Impact of wild-type and genetically modified Pseudomonas fluorescens on soil enzyme activities and microbial population structure in the rhizosphere of pea

The definitive version is available at www.blackwell-synergy.com. Copyright Blackwell Publishing DOI : 10.1046/j.1365-294x.1998.00367.xThe aim of this work was to determine the impact of wild type along with functionally and non-functionally modified Pseudomonas fluorescens strains in the rhizosphere. The wild type F113 strain carried a gene encoding the production of the antibiotic 2,4 diacetylphloroglucinol (DAPG) useful in plant disease control, and was marked with a lacZY gene cassette. The first modified strain was a functional modification of strain F113 with repressed production of DAPG, creating the DAPG negative strain F113 G22. The second paired comparison was a non-functional modification of wild type (unmarked) strain SBW25, constructed to carry marker genes only, creating strain SBW25 EeZY-6KX. Significant perturbations were found in the indigenous bacterial population structure, with the F113, (DAPG+) strain causing a shift towards slower growing colonies (K strategists) compared with the non-antibiotic producing derivative (F113 G22) and the SBW25 strains. The DAPG+ strain also significantly reduced, in comparison with the other inocula, the total Pseudomonas populations but did not affect the total microbial populations. The survival of F113 and F113 G22 were an order of magnitude lower than the SBW 25 strains. The DAPG+ strain caused a significant decrease in the shoot to root ratio in comparison to the control and other inoculants, indicating plant stress. F113 increased soil alkaline phosphatase, phosphodiesterase and aryl sulphatase activities compared to the other inocula, which themselves reduced the same enzyme activities compared to the control. In contrast to this, the -glucosidase, -galactosidase and N-acetyl glucosaminidase activities decreased with the inoculation of the DAPG+ strain. These results indicate that soil enzymes are sensitive to the impact of GMM inoculation.Peer reviewe

Uterus: Leiomyoma

Review on Uterus: Leiomyoma, with data on clinics, and the genes involved

Time-Efficient Read/Write Register in Crash-prone Asynchronous Message-Passing Systems

The atomic register is certainly the most basic object of computing science. Its implementation on top of an n-process asynchronous message-passing system has received a lot of attention. It has been shown that t \textless{} n/2 (where t is the maximal number of processes that may crash) is a necessary and sufficient requirement to build an atomic register on top of a crash-prone asynchronous message-passing system. Considering such a context, this paper visits the notion of a fast implementation of an atomic register, and presents a new time-efficient asynchronous algorithm. Its time-efficiency is measured according to two different underlying synchrony assumptions. Whatever this assumption, a write operation always costs a round-trip delay, while a read operation costs always a round-trip delay in favorable circumstances (intuitively, when it is not concurrent with a write). When designing this algorithm, the design spirit was to be as close as possible to the one of the famous ABD algorithm (proposed by Attiya, Bar-Noy, and Dolev)

Treatment of Porphyromonas gulae infection and downstream pathology in the aged dog by lysine-gingipain inhibitor COR388.

COR388, a small-molecule lysine-gingipain inhibitor, is currently being investigated in a Phase 2/3 clinical trial for Alzheimer's disease (AD) with exploratory endpoints in periodontal disease. Gingipains are produced by two species of bacteria, Porphyromonas gingivalis and Porphyromonas gulae, typically associated with periodontal disease and systemic infections in humans and dogs, respectively. P. gulae infection in dogs is associated with periodontal disease, which provides a physiologically relevant model to investigate the pharmacology of COR388. In the current study, aged dogs with a natural oral infection of P. gulae and periodontal disease were treated with COR388 by oral administration for up to 90 days to assess lysine-gingipain target engagement and reduction of bacterial load and downstream pathology. In a 28-day dose-response study, COR388 inhibited the lysine-gingipain target and reduced P. gulae load in saliva, buccal cells, and gingival crevicular fluid. The lowest effective dose was continued for 90 days and was efficacious in continuous reduction of bacterial load and downstream periodontal disease pathology. In a separate histology study, dog brain tissue showed evidence of P. gulae DNA and neuronal lysine-gingipain, demonstrating that P. gulae infection is systemic and spreads beyond its oral reservoir, similar to recent observations of P. gingivalis in humans. Together, the pharmacokinetics and pharmacodynamics of COR388 lysine-gingipain inhibition, along with reduction of bacterial load and periodontal disease in naturally occurring P. gulae infection in the dog, support the use of COR388 in targeting lysine-gingipain and eliminating P. gingivalis infection in humans

