Allosteric Control of O2 Reactivity in Rieske Oxygenases

Oxygen is Nature’s perfect reagent. On one hand, it is potentially a very strong oxidant. On the other hand, this potential is caged because the two highest energy valence electrons of the O2 molecule are unpaired. As a result, O2 is relatively unreactive with most other molecules, as almost all of these have paired electrons. Consequently, by modulating the properties of the O2 valence electrons, Nature can generate a reactive species under controlled conditions, catalyzing difficult reactions while still rigorously enforcing specificity. Special sets of enzymes termed oxygenases and oxidases have evolved to perform this task

Lipopolysaccharide and toll-like receptor 4 in dogs with congenital portosystemic shunts

Surgical attenuation of a congenital portosystemic shunt (CPSS) results in increased portal vein perfusion, liver growth and clinical improvement. Portal lipopolysaccharide (LPS) is implicated in liver regeneration via toll-like receptor (TLR) 4 mediated cytokine activation. The aim of this study was to investigate factors associated with LPS in dogs with CPSS. Plasma LPS concentrations were measured in the peripheral and portal blood using a limulus amoebocyte lysate (LAL) assay. LPS concentration was significantly greater in the portal blood compared to peripheral blood in dogs with CPSS (P = 0.046) and control dogs (P = 0.002). LPS concentrations in the peripheral (P = 0.012) and portal (P = 0.005) blood of dogs with CPSS were significantly greater than those of control dogs. The relative mRNA expression of cytokines and TLRs was measured in liver biopsies from dogs with CPSS using quantitative PCR. TLR4 expression significantly increased following partial CPSS attenuation (P = 0.020). TLR4 expression was significantly greater in dogs that tolerated complete CPSS attenuation (P = 0.011) and those with good portal blood flow on pre-attenuation (P = 0.004) and post-attenuation (P = 0.015) portovenography. Serum interleukin (IL)-6 concentration was measured using a canine specific ELISA and significantly increased 24 h following CPSS attenuation (P < 0.001). Portal LPS was increased in dogs with CPSS, consistent with decreased hepatic clearance. TLR4 mRNA expression was significantly associated with portal blood flow and increased following surgery. These findings support the concept that portal LPS delivery is important in the hepatic response to surgical attenuation. Serum IL-6 significantly increased following surgery, consistent with LPS stimulation via TLR4, although this increase might be non-specific

Training Program Evaluation: A Comparison of the Effectiveness of School Versus On-the-Job Training

The hypothesis was investigated that school training was more effective than on-the-job training. Of a sample of 349 male subjects, 217 received on-the-job training and 132 received school training. Data were collected and analyzed on tenure, performance, promotions, salary increases, and accidents. Training type had a significant positive correlation with tenure and accident occurrence at the .01 and .05 level, respectively, and a significant correlation with salary increase at the .05 level. A regression model using accident occurrence and salary increase yielded a prediction of training type significant at the .05 level. No difference was found between the two types of training, as measured by the study variables

Facile O-atom insertion into C-C and C-H bonds by a trinuclear copper complex designed to harness a singlet oxene

Two trinuclear copper [CuICuICuI(L)]1+ complexes have been prepared with the multidentate ligands (L) 3,3'-(1,4-diazepane-1,4-diyl)bis(1-((2-(dimethylamino)ethyl)(methyl)amino)propan-2-ol) (7-Me) and (3,3'-(1,4-diazepane-1,4-diyl)bis(1-((2-(diethylamino) ethyl)(ethyl) amino)propan-2-ol) (7-Et) as models for the active site of the particulate methane monooxygenase (pMMO). The ligands were designed to form the proper spatial and electronic geometry to harness a "singlet oxene," according to the mechanism previously suggested by our laboratory. Consistent with the design strategy, both [CuICuICuI(L)]1+ reacted with dioxygen to form a putative bis(µ3-oxo)CuIICuIICuIII species, capable of facile O-atom insertion across the central C-C bond of benzil and 2,3-butanedione at ambient temperature and pressure. These complexes also catalyze facile O-atom transfer to the C-H bond of CH3CN to form glycolonitrile. These results, together with our recent biochemical studies on pMMO, provide support for our hypothesis that the hydroxylation site of pMMO contains a trinuclear copper cluster that mediates C-H bond activation by a singlet oxene mechanism

Serum anti-Müllerian hormone concentrations before and after treatment of an ovarian granulosa cell tumour in a cat

Case summary A 15-year-old female cat was presented for investigation of progressive behavioural changes, polyuria, polydipsia and periuria. An ovarian granulosa cell tumour was identified and the cat underwent therapeutic ovariohysterectomy (OHE). The cat’s clinical signs resolved, but 6 months later it was diagnosed as having an anaplastic astrocytoma and was euthanased. Serum anti-Müllerian hormone (AMH) concentration prior to OHE was increased vs a control group of entire and neutered female cats. Following OHE, serum AMH concentration decreased to <1% of the original value. Relevance and novel information Serum AMH measurement may represent a novel diagnostic and monitoring tool for functional ovarian neoplasms in cats

Advancing the science of cancer cost measurement: challenges and opportunities

Cancer accounts for a major proportion of national health expenditures, which are expected to increase in the future. This paper aims to identify major challenges with estimating cancer related costs, and discuss international comparisons, and recommendations for future research. Methods. It starts from the experience of an international workshop aimed at comparing cancer burden evaluation methods, improving results comparability, discussing strengths and criticisms of different approaches. Results. Three methodological themes necessary to inform the analysis are identified and discussed: data availability; costs definition; epidemiological measures. Conclusions. Cost evaluation is applied to cancer control interventions and is relevant for public health planners. Despite their complexity, international comparisons are fundamental to improve, generalize and extend cost evaluation to different contexts