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| 2. |
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| 3. |
- Tobias, Deirdre K, et al.
(author)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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In: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Research review (peer-reviewed)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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| 4. |
- Spronk, H. M. H., et al.
(author)
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Atherothrombosis and Thromboembolism : Position Paper from the Second Maastricht Consensus Conference on Thrombosis
- 2018
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In: Thrombosis and Haemostasis. - : SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN. - 0340-6245 .- 2567-689X. ; 118:2, s. 229-250
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Research review (peer-reviewed)abstract
- Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics:1. Risk factors, biomarkers and plaque instability: In atherothrombosis research, more focus on the contribution of specific risk factors like ectopic fat needs to be considered; definitions of atherothrombosis are important distinguishing different phases of disease, including plaque (in) stability; proteomic and metabolomics data are to be added to genetic information.2. Circulating cells including platelets and atherothrombosis: Mechanisms of leukocyte and macrophage plasticity, migration, and transformation in murine atherosclerosis need to be considered; diseasemechanism-based biomarkers need to be identified; experimental systems are needed that incorporatewhole-blood flow to understand how red blood cells influence thrombus formation and stability; knowledge on platelet heterogeneity and priming conditions needs to be translated toward the in vivo situation.3. Coagulation proteases, fibrin(ogen) and thrombus formation: The role of factor (F) XI in thrombosis including the lower margins of this factor related to safe and effective antithrombotic therapy needs to be established; FXI is a key regulator in linking platelets, thrombin generation, and inflammatory mechanisms in a renin-angiotensin dependent manner; however, the impact on thrombin-dependent PAR signaling needs further study; the fundamental mechanisms in FXIII biology and biochemistry and its impact on thrombus biophysical characteristics need to be explored; the interactions of red cells and fibrin formation and its consequences for thrombus formation and lysis need to be addressed. Platelet-fibrin interactions are pivotal determinants of clot formation and stability with potential therapeutic consequences.4. Preventive and acute treatment of atherothrombosis and arterial embolism; novel ways and tailoring? The role of protease-activated receptor (PAR)-4 vis a vis PAR-1 as target for antithrombotic therapy merits study; ongoing trials on platelet function test-based antiplatelet therapy adjustment support development of practically feasible tests; risk scores for patients with atrial fibrillation need refinement, taking new biomarkers including coagulation into account; risk scores that consider organ system differences in bleeding may have added value; all forms of oral anticoagulant treatment require better organization, including education and emergency access; laboratory testing still needs rapidly available sensitive tests with short turnaround time.5. Pleiotropy of coagulation proteases, thrombus resolution and ischaemia-reperfusion: Biobanks specifically for thrombus storage and analysis are needed; further studies on novelmodified activated protein C-based agents are required including its cytoprotective properties; new avenues for optimizing treatment of patients with ischaemic stroke are needed, also including novel agents that modify fibrinolytic activity (aimed at plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor.
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| 5. |
- Tai, F, et al.
(author)
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Abdominal Wall Miscellaneous
- 2015
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In: Hernia : the journal of hernias and abdominal wall surgery. - 1248-9204. ; 19 Suppl 1, s. S5-S12
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Journal article (peer-reviewed)
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| 6. |
- Falster, Daniel, et al.
(author)
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AusTraits, a curated plant trait database for the Australian flora
- 2021
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In: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
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Journal article (peer-reviewed)abstract
- We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
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| 7. |
- Geersing, G. J., et al.
