Covering up to 2013. Cofactor-dependent enzymes which need small organic molecule cofactors to accomplish enzymatic activity are widespread. The number of newly discovered reactions within ...cofactor-dependent enzyme families increases continuously. A knowledge based categorization of cofactors with respect to their chemical properties shows that within enzymes they are not used for the catalysis of singular types of reactions and functionalities. Therefore, in many cases an unambiguous and narrow classification does not seem sufficient. Rather, the functional diversity of cofactors found in enzymes represents variations around specific themes with regard to a catalysed reaction and the cofactor chemistry. Furthermore, organic cofactor molecules are also used for non-enzymatic functions. Two representative cofactors are exemplarily discussed in detail, thiamin diphosphate (ThDP) as a self-sufficient cofactor and S-adenosyl-L-methionine (SAM), as both a catalytic and building-block-delivering cofactor. A further synopsis on selected examples of organic cofactors emphasizes the discovery and application of new enzymatic activities based on the cofactor-dependent chemistry and shows how bioinspired synthesis approaches expand catalytic and non-catalytic synthesis applications beyond natural solutions.
Jungen als Bildungsverlierer: So werden sie im öffentlichen wie auch im wissenschaftlichen Diskurs derzeit primär wahrgenommen. Zu erklären ist diese Zuschreibung vor dem Hintergrund von Befunden ...z.B. hinsichtlich des prozentualen Anteils an weiterführenden Schularten, erreichten Schulabschlüssen, aber auch den Ergebnissen in internationalen und nationalen Schulleistungsuntersuchungen. Eine besondere Rolle nehmen die männlichen Heranwachsenden ein, deren Lebenswirklichkeit von Risikolagen, wie etwa elterlicher Arbeitslosigkeit, Bildungsferne, oder einem Zuwanderungshintergrund geprägt wird. Der Autor setzt sich daher mit der Frage auseinander, welche Faktoren eine erwartungswidrig bildungserfolgreiche Entwicklung trotz negativer Rahmenbedingungen begünstigen. Auf Basis autobiografisch-narrativer Interviews werden die handlungsleitenden Orientierungen von Jungen und jungen Männern herausgearbeitet, die erfolgreich an formalen und non-formalen Bildungssettings partizipieren.; Boys as underachievers in school: This is how they are currently perceived in public and academic discourse. This attribution can be explained against the background of findings, for example, regarding the percentage of boys attending secondary schools or the school-leaving qualifications achieved. The author asks which factors favour a development that is contrary to expectations and successful in terms of education, despite negative framework conditions. On the basis of autobiographical narrative interviews, orientations guiding male adolescents' actions are elaborated.
DNA-DNA hybridization (DDH) has been used for nearly 50 years as the gold standard for prokaryotic species circumscriptions at the genomic level. It has been the only taxonomic method that offered a ...numerical and relatively stable species boundary, and its use has had a paramount influence on how the current classification has been constructed. However, now, in the era of genomics, DDH appears to be an outdated method for classification that needs to be substituted. The average nucleotide identity (ANI) between two genomes seems the most promising method since it mirrors DDH closely. Here we examine the work package JSpecies as a user-friendly, biologist-oriented interface to calculate ANI and the correlation of the tetranucleotide signatures between pairwise genomic comparisons. The results agreed with the use of ANI to substitute DDH, with a narrowed boundary that could be set at almost equal to95-96%. In addition, the JSpecies package implemented the tetranucleotide signature correlation index, an alignment-free parameter that generally correlates with ANI and that can be of help in deciding when a given pair of organisms should be classified in the same species. Moreover, for taxonomic purposes, the analyses can be produced by simply randomly sequencing at least 20% of the genome of the query strains rather than obtaining their full sequence.
