Evidence for Ordered Magnetic Fields in the Quasar Environment

At a distance of 20 pc from the purported supermassive black hole powering quasars, temperatures and densities are inferred from optical observations to be ~10**4 K and ~10**4 cm**-3. Here we present Very Long Baseline Interferometry radio observations revealing organized magnetic fields on the parsec scale in the hot plasma surrounding the quasar OQ172 (1442+101). These magnetic fields rotate the plane of polarization of the radio emission coming from the core and inner jet of the quasar. The derived rotation measure (RM) is 40,000 rad m**-2 in the rest frame of the quasar. Only 10 mas (a projected distance of 68 pc) from the nucleus the jet absolute values of RM fall to less than 100 rad m**-2.Comment: in press at ApJ Letters, 12 page LaTeX document includes 4 postscript figure

Glucose tolerance abnormalities in Australian women with polycystic ovary syndrome

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Objectives: To determine the prevalence of glucose tolerance abnormalities and to identify associated risk factors in women with polycystic ovary syndrome (PCOS) attending a reproductive endocrinology clinic. Design: Retrospective chart review. Participants and setting: 372 women with confirmed PCOS attending a reproductive endocrinology clinic at Adelaide University’s Research Centre for Reproductive Health. Main outcome measures: Prevalence of glucose tolerance abnormalities and association of such abnormalities with potential risk factors. Results: 4.0% (15 women) had diabetes mellitus, 15.6% (58) had impaired glucose tolerance and 80.4% (299) had normal glucose tolerance. There was a significant trend towards increasing prevalence of diabetes with increasing age (odds ratio [OR], 0.60; P= 0.0085). The prevalence of abnormal glucose tolerance (diabetes and impaired glucose tolerance together) was significantly higher with higher waist circumference (OR, 2.9; P = 0.05), higher body mass index (OR, 8.02; P= 0.0253), a family history of diabetes (OR, 1.56; P =0.0192) and the presence of metabolic syndrome (OR, 5.62; P<0.001). Conclusion: The prevalence of diabetes and impaired glucose tolerance is high in women with PCOS, especially in older women and those with abdominal obesity and a MJA 2007; 187: 328–331 family history of diabetes.Preeti Dabadghao, Bronwen J Roberts, Jim Wang, Michael J Davies and Robert J Norma

Ursinus College Alumni Journal, March 1954

President\u27s page • Dr. Gaylord P. Harnwell to speak at commencement • Ursinus confers honorary degree on Dr. James Wagner • William S. Pettit named Dean of Ursinus College • Prospective students entertained at Ursinus • May queen 1954 • Annual Messiah sung by largest chorus • Charles Roberts makes first 1954 loyalty fund report • Evelyn Glazier Henzel candidate for state legislature • Ursinus places nineteenth in mathematical competition • Lloyd Wood candidate for nomination of governor • Pre-meds enjoy hospital tours with Dr. Tornetta, \u2738 • Ursinus Women\u27s Club sets important spring dates • Watch for news of your Ursinus regional group spring meeting • Meeting of the Washington alumni on April 29 • Harrisburg-Hershey to organize • Berks Co. alumni dinner April 21 • Floyd Justice president of Philadelphia alumni • New York meeting on May 5 • Lehigh Valley dinner April 29 • Don\u27t miss Alumni Day - it\u27s May 29 • Be sure to vote for your alumni officers! • Watch for your ballot in April • Sports review • Mermaids open season with Drexel • Best football record in twenty years • Basketball belles take opener 51-21 • Coach Gurzynski reviews 1954 track prospects • Coach Spangler has hustling basketball squad • Basketball and hilarity at alumni-varsity game • Wrestling captain • Wrestling resume • Doc Baker reviews the 1953 soccer season • Hockey players Merrifield and Price honored • A day with the Dean of Women at Ursinus • News about ourselves • Ziegler awarded air medal • Engagements • Weddings • Births • Necrology • Carters enjoy life in Coloradohttps://digitalcommons.ursinus.edu/alumnijournal/1050/thumbnail.jp

Comprehensive Biotransformation Analysis of Phenylalanine-Tyrosine Metabolism Reveals Alternative Routes of Metabolite Clearance in Nitisinone-Treated Alkaptonuria