(author)
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Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis
- 2014
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In: BMJ: British Medical Journal. - : BMJ. - 1756-1833. ; 348, s. 1340-1340
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Journal article (peer-reviewed)abstract
- Objective To assess the accuracy of the Wells rule for excluding deep vein thrombosis and whether this accuracy applies to different subgroups of patients. Design Meta-analysis of individual patient data. Data sources Authors of 13 studies (n=10 002) provided their datasets, and these individual patient data were merged into one dataset. Eligibility criteria Studies were eligible if they enrolled consecutive outpatients with suspected deep vein thrombosis, scored all variables of the Wells rule, and performed an appropriate reference standard. Main outcome measures Multilevel logistic regression models, including an interaction term for each subgroup, were used to estimate differences in predicted probabilities of deep vein thrombosis by the Wells rule. In addition, D-dimer testing was added to assess differences in the ability to exclude deep vein thrombosis using an unlikely score on the Wells rule combined with a negative D-dimer test result. Results Overall, increasing scores on the Wells rule were associated with an increasing probability of having deep vein thrombosis. Estimated probabilities were almost twofold higher in patients with cancer, in patients with suspected recurrent events, and (to a lesser extent) in males. An unlikely score on the Wells rule (<= 1) combined with a negative D-dimer test result was associated with an extremely low probability of deep vein thrombosis (1.2%, 95% confidence interval 0.7% to 1.8%). This combination occurred in 29% (95% confidence interval 20% to 40%) of patients. These findings were consistent in subgroups defined by type of D-dimer assay (quantitative or qualitative), sex, and care setting (primary or hospital care). For patients with cancer, the combination of an unlikely score on the Wells rule and a negative D-dimer test result occurred in only 9% of patients and was associated with a 2.2% probability of deep vein thrombosis being present. In patients with suspected recurrent events, only the modified Wells rule (adding one point for the previous event) is safe. Conclusion Combined with a negative D-dimer test result (both quantitative and qualitative), deep vein thrombosis can be excluded in patients with an unlikely score on the Wells rule. This finding is true for both sexes, as well as for patients presenting in primary and hospital care. In patients with cancer, the combination is neither safe nor efficient. For patients with suspected recurrent disease, one extra point should be added to the rule to enable a safe exclusion.
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| 8. |
- d'Alessandro, Elisa, et al.
(author)
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Thrombo-Inflammation in Cardiovascular Disease : An Expert Consensus Document from the Third Maastricht Consensus Conference on Thrombosis
- 2020
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In: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 120:4, s. 538-564
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Journal article (peer-reviewed)abstract
- Thrombo-inflammation describes the complex interplay between blood coagulation and inflammation that plays a critical role in cardiovascular diseases. The third Maastricht Consensus Conference on Thrombosis assembled basic, translational, and clinical scientists to discuss the origin and potential consequences of thrombo-inflammation in the etiology, diagnostics, and management of patients with cardiovascular disease, including myocardial infarction, stroke, and peripheral artery disease. This article presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following topics: (1) challenges of the endothelial cell barrier; (2) circulating cells and thrombo-inflammation, focused on platelets, neutrophils, and neutrophil extracellular traps; (3) procoagulant mechanisms; (4) arterial vascular changes in atherogenesis; attenuating atherosclerosis and ischemia/reperfusion injury; (5) management of patients with arterial vascular disease; and (6) pathogenesis of venous thrombosis and late consequences of venous thromboembolism.
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| 11. |
- Lin, Yan-Shih, et al.
(author)
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Optimal stomatal behaviour around the world
- 2015
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In: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 5, s. 459-464
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Journal article (peer-reviewed)abstract
- Stomatal conductance (gs) is a key land-surface attribute as it links transpiration, the dominant component of global land evapotranspiration, and photosynthesis, the driving force of the global carbon cycle. Despite the pivotal role of gs in predictions of global water and carbon cycle changes, a globalscale database and an associated globally applicable model of gs that allow predictions of stomatal behaviour are lacking. Here,we present a database of globally distributed gs obtained in the field for a wide range of plant functional types (PFTs) and biomes. We find that stomatal behaviour differs among PFTs according to their marginal carbon cost of water use, as predicted by the theory underpinning the optimal stomatal model1 and the leaf and wood economics spectrum2,3.We also demonstrate a global relationship with climate. These findings provide a robust theoretical framework for understanding and predicting the behaviour of gs across biomes and across PFTs that can be applied to regional, continental and global-scale modelling of ecosystem productivity, energy balance and ecohydrological processes in a future changing climate.
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| 12. |
- Lin, Yan-Shih, et al.
(author)
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Optimal stomatal behaviour around the world
- 2015
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In: Nature Climate Change. - 1758-6798 .- 1758-678X. ; 5:5, s. 459-464
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Journal article (peer-reviewed)abstract
- Stomatal conductance (g(s)) is a key land-surface attribute as it links transpiration, the dominant component of global land evapotranspiration, and photosynthesis, the driving force of the global carbon cycle. Despite the pivotal role of g(s) in predictions of global water and carbon cycle changes, a global-scale database and an associated globally applicable model of g(s) that allow predictions of stomatal behaviour are lacking. Here, we present a database of globally distributed g(s) obtained in the field for a wide range of plant functional types (PFTs) and biomes. We find that stomatal behaviour differs among PFTs according to their marginal carbon cost of water use, as predicted by the theory underpinning the optimal stomatal model(1) and the leaf and wood economics spectrum(2,3). We also demonstrate a global relationship with climate. These findin g(s) provide a robust theoretical framework for understanding and predicting the behaviour of g(s) across biomes and across PFTs that can be applied to regional, continental and global-scale modelling of ecosystem productivity, energy balance and ecohydrological processes in a future changing climate.
