Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

Effects of postmortem calcium chloride injection on meat palatability traits of strip loin steaks from cattle supplemented with or without zilpaterol hydrochloride

An experiment was conducted to determine the effects of zilpaterol hydrochloride mM supplementation (ZH; 8.3 mg/kg on a DM basis for 20 d) and calcium chloride injection [CaCl2, 200 at 5% (wt/wt) at 72 h postmortem] on palatability traits of beef (Bos taurus) strip loin steaks. Select (USDA) strip loins were obtained from control (no ZH = 19) and ZH-supplemented carcasses (n = 20). Right and left sides were selected alternatively to serve as a control (no INJ) or CaCl2-injected (INJ) and stored at 4 degrees C Before injecting the subprimals (72 h postmortem), 2 steaks were cut for proximate, sarcomere length, and myofibrillar fragmentation index (MFI) analyses. At 7 d postmortem each strip loin was portioned into steaks, vacuum packaged, and aged for the appropriate period for Warner-Bratzler shear force (WBSF; 7, 14, 21, and 28 d postmortem), trained sensory analysis (14 and 21 d postmortem), purge loss (7 d), and MFI (3, 7, 14, 21, and 28 d postmortem). Results indicated steaks from both ZH supplementation and INJ had reduced WBSF values as days of postmortem aging increased. The WBSF values of ZH steaks were greater (P 0.05) due to ZH at 14, 21, or 28 d or due to INJ at any aging period. Trained panelists rated tenderness less in ZH steaks than steaks with no ZH at 14 d and 21 d. However, INJ improved (P < 0.05) the tenderness ratings and flavor intensity of the trained panelists, compared with their non-injected cohorts at 21 d. Zilpaterol hydrochloride supplementation reduced (P < 0.05) MFI values, but INJ resulted in greater (P < 0.05) MFI values compared with no INJ. Subprimals from ZH and INJ showed greater purge loss (P < 0.05). Although no interactions were found with ZH and CaCl2, injecting USDA Select strip loins from ZH-fed cattle can help reduce the normal WBSF variation as it does in steaks from non-ZH-fed cattle.90103584359

Duckweed (Lemna minor) as a Model Plant System for the Study of Human Microbial Pathogenesis

BACKGROUND: Plant infection models provide certain advantages over animal models in the study of pathogenesis. However, current plant models face some limitations, e.g., plant and pathogen cannot co-culture in a contained environment. Development of such a plant model is needed to better illustrate host-pathogen interactions. METHODOLOGY/PRINCIPAL FINDINGS: We describe a novel model plant system for the study of human pathogenic bacterial infection on a large scale. This system was initiated by co-cultivation of axenic duckweed (Lemna minor) plants with pathogenic bacteria in 24-well polystyrene cell culture plate. Pathogenesis of bacteria to duckweed was demonstrated with Pseudomonas aeruginosa and Staphylococcus aureus as two model pathogens. P. aeruginosa PAO1 caused severe detriment to duckweed as judged from inhibition to frond multiplication and chlorophyll formation. Using a GFP-marked PAO1 strain, we demonstrated that bacteria colonized on both fronds and roots and formed biofilms. Virulence of PAO1 to duckweed was attenuated in its quorum sensing (QS) mutants and in recombinant strains overexpressing the QS quenching enzymes. RN4220, a virulent strain of S. aureus, caused severe toxicity to duckweed while an avirulent strain showed little effect. Using this system for antimicrobial chemical selection, green tea polyphenols exhibited inhibitory activity against S. aureus virulence. This system was further confirmed to be effective as a pathogenesis model using a number of pathogenic bacterial species. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that duckweed can be used as a fast, inexpensive and reproducible model plant system for the study of host-pathogen interactions, could serve as an alternative choice for the study of some virulence factors, and could also potentially be used in large-scale screening for the discovery of antimicrobial chemicals

Space Telescope and Optical Reverberation Mapping Project. IX. Velocity–Delay Maps for Broad Emission Lines in NGC 5548

In this contribution, we achieve the primary goal of the active galactic nucleus (AGN) STORM campaign by recovering velocity–delay maps for the prominent broad emission lines (Lyα, C iv, He ii, and Hβ) in the spectrum of NGC 5548. These are the most detailed velocity–delay maps ever obtained for an AGN, providing unprecedented information on the geometry, ionization structure, and kinematics of the broad-line region. Virial envelopes enclosing the emission-line responses show that the reverberating gas is bound to the black hole. A stratified ionization structure is evident. The He ii response inside 5–10 lt-day has a broad single-peaked velocity profile. The Lyα, C iv, and Hβ responses extend from inside 2 to outside 20 lt-day, with double peaks at ±2500 km s−1 in the 10–20 lt-day delay range. An incomplete ellipse in the velocity–delay plane is evident in Hβ. We interpret the maps in terms of a Keplerian disk with a well-defined outer rim at R = 20 lt-day. The far-side response is weaker than that from the near side. The line-center delay $\tau =(R/c)(1-\sin i)\approx 5$ days gives the inclination i ≈ 45°. The inferred black hole mass is MBH ≈ 7 × 107 M⊙. In addition to reverberations, the fit residuals confirm that emission-line fluxes are depressed during the "BLR Holiday" identified in previous work. Moreover, a helical "Barber-Pole" pattern, with stripes moving from red to blue across the C iv and Lyα line profiles, suggests azimuthal structure rotating with a 2 yr period that may represent precession or orbital motion of inner-disk structures casting shadows on the emission-line region farther out

Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component.

Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurode- generative disorders are very complicated and multifacto- rial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very di cult to be interpretated and often useless. Mouse models could be condiderated a ‘pathway models’, rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high eld Magnetic resonance, Optical Imaging scanners and of highly speci c contrast agents. Behavioral test are useful tool to characterize di erent ani- mal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the di erent neurodegenerative disorders. Aim of this review is to focus on the di erent existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Learning to represent exact numbers

This article focuses on how young children acquire concepts for exact, cardinal numbers (e.g., three, seven, two hundred, etc.). I believe that exact numbers are a conceptual structure that was invented by people, and that most children acquire gradually, over a period of months or years during early childhood. This article reviews studies that explore children’s number knowledge at various points during this acquisition process. Most of these studies were done in my own lab, and assume the theoretical framework proposed by Carey (2009). In this framework, the counting list (‘one,’ ‘two,’ ‘three,’ etc.) and the counting routine (i.e., reciting the list and pointing to objects, one at a time) form a placeholder structure. Over time, the placeholder structure is gradually filled in with meaning to become a conceptual structure that allows the child to represent exact numbers (e.g., There are 24 children in my class, so I need to bring 24 cupcakes for the party.) A number system is a socially shared, structured set of symbols that pose a learning challenge for children. But once children have acquired a number system, it allows them to represent information (i.e., large, exact cardinal values) that they had no way of representing before

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM