Effects of suppression of bone turnover on cortical and trabecular load sharing in the canine vertebral body

The relative biomechanical effects of antiresorptive treatment on cortical thickness vs. trabecular bone microarchitecture in the spine are not well understood. To address this, T-10 vertebral bodies were analyzed from skeletally mature female beagle dogs that had been treated with oral saline (n=8 control) or a high dose of oral risedronate (0.5 mg/kg/day, n=9 RIS-suppressed) for 1 year. Two linearly elastic finite element models (36-μm voxel size) were generated for each vertebral body—a whole-vertebra model and a trabecular-compartment model—and subjected to uniform compressive loading. Tissue-level material properties were kept constant to isolate the effects of changes in microstructure alone. Suppression of bone turnover resulted in increased stiffness of the whole vertebra (20.9%, p=0.02) and the trabecular compartment (26.0%, p=0.01), while the computed stiffness of the cortical shell (difference between whole-vertebra and trabecular-compartment stiffnesses, 11.7%, p=0.15) was statistically unaltered. Regression analyses indicated subtle but significant changes in the relative structural roles of the cortical shell and the trabecular compartment. Despite higher average cortical shell thickness in RIS-suppressed vertebrae (23.1%, p=0.002), the maximum load taken by the shell for a given value of shell mass fraction was lower (p=0.005) for the RIS-suppressed group. Taken together, our results suggest that—in this canine model—the overall changes in the compressive stiffness of the vertebral body due to suppression of bone turnover were attributable more to the changes in the trabecular compartment than in the cortical shell. Such biomechanical studies provide an unique insight into higher-scale effects such as the biomechanical responses of the whole vertebra

Modular Building Design: Post-Brexit Housing

The use of modular building systems (MBSs) in the construction sector is increasing. MBSs enhance structural performance of buildings, quality control, and construction speed than traditional methods at a lower cost. Additional benefits can be associated with resource efficiency at both the production and construction phases, which may increase MBSs' attractiveness and popularity in the short‐ and long‐term future. In the UK, the government is planning to solve Britain's housing crisis by constructing more than 100,000 modular homes in an effort to meet its target to provide a million new homes by 2020. At the same time, the construction sector is facing post‐Brexit skills shortages, while it is undergoing a technological revolution. One outcome of the latter has been the production of cold‐formed steel (CFS) hollow flange sections, which can be optimised using genetic algorithm and finite element analyses in order to improve the load‐carrying capacity of modular buildings. These optimised CFS beams, employed in MBSs, can light gauge the frame building constructions. This paper presents a review of MBSs and the application of CFS hollow flange steel sections in construction. It then summarises some of the key outputs of numerical studies on the structural behaviour of hollow flange beams to justify its applicability in MBS

Synthesis and evaluation of stilbene and dihydrostilbene derivatives as potential anticancer agents that inhibit tubulin polymerization

An array of cis-, trans-, and dihydrostilbenes and some N-arylbenzylamines were synthesized and evaluated for their cytotoxicity in the five cancer cell cultures A-549 lung carcinoma, MCF-7 breast carcinoma, HT-29 colon adenocarcinoma, SKMEL-5 melanoma, and MLM melanoma. Several cis-stilbenes, structurally similar to combretastatins, were highly cytotoxic in all five cell lines and these were also found to be active as inhibitors of tubulin polymerization. The most active compounds also inhibited the binding of colchicine to tubulin. The most potent of the new compounds, both as a tubulin polymerization inhibitor and as a cytotoxic agent, was (Z)-1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethene (5a). This substance was almost as potent as combretastatin A-4 (1a), the most active of the combretastatins, as a tubulin polymerization inhibitor. Compound 5a was found to be approximately 140 times more cytotoxic against HT-29 colon adenocarcinoma cells and about 10 times more cytotoxic against MCF-7 breast carcinoma cells than combretastatin A-4. However, 5a was found to be about 20 times less cytotoxic against A-549 lung carcinoma cells, 30 times less cytotoxic against SKMEL-5 melanoma cells, and 7 times less cytotoxic against MLM melanoma cells than combretastatin A-4. The relative potencies 5a greater than 8a greater than 6a for the cis, dihydro, and trans compounds, respectively, as inhibitors of tubulin polymerization are in agreement with the relative potencies previously observed for combretastatin A-4 (1a), dihydrocombretastatin A-4 (1c), and trans-combretastatin A-4 (1b). The relative potencies 5a greater than 8a greater than 6a were also reflected in the results of the cytotoxicity assays. Structure-activity relationships of this group of compounds are also discussed