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| 13. |
- Phillip, Moshe, et al.
(author)
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Consensus Guidance for Monitoring Individuals With Islet Autoantibody-Positive Pre-Stage 3 Type 1 Diabetes
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In: Diabetes Care. - 1935-5548.
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Journal article (peer-reviewed)abstract
- Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programs are being increasingly emphasized. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk for (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in nonspecialized settings. To inform this monitoring, JDRF, in conjunction with international experts and societies, developed consensus guidance. Broad advice from this guidance includes the following: 1) partnerships should be fostered between endocrinologists and primary care providers to care for people who are IAb+; 2) when people who are IAb+ are initially identified, there is a need for confirmation using a second sample; 3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; 4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; 5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and 6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasizes significant unmet needs for further research on early-stage type 1 diabetes to increase the rigor of future recommendations and inform clinical care.
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| 14. |
- Phillip, Moshe, et al.
(author)
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Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes
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In: Diabetologia. - 1432-0428.
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Journal article (peer-reviewed)abstract
- Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk of (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings. To inform this monitoring, JDRF in conjunction with international experts and societies developed consensus guidance. Broad advice from this guidance includes the following: (1) partnerships should be fostered between endocrinologists and primary-care providers to care for people who are IAb+; (2) when people who are IAb+ are initially identified there is a need for confirmation using a second sample; (3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; (4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; (5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and (6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasises significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care.
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| 15. |
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| 16. |
- Al-Khateeb, S, et al.
(author)
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Light-induced fluorescence studies on dehydration of incipient enamel lesions
- 2002
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In: Caries research. - : S. Karger AG. - 0008-6568 .- 1421-976X. ; 36:1, s. 25-30
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Journal article (peer-reviewed)abstract
- Changes in the hydration state of enamel affect its optical qualities, such as light scattering and fluorescence. In this study, the rate of fluorescence loss was measured when incipient enamel lesions with different de-remineralization history were left to dehydrate. Four groups of lesions were studied. In groups A, B and C, the lesions were prepared in vitro in an acid-gel system. Group A was kept as control, and groups B and C were remineralized (4 weeks) without and with 1 ppm F in solution, respectively. Group D consisted of natural incipient lesions. Enamel fluorescence was measured for all lesions immediately after removal from water and subsequently at short intervals for 30 min. The change in fluorescence with dehydration varied between the groups. In lesions from groups A and B, it followed a double exponential decrease, while in lesions from groups C and D, it followed a mono-exponential decrease. In all groups, the fluorescence of sound surfaces declined mono-exponentially. The ‘fractional fluorescence difference’, defined as (L<sub>sound</sub> – L<sub>carious</sub> )/L<sub>sound</sub>, became constant after periods of dehydration of about 5, 5, 20 and 5 min for groups A to D, respectively. The observation of the change of fluorescence with dehydration should be taken into consideration when planning studies that use fluorescence as an assessment method. However, it might also be used to gain insight into the properties for fluid transport inside the various lesions, relevant to de-remineralization or fluoride treatments.
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| 17. |
- Bull, James N., et al.
