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Article ; Online: Reliability of alternative devices for postoperative patient temperature measurement: two prospective, observational studies.

Aykanat, V M / Broadbent, E / Peyton, P J

2020 Volume 76, Issue 4, Page(s) 514–519

Abstract: Peri-operative hypothermia is associated with significant morbidity, yet limitations exist regarding non-invasive temperature assessment in the post-anaesthesia care unit (PACU). In this prospective study of 100 patients, we aimed to determine the ... ...

Abstract	Peri-operative hypothermia is associated with significant morbidity, yet limitations exist regarding non-invasive temperature assessment in the post-anaesthesia care unit (PACU). In this prospective study of 100 patients, we aimed to determine the reliability of two commonly used temperature measurement devices, forehead temporal artery temperature and tympanic measurement, in addition to an indwelling urinary catheter with temperature probe, in comparison with the final nasopharyngeal core temperature at the end of surgery. Agreement of forehead measurement with nasopharyngeal temperature showed a mean bias (±95% limits of agreement) of 0.15 °C (±1.4 °C), with a steep slope of the relationship on the Bland-Altman plot of -0.8, indicating a tendency to normalise patient temperature readings to 36.4 °C. Only 54% of hypothermic cases were correctly detected by the forehead measurement device. Agreement of tympanic measurement with nasopharyngeal core temperature measurement was marginally improved with a mean bias of 0.13 °C (95% limits of agreement ±1.15 °C). In contrast, agreement of bladder temperature with nasopharyngeal temperature showed a mean (SD) bias of 0.19 (0.28) °C (95% limits of agreement ±0.54 °C), with a relatively flat line of best fit. We demonstrated that two commonly used temperature measurement devices, forehead temporal artery temperature and tympanic measurement, compared with nasopharyngeal core temperature, were imprecise and unreliable following major surgery. However, the indwelling catheter with temperature sensor was precise and acceptable for continuous core temperature measurement in the PACU.
MeSH term(s)	Aged ; Area Under Curve ; Body Temperature ; Female ; Forehead/physiology ; Humans ; Male ; Middle Aged ; Monitoring, Physiologic/instrumentation ; Monitoring, Physiologic/methods ; Nasopharynx/physiology ; Postoperative Period ; Prospective Studies ; ROC Curve ; Urinary Bladder/physiology
Language	English
Publishing date	2020-08-26
Publishing country	England
Document type	Journal Article ; Observational Study
ZDB-ID	80033-8
ISSN	1365-2044 ; 0003-2409
ISSN (online)	1365-2044
ISSN	0003-2409
DOI	10.1111/anae.15248
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Article ; Online: Heterologous expression and characterization of a MoAA16 polysaccharide monooxygenase from the rice blast fungus Magnaporthe oryzae

Hung M. Nguyen / Loan Q. Le / Luca Sella / Luke M. Broadbent / Roslyn M. Bill / Van V. Vu

Electronic Journal of Biotechnology, Vol 66, Iss , Pp 1-

2023 Volume 16

Abstract: Background: Cellulose is an organic carbon source that can be used as a sustainable alternative for energy, materials, and chemicals. However, the substantial challenge of converting it into soluble sugars remains a major obstacle in its use as a biofuel ...

Abstract	Background: Cellulose is an organic carbon source that can be used as a sustainable alternative for energy, materials, and chemicals. However, the substantial challenge of converting it into soluble sugars remains a major obstacle in its use as a biofuel and chemical feedstock. A new class of enzymes knowns as copper-dependent polysaccharide monooxygenases (PMOs) or lytic polysaccharide monooxygenases (LPMOs) can break down polysaccharides such as cellulose, chitin, and starch through oxidation. This process enhances the efficiency of cellulose degradation by cellulase. Results: The genome of the fungus Magnaporthe oryzae, the causal agent of rice blast disease, contains the MGG_00245