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Structural definition of the lysine swing in Arabidopsis thaliana PDX1
Vitamin B₆ is indispensible for all organisms, notably as the coenzyme form pyridoxal 5′-phosphate. Plants make the compound de novo using a relatively simple pathway comprising pyridoxine synthase (PDX1) and pyridoxine glutaminase (PDX2). PDX1 is remarkable given its multifaceted synthetic ability to carry out isomerization, imine formation, ammonia addition, aldol-type condensation, cyclization, and aromatization, all in the absence of coenzymes or recruitment of specialized domains. Two active sites (P1 and P2) facilitate the plethora of reactions, but it is not known how the two are coordinated and, moreover, if intermediates are tunneled between active sites. Here we present X-ray structures of PDX1.3 from Arabidopsis thaliana, the overall architecture of which is a dodecamer of (β/α)₈ barrels, similar to the majority of its homologs. An apoenzyme structure revealed that features around the P1 active site in PDX1.3 have adopted inward conformations consistent with a catalytically primed state and delineated a substrate accessible cavity above this active site, not noted in other reported structures. Comparison with the structure of PDX1.3 with an intermediate along the catalytic trajectory demonstrated that a lysine residue swings from the distinct P2 site to the P1 site at this stage of catalysis and is held in place by a molecular catch and pin, positioning it for transfer of serviced substrate back to P2. The study shows that a simple lysine swinging arm coordinates use of chemically disparate sites, dispensing with the need for additional factors, and provides an elegant example of solving complex chemistry to generate an essential metabolite.
Journal Article
Organizations are people: reflections, obstacles and learning opportunities
Purpose
The purpose of this paper is to place the idea of the learning organization in a historical, multidisciplinary context with the aim of identifying obstacles and opportunities for its greater realization in practice.
Design/methodology/approach
Marking the 30th anniversary of publication of Peter Senge's “The Fifth Discipline”, the paper reflects on approaches to the study and analysis of organizations over the past century from German sociology, human relations, organization development, the learning organization to responses to the Covid-19 pandemic.
Findings
It is suggested that distributed leadership is critical to the realization of organizational learning and its absence is a major inhibitor of such learning. Following Argyris, it is argued that high levels of skill (personal mastery) may, in some circumstances, provide a barrier to organizational learning in the face of contextual uncertainty and change.
Research limitations/implications
While no specific areas of research are proposed, questions are raised which may only be answered in the wake of appropriate (interdisciplinary) research.
Practical implications
The reflective nature of the paper suggests that significant reform is required in the legislation that encourages short-term thinking on the part of institutional investors to the detriment of strategic thinking and long-term planning.
Social implications
The Covid-19 pandemic seems to have provided an opportunity to redress a perceived imbalance between traditional organizational thinking and opportunities demonstrated by effective community action, for reappraisal of organizations as communities of people as well as being formalized structures, systems and processes.
Originality/value
This paper seeks to synthesize diverse theories of organization with the aim of stimulating further innovation in approaches to organizational learning.
Journal Article
Randomized Trial of the SMART Stent versus Balloon Angioplasty in Long Superficial Femoral Artery Lesions: The SUPER Study
Purpose
To determine whether primary stenting reduces the rate of restenosis compared with balloon angioplasty alone in the endovascular treatment of long superficial femoral artery lesions; and to assess the effect of treatment on quality of life.
Methods
A total of 150 patients with superior femoral artery occlusion or severe stenosis of 5–22 cm length from 17 UK centers were randomized to either primary stenting with the SMART stent or balloon angioplasty (i.e., percutaneous transluminal angioplasty, PTA). Bailout stent placement was permitted in case of inadequate result from PTA. The primary end point was restenosis measured by duplex ultrasound at 1 year. Quality-of-life assessments were performed by the EuroQol (EQ)-5D questionnaire.