Metabolomic analyses in alkaptonuria (AKU) have recently revealed alternative pathways in phenylalanine-tyrosine (phe-tyr) metabolism from biotransformation of homogentisic acid (HGA), the active molecule in this disease. The aim of this research was to study the phe-tyr metabolic pathway and whether the metabolites upstream of HGA, increased in nitisinone-treated patients, also undergo phase 1 and 2 biotransformation reactions. Metabolomic analyses were performed on serum and urine from patients partaking in the SONIA 2 phase 3 international randomised-controlled trial of nitisinone in AKU (EudraCT no. 2013-001633-41). Serum and urine samples were taken from the same patients at baseline (pre-nitisinone) then at 24 and 48 months on nitisinone treatment (patients N = 47 serum; 53 urine) or no treatment (patients N = 45 serum; 50 urine). Targeted feature extraction was performed to specifically mine data for the entire complement of theoretically predicted phase 1 and 2 biotransformation products derived from phenylalanine, tyrosine, 4-hydroxyphenylpyruvic acid and 4-hydroxyphenyllactic acid, in addition to phenylalanine-derived metabolites with known increases in phenylketonuria. In total, we observed 13 phase 1 and 2 biotransformation products from phenylalanine through to HGA. Each of these products were observed in urine and two were detected in serum. The derivatives of the metabolites upstream of HGA were markedly increased in urine of nitisinone-treated patients (fold change 1.2–16.2) and increases in 12 of these compounds were directly proportional to the degree of nitisinone-induced hypertyrosinaemia (correlation coefficient with serum tyrosine = 0.2–0.7). Increases in the urinary phenylalanine metabolites were also observed across consecutive visits in the treated group. Nitisinone treatment results in marked increases in a wider network of phe-tyr metabolites than shown before. This network comprises alternative biotransformation products from the major metabolites of this pathway, produced by reactions including hydration (phase 1) and bioconjugation (phase 2) of acetyl, methyl, acetylcysteine, glucuronide, glycine and sulfate groups. We propose that these alternative routes of phe-tyr metabolism, predominantly in urine, minimise tyrosinaemia as well as phenylalanaemia

Metabolomic studies in the inborn error of metabolism alkaptonuria reveal new biotransformations in tyrosine metabolism

Alkaptonuria (AKU) is an inherited disorder of tyrosine metabolism caused by lack of active enzyme homogentisate 1,2-dioxygenase (HGD). The primary consequence of HGD deficiency is increased circulating homogentisic acid (HGA), the main agent in the pathology of AKU disease. Here we report the first metabolomic analysis of AKU homozygous Hgd knockout (Hgd(−/−)) mice to model the wider metabolic effects of Hgd deletion and the implication for AKU in humans. Untargeted metabolic profiling was performed on urine from Hgd(−/−) AKU (n = 15) and Hgd(+/−) non-AKU control (n = 14) mice by liquid chromatography high-resolution time-of-flight mass spectrometry (Experiment 1). The metabolites showing alteration in Hgd(−/−) were further investigated in AKU mice (n = 18) and patients from the UK National AKU Centre (n = 25) at baseline and after treatment with the HGA-lowering agent nitisinone (Experiment 2). A metabolic flux experiment was carried out after administration of (13)C-labelled HGA to Hgd(−/−)(n = 4) and Hgd(+/−)(n = 4) mice (Experiment 3) to confirm direct association with HGA. Hgd(−/−) mice showed the expected increase in HGA, together with unexpected alterations in tyrosine, purine and TCA-cycle pathways. Metabolites with the greatest abundance increases in Hgd(−/−) were HGA and previously unreported sulfate and glucuronide HGA conjugates, these were decreased in mice and patients on nitisinone and shown to be products from HGA by the (13)C-labelled HGA tracer. Our findings reveal that increased HGA in AKU undergoes further metabolism by mainly phase II biotransformations. The data advance our understanding of overall tyrosine metabolism, demonstrating how specific metabolic conditions can elucidate hitherto undiscovered pathways in biochemistry and metabolism

The Enthusiast’s Eye: The Value of Unsanctioned Knowledge in Design Historical Scholarship

If design history research relies solely on institutionalized documentation and academic scholarship – that is, sanctioned knowledge – not only will its purview be limited to a very narrow segment of design culture, it will also lose out on a vast array of sources to valuable knowledge about our material environment produced by amateurs, collectors, and enthusiasts – what we in this article define as “unsanctioned knowledge.” Because of its dissociation with professional institutions and academic protocols and their – albeit admittedly utopian, but nonetheless upheld – ideals of objectivity, this type of knowledge is typically considered fundamentally subjective in nature and therefore of little or no relevance and value to academic scholarship. In this article, we argue that, to the contrary, design historical scholarship has much to gain from engaging more seriously with the unsanctioned knowledge represented by the enthusiast's eye

Pigmentation Chemistry and Radical-Based Collagen Degradation in Alkaptonuria and Osteoarthritic Cartilage

Alkaptonuria (AKU) is a rare disease characterized by high levels of homogentisic acid (HGA); patients suffer from tissue ochronosis: dark brown pigmentation, especially of joint cartilage, leading to severe early osteoarthropathy. No molecular mechanism links elevated HGA to ochronosis; the pigment's chemical identity is still not known, nor how it induces joint cartilage degradation. Here we give key insight on HGA-derived pigment composition and collagen disruption in AKU cartilage. Synthetic pigment and pigmented human cartilage tissue both showed hydroquinone-resembling NMR signals. EPR spectroscopy showed that the synthetic pigment contains radicals. Moreover, we observed intrastrand disruption of collagen triple helix in pigmented AKU human cartilage, and in cartilage from patients with osteoarthritis. We propose that collagen degradation can occur via transient glycyl radicals, the formation of which is enhanced in AKU due to the redox environment generated by pigmentation

Studies in alkaptonuria reveal new roles beyond drug clearance for phase I and II biotransformations in tyrosine metabolism

AbstractBackground and Purposealkaptonuria (AKU) is an inherited disorder of tyrosine metabolism caused by lack of the enzyme homogentisate 1,2-dioxygenase (HGD). The primary biochemical consequence of HGD-deficiency is increased circulating homogentisic acid (HGA), which is central to AKU disease pathology. The aim of this study was to investigate the wider metabolic consequences of targeted Hgd disruption.Experimental Approachthe first metabolomic analysis of the Hgd−/− AKU mouse model was performed. Urinary metabolites altered in Hgd−/− were further validated by showing that the HGA-lowering drug nitisinone reversed their direction of alteration in AKUKey Resultscomparison of Hgd−/− (AKU) versus Hgd+/− (heterozygous control) urine revealed increases in HGA and a group of 8 previously unreported HGA-derived transformation products from phase I and II metabolism. HGA biotransformation products HGA-sulfate, HGA-glucuronide, HGA-hydrate and hydroxymethyl-HGA were also decreased in urine from both mice and patients with AKU on the HGA-lowering agent nitisinone. Hgd knockout also revealed a host of previously unrecognised associations between tyrosine, purine and TCA cycle metabolic pathways.Conclusion and ImplicationsAKU is rare, but our findings further what is currently understood about tyrosine metabolism more generally, and show for the first time that phase I and II detoxification is recruited to prevent accumulation of endogenously-produced metabolites in inborn errors of metabolism. The data highlight the misconception that phase I and II metabolic biotransformations are reserved solely for drug clearance; these are ancient mechanisms, which represent new potential treatment targets in inherited metabolic diseases.Abstract FigureBullet point summaryWhat is already known Increased circulating homogentisic acid is central to disease pathology in the inherited metabolic disease alkaptonuriaThe Hgd knockout mouse, created in our laboratory, accurately models human alkaptonuriaWhat this study adds Phase I and II biotransformations are recruited in alkaptonuria for detoxification of homogentisic acidThese data challenge misconceptions that phase I and II metabolism is solely for drug clearanceClinical significance Phase I and II metabolic processes represent new treatment targets in inherited metabolic diseasesThe molecular pathology of AKU extends much further than the known alteration to tyrosine metabolism</jats:sec