JSpecies Web Server (JSpeciesWS) is a user-friendly online service for in silico calculating the extent of identity between two genomes, a parameter routinely used in the process of polyphasic ...microbial species circumscription. The service measures the average nucleotide identity (ANI) based on BLAST+ (ANIb) and MUMmer (ANIm), as well as correlation indexes of tetra-nucleotide signatures (Tetra). In addition, it provides a Tetra Correlation Search function, which allows to rapidly compare selected genomes against a continuously updated reference database with currently about 32 000 published whole and draft genome sequences. For comparison, own genomes can be uploaded and references can be selected from the JSpeciesWS reference database. The service indicates whether two genomes share genomic identities above or below the species embracing thresholds, and serves as a fast way to allocate unknown genomes in the frame of the hitherto sequenced species.
JSpeciesWS is available at http://jspecies.ribohost.com/jspeciesws
Supplementary data are available at Bioinformatics online.
mrichter@ribocon.com.
Adenosine‐5′‐triphosphate‐dependent enzyme catalysed reactions are widespread in nature. Consequently, the enzymes involved have an intrinsic potential for use in syntheses of high value products. ...Although regeneration systems for ATP starting from adenosine‐5′‐diphosphate are available, certain limitations exist for both in vitro and in vivo applications requiring ATP regeneration from adenosine‐5′‐monophosphate, or adenosine. Following a short overview of the chemical and thermodynamic background, this Minireview focuses on emerging enzymes and methodologies for ATP regeneration. A large range of as yet unexploited reactions will be accessible with new, powerful, multistep ATP regeneration systems that use cheap phosphate donors and provide high longevity, compatibility, and robustness under process conditions. Their potential might go far beyond the direct use of ATP in enzymatic reactions; enzyme discovery, and engineering, as well as immobilisation strategies, will help to realise such systems.
New energy sources: The development of flexible and efficient multistep ATP regeneration systems could make a range of as yet unexploited biocatalytic reactions accessible for technical applications. Their potential might go far beyond the direct use of ATP in enzymatic reactions.
Objective
To describe the prevalence, clinical presentation, and management of rheumatic immune‐related adverse effects (Rh‐irAEs) from immune checkpoint inhibitor (ICI) therapy.
Methods
From a ...database of all patients who received any ICI at the Mayo Clinic Rochester, Minnesota campus between January 1, 2011 and March 1, 2018, we retrospectively identified those with Rh‐irAEs, using diagnostic codes, search terms, and manual chart review.
Results
Of the 1,293 patients who received any ICI, Rh‐irAEs were clinically diagnosed in 43. Eighteen patients with Rh‐irAEs who received ICI therapy elsewhere were also analyzed. Clinical syndromes included inflammatory arthritis (n = 34 prevalence 2%), myopathy (n = 10), and other rheumatic syndromes (n = 17). Inflammatory arthritis was most commonly polyarticular, and glucocorticoid treatment was required in 26 patients (76%). The mean ± SD duration of treatment was 18 ± 18 weeks. Five patients (15%) also received disease‐modifying antirheumatic drugs, and ICI therapy had to be discontinued in 3 patients (9%). Myopathy was treated with glucocorticoids in all cases (mean ± SD treatment duration 15 ± 17 weeks) and led to 2 deaths and permanent ICI discontinuation in 9 patients (90%). Other syndromes included connective tissue diseases, vasculitis, polymyalgia rheumatica–like syndrome, and flare of preexisting rheumatic disease. Most (71%) were treated with immunosuppression, with 12% requiring ICI discontinuation.
Conclusion
This study represents the largest cohort of patients with Rh‐irAEs reported to date. Most patients received long courses of immunosuppressive treatment, although discontinuation of ICI therapy was required in only a minority.
Objective
To determine the risk of rheumatic disease flare and adverse effects in patients with preexisting rheumatic disease who were receiving immune checkpoint inhibitor (ICI) therapy.
Methods
A ...retrospective medical record review was performed to identify all patients who received ICI therapy at Mayo Clinic in Rochester, Minnesota between 2011 and 2016 (~700 patients). Those with a preexisting rheumatic disease were identified using specific diagnostic codes.