Results
Mean lesion length was 123.0 mm in the stent group and 116.8 mm in the PTA group. A total of 140 (93.3 %) of 150 had total occlusions. At 12 months’ follow-up, restenosis measured by Duplex ultrasound was not significantly different between the stent and PTA groups by intention-to-treat or as-treated analyses: 47.2 versus 43.5 % (
p
= 0.84) and 40.8 versus 46.7 % (
p
= 0.68), respectively. There were fewer target lesion revascularizations in patients randomized to stenting, but this did not reach statistical significance (12.5 vs. 20.8 %,
p
= 0.26). There was no difference in the rate of amputation. Patients in both groups reported improved quality of life.
Conclusion
Primary stenting of long lesions in predominantly occluded superficial femoral arteries does not reduce the rate of binary restenosis compared with balloon angioplasty and bailout stenting. Both treatment strategies conferred a meaningful and sustained improvement to the quality of life of patients with severe superficial femoral artery disease.
Journal Article
An appreciation of Arie de Geus’ contribution to the learning organization
Purpose
This paper aims to locate its appreciation of the life and work of Arie de Geus within the context of developments in approaches to management practice, education and learning since the Second World War. It emphasizes the important influence of top management-led applications of social science (Beckhard) and the impact of crises upon planning and the generation of memories of the future for effective organizational learning. The paper also describes the roles of learning from experience and of reflective practice in shaping de Geus’ contribution.
Design/methodology/approach
The approach traces the development of de Geus' career and thinking from Shell cost accountant, to top line manager in three continents, to Head of Shell Group Planning, to prize winning author, to global adviser to the World bank, etc., and as an inspirational speaker as champion of the learning organization.
Findings
The paper acknowledges Arie de Geus as coining the phrase “The Learning Organization” together with his role in the foundation and development of the Society for Organizational Learning (SOL) and as an international champion of young people's learning through the processes of the Finnish Team Academy model.
Social implications
Arie de Geus was an exemplar of reflective practice and applied learning. As such, his contribution might be considered as that of a sage rather than as a guru.
Originality/value
The paper endeavours to emphasize the importance of the role of both the internal and external contexts for effective organizational learning, suggesting that the contribution of Arie de Geus to the field exemplifies this importance.
Journal Article
Linguistic Markers of CEO Hubris
This article explores the link between CEOs' language and hubristic leadership. It is based on the precepts that leaders' linguistic utterances provide insights into their personality and behaviours; hubris is associated with unethical and potentially destructive leadership behaviours; if it is possible to identify linguistic markers of CEO hubris then these could serve as early warnings sign and help to mitigate the associated risks. Using computational linguistics, we analysed spoken utterances from a sample of hubristic CEOs and compared them with non-hubristic CEOs. We found that hubristic CEOs' linguistic utterances show systematic and consistent differences from the linguistic utterances of non-hubristic CEOs. Demonstrating how hubristic leadership manifests in CEO language contributes to wider research regarding the diagnosis and prevention of the unethical and potentially destructive effects of hubristic leadership. This research contributes to the wider study of hubris and unethical leadership by applying a novel method for identifying linguistic markers and offers a way of militating against the risk of unethical and destructive CEO behaviours induced or aggravated by hubristic leadership.
Journal Article
Carotid Stump Syndrome: Pathophysiology and Endovascular Treatment Options
Carotid stump syndrome is one of the recognised causes of recurrent ipsilateral cerebrovascular events after occlusion of the internal carotid artery. It is believed that microemboli arising from the stump of the occluded internal carotid artery or the ipsilateral external carotid artery can pass into the middle cerebral artery circulation as a result of patent external carotid–internal carotid anastomotic channels. Different pathophysiologic causes of this syndrome and endovascular options for treatment are discussed.
Journal Article
Managing Inadvertent Arterial Catheterization During Central Venous Access Procedures
Approximately 200,000 central venous catheterizations are carried out annually in the National Health Service in the United Kingdom. Inadvertent arterial puncture occurs in up to 3.7%. Significant morbidity and death has been reported. We report on our experience in the endovascular treatment of this iatrogenic complication.
Retrospective analysis was carried out of 9 cases referred for endovascular treatment of inadvertent arterial puncture during central venous catheterization over a 5 year period.
