significantly higher systolic blood pressure than mice heterozygous or homozygous for the C57BL/6 allele. Similarly, at D1Mit308, there was an excellent correlation between genotype and the blood pressure phenotype. The effect of the chromosome 11 locus was verified with a separate cohort of F2 mice. For the albuminuria trait, a significant locus was found at D11Mit143, which overlaps the blood pressure trait locus. Our studies have identified a region spanning ∼8 cM on mouse chromosome 11 that is associated with susceptibility to hypertension and albuminuria in CKD

Impact of early remission by induction therapy on allogeneic stem cell transplantation for acute myeloid leukemia with an intermediate risk karyotype in first complete remission

For patients with acute myeloid leukemia (AML) early achievement of remission during induction treatment is an important predictor for long-term outcome irrespective of the type of consolidation therapy employed. Here, we retrospectively examined the prognostic impact of early remission (ER) versus delayed remission (DR) in a cohort of 132 AML patients with an intermediate risk karyotype undergoing allogeneic stem cell transplantation (alloSCT) in first complete remission (CR1). In contrast to patients showing DR, patients achieving ER had a significantly higher 3-year overall survival (OS) and disease-free survival (DFS) of 76% versus 54% (p=0.03) and 76% versus 53% (p=0.03). Likewise, three years after alloSCT the cumulative incidence of relapse (CI-R) was significantly lower in the ER subgroup as compared to patients achieving DR, i.e. 10% versus 35% (p=0.004), whereas non-relapse mortality (NRM) did not differ significantly. Multivariate analysis identified DR as an independent prognosticator for an inferior DFS (HR 3.37, p=0.002) and a higher CI-R (HR 3.55, p=0.002). Taken together, these data may indicate that the rapid achievement of remission predicts a favorable outcome in patients with intermediate risk AML undergoing alloSCT in CR1. In turn, the adverse effect of DR may not be fully overcome by alloSCT

Stress corrosion cracking in Al-Zn-Mg-Cu aluminum alloys in saline environments

Copyright 2013 ASM International. This paper was published in Metallurgical and Materials Transactions A, 44A(3), 1230 - 1253, and is made available as an electronic reprint with the permission of ASM International. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplications of any material in this paper for a fee or for commercial purposes, or modification of the content of this paper are prohibited.Stress corrosion cracking of Al-Zn-Mg-Cu (AA7xxx) aluminum alloys exposed to saline environments at temperatures ranging from 293 K to 353 K (20 °C to 80 °C) has been reviewed with particular attention to the influences of alloy composition and temper, and bulk and local environmental conditions. Stress corrosion crack (SCC) growth rates at room temperature for peak- and over-aged tempers in saline environments are minimized for Al-Zn-Mg-Cu alloys containing less than ~8 wt pct Zn when Zn/Mg ratios are ranging from 2 to 3, excess magnesium levels are less than 1 wt pct, and copper content is either less than ~0.2 wt pct or ranging from 1.3 to 2 wt pct. A minimum chloride ion concentration of ~0.01 M is required for crack growth rates to exceed those in distilled water, which insures that the local solution pH in crack-tip regions can be maintained at less than 4. Crack growth rates in saline solution without other additions gradually increase with bulk chloride ion concentrations up to around 0.6 M NaCl, whereas in solutions with sufficiently low dichromate (or chromate), inhibitor additions are insensitive to the bulk chloride concentration and are typically at least double those observed without the additions. DCB specimens, fatigue pre-cracked in air before immersion in a saline environment, show an initial period with no detectible crack growth, followed by crack growth at the distilled water rate, and then transition to a higher crack growth rate typical of region 2 crack growth in the saline environment. Time spent in each stage depends on the type of pre-crack (“pop-in” vs fatigue), applied stress intensity factor, alloy chemistry, bulk environment, and, if applied, the external polarization. Apparent activation energies (E a) for SCC growth in Al-Zn-Mg-Cu alloys exposed to 0.6 M NaCl over the temperatures ranging from 293 K to 353 K (20 °C to 80 °C) for under-, peak-, and over-aged low-copper-containing alloys (~0.8 wt pct), they are typically ranging from 20 to 40 kJ/mol for under- and peak-aged alloys, and based on limited data, around 85 kJ/mol for over-aged tempers. This means that crack propagation in saline environments is most likely to occur by a hydrogen-related process for low-copper-containing Al-Zn-Mg-Cu alloys in under-, peak- and over-aged tempers, and for high-copper alloys in under- and peak-aged tempers. For over-aged high-copper-containing alloys, cracking is most probably under anodic dissolution control. Future stress corrosion studies should focus on understanding the factors that control crack initiation, and insuring that the next generation of higher performance Al-Zn-Mg-Cu alloys has similar longer crack initiation times and crack propagation rates to those of the incumbent alloys in an over-aged condition where crack rates are less than 1 mm/month at a high stress intensity factor