Confocal laser scanning microscopy and immunohistochemistry of cerebellar Lugaro cells

The present paper shows by means of confocal laser scanning microscopy the immunoreactivity of rat cerebellar Lugaro cells for calbindin, synapsin-I, PSD-95, GluR1, CaMKII alpha, and N-cadherin. Lugaro cells were easily characterized by their location beneath Purkinje cells. Calbindin revealed immunoreactivity in the cell body, and the axonal and dendritic processes. Synapsin-I labelled the presynaptic endings on Lugaro cells. Synapsin-I and PSD-95 immunoreactivity demonstrated the localization of presynaptic and postsynaptic endings surrounding cell soma, corresponding to afferent extrinsic and intrinsic cerebellar fi bers. GluR1 immunoreactivity of the soma and cell processes indicates that Lugaro cells have functional ionotropic glutamate receptors that regulate calcium levels. CaMKII alpha immunoreactivity of Lugaro cell soma and processes suggest its participation as a molecular switch for long-term information storage, and serving as a molecular basis of long-term synaptic memory. N-cadherin immunoreactivity was correlated with somato-somatic and somato-dendritic junctions between Lugaro cells and their synaptic connections.     

Using the annular shear cell as a rheometer for rapidly sheared granular materials: a DEM study

Discrete element simulations are performed to examine the kinematics of granular shear flows in an annular shear cell at high shearing rates. The interstitial fluid is absent and gravity is included. To investigate the feasibility of using annular shear cells as rheometers for rapidly sheared dense granular materials, this study focuses on the coupled effect of boundary conditions and the relative particle to shear cell size. Four different particle diameters and three different boundary types are used in the same annular shear cell. These cases correspond to physical experiments reported earlier by the authors. For many cases both shearing and non-shearing regions coexist. The transition from partially to fully shearing flow is shown to depend on the particle diameter, solids concentration, and the boundary conditions. The particles form layers at high solids concentration and with larger particles, as evidenced by the reduction of the flow diffusivity. The slip velocity at the bottom boundary is absent; at the top it varies. This variation is sensitive to the type of boundaries but insensitive to bulk solids concentration. This study shows the interconnectivity of the boundary, the particle to shear cell size, and the flow condition in an annular shear cell. Prior to using these cells as rheometers, a thorough understanding of this interconnectivity needs to be developed.     

The Efficacy of the Quorum Sensing Inhibitor FS8 and Tigecycline in Preventing Prosthesis Biofilm in an Animal Model of Staphylococcal Infection

We investigated the efficacy of tigecycline and FS8, alone or combined, in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2 × 10⁷ colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis, and three contaminated groups that received: (i) intraperitoneal tigecycline, (ii) FS8-soaked graft, and (iii) tigecycline plus FS8-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS8 was coated to the surface of the prosthesis. Tigecycline, combined with FS8, against the adherent bacteria showed MICs (2.00 mg/L) and MBCs (4.00 mg/L) four-fold lower with respect to tigecycline alone in in vitro studies. The rat groups treated with tigecycline showed the lowest bacterial numbers (4.4 × 10⁴ ± 1.2 × 10⁴ CFU/mL). The FS8-treated group showed a good activity and significant differences compared to control group with bacterial numbers of 6.8 × 10⁴ ± 2.0 × 10⁴ CFU/mL. A stronger inhibition of bacterial growth was observed in rats treated with a combined FS8 and tigecycline therapy than in those that were singly treated with bacterial numbers of 10¹ CFU/mL graft. In conclusion, the ability to affect biofilm formation as well, its property to be an antibiotic enhancer suggests FS8 as alternative or additional agent to use in conjunction with conventional antimicrobial for prevention of staphylococcal biofilm related infection.     

Summed-score linking using item response theory: Application to depression measurement.

An item response theory (IRT) approach to test linking based on summed scores is presented and demonstrated by calibrating a modified 23-item version of the Center for Epidemiologic Studies Depression Scale (CES-D) to the standard 20-item CES-D. Data are from the Depression Patient Outcomes Research Team, 11, which used a modified CES-D to measure risk for depression. Responses (N?=?1,120) to items on both the original and modified versions were calibrated simultaneously using F. Samejima's (1969, 1997) graded IRT model. The 2 scales were linked on the basis of derived summed-score-to-IRT-score translation tables. The established cut score of 16 on the standard CES-D corresponded most closely to a summed score of 20 on the modified version. The IRT summed-score approach to test linking is a straightforward, valid, and practical method that can be applied in a variety of situations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

GANAB and N-Glycans Substrates Are Relevant in Human Physiology,Polycystic Pathology and Multiple Sclerosis: A Review