It was not possible to obtain accurate figures on the numbers of central venous catheterizations carried out during the time period. Five patients were referred with carotid or subclavian pseudoaneurysms and hemothorax following inadvertent arterial catheter insertion and subsequent removal. These patients all underwent percutaneous balloon tamponade and/or stent-graft insertion. More recently 4 patients were referred with the catheter still in situ and were successfully treated with a percutaneous closure device.
If inadvertent arterial catheterization during central venous access procedures is recognized and catheters removed, sequelae can be treated percutaneously. However, once the complication is recognized it is better to leave the catheter in situ and seal the artery percutaneously with a closure device.
Journal Article
Axial Disease in Psoriatic Arthritis study: defining the clinical and radiographic phenotype of psoriatic spondyloarthritis
ObjectivesTo compare the prevalence, clinical and radiographic characteristics of psoriatic spondyloarthritis (PsSpA) in psoriatic arthritis (PsA), with ankylosing spondylitis (AS).MethodsA prospective single-centre cross-sectional observational study recruited consecutive PsA and AS cases. Participants completed outcome measures, and underwent clinical examination, axial radiographic scoring and HLA-sequencing. Multivariable analyses are presented.ResultsThe 402 enrolled cases (201 PsA, 201 AS; fulfilling classification criteria for respective conditions) were reclassified based upon radiographic axial disease and psoriasis, as: 118 PsSpA, 127 peripheral-only PsA (pPsA), and 157 AS without psoriasis (AS) cases. A significant proportion of patients with radiographic axial disease had PsSpA (118/275; 42.91%), and often had symptomatically silent axial disease (30/118; 25.42%). Modified New York criteria for AS were fulfilled by 48/201 (23.88%) PsA cases, and Classification of Psoriatic Arthritis criteria by 49/201 (24.38%) AS cases. pPsA compared with PsSpA cases had a lower frequency of HLA-B*27 (OR 0.12; 95% CI 0.05 to 0.25). Disease activity, metrology and disability were comparable in PsSpA and AS. A significant proportion of PsSpA cases had spondylitis without sacroiliitis (39/118; 33.05%); they less frequently carried HLA-B*27 (OR 0.11; 95% CI 0.04 to 0.33). Sacroiliac joint complete ankylosis (adjusted OR, ORadj 2.96; 95% CI 1.42 to 6.15) and bridging syndesmophytes (ORadj 2.78; 95% CI 1.49 to 5.18) were more likely in AS than PsSpA. Radiographic axial disease was more severe in AS than PsSpA (Psoriatic Arthritis Spondylitis Radiology Index Score: adjusted incidence risk ratio 1.13; 95% CI 1.09 to 1.19).ConclusionsIn a combined cohort of patients with either PsA or AS from a single centre, 24% fulfilled classification criteria for both conditions. The pattern of axial disease was influenced significantly by the presence of skin psoriasis and HLA-B*27.
Journal Article
Popliteal Venous Aneurysm: A Rare Cause of Recurrent Pulmonary Emboli and Limb Swelling
Popliteal venous aneurysm is a rare cause of recurrent pulmonary embolism, although the true incidence of aneurysm is probably underestimated. One-third of patients suffer further embolic events despite therapeutic anticoagulation. We report the case of a 59-year-old male who presented with recurrent PEs over a period of 12 years despite anticoagulation therapy. A thrombophilia screen and abdominal ultrasound were normal at that time. He reattended with recurrent pulmonary emboli, left calf swelling, and a mass in his left popliteal fossa causing limitation of knee movement. Venous duplex and MRI of his popliteal fossa demonstrated a thrombosed true popliteal venous aneurysm with popliteal and superficial femoral vein occlusion. In view of the mass effect we proceeded to surgical excision of his aneurysm after prophylactic placement of an IVC filter. The patient regained normal knee function with intensive inpatient physiotherapy. He has been recommenced on lifelong anticoagulant. The presentation, investigation, and management of the condition are briefly discussed. We suggest that a bilateral lower limb duplex is performed to exclude venous aneurysm in all patients presenting with pulmonary embolism in which an underlying source cannot otherwise be identified and no thrombophilic tendency is detected.
Journal Article