While the link between servant leadership and organizational citizenship behavior (OCB) has been established, the individual-level mechanisms underlying this relationship and its boundary conditions ...remain poorly understood. In this study, we investigate the salience of the mediating mechanisms of leader-member exchange (LMX) and psychological empowerment in explaining the process by which servant leaders elicit discretionary OCB among followers. We also examine the role of followers' proactive personality in moderating the indirect effects of servant leadership on OCB through LMX and psychological empowerment. Analysis of survey data collected from 446 supervisor-subordinate dyads in a large Chinese stateowned enterprise suggests that while servant leadership is positively related to subordinate OCB through LMX, psychological empowerment does not explain any additional variance in OCB above that accounted for by LMX. Moderated mediation tests confirm the moderating effect of proactive personality through LMX. By providing a nuanced understanding of how and when servant leadership leads followers to go above and beyond their job role, our study assists organizations in deciding how to develop and utilize servant leaders in their organizations.
The molybdenum cofactor (Moco) forms the active site of all molybdenum (Mo) enzymes, except nitrogenase. Mo enzymes catalyze important redox reactions in global metabolic cycles. Moco consists of Mo ...covalently bound to one or two dithiolates attached to a unique tricyclic pterin moiety commonly referred to as molybdopterin (MPT). Moco is synthesized by an ancient and conserved biosynthetic pathway that can be divided into four steps, according to the biosynthetic intermediates precursor Z (cyclic pyranopterin monophosphate), MPT and adenylated MPT. In a fifth step modifications such as attachment of nucleotides, sulfuration or bond formation between Mo and the protein result in different catalytic Mo centers. A defect in any of the steps of Moco biosynthesis results in the pleiotropic loss of all Mo enzyme activities. Human Moco deficiency is a hereditary metabolic disorder characterized by severe neurodegeneration resulting in early childhood death. Recently, a first substitution therapy was established.
We describe a titanocene(III)‐catalyzed deuterosilylation of epoxides that provides β‐deuterated anti‐Markovnikov alcohols with excellent D‐incorporation, in high yield, and often excellent ...diastereoselectivity after desilylation. The key to the success of the reaction is a novel activation method of Cp2TiCl2 and (tBuC5H4)2TiCl2 with BnMgBr and PhSiD3 to provide (RC5H4)2Ti(III)D without isotope scrambling. It was developed after discovering an off‐cycle scrambling with the previously described method. Our precision deuteration can be applied to the synthesis of drug precursors and highlights the power of combining radical chemistry with organometallic catalysis.
Titanocene catalysis delivers D to the more substituted C‐atom of epoxides with high efficiency, deuterium incorporation, and stereoselectivity. A novel method of catalyst activation that prevents isotope scrambling warrants the excellent performance of the reaction.
Understanding how antibiotics impact bacterial metabolism may provide insight into their mechanisms of action and could lead to enhanced therapeutic methodologies. Here, we profiled the metabolome of ...Escherichia coli after treatment with three different classes of bactericidal antibiotics (β-lactams, aminoglycosides, quinolones). These treatments induced a similar set of metabolic changes after 30 min that then diverged into more distinct profiles at later time points. The most striking changes corresponded to elevated concentrations of central carbon metabolites, active breakdown of the nucleotide pool, reduced lipid levels, and evidence of an elevated redox state. We examined potential end-target consequences of these metabolic perturbations and found that antibiotic-treated cells exhibited cytotoxic changes indicative of oxidative stress, including higher levels of protein carbonylation, malondialdehyde adducts, nucleotide oxidation, and double-strand DNA breaks. This work shows that bactericidal antibiotics induce a complex set of metabolic changes that are correlated with the buildup of toxic metabolic by-products.
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•Diverse bactericidal antibiotics induced similar metabolic changes•Bactericidal antibiotics induced biomarkers of oxidative stress•Bactericidal antibiotics induced dsDNA breaks
Belenky et al. profile the metabolome of Escherichia coli after treatment with different classes of bactericidal antibiotics and find that these treatments induce a similar set of metabolic changes. Antibiotic-treated cells were also found to exhibit cytotoxic changes indicative of oxidative stress. This insight could lead to enhanced therapeutic methodologies.