(author)
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Autoionization from the plasmon resonance in isolated 1-cyanonaphthalene
- 2023
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In: Journal of Chemical Physics. - 0021-9606 .- 1089-7690. ; 158:24
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Journal article (peer-reviewed)abstract
- Polycyclic aromatic hydrocarbons have widely been conjectured to be ubiquitous in space, as supported by the recent discovery of two isomers of cyanonaphthalene, indene, and 2-cyanoindene in the Taurus molecular cloud-1 using radioastronomy. Here, the photoionization dynamics of 1-cyanonaphthalene (1-CNN) are investigated using synchrotron radiation over the hν = 9.0–19.5 eV range, revealing that prompt autoionization from the plasmon resonance dominates the photophysics for hν = 11.5–16.0 eV. Minimal photo-induced dissociation, whether originating from an excited state impulsive bond rupture or through internal conversion followed by a statistical bond cleavage process, occurs over the microsecond timescale (as limited by the experimental setup). The direct photoionization cross section and photoelectron angular distributions are simulated using an ezDyson model combining Dyson orbitals with Coulomb wave photoejection. When considering these data in conjunction with recent radiative cooling measurements on 1-CNN+, which showed that cations formed with up to 5 eV of internal energy efficiently stabilize through recurrent fluorescence, we conclude that the organic backbone of 1-CNN is resilient to photodestruction by VUV and soft XUV radiation. These dynamics may prove to be a common feature for the survival of small polycyclic aromatic hydrocarbons in space, provided that the cations have a suitable electronic structure to support recurrent fluorescence.
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| 18. |
- Bull, James N., et al.
(author)
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Nonadiabatic Dynamics between Valence, Nonvalence, and Continuum Electronic States in a Heteropolycyclic Aromatic Hydrocarbon
- 2021
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In: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 12:49, s. 11811-11816
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Journal article (peer-reviewed)abstract
- Internal conversion between valence-localized and dipole-bound states is thought to be a ubiquitous process in polar molecular anions, yet there is limited direct evidence. Here, photodetachment action spectroscopy and time-resolved photoelectron imaging with a heteropolycyclic aromatic hydrocarbon (hetero-PAH) anion, deprotonated 1-pyrenol, is used to demonstrate a subpicosecond (τ1 = 160 ± 20 fs) valence to dipole-bound state internal conversion following excitation of the origin transition of the first valence-localized excited state. The internal conversion dynamics are evident in the photoelectron spectra and in the photoelectron angular distributions (β2 values) as the electronic character of the excited state population changes from valence to nonvalence. The dipole-bound state subsequently decays through mode-specific vibrational autodetachment with a lifetime τ2 = 11 ± 2 ps. These internal conversion and autodetachment dynamics are likely common in molecular anions but difficult to fingerprint due to the transient existence of the dipole-bound state. Potential implications of the present excited state dynamics for interstellar hetero-PAH anion formation are discussed.
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| 19. |
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| 20. |
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| 21. |
- Lachlan, Robert F., et al.
(author)
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The Progressive Loss of Syntactical Structure in Bird Song along an Island Colonization Chain
- 2013
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In: Current Biology. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 23:19, s. 1896-1901
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Journal article (peer-reviewed)abstract
- Cultural transmission can increase the flexibility of behavior, such as bird song. Nevertheless, this flexibility often appears to be constrained, sometimes by preferences for learning certain traits over others, a phenomenon known as "biased" learning or transmission [1]. The sequential colonization of the Atlantic Islands by the chaffinch (Fringilla coelebs) [2] provides a unique model system in which to investigate how the variability of a cultural trait has evolved. We used novel computational methods to analyze chaffinch song from twelve island and continental populations and to infer patterns of evolution in song structure. We found that variability of the subunits within songs ("syllables") differed moderately between populations but was not predicted by whether the population was continental or not. In contrast, we found that the sequencing of syllables within songs ("syntax") was less structured in island than continental populations and in fact decreased significantly after each colonization. Syntactical structure was very clear in the mainland European populations but was almost entirely absent in the most recently colonized island, Gran Canaria. Our results suggest that colonization leads to the progressive loss of a species-specific feature of song, syntactical structure.
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| 22. |
- Saad-Magalhaes, C., et al.
(author)
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Does removal of aids/devices and help make a difference in the Childhood Health Assessment Questionnaire disability index?
