Effect of the First Feeding on Enterocytes of Newborn Rats

The transcytosis of lipids through enterocytes occurs through the delivery of lipid micelles to the microvilli of enterocytes, consumption of lipid derivates by the apical plasma membrane (PM) and then their delivery to the membrane of the smooth ER attached to the basolateral PM. The SER forms immature chylomicrons (iChMs) in the ER lumen. iChMs are delivered at the Golgi complex (GC) where they are subjected to additional glycosylation resulting in maturation of iChMs. ChMs are secreted into the intercellular space and delivered into the lumen of lymphatic capillaries (LCs). The overloading of enterocytes with lipids induces the formation of lipid droplets inside the lipid bilayer of the ER membranes and transcytosis becomes slower. Here, we examined components of the enterocyte-to-lymphatic barriers in newly born rats before the first feeding and after it. In contrast to adult animals, enterocytes of newborns rats exhibited apical endocytosis and a well-developed subapical endosomal tubular network. These enterocytes uptake membranes from amniotic fluid. Then these membranes are transported across the polarized GC and secreted into the intercellular space. The enterocytes did not contain COPII-coated buds on the granular ER. The endothelium of blood capillaries situated near the enterocytes contained only a few fenestrae. The LCs were similar to those in adult animals. The first feeding induced specific alterations of enterocytes, which were similar to those observed after the lipid overloading of enterocytes in adult rats. Enlarged chylomicrons were stopped at the level of the LAMP2 and Neu1 positive post-Golgi structures, secreted, fused, delivered to the interstitial space, captured by the LCs and transported to the lymph node, inducing the movement of macrophages from lymphatic follicles into its sinuses. The macrophages captured the ChMs, preventing their delivery into the blood.     

艺术农场

中国当代艺术于世界范围内的兴盛是最近几年的事情。在如此的背景下,具备该主题的独立画廊则不断出现。国内的情况自不必多说,在国外．此类的艺术展示空间也无一不是深得中国当代艺术的精髓,甚至有中国设计师参与建造与规划。而其本身,往往也是独立的一件艺术作品,与来自中国的当代艺术一起．向国外的参观者展示。     

Helical Rotor Module of Rotary Hydraulic Drive Turbine

Chemical and Petroleum Engineering - This paper presents the developed design of a rotor module of the turbine of a hydraulic drive, the distinctive feature of which is a helical relief on the...     

Decoupling of Confined Normal 3He

Anodic bonding was used to fabricate a 10 mm diameter × 640 nm tall annular geometry suitable for torsion pendulum studies of confined ³He. For pure ³He at saturated vapor pressure the inertia of the confined fluid was seen to be only partially coupled to the pendulum at 160 mK. Below 100 mK the liquid’s inertial contribution was negligible, indicating a complete decoupling of the ³He from the pendulum.     

Identification of Phenylphthalazinones as a New Class of Leishmania infantum Inhibitors

Leishmaniasis is a neglected parasitic disease caused by over 20 different Leishmania species. Current treatments often rely on harsh regimes of pentavalent antimonials such as sodium stibogluconate, while more recent drugs suffer other shortcomings such as low stability and rapid emergence of treatment failure, amongst others. Furthermore, the effectiveness of drugs varies depending on the infecting Leishmania species, thus there is an urgent need for new and effective anti-leishmanial drugs. Screening of an in-house compound library identified the hexahydrophthalazinone NPD-2942 as a low micromolar hit with a pIC₅₀ of 5.8 against L. infantum and a pIC₅₀ of 4.6 for cytotoxicity against human MRC-5 fibroblasts. To derive structure–activity relationships, we modified the cyclohexyl ring of the hexahydrophthalazinone scaffold and 1,2,3-triazoles were attempted as replacement for the pyrazole ring, amongst others. Ultimately, the 2,3-pyrazole-substituted hexahydrophthalazinone NPD-1289 was identified as the most potent analogue in this series with a pIC₅₀ of 6.3, although some cytotoxicity toward MRC-5 cells (pIC₅₀=5.1) was recorded as well. Replacement of the unsubstituted 2,3-pyrazole with 1,2,3-triazoles led to compounds with lower anti-leishmanial activity. The current scaffold is a valuable new starting point for optimization toward novel anti-leishmanial drugs.     