Bacteriostatic and bactericidal antibiotic treatments result in two fundamentally different phenotypic outcomesâthe inhibition of bacterial growth or, alternatively, cell death. Most antibiotics ...inhibit processes that are major consumers of cellular energy output, suggesting that antibiotic treatment may have important downstream consequences on bacterial metabolism. We hypothesized that the specific metabolic effects of bacteriostatic and bactericidal antibiotics contribute to their overall efficacy. We leveraged the opposing phenotypes of bacteriostatic and bactericidal drugs in combination to investigate their activity. Growth inhibition from bacteriostatic antibiotics was associated with suppressed cellular respiration whereas cell death from most bactericidal antibiotics was associated with accelerated respiration. In combination, suppression of cellular respiration by the bacteriostatic antibiotic was the dominant effect, blocking bactericidal killing. Global metabolic profiling of bacteriostatic antibiotic treatment revealed that accumulation of metabolites involved in specific drug target activity was linked to the buildup of energy metabolites that feed the electron transport chain. Inhibition of cellular respiration by knockout of the cytochrome oxidases was sufficient to attenuate bactericidal lethality whereas acceleration of basal respiration by genetically uncoupling ATP synthesis from electron transport resulted in potentiation of the killing effect of bactericidal antibiotics. This work identifies a link between antibiotic-induced cellular respiration and bactericidal lethality and demonstrates that bactericidal activity can be arrested by attenuated respiration and potentiated by accelerated respiration. Our data collectively show that antibiotics perturb the metabolic state of bacteria and that the metabolic state of bacteria impacts antibiotic efficacy.
Schistosomiasis is a common disease in endemic areas of Sub-Saharan Africa, South America and Asia. It is rare in Europe, mainly imported from endemic countries due to travelling or human migration. ...Available methods for the diagnosis of schistosomiasis comprise microscopic, molecular and serological approaches, with the latter detecting antigens or antibodies associated with Schistosoma spp. infection. The serological approach is a valuable screening tool in low-endemicity settings and for travel medicine, though the interpretation of any diagnostic results requires knowledge of test characteristics and a patient's history.
Specific antibody detection by most currently used assays is only possible in a relatively late stage of infection and does not allow for the differentiation of acute from previous infections for therapeutic control or the discrimination between persisting infection and re-infection. Throughout the last decades, new target antigens have been identified, and assays with improved performance and suitability for use in the field have been developed. For numerous assays, large-scale studies are still required to reliably characterise assay characteristics alone and in association with other available methods for the diagnosis of schistosomiasis. Apart from S. mansoni, S. haematobium and S. japonicum, for which most available tests were developed, other species of Schistosoma that occur less frequently need to be taken into account.
This narrative review describes and critically discusses the results of published studies on the evaluation of serological assays that detect antibodies against different Schistosoma species of humans. It provides insights into the diagnostic performance and an overview of available assays and their suitability for large-scale use or individual diagnosis, and thus sets the scene for serological diagnosis of schistosomiasis and the interpretation of results.
•Narrative review on evaluated published serological assays for detection of antibodies against different Schistosoma spp.•Overview on diagnostic performance and value, availability and suitability for large-scale use.•Serological diagnosis is valuable for schistosomiasis control in low endemicity settings and for travel medicine.•The establishment of a sensitive and specific gold standard could facilitate future evaluation studies.
