bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biochemical and structural characterization of CYP109A2, a vitamin D3 25‐hydroxylase from Bacillus megaterium
Authors: Abdulmughni Ammar , Jóźwik Ilona K. , Brill Elisa , Hannemann Frank , Thunnissen Andy‐Mark W. H. , Bernhardt Rita 
Published: September 2017

Cytochrome P450 enzymes are increasingly investigated due to their potential application as biocatalysts with high regio‐ and/or stereo‐selectivity and under mild conditions. Vitamin D3 (VD3) metabolites are of pharmaceutical importance and are applied for the treatment of VD3 deficiency and other disorders. However, the chemical synthesis of VD3 derivatives shows low specificity and low yields. In this study, cytochrome P450 CYP109A2 from Bacillus megaterium DSM319 was expressed, purified, and shown to oxidize VD3 with high regio‐selectivity. The in vitro conversion, using cytochrome P450 reductase (BmCPR) and ferredoxin (Fdx2) from the same strain, showed typical Michaelis–Menten reaction kinetics. A whole‐cell system in B. megaterium overexpressing CYP109A2 reached 76 ± 5% conversion after 24 h and allowed to identify the main product by NMR analysis as 25‐hydroxylated VD3. Product yield amounted to 54.9 mg·L−1·day−1, rendering the established whole‐cell system as a highly promising biocatalytic route for the production of this valuable metabolite. The crystal structure of substrate‐free CYP109A2 was determined at 2.7 Å resolution, displaying an open conformation. Structural analysis predicts that CYP109A2 uses a highly similar set of residues for VD3 binding as the related VD3 hydroxylases CYP109E1 from B. megaterium and CYP107BR1 (Vdh) from Pseudonocardia autotrophica. However, the folds and sequences of the BC loops in these three P450s are highly divergent, leading to differences in the shape and apolar/polar surface distribution of their active site pockets, which may account for the observed differences in substrate specificity and the regio‐selectivity of VD3 hydroxylation.DatabaseThe atomic coordinates and structure factors have been deposited in the Protein Data Bank with accession code 5OFQ (substrate‐free CYP109A2).EnzymesCytochrome P450 monooxygenase CYP109A2, EC 1.14.14.1, UniProt ID: D5DF88, Ferredoxin, UniProt ID: D5DFQ0, cytochrome P450 reductase, EC 1.8.1.2, UniProt ID: D5DGX1.
Anticholinergic burden and dry mouth among Finnish, community‐dwelling older adults
Authors: Tiisanoja Antti , Syrjälä Anna‐Maija , Komulainen Kaija , Lampela Pasi , Hartikainen Sirpa , Taipale Heidi , Knuuttila Matti , Ylöstalo Pekka 
Published: September 2017

ObjectiveThe aim was to study whether the anticholinergic burden of drugs is related to xerostomia and salivary secretion among community‐dwelling elderly people.BackgroundAnticholinergic drugs have been shown to be a risk factor for dry mouth, but little is known about the effects of cumulative exposure to anticholinergic drugs measured by anticholinergic burden on salivary secretion or xerostomia.MethodsThe study population consisted of 152 community‐dwelling, dentate, non‐smoking, older people from the Oral Health GeMS study. The data were collected by interviews and clinical examinations. Anticholinergic burden was determined using the Anticholinergic Drug Scale (ADS). A Poisson regression model with robust error variance was used to estimate relative risks (RR) with 95% confidence intervals (CI 95%).ResultsParticipants with a high‐anticholinergic burden (ADS ≥ 3) were more likely to have xerostomia (RR: 3.17; CI: 1.44‐6.96), low‐unstimulated salivary flow (<0.1 mL/min; RR: 2.31, CI: 1.22‐4.43) and low‐stimulated salivary flow (<1.0 mL/min; RR: 1.50, CI: 0.80‐2.81) compared to reference group (ADS 0). In participants with a moderate anticholinergic burden (ADS 1‐2), all the risk estimates for xerostomia, unstimulated and stimulated salivary secretion varied between 0.55 and 3.13. Additional adjustment for the total number of drugs, antihypertensives and sedative load caused only slight attenuation of the risk estimates.ConclusionA high‐anticholinergic burden was associated with low‐unstimulated salivary secretion and xerostomia.
Lipid homeostasis and inflammatory activation are disturbed in classically activated macrophages with peroxisomal β‐oxidation deficiency
Authors: Geric Ivana , Tyurina Yulia Y. , Krysko Olga , Krysko Dmitri V. , De Schryver Evelyn , Kagan Valerian E. , Van Veldhoven Paul P. , Baes Myriam , Verheijden Simon 
Published: September 2017