DataSheet_1_‘Priming’ protects Piper nigrum L. from Phytophthora capsici through reinforcement of phenylpropanoid pathway and possible enhancement of Piperine biosynthesis.docx

Piper nigrum L. (black pepper), a woody perennial spice crop indigenous to India is positioned at the phylogenetically unique basal lineage of angiosperms. Cultivation of this major spice crop is constrained by rampant fungal and viral infections leading to a lack of disease-free planting material. The major disease that poses severe threat to P. nigrum plantations and nurseries is ‘quick wilt’ caused by the oomycete Phytophthora capsici, which affects the leaf, stem, spike, collar and root. In this paper, we report the consequence of priming in modulating Piper nigrum defense against Phytophthora capsici. Glycol Chitosan (GC) was used to infiltrate detached leaves of mature P. nigrum plants. It was observed that pre-treatment of GC for 24 hours resulted in significant reduction of disease symptoms in infected leaves, as evidenced by the marked decrease in the size of lesions, and also delayed the appearance of symptoms up to 72 hpi. Experiments repeated in P. nigrum seedlings under controlled growth conditions indicate that delayed disease symptoms of GC pre-treated leaves do not spread to healthy uninfiltrated leaves suggesting a priming-associated systemic defense response. An ROS-mediated manifestation of Hypersensitive Response (HR) induced by Chitosan was also evident in pre-treated leaves. A corresponding visual indication of increased lignification was observed, which correlated with an enhanced lignin content of GC-treated leaves. Enhanced callose deposition was also apparent in GC infiltrated leaves, establishing a stimulatory effect of GC in triggering HR through ROS production, enhanced lignification and callose deposition. Key genes of the core phenylpropanoid and isoprenoid pathways along with major defense signalling pathway genes of P. nigrum, including pathogenesis-related genes and hormone signalling genes showed significant transcript enrichment consequential to GC treatment. A significant quantitative enhancement in Piperine content was evident in GC-infiltrated leaves. The systemic nature of priming on disease protection was established through experiments conducted in rooted cuttings monitored for 30 days after disease infection. This is the first report that provides strong molecular evidence endorsing the twofold advantage of defense priming in P. nigrum by improving crop protection with a concomitant enhancement in Piperine biosynthesis.</p

Table_1_‘Priming’ protects Piper nigrum L. from Phytophthora capsici through reinforcement of phenylpropanoid pathway and possible enhancement of Piperine biosynthesis.xlsx

Piper nigrum L. (black pepper), a woody perennial spice crop indigenous to India is positioned at the phylogenetically unique basal lineage of angiosperms. Cultivation of this major spice crop is constrained by rampant fungal and viral infections leading to a lack of disease-free planting material. The major disease that poses severe threat to P. nigrum plantations and nurseries is ‘quick wilt’ caused by the oomycete Phytophthora capsici, which affects the leaf, stem, spike, collar and root. In this paper, we report the consequence of priming in modulating Piper nigrum defense against Phytophthora capsici. Glycol Chitosan (GC) was used to infiltrate detached leaves of mature P. nigrum plants. It was observed that pre-treatment of GC for 24 hours resulted in significant reduction of disease symptoms in infected leaves, as evidenced by the marked decrease in the size of lesions, and also delayed the appearance of symptoms up to 72 hpi. Experiments repeated in P. nigrum seedlings under controlled growth conditions indicate that delayed disease symptoms of GC pre-treated leaves do not spread to healthy uninfiltrated leaves suggesting a priming-associated systemic defense response. An ROS-mediated manifestation of Hypersensitive Response (HR) induced by Chitosan was also evident in pre-treated leaves. A corresponding visual indication of increased lignification was observed, which correlated with an enhanced lignin content of GC-treated leaves. Enhanced callose deposition was also apparent in GC infiltrated leaves, establishing a stimulatory effect of GC in triggering HR through ROS production, enhanced lignification and callose deposition. Key genes of the core phenylpropanoid and isoprenoid pathways along with major defense signalling pathway genes of P. nigrum, including pathogenesis-related genes and hormone signalling genes showed significant transcript enrichment consequential to GC treatment. A significant quantitative enhancement in Piperine content was evident in GC-infiltrated leaves. The systemic nature of priming on disease protection was established through experiments conducted in rooted cuttings monitored for 30 days after disease infection. This is the first report that provides strong molecular evidence endorsing the twofold advantage of defense priming in P. nigrum by improving crop protection with a concomitant enhancement in Piperine biosynthesis.</p