Deeper understanding of antibiotic-induced physiological responses is critical to identifying means for enhancing our current antibiotic arsenal. Bactericidal antibiotics with diverse targets have ...been hypothesized to kill bacteria, in part by inducing production of damaging reactive species. This notion has been supported by many groups but has been challenged recently. Here we robustly test the hypothesis using biochemical, enzymatic, and biophysical assays along with genetic and phenotypic experiments. We first used a novel intracellular H ₂O ₂ sensor, together with a chemically diverse panel of fluorescent dyes sensitive to an array of reactive species to demonstrate that antibiotics broadly induce redox stress. Subsequent gene-expression analyses reveal that complex antibiotic-induced oxidative stress responses are distinct from canonical responses generated by supraphysiological levels of H ₂O ₂. We next developed a method to quantify cellular respiration dynamically and found that bactericidal antibiotics elevate oxygen consumption, indicating significant alterations to bacterial redox physiology. We further show that overexpression of catalase or DNA mismatch repair enzyme, MutS, and antioxidant pretreatment limit antibiotic lethality, indicating that reactive oxygen species causatively contribute to antibiotic killing. Critically, the killing efficacy of antibiotics was diminished under strict anaerobic conditions but could be enhanced by exposure to molecular oxygen or by the addition of alternative electron acceptors, indicating that environmental factors play a role in killing cells physiologically primed for death. This work provides direct evidence that, downstream of their target-specific interactions, bactericidal antibiotics induce complex redox alterations that contribute to cellular damage and death, thus supporting an evolving, expanded model of antibiotic lethality.
Immediate lymphatic reconstruction (ILR), performed at the time of axillary lymph node dissection (ALND), has demonstrated promising reductions in breast cancer-associated lymphedema. However, ...questions remain over the effects of adjuvant therapies on the continued patency of the lymphaticovenous anastomosis. Our study aimed to assess lymphographic outcomes, including ICG pattern and LVB patency, in patients at high risk for breast cancer-associated lymphedema following axillary ILR.
Baseline ICG lymphography studies performed during ILR of 15 patients were compared to repeat ICG studies obtained during second-stage breast reconstructive procedures to assess for changes in lymphatic flow patterns through the at-risk arm and transit into the axilla.
All 15 patients in this study demonstrated linear lymphatic flow in baseline lymphography. Repeat lymphographic studies showed linear lymphatic transit in 12/15 patients. Of these 12 patients, 10 received chemotherapy, and all 12 received post-mastectomy radiation (PMRT). Dermal backflow patterns were recorded in 3/15 patients. All 3 patients received chemotherapy and 2/3 underwent PMRT. Additionally, repeat ICG studies of 7/12 lymphedema-free patients demonstrated clear visualization of linear ICG flow from the lymphatics of the arm into the axilla.
We have demonstrated that ICG lymphography can be implemented as a postoperative tool to assess lymphatic function in patients who have undergone ILR in the axilla. Repeat ICG studies in the majority of patients demonstrated linear ICG flow similar to baseline studies. Additionally, ICG flow patterns through the axilla in repeat lymphography provided visual evidence supporting sustained LVB patency, despite axillary irradiation.
► We review result-oriented agri-environmental schemes (roAES) in Europe. ► We analyse their success in promoting behavioural change. ► We present a framework for defining ‘strong’ and ‘weak’ forms ...of roAESs. ► We discuss the future of this approach in Europe.
Increasing interest is being shown in result-oriented agri-environmental schemes. Such schemes have the advantage of encouraging farmers to innovate to produce environmental goods – thus promoting the development of new skills and knowledge and, theoretically, ensuring that farmers are paid for provision rather than for performing management behaviours that may, or may not, lead to provision. In Europe a number of projects have trialled result-based payments over the last decade and calls for a stronger connection between agri-environmental payments and outcomes are growing. However, while the amount of information available on result-oriented schemes is increasing, there is currently no overview of the approach in the literature. This paper seeks to address this gap through a review of existing literature. It discusses why we might consider the use of result-oriented schemes, outlines two key ‘problem areas’ (the increased risk schemes represent to farmers, and the difficulties of developing and monitoring indicators), and, finally, proposes a framework for examining the strength of results orientation based on three dimensions – proportion of result-oriented payments, sensitivity of payments, and duration of schemes/payments. Although economic and ecological arguments are outlined, our focus in the analysis is on how the result-oriented approach is likely to institute cultural/social change, and how to optimise schemes to ensure cultural embeddedness.
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