Results
Sixteen patients were identified (81% female, median age 68.5 years). The most common rheumatic diseases were rheumatoid arthritis (n = 5), polymyalgia rheumatica (n = 5), Sjögren's syndrome (n = 2), and systemic lupus erythematosus (n = 2). Seven patients were receiving immunosuppressive therapy or glucocorticoids for their rheumatic disease at the time of initiation of the ICI. The primary malignancies were melanoma (n = 10), pulmonary (n = 4), or hematologic (n = 2). In most cases, ICIs were offered only after failure of several other therapies. Immune‐related adverse effects (IRAEs) occurred in 6 patients, and all were treated successfully with glucocorticoids and discontinuation of the ICI therapy. There were no significant differences in time from cancer diagnosis to immunotherapy, duration of immunotherapy, age, or sex between the patients with and those without IRAEs.
Conclusion
To our knowledge, this represents the largest single‐center cohort of patients with rheumatic diseases who were exposed to modern cancer immunotherapy. Only a minority of these patients experienced a flare of their preexisting rheumatic disease or any other IRAE.
Numerous studies on democratic backsliding mostly focus on the state executive as a driving force. In contrast, the analysis presented here highlights the role of vested interests as the main actors ...behind backsliding processes in hybrid regimes. In a focused case study of anti‐corruption reforms in Ukraine, this contribution analyses the initiation of backsliding by these actors through their influence on nominally independent branches of power as well as the subtle takeover of the legislative repair process that followed. The case study is based on original semi‐structured expert interviews and document analysis. The main argument is that the distinct role played by the state executive also substantially changes the interaction between the actors involved. For the case of Ukraine, the study shows that the leverage of Western organisations in conjunction with the expertise and swift reaction of Ukrainian civil society organisations constitute a necessary precondition for the containment of backsliding attempts.
Objective
To identify risk factors for large‐joint surgery (LJS) versus small‐joint surgery (SJS) in rheumatoid arthritis (RA) and evaluate trends in surgery rates over time.
Methods
A retrospective ...medical record review of all orthopedic surgeries following first fulfillment of the 1987 American College of Rheumatology criteria for adult‐onset RA among residents of Olmsted County, Minnesota between 1980 and 2013 was performed. Risk factors were examined using Cox models adjusted for age, sex, and calendar year of RA incidence. Trends in incidence of joint surgeries were examined using Poisson regression models.
Results
A total of 1,077 patients with RA (mean age 56 years, 69% female, 66% seropositive for rheumatoid factor RF and anti–cyclic citrullinated peptide anti‐CCP antibodies) were followed for a median of 10.7 years, during which 112 patients (90 women) underwent at least 1 SJS and 204 (141 women) underwent at least 1 LJS. Risk factors included advanced age, and RF and anti‐CCP antibody positivity for both SJS and LJS, and body mass index ≥30 kg/m2 for LJS. Risk factors for SJS and LJS at any time during followup included the presence of radiographic erosions, large‐joint swelling, and methotrexate use. SJS rates decreased by calendar year of incidence (hazard ratio 0.53, P = 0.001), with significant decline in the rates of SJS after 1995. The cumulative incidence of SJS was higher in women than men (P = 0.008).
Conclusion
In recent years, there has been a significant decline in the rates of SJS but not LJS in patients with RA. The incidence of SJS is higher among women. Traditional RA risk factors are strong predictors for SJS and LJS. Increasing age and obesity are predictive of LJS.
Stable personality dispositions, like motives, are often assumed to exert a direct, stable impact on behavior. This also applies to the explicit achievement motive, which is supposed to influence the ...behavior that individuals select and how strongly they engage in it. Drawing on motivational intensity theory, we demonstrated in two studies that explicit achievement motive strength only predicted exerted force in a hand grip task if task difficulty was unclear. If task difficulty was clear, explicit achievement motive strength did not influence exerted force. Our findings suggest that the availability of information about the difficulty of motive satisfaction moderates the impact of the explicit achievement motive on behavior.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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