A decade of Australian methotrexate dosing errors

"OBJECTIVE: Accidental daily dosing of methotrexate can result in life-threatening toxicity. We investigated methotrexate dosing errors reported to the National Coronial Information System (NCIS), the Therapeutic Goods Administration Database of Adverse Event Notifications (TGA DAEN) and Australian Poisons Information Centres (PICs). DESIGN AND SETTING: A retrospective review of coronial cases in the NCIS (2000-2014), and of reports to the TGA DAEN (2004-2014) and Australian PICs (2004-2015). Cases were included if dosing errors were accidental, with evidence of daily dosing on at least 3 consecutive days. MAIN OUTCOME MEASURES: Events per year, dose, consecutive days of methotrexate administration, reasons for the error, clinical features. RESULTS: Twenty-two deaths linked with methotrexate were identified in the NCIS, including seven cases in which erroneous daily dosing was documented. Methotrexate medication error was listed in ten cases in the DAEN, including two deaths. Australian PIC databases contained 92 cases, with a worrying increase seen during 2014-2015. Reasons for the errors included patient misunderstanding and incorrect packaging of dosette packs by pharmacists. The recorded clinical effects of daily dosage were consistent with those previously reported for methotrexate toxicity. CONCLUSION: Dosing errors with methotrexate can be lethal and continue to occur despite a number of safety initiatives in the past decade. Further strategies to reduce these preventable harms need to be implemented and evaluated. Recent suggestions include further changes in packet size, mandatory weekly dosing labelling on packaging, improving education, and including alerts in prescribing and dispensing software."NHMRC Program Grant: 105517

Glucose metabolism during liver transplantation in dogs

Arterial and hepatic venous blood levels of glucose were studied in 12 dogs during orthotopic liver transplantation peformed under ketamine anesthesia without exogenous glucose administration. During the early part of surgery, arterial blood glucose levels were stable: 161 ± 12 mg/dl (mean ± SEM) after laparotomy and 183 ± 16 mg/dl 5 min before the anhepatic stage. During the anhepatic stage, arterial blood glucose levels decreased progressively to 135 ± 9 and 88 ± 8 mg/dl, 5 min in the anhepatic stage and 5 min before reperfusion of the graft liver, respectively (P < 0.05). Reperfusion of the graft liver resulted in an increase in arterial glucose levels to 206 ± 17 and 240 ± 24 mg/dl, 5 and 30 min after reperfusion, respectively (P < 0.05). Hepatic venous blood glucose levels increased after reperfusion (405 ± 37 and 346 ± 41 mg/dl, 5 and 30 min after reperfusion, respectively) and were significantly higher than in arterial blood (P < 0.05). Arterial lasma insulin, measured in 5 animals, did not change significantly during the procedure, whereas plasma glucagon levels, stable during the preanhepatic and anhepatic stages, increased steadily after reperfusion of the graft liver, from 66.1 ± 14.2 to 108.4 ± 38.1 pg/ml (P < 0.05). This study shows that in dogs with ketamine anesthesia mild hypoglycemia occurs during the anhepatic stage of liver transplantation without exogenous glucose administration followed by hyperglycemia on reperfusion of the graft liver, possibly secondary to the release of glucose from the donor liver

A Stochastic Approach to Shortcut Bridging in Programmable Matter

In a self-organizing particle system, an abstraction of programmable matter, simple computational elements called particles with limited memory and communication self-organize to solve system-wide problems of movement, coordination, and configuration. In this paper, we consider a stochastic, distributed, local, asynchronous algorithm for "shortcut bridging", in which particles self-assemble bridges over gaps that simultaneously balance minimizing the length and cost of the bridge. Army ants of the genus Eciton have been observed exhibiting a similar behavior in their foraging trails, dynamically adjusting their bridges to satisfy an efficiency trade-off using local interactions. Using techniques from Markov chain analysis, we rigorously analyze our algorithm, show it achieves a near-optimal balance between the competing factors of path length and bridge cost, and prove that it exhibits a dependence on the angle of the gap being "shortcut" similar to that of the ant bridges. We also present simulation results that qualitatively compare our algorithm with the army ant bridging behavior. Our work gives a plausible explanation of how convergence to globally optimal configurations can be achieved via local interactions by simple organisms (e.g., ants) with some limited computational power and access to random bits. The proposed algorithm also demonstrates the robustness of the stochastic approach to algorithms for programmable matter, as it is a surprisingly simple extension of our previous stochastic algorithm for compression.Comment: Published in Proc. of DNA23: DNA Computing and Molecular Programming - 23rd International Conference, 2017. An updated journal version will appear in the DNA23 Special Issue of Natural Computin

Formation of regulatory modules by local sequence duplication

Turnover of regulatory sequence and function is an important part of molecular evolution. But what are the modes of sequence evolution leading to rapid formation and loss of regulatory sites? Here, we show that a large fraction of neighboring transcription factor binding sites in the fly genome have formed from a common sequence origin by local duplications. This mode of evolution is found to produce regulatory information: duplications can seed new sites in the neighborhood of existing sites. Duplicate seeds evolve subsequently by point mutations, often towards binding a different factor than their ancestral neighbor sites. These results are based on a statistical analysis of 346 cis-regulatory modules in the Drosophila melanogaster genome, and a comparison set of intergenic regulatory sequence in Saccharomyces cerevisiae. In fly regulatory modules, pairs of binding sites show significantly enhanced sequence similarity up to distances of about 50 bp. We analyze these data in terms of an evolutionary model with two distinct modes of site formation: (i) evolution from independent sequence origin and (ii) divergent evolution following duplication of a common ancestor sequence. Our results suggest that pervasive formation of binding sites by local sequence duplications distinguishes the complex regulatory architecture of higher eukaryotes from the simpler architecture of unicellular organisms