SummaryMacrophage activation is characterized by pronounced metabolic adaptation. Classically activated macrophages show decreased rates of mitochondrial fatty acid oxidation and oxidative phosphorylation and acquire a glycolytic state together with their pro‐inflammatory phenotype. In contrast, alternatively activated macrophages require oxidative phosphorylation and mitochondrial fatty acid oxidation for their anti‐inflammatory function. Although it is evident that mitochondrial metabolism is regulated during macrophage polarization and essential for macrophage function, little is known on the regulation and role of peroxisomal β‐oxidation during macrophage activation. In this study, we show that peroxisomal β‐oxidation is strongly decreased in classically activated bone‐marrow‐derived macrophages (BMDM) and mildly induced in alternatively activated BMDM. To examine the role of peroxisomal β‐oxidation in macrophages, we used Mfp2−/− BMDM lacking the key enzyme of this pathway. Impairment of peroxisomal β‐oxidation in Mfp2−/− BMDM did not cause lipid accumulation but rather an altered distribution of lipid species with very‐long‐chain fatty acids accumulating in the triglyceride and phospholipid fraction. These lipid alterations in Mfp2−/− macrophages led to decreased inflammatory activation of Mfp2−/− BMDM and peritoneal macrophages evidenced by impaired production of several inflammatory cytokines and chemokines, but did not affect anti‐inflammatory polarization. The disturbed inflammatory responses of Mfp2−/− macrophages did not affect immune cell infiltration, as mice with selective elimination of MFP2 from myeloid cells showed normal monocyte and neutrophil influx upon challenge with zymosan. Together, these data demonstrate that peroxisomal β‐oxidation is involved in fine‐tuning the phenotype of macrophages, probably by influencing the dynamic lipid profile during macrophage polarization.
Investment and Exit under Uncertainty with Utility from Anticipation
Authors: Du Jianjun , Yang Jinqiang , Zou Zhentao 
Published: September 2017

AbstractThis paper explores investment and exit decisions under uncertainty when the entrepreneur has anticipatory utility, which leads to the time‐inconsistency problem. Our model predicts that anticipatory utility has ambiguous effects on the investment strategy, which depends on the form of the project’s payoff. Under a lump‐sum payoff, an entrepreneur with anticipatory utility will under‐invest. However, she prefers over‐investing if the project delivers a flow payoff. Moreover, the model predicts that an entrepreneur with anticipatory utility is more reluctant to abandon an existing project. Finally, our model provides theoretical support and alternative explanation for the empirical evidence that people procrastinate to terminate projects from the perspective of time‐inconsistent preferences.
Microribonucleic acid‐192 as a specific biomarker for the early diagnosis of diabetic kidney disease
Authors: Yang Xinyi , Liu Shuaihui , Zhang Rui , Sun Bei , Zhou Saijun , Chen Rui , Yu Pei 
Published: September 2017

AbstractAims/IntroductionTo evaluate the diagnostic value of microribonucleic acid (miR) as biomarkers in patients with diabetic kidney disease (DKD).Materials and MethodsA total of 230 diabetes mellitus patients and 53 healthy participants were enrolled, and the diabetes mellitus group was further divided into normoalbuminuria, microalbuminuria and large amount of albuminuria group. MiRs of serum and urine were quantificated using real‐time polymerase chain reaction. General clinical information was collected and analyzed for the risk factors. Cut‐off values of diagnosis sensitivity were determined by receiver operating characteristic curves and the Youden Index.ResultsCompared with the healthy participants, the expression of miR‐192 in serum decreased, whereas in urine it increased with the progression of DKD. The expression of both serum and urine miR‐126 increased in the diabetes mellitus group, but no significant change was obtained among the DKD groups. The area under the curve receiver operating characteristic of both serum and urine miR‐192 was higher than that of the albumin‐to‐creatinine ratio. Combined detection of urine and serum miR‐192 has a higher specificity and lower misdiagnosis rate.ConclusionsBoth serum and urinary miR‐192 could be a potential biomarker of DKD, playing a crucial role in the prevention and treatment of DKD.
Prolonged azathioprine treatment reduces the need for surgery in early Crohn's disease
Authors: Qiu Yun , Chen Bai‐Li , Feng Rui , Zhang Sheng‐Hong , He Yao , Zeng Zhi‐Rong , Ben‐Horin Shomron , Peyrin‐Biroulet Laurent , Mao Ren , Chen Min‐Hu 
Published: September 2017

