The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide

The production of nitric oxide and other reactive nitrogen intermediates (RNI) by macrophages helps to control infection by Mycobacterium tuberculosis (Mtb). However, the protection is imperfect and infection persists. To identify genes that Mtb requires to resist RNI, we screened 10,100 Mtb transposon mutants for hypersusceptibility to acidified nitrite. We found 12 mutants with insertions in seven genes representing six pathways, including the repair of DNA (uvrB) and the synthesis of a flavin cofactor (fbiC). Five mutants had insertions in proteasome-associated genes. An Mtb mutant deficient in a presumptive proteasomal adenosine triphosphatase was attenuated in mice, and exposure to proteasomal protease inhibitors markedly sensitized wild-type Mtb to RNI. Thus, the mycobacterial proteasome serves as a defense against oxidative or nitrosative stress.     

Uncertainty and adaptive management for biodiversity conservation

Adaptive management of natural resources is widely supported, but in biodiversity conservation there have been few practical applications of the approach in its entirety. Some of the contributions to this special publication examine progress in the implementation of adaptive approaches into conservation policy, while others explore novel theoretical and modeling approaches that seek to accommodate the complexities of real-world applications. Several of the papers address the treatment of uncertainty in adaptive management through innovative approaches to experimentation and monitoring, use and characterisation of expert knowledge and reconciliation of differences of opinion about parameters or systems. Drawing on these contributions, we discuss the major impediments to implementing adaptive management, why adaptive management has been slow to be implemented and how this can be redressed.     

Synthesis of new compounds related to the commercial fungicide tricyclazole

BACKGROUND: Tricyclazole is a commercial fungicide used to control rice blast. As part of re‐registration activities, samples of metabolites and process impurities are required. In addition, isotopically labeled tricyclazole samples are also required. RESULTS: Four new compounds related to tricyclazole are reported. An isotopically labeled sample of tricyclazole was prepared that contained two ¹⁵N atoms and one ¹³C atom. Radiolabeled tricyclazole with ¹⁴C at the triazole C3 position was also synthesized. A new process impurity in technical tricyclazole was identified and synthesized. A new metabolite of tricyclazole was identified, independently synthesized and characterized by X‐ray crystallography. CONCLUSION: A previously unreported metabolite of tricyclazole has been identified and structurally characterized. In addition, a new process impurity has been identified by independent synthesis. Identification of these new compounds has facilitated the continued registration of this important fungicide. Copyright © 2011 Society of Chemical Industry     

Nutritional value of a highly digestible sorghum cultivar for meat-type chickens

The nutritional value of a newly discovered sorghum mutant cultivar (P851171), with high in vitro protein digestibility, was compared to those of corn and two normal sorghums (P721N and 611Y) in two chick feeding trials. Although 8-20 day protein efficiency ratios and net protein ratios of all three sorghums were inferior to those of corn, P851171 and 611Y had markedly greater mean true amino acid digestibilities (TAAD) than either corn or P721N. In a subsequent 42-day experiment, all three sorghums supported weight gains equal to those of the corn-fed chicks. Feeding suboptimal levels of dietary protein resulted in reduced weight gains and no observed benefits of P851171 or 611Y. Furthermore, chicks fed P851171 exhibited poorer feed/gain values as compared to those fed the other cereals. It is possible that the starch content/carbohydrate profile of P851171 was inferior to that of the other sorghums, which offset its superior TAAD and resulted in poorer broiler performance.     

Evaluation of the association between initial proteinuria and morbidity rate or death in dogs with naturally occurring chronic renal failure

OBJECTIVE: To determine whether urine protein-to-creatinine ratio (UP:C) > or = 1.0 at initial diagnosis of chronic renal failure (CRF) is associated with greater risk of development of uremic crises, death, and progression of renal failure in dogs. DESIGN: Prospective cohort study. ANIMALS: 45 dogs with CRF PROCEDURE: Dogs were prospectively assigned to 2 groups on the basis of initial UP:C < 1.0 or 2 > or = 1.0. The association between magnitude of proteinuria and development of uremic crises and death was determined before and after dogs with initial UP:C > or =1.0 were assigned to 3 subgroups and compared with dogs with initial UP:C < 1.0. Changes in reciprocal serum creatinine concentration were used to estimate decrease in renal function. RESULTS: Initially, dogs had similar clinical characteristics with the exception of systolic blood pressure and UP:C. Relative risks of development of uremic crises and death were approximately 3 times higher in dogs with UP:C > or =1.0, compared with dogs with UP:C < 1.0. Relative risk of adverse outcome was approximately 1.5 times higher for every 1-unit increment in UP:C. The decrease in renal function was of greater magnitude in dogs with UP:C > or =1.0, compared with dogs with UP:C < 1.0. CONCLUSIONS AND CLINICAL RELEVANCE: Initial UP:C > or =1.0 in dogs with CRF was associated with greater risk of development of uremic crises and death, compared with dogs with UP:C < 1.0. Initial determinations of UP:C in dogs with naturally occurring CRF may be of value in refining prognoses.     

Factors associated with the clinical diagnosis of foot and mouth disease during the 2001 epidemic in the UK

The purpose of this investigation was to identify factors associated with the clinical diagnosis of foot and mouth disease during the 2001 epidemic in the United Kingdom. Using logistic regression, we compared: (1) reports of suspect disease that resulted in the declaration of FMD to reports that did not, and (2) laboratory-positive cases to laboratory-negative cases. From 6,801 reports of suspect disease, 2,026 cases of FMD were identified. Suspect cases were more likely to become clinical cases if: (1) the report originated from the disease control authorities ('active surveillance') rather than the public, usually farmers ('passive surveillance'); (2) cattle were the species suspected of disease, as opposed to sheep; (3) the report was filed during the peak of the epidemic; (4) the reporting premises was within 3 km of an FMD case detected within the previous 2 weeks; or (5) the report originated from certain local disease control centres. There were significant two-way interactions between: type of surveillance and species suspected of disease, type of surveillance and proximity of other infected premises, species suspected and time in the epidemic, and time in the epidemic and proximity of other infected premises. Clinical cases were more likely to be laboratory positive if: (1) they were found by passive versus active surveillance, (2) cattle were suspected of disease (versus sheep), (3) oldest lesions were less than 3 days, (4) the report was filed at any time other than the peak of the epidemic, or (5) the report originated from certain local disease control centres. Significant two-way interactions were found between: type of surveillance and species suspected of disease, and type of surveillance and time in the epidemic.