Conduction abnormalities are restricted to the central nervous system in experimental autoimmune encephalomyelitis induced by inoculation with proteolipid protein but not with myelin basic protein

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system (CNS) and can be induced by inoculation of animals with homogenized CNS tissue or highly purified myelin proteins such as myelin basic protein (MBP) or proteolipid protein (PLP). It is widely studied as a possible animal model of multiple sclerosis. We performed the present neurophysiological study to define the location of nerve conduction abnormalities in EAE induced by immunization with PLP (PLP-EAE) and in EAE induced by immunization with MBP (MBP-EAE) in the Lewis rat. In rats with tail weakness due to acute PLP-EAE, conduction was normal in the spinal nerve roots and peripheral nerves but there was evidence of conduction block in a high proportion of the fibres in the dorsal columns of the lumbosacral spinal cord. In contrast, in acute MBP-EAE, there was conduction block in a high proportion of fibres in the sacral dorsal and ventral roots of the peripheral nervous system (PNS) and in the dorsal columns of the lumbosacral spinal cord. The distribution of nerve conduction abnormalities is consistent with previous histological studies showing that inflammation and primary demyelination are restricted to the CNS in PLP-EAE, but are present in the CNS and in the spinal roots of the PNS in MBP-EAE. The restriction of functional abnormalities to the CNS in PLP-EAE but not in MBP-EAE may have implications for the human inflammatory demyelinating diseases, including multiple sclerosis

Flight Evaluation of an Aircraft with Side and Center Stick Controllers and Rate-Limited Ailerons

As part of an ongoing government and industry effort to study the flying qualities of aircraft with rate-limited control surface actuators, two studies were previously flown to examine an algorithm developed to reduce the tendency for pilot-induced oscillation when rate limiting occurs. This algorithm, when working properly, greatly improved the performance of the aircraft in the first study. In the second study, however, the algorithm did not initially offer as much improvement. The differences between the two studies caused concern. The study detailed in this paper was performed to determine whether the performance of the algorithm was affected by the characteristics of the cockpit controllers. Time delay and flight control system noise were also briefly evaluated. An in-flight simulator, the Calspan Learjet 25, was programmed with a low roll actuator rate limit, and the algorithm was programmed into the flight control system. Side- and center-stick controllers, force and position command signals, a rate-limited feel system, a low-frequency feel system, and a feel system damper were evaluated. The flight program consisted of four flights and 38 evaluations of test configurations. Performance of the algorithm was determined to be unaffected by using side- or center-stick controllers or force or position command signals. The rate-limited feel system performed as well as the rate-limiting algorithm but was disliked by the pilots. The low-frequency feel system and the feel system damper were ineffective. Time delay and noise were determined to degrade the performance of the algorithm

Nitrogen and carbon isotope composition of organic Fertilizers.

Synthetic (e.g. urea) and organic fertilizers (e.g. compost) differed markedly in N isotope composition and the greater the difference between organic and synthetic fertilizer the more robust will be the differentiation of crops and vegetable grown under different farming systems. The objective of this study was to compare nitrogen and carbon isotope composition of organic fertilizers and manures available for conventional and organic farming in Brazil. Seven samples of organic fertilizer, two of organo-mineral fertilizers and two of different animal manures were analyzed for nitrogen and carbon isotope composition (15N, 13C). Organic fertilizers and manure samples were enriched in 15N as expected. Using synthetic fertilizers as the primary material of organo-mineral fertilizer can imprint a low 15N value to the final product. Organic fertilizers, organo-mineral fertilizers and manures can have their organic feedstock differentiated using 13C. These are preliminary data of the isotopic composition of organic fertilizer in Brazil. Therefore, a wider survey of fertilizers and an experimental approach for organic- and organo-mineral fertilizer production is needed to elucidate the natural isotope variation of the array of available products

Nitrogen loss (NH3, N2O) patterns in bench-scale composting.

Nitrogen (N) losses during composting reduce the value of the end product as a fertilizer. Nitrogen is lost during composting mainly by ammonia (NH3) volatilization in the thermophilic phase. We used three bench-scale aerobic bioreactors with a controlled temperature difference (CDT) system as an experimental approach to investigate the pattern of N losses during composting. N2O peak emission occurred much earlier (7h) than NH3 volatilization (48-60h) during the thermophilic phase (~55°C) of bench-scale composting. The NH3 volatilization peak rate occurred following the greater biological activity (O2 consumed/CO2 evolved) at 40°C which could coincide with greater ammonification, but immobilization of NH4+/NH3 also occurs at this point affecting NH3 volatilization. Differences in temperature curves and accumulated NH3-N were related to the biological activity in each vessel. Therefore, O2 consumed/CO2 evolved measurements must be part of the evaluation of composting in further studies for comparisons of techniques to reduce NH3 volatilizatio

The isotopic composition (d15N, d13C) of agricultural wastes and derived composts.

The aim of this study was to measure variations in the isotopic composition (d13C and d15N) during the composting of different agricultural wastes using bench-scale bioreactors. Four different feedstocks of agricultural wastes (Horse bedding manure + legumes residues; Dairy manure + Jatropha mill cake; Dairy manure + sugarcane residues; Dairy manure) were used for aerobic-thermophilic composting. During composting no significant differences were found between the d13C values of the source material and the compost, except for Dairy manure + sugarcane residues. d15N values increased significantly in composts of Horse bedding manure + legumes residues and Dairy manure + Jatropha mill cake. d15N values of composts may be related to NH3 volatilization during the composting process. Isotopic signatures (d13C, d15N) can be used to differentiate composts from different feedstock sources and d15N values may be a quantitative indicator of NH3 volatilization during composting. Use of bench-scale bioreactors is a promising apparatus to study the dynamics of C and N and stable isotopes signatures during composting, but future adjustments regarding sampling methodology are necessary

Activation of PTHrP-cAMP-CREB1 signaling following p53 loss is essential for osteosarcoma initiation and maintenance

Mutations in the P53 pathway are a hallmark of human cancer. The identification of pathways upon which p53-deficient cells depend could reveal therapeutic targets that may spare normal cells with intact p53. In contrast to P53 point mutations in other cancer, complete loss of P53 is a frequent event in osteosarcoma (OS), the most common cancer of bone. The consequences of p53 loss for osteoblastic cells and OS development are poorly understood. Here we use murine OS models to demonstrate that elevated Pthlh (Pthrp), cAMP levels and signalling via CREB1 are characteristic of both p53-deficient osteoblasts and OS. Normal osteoblasts survive depletion of both PTHrP and CREB1. In contrast, p53-deficient osteoblasts and OS depend upon continuous activation of this pathway and undergo proliferation arrest and apoptosis in the absence of PTHrP or CREB1. Our results identify the PTHrP-cAMP-CREB1 axis as an attractive pathway for therapeutic inhibition in OS.Mannu K Walia, Patricia MW Ho, Scott Taylor, Alvin JM Ng, Ankita Gupte, Alistair M Chalk, Andrew CW Zannettino, T John Martin, Carl R Walkle

Improvement in Chronic Hepatocerebral Degeneration Following Liver Transplantation

Chronic progressive hepatocerebral degeneration with spastic paraparesis, dementia, dysarthria, ataxia, tremor, and neuropsychiatric symptoms follows long-standing portal-systemic shunting, is associated with structural changes in the central nervous system, and does not respond to conventional therapy for hepatic encephalopathy. A case of advanced chronic liver disease with severe, progressive hepatocerebral degeneration after 23 yr of portal-systemic shunting is reported in whom there was significant objective improvement in intellectual function and in the chronic neurological signs 3 mo after orthotopic liver transplantation and further improvement 12 mo after transplantation