- 2010
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In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 69:1, s. 82-87
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To assess whether the removal of aids/devices and/or help from another person in the Childhood Health Assessment Questionnaire (C-HAQ) leads to a significant change in the disability index (DI) score and responsiveness in juvenile idiopathic arthritis (JIA).METHODS: Changes in the C-HAQ DI score in a cross-sectional sample of 2663 children with JIA and in 530 active patients with JIA in a trial of methotrexate (MTX) were compared.RESULTS: Patients in the MTX trial had higher disease activity and disability than the cross-sectional sample. The frequency of aids/devices (range 1.2-10.2%) was similar between the two samples, while help (range 5.3-38.1%) was more frequently used in the MTX group. Correlation between disease severity variables and the two different C-HAQ DI scoring methods did not change substantially. There was a decrease in the C-HAQ DI score for both the cross-sectional (mean score from 0.64 with the original method to 0.54 without aids/devices and help, p<0.0001) and the MTX sample (mean score from 1.23 to 1.07, p<0.0001). A linear regression analysis of the original C-HAQ DI score versus the score without aids/devices and help demonstrated the substantial overlap of the different scoring methods. Responsiveness in the responders to MTX treatment did not change with the different C-HAQ DI scoring methods (range 0.86-0.82).CONCLUSION: The removal of aids/devices and help from the C-HAQ does not alter the interpretation of disability at a group level. The simplified C-HAQ is a more feasible and valid alternative for the evaluation of disability in patients with JIA.
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| 26. |
- Timmer, S A J, et al.
(author)
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Right ventricular energetics in patients with hypertrophic cardiomyopathy and the effect of alcohol septal ablation
- 2011
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In: Journal of Cardiac Failure. - : Elsevier BV. - 1071-9164 .- 1532-8414. ; 17:10, s. 827-831
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Journal article (peer-reviewed)abstract
- BACKGROUND:Diastolic dysfunction in hypertrophic cardiomyopathy (HCM) is accompanied by augmented left ventricular (LV) end-diastolic pressure, above all in the presence of LV outflow tract (LVOT) obstruction. Increased back-pressure may augment right ventricular (RV) afterload and induce an oxidative metabolic imbalance between the 2 ventricles. The aim was to study right-to-left ventricular oxidative metabolism in HCM and the effects of alcohol septal ablation (ASA).METHODS AND RESULTS:Twenty-one HCM patients were enrolled. Eleven healthy subjects served as a control group. Subjects underwent 2-dimensional echocardiography to assess LVOT gradient, left atrial size, and diastolic function. [11C]Acetate positron-emission tomography (PET) was performed to determine RVk2 and LVk2, as a noninvasive index of oxidative metabolism. Seven HCM patients with LVOT obstruction, scheduled to undergo ASA, were also studied 6 months after the procedure. RVk2 was higher in HCM patients than i control subjects (0.081 ± 0.021 min−1 vs. 0.061 ± 0.017 min−1; P = .05), whereas LVk2 was similar between groups. Consequently, RVk2/LVk2 was increased in the patients (0.85 ± 0.19 vs 0.59 ± 0.13; P = .004). In patients with obstructive HCM, ASA reduced RVk2 (0.085 ± 0.021 min−1 to 0.072 ± 0.022 min−1; P = .001). Inasmuch as LVk2 remained unaffected by the procedure, RVk2/LVk2 was decreased after ASA (0.66 ± 0.18; P = .03). The absolute change in LVOT gradient was related to the absolute change in RVk2 (r = 0.77; P = .044).CONCLUSIONS:In HCM patients, RV oxygen consumption is increased in relation to the LV. ASA reduces RV oxygen consumption in HCM patients with LVOT obstruction, suggesting that increased LV loading conditions and diastolic dysfunction play a predominant role in augmenting RV workload in these patients.
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| 27. |
- Travin, Dmitrii Y., et al.
(author)
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Structure of ribosome-bound azole-modified peptide phazolicin rationalizes its species-specific mode of bacterial translation inhibition
- 2019
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 10
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Journal article (peer-reviewed)abstract
- Ribosome-synthesized post-translationally modified peptides (RiPPs) represent a rapidly expanding class of natural products with various biological activities. Linear azol(in)e-containing peptides (LAPs) comprise a subclass of RiPPs that display outstanding diversity of mechanisms of action while sharing common structural features. Here, we report the discovery of a new LAP biosynthetic gene cluster in the genome of Rhizobium Pop5, which encodes the precursor peptide and modification machinery of phazolicin (PHZ) - an extensively modified peptide exhibiting narrow-spectrum antibacterial activity against some symbiotic bacteria of leguminous plants. The cryo-EM structure of the Escherichia coli 70S-PHZ complex reveals that the drug interacts with the 23S rRNA and uL4/uL22 proteins and obstructs ribosomal exit tunnel in a way that is distinct from other compounds. We show that the uL4 loop sequence determines the species-specificity of antibiotic action. PHZ expands the known diversity of LAPs and may be used in the future as biocontrol agent for agricultural needs.
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