Glycans are one of the four fundamental macromolecular components of living matter, and they are highly regulated in the cell. Their functions are metabolic, structural and modulatory. In particular, ER resident N-glycans participate with the Glc₃Man₉GlcNAc₂ highly conserved sequence, in protein folding process, where the physiological balance between glycosylation/deglycosylation on the innermost glucose residue takes place, according GANAB/UGGT concentration ratio. However, under abnormal conditions, the cell adapts to the glucose availability by adopting an aerobic or anaerobic regimen of glycolysis, or to external stimuli through internal or external recognition patterns, so it responds to pathogenic noxa with unfolded protein response (UPR). UPR can affect Multiple Sclerosis (MS) and several neurological and metabolic diseases via the BiP stress sensor, resulting in ATF6, PERK and IRE1 activation. Furthermore, the abnormal GANAB expression has been observed in MS, systemic lupus erythematous, male germinal epithelium and predisposed highly replicating cells of the kidney tubules and bile ducts. The latter is the case of Polycystic Liver Disease (PCLD) and Polycystic Kidney Disease (PCKD), where genetically induced GANAB loss affects polycystin-1 (PC1) and polycystin-2 (PC2), resulting in altered protein quality control and cyst formation phenomenon. Our topics resume the role of glycans in cell physiology, highlighting the N-glycans one, as a substrate of GANAB, which is an emerging key molecule in MS and other human pathologies.     

Exploiting Supramolecular Interactions from Polymeric Colloids for Strong Anisotropic Adhesion between Solid Surfaces

Adhesion occurs by covalent bonding, as in reactive structural adhesives, or through noncovalent interactions, which are nearly ubiquitous in nature. A classic example of the latter is gecko feet, where hierarchical features enhance friction across the contact area. Biomimicry of such structured adhesion is regularly achieved by top-down lithography, which allows for direction-dependent detachment. However, bottom-up approaches remain elusive given the scarcity of building blocks that yield strong, cohesive, self-assembly across multiple length scales. Herein, an exception is introduced, namely, aqueous dispersions of cellulose nanocrystals (CNCs) that form superstructured, adherent layers between solid surfaces upon confined evaporation-induced self-assembly (C-EISA). The inherently strong CNCs (E_A > 140 GPa) align into rigid, nematically ordered lamellae across multiple length scales as a result of the stresses associated with confined evaporation. This long-range order produces remarkable anisotropic adhesive strength when comparing in-plane (≈7 MPa) and out-of-plane (≤0.08 MPa) directions. These adhesive attributes, resulting from self-assembly, substantially outperform previous biomimetic adhesives obtained by top-down microfabrication (dry adhesives, friction driven), and represent a unique fluid (aqueous)-based system with significant anisotropy of adhesion. By using C-EISA, new emergent properties will be closely tied with the nature of colloids and their hierarchical assemblies.     

Modelling and solving spare parts supply chain network design problems

Spare parts are key operational assets in order to minimise unexpected equipment downtimes that may significantly impact a company’s results. The spare parts supply chain network supports the entire spare parts operations management and it is essential to achieve the planned goals. However, most of the traditional literature on spare parts management has not focused on the underlying supply chain network. Thus, this paper studies the integration of supply chain network design and control with traditional spare parts management. In particular, a generic network optimisation modelling structure is proposed, with simultaneous optimisation of warehouse locations and inventory control decisions, allowing minimising the total costs associated with the spare parts supply chain network. The generic model is specified based on three inventory control policies widely employed in the industry, which are suitable for managing a great variety of spare parts, i.e. (s, Q), (R, s, S) and (S-1, S). Furthermore, a solution approach is proposed based on Generalised Benders Decomposition. Finally, numerical results from a real-world application case in the process industry are shown and discussed.     

Effect of satisfaction with one''s abilities on positive and negative affect among individuals with recently diagnosed rheumatoid arthritis

An improved procedure for the synthesis of 3 beta-hydroxyandrost-5-ene-7,17-dione, a natural metabolite of dehydroepiandrosterone (DHEA) is described. The synthesis and magnetic resonance spectra of several other related steroids are presented. Feeding dehydroepiandrosterone to rats induces enhanced formation of several liver enzymes among which are mitochondrial sn-glycerol 3-phosphate dehydrogenase (GPDH) and cytosolic malic enzyme. The induction of these two enzymes, that complete a thermogenic system in rat liver, was used as an assay to search for derivatives of DHEA that might be more active than the parent steroid. Activity is retained in steroids that are reduced to the corresponding 17 beta-hydroxy derivative, or hydroxylated at 7 alpha or 7 beta, and is considerably enhanced when the 17-hydroxy or 17-carbonyl steroid is converted to the 7-oxo derivative. Several derivatives of DHEA did not induce the thermogenic enzymes whereas the corresponding 7-oxo compounds did. Both short and long chain acyl esters of DHEA and of 7-oxo-DHEA are active inducers of the liver enzymes when fed to rats. 7-Oxo-DHEA-3-sulfate is as active as 7-oxo-DHEA or its 3-acetyl ester, whereas DHEA-3-sulfate is much less active than DHEA. Among many steroids tested, those possessing a carbonyl group at position 3, a methyl group at 7, a hydroxyl group at positions 1, 2, 4, 11, or 19, or a saturated B ring, with or without a 4-5 double bond, were inactive.