Puckering the Planar Landscape of Fragments: Design and Synthesis of a 3D Cyclobutane Fragment Library

Fragment-based drug discovery (FBDD) has a growing need for unique screening libraries. The cyclobutane moiety was identified as an underrepresented yet attractive three-dimensional (3D) scaffold. Synthetic strategies were developed via a key 3-azido-cyclobutanone intermediate, giving potential access to a range of functional groups with accessible growth vectors. A focused set of 33 novel 3D cyclobutane fragments was synthesised, comprising three functionalities: secondary amines, amides, and sulfonamides. This library was designed using Principal Component Analysis (PCA) and an expanded version of the rule of three (RO3), followed by Principal Moment of Inertia (PMI) analysis to achieve both chemical diversity and high 3D character. Cis and trans ring isomers of library members were generated to maximise the shape diversity obtained, while limiting molecular complexity through avoiding enantiomers. Property analyses of the cyclobutane library indicated that it fares favourably against existing synthetic 3D fragment libraries in terms of shape and physicochemical properties.     

Biocompatibility of calcium phosphate bone cement with optimised mechanical properties: an in vivo study

This work establishes the in vivo performance of modified calcium phosphate bone cements for vertebroplasty of spinal fractures using a lapine model. A non-modified calcium phosphate bone cement and collagen-calcium phosphate bone cements composites with enhanced mechanical properties, utilising either bovine collagen or collagen from a marine sponge, were compared to a commercial poly(methyl methacrylate) cement. Conical cement samples (8?mm height?×?4?mm base diameter) were press-fit into distal femoral condyle defects in New Zealand White rabbits and assessed after 5 and 10 weeks. Bone apposition and tartrate-resistant acid phosphatase activity around cements were assessed. All implants were well tolerated, but bone apposition was higher on calcium phosphate bone cements than on poly(methyl methacrylate) cement. Incorporation of collagen showed no evidence of inflammatory or immune reactions. Presence of positive tartrate-resistant acid phosphatase staining within cracks formed in calcium phosphate bone cements suggested active osteoclasts were present within the implants and were actively remodelling within the cements. Bone growth was also observed within these cracks. These findings confirm the biological advantages of calcium phosphate bone cements over poly(methyl methacrylate) and, coupled with previous work on enhancement of mechanical properties through collagen incorporation, suggest collagen-calcium phosphate bone cement composite may offer an alternative to calcium phosphate bone cements in applications where low setting times and higher mechanical stability are important.     

Calvert Richard Jones the earlier wark

Abstract

For almost a century after his death in 1877, Calvert Jones's work was neglected and his photographs commonly attributed to Henry Fox Talbot. Only in the past few years has it become evident that Jones was responsible for some of the most visually exciting images of early photography and that his pictures represent a coherent and notably well-directed body of work. It is now clear that Jones possessed a remarkable and original artistic vision; he was also one of the most irresistible personalities of photography's beginning.     

Method of Monte Carlo simulation verification in hadron therapy with non-tissue equivalent detectors

In hadron therapy the spectra of secondary particles can be very broad in type and energy. The most accurate calculations of tissue equivalent (TE) absorbed dose and biological effect can be achieved using Monte Carlo (MC) simulations followed by the application of an appropriate radiobiological model. The verification of MC simulations is therefore an important quality assurance (QA) issue in dose planning. We propose a method of verification for MC dose calculations based on measurements of either the integral absorbed dose or the spectra of deposited energies from single secondary particles in non-TE material detectors embedded in a target of interest (phantom). This method was tested in boron neutron capture therapy and fast neutron therapy beams.