AbstractBackground and AimWhether an early use of azathioprine (AZA) can alter the natural history of Crohn's disease (CD) remains debated. The aim of this study is to evaluate the impact of AZA on disease progression in a cohort of patients with early CD.MethodsThis longitudinal cohort study examined patients with early CD defined as disease duration ≤ 18 months and no previous use of disease‐modifying agents according to Paris definition. The primary outcome was the proportion of CD‐related intestinal surgery. Cox regression analysis was performed to identify potential predictive factors of CD progression.ResultsOne‐hundred and ninety patients with early CD were enrolled in the study. After a median follow‐up of 57 months (interquartile range, 31.3–76.2), 31 patients underwent abdominal surgeries, 48 patients were hospitalized, and 68 patients experienced clinical flares. The cumulative rate of remaining free of CD‐related bowel surgery, hospitalization, and flare at 5 years on AZA treatment was 0.65, 0.59, and 0.39, respectively. Three independent predictors of CD‐related operations were identified: prior bowel resection (hazard ratio [HR], 9.23; 95% confidence interval [CI] 3.67–23.23), smoker (HR, 4.0; 95% CI 1.38–11.65), and hemoglobin < 110 g/L at the time of initiation of AZA (HR, 4.36; 95% CI 1.80–10.58). Conversely, AZA treatment duration > 36 months (HR, 0.04; 95% CI 0.01–0.15) was associated with reduced CD‐related operations.ConclusionPrior bowel resection, smoking, and hemoglobin < 110 g/L at the time of initiation of AZA were risk factors associated with intestinal surgery in patients with early CD. However, prolonged use (≥ 36 months) of AZA was associated with a more favorable disease course of early CD.
THE STOREROOM AS PROMISE: The Discovery of the Ethnological Museum Depot as an Exhibition Method in the 1970s
Authors: Thiemeyer Thomas 
Published: September 2017

AbstractThis article concerns an exhibition format that I call the depot exhibition. These exhibitions are museum presentations that turn the depot into their subject matter. (“Visible storage” is the most well‐known variant.) While this approach to museum exhibition has a current appeal, especially in German‐speaking countries, it is not new. Its appearance in North America in the 1970s was connected with postcolonial debates and coincided with a controversial sociopolitical discourse in which the concept of the depot promised to solve the central problems of a particular type of museum: the ethnological museum. I argue that the concept of the depot exhibition had an effect on other types of museums because these kinds of exhibitions made promises that concerned museums in general. The concept is at the root of an influential reflexive museum praxis that is distinguished by self‐criticism and the relinquishment of authority from the museum to visitors.
In vitro biofilms and antifungal susceptibility of dermatophyte and non‐dermatophyte moulds involved in foot mycosis
Authors: Toukabri Nourchéne , Corpologno Serena , Bougnoux Marie‐Elisabeth , El Euch Dalenda , Sadfi‐Zouaoui Najla , Simonetti Giovanna 
Published: September 2017

SummaryTinea pedis and onychomycosis are among the commonest fungal diseases in the world. Dermatophytes and, less frequently, non‐dermatophyte moulds are aetiological agents of foot mycosis and are capable of forming biofilms. Fungal biofilm has demonstrated increasing drug resistance. This work aims to evaluate, in vitro, the ability to form biofilm and the susceptibility to antifungal drugs of sessile dermatophytes and non‐dermatophyte moulds involved in foot mycosis. Thirty‐six dermatophytes and non‐dermatophyte moulds isolated from Tunisian patients with foot mycoses, and identified with MALDI‐TOF have been tested. MICs of fluconazole, econazole, itraconazole, terbinafine and griseofulvin were carried out using CLSI broth microdilution method. The ability to form biofilm and antifungal activities of drugs against fungal biofilm formation has been quantified by Crystal Violet and Safranin Red staining. Biomass quantification revealed that all species studied were able to form biofilms in vitro after 72 hours. Fluconazole, econazole, itraconazole and terbinafine inhibited fungal growth with MIC values ranging from 0.031 to >64 μg mL−1. The best antifungal activity has been obtained with terbinafine against Fusarium solani. Econazole showed the highest activity against fungal biofilm formation. These findings can help clinicians to develop the appropriate therapy of foot mycosis.
Rosuvastatin pretreatment suppresses distant organ injury following unilateral renal ischemia‐reperfusion in hypertensive Dahl salt‐sensitive rats
Authors: Kanno Makoto , Nakayama Masaaki , Zhu Wan‐Jun , Hayashi Yoshimitsu , Kazama Junichiro J 
Published: September 2017

ABSTRACTAimIschaemia‐reperfusion (I/R) induces distant organ injury (DOI) via inflammation and oxidative stress. Statins have anti‐inflammatory and anti‐oxidant effects independent of their cholesterol‐lowering properties. To clarify whether statins could suppress DOI, we investigated the effect of rosuvastatin (RO) on the contralateral kidney following unilateral renal I/R.MethodsDahl salt‐sensitive rats (6 weeks old) were randomly divided into four groups: sham, sham with RO, I/R, and I/R with RO. All rats were fed a high‐salt (8%) diet for 6 weeks. RO (10 mg/kg per day) was pre‐administered by supplementation to the drinking water for 2 weeks before I/R. The rats then underwent unilateral renal I/R (ischemia for 45 min). Three days after I/R, laboratory data, histological changes and protein expression levels of the contralateral kidney were assessed.ResultsI/R significantly elevated serum creatinine and malondialdehyde levels and induced a significantly higher glomerular sclerosis index and tubular dilation area of the contralateral kidney, with about 2‐fold infiltration of ED‐1‐positive cells. In the I/R group, protein expression of superoxide dismutase (SOD) of the contralateral kidney was reduced to about 50% of the sham group. RO‐pretreatment significantly suppressed all of these changes following I/R.ConclusionRO‐pretreatment diminished contralateral kidney injury with the suppression of ED‐1‐positive cell infiltration and SOD reduction after I/R. RO appears to have a protective effect on DOI by its anti‐inflammatory and anti‐oxidant effects.
Comparison between small bowel manometric patterns and full‐thickness biopsy histopathology in severe intestinal dysmotility
Authors: Malagelada C. , Karunaratne T. B. , Accarino A. , Cogliandro R. F. , Landolfi S. , Gori A. , Boschetti E. , Malagelada J. R. , Stanghellini V. , Azpiroz F. , De Giorgio R. 
Published: September 2017

AbstractBackgroundIntestinal manometry is the current standard for direct evaluation of small bowel dysmotility. Patients with abnormal motility can either be diagnosed of pseudo‐obstruction when there are radiological findings mimicking mechanical intestinal obstruction or of enteric dysmotility when these findings are absent. The aim of the present study was to prospectively compare small bowel manometric abnormalities with histopathological findings in intestinal full‐thickness biopsies in patients with severe dysmotility disorders.MethodsWe investigated 38 patients with intestinal manometry and a subsequent full‐thickness intestinal biopsy. Manometric recordings were read by 4 investigators and a diagnostic consensus was obtained in 35 patients. Histopathological analysis, including specific immunohistochemical techniques of small bowel biopsies was performed and compared to manometric readings.Key ResultsPatients with abnormal intestinal manometry had abnormal histopathological findings in 73% of cases. However, manometric patterns did not match with the specific neuromuscular abnormalities. Among patients with a neuropathic manometry pattern and abnormal histopathology, only 23% had an enteric neuropathy, whereas 62% had neuromuscular inflammation, and 15% an enteric myopathy. On the other hand, patients with a myopathic manometry pattern all had abnormal histopathology, however, none of them with signs of enteric myopathy.Conclusion & InferencesSmall bowel dysmotility detected by intestinal manometry is often associated with abnormal neuromuscular findings in full‐thickness biopsies. However, there is no correlation between the specific manometric patterns and the histopathological findings.
Eruptive milia during isotretinoin therapy
Authors: Farmer William , Cheng Kyle , Marathe Kalyani 
Published: September 2017

AbstractIsotretinoin (13‐cis‐retinoic acid) is a synthetic vitamin A derivative that is effective in the treatment of recalcitrant, nodulocystic acne. To our knowledge, there are no reports in the medical literature of milia as a side effect of isotretinoin. We report a case of eruptive facial milia in the setting of isotretinoin treatment for acne.
The Buck Stops with the Education Mayor: Mayoral Control and Local Test Scores in U.S. Urban Mayoral Elections
Authors: Lay J. Celeste , Tyburski Michael D. 
Published: September 2017

Several U.S. cities have turned control of their schools from elected boards to the mayor. Advocates of mayoral control have argued that this structure allows voters to hold the mayor directly accountable for the performance of local schools. Now that public schools have to report their test scores each year, it is possible for voters to attribute responsibility for test scores. This article analyzes survey data from 16 cities in the United States that have been matched with data on test scores. We find that, in general, test score changes are not associated with support for incumbent mayors, except in districts with mayoral control, where voters reward incumbents when test scores rise. Further, voters' beliefs about local schools condition their support for the incumbent. In cities with mayoral control, voters who evaluate schools positively reward mayors while voters who believe their schools are poor are not swayed by this positive information.Related Articles

Ertas, Nevbahar. 2015. “.” Politcs & Policy 43 (): 426‐451. http://onlinelibrary.wiley.com/doi/10.1111/polp.12120/abstract

Roch, Christine, and
Amanda Wilsker. 2010. “.” Politics & Policy 38 (): 1187‐1210. http://onlinelibrary.wiley.com/doi/10.1111/j.1747-1346.2010.00274.x/abstract

Webber, David J. 2010. “.” Politics & Policy 38 (): 81‐95. http://onlinelibrary.wiley.com/doi/10.1111/j.1747-1346.2009.00229.x/full
Related Media
. 2017. “Make the Mayor Accountable for the Schools.” February 23. http://www.baltimoresun.com/news/opinion/editorial/bs-ed-city-schools-20170223-story.html

Fertig, Beth. 2013. “After 12 Years of Bloomberg, Data Reigns in the Schools.” WNYC. http://www.wnyc.org/story/303900-bloombergs-schools-legacy-use-data/
Optimality of (s, S) Inventory Policies under Renewal Demand and General Cost Structures
Authors: Perera Sandun , Janakiraman Ganesh , Niu Shun‐Chen 
Published: September 2017

We study a single‐stage, continuous‐time inventory model where unit‐sized demands arrive according to a renewal process and show that an ( s, S) policy is optimal under minimal assumptions on the ordering/procurement and holding/backorder cost functions. To our knowledge, the derivation of almost all existing ( s, S)‐optimality results for stochastic inventory models assume that the ordering cost is composed of a fixed setup cost and a proportional variable cost; in contrast, our formulation allows virtually any reasonable ordering‐cost structure. Thus, our paper demonstrates that ( s, S)‐optimality actually holds in an important, primitive stochastic setting for all other practically interesting ordering cost structures such as well‐known quantity discount schemes (e.g., all‐units, incremental and truckload), multiple setup costs, supplier‐imposed size constraints (e.g., batch‐ordering and minimum‐order‐quantity), arbitrary increasing and concave cost, as well as any variants of these. It is noteworthy that our proof only relies on elementary arguments.
Predictors and moderators of quality of life in caregivers of amputee patients by type 2 diabetes
Authors: Alves Costa Maria Suely , Pereira Maria Graça 
Published: September 2017

BackgroundThe amputation of a foot or a leg is one of the complications caused by diabetes that creates fear. After the amputation, the patient becomes dependent on a caregiver, who is often not prepared for this new phase of life. Knowing the factors that influence care delivery in caregivers of amputee type 2 diabetes patients is important from an heuristic point of view, since very few studies have focused on this population.ObjectivesThis study analysed the predictors and moderators of quality of life, in caregivers of amputee patients due to type 2 diabetes.MethodsThis study has a cross‐sectional design. All ethical standards were followed in the conduct of this study. The sample comprised 101 caregivers who answered the following instruments: Carer's Assessment of Managing Index, Burden Assessment Scale, Depression Anxiety Stress Scales, Revised Impact of Events Scale, Family Assessment Device, Family Disruption from Illness Scale and the Short Form Health Survey‐36.ResultsThe practice of physical activity, lower burden, better family functioning and less traumatic symptoms were predictors of better mental quality of life. Having no chronic disease and less physical symptoms predicted better physical quality of life. Duration of care moderated the relationship between traumatic symptoms and mental quality of life, but not with physical quality of life. Receiving help in caregiving moderated the relationship between traumatic symptoms and mental quality of life. The limitations of this study include the exclusive use of self‐report instruments and the fact that the caregivers who have participated in this study were those who accompanied the patient to the hospital.ConclusionIn order to promote physical quality of life, future intervention programmes should consider the presence of chronic disease in the caregiver and the duration of care, as well as the caregivers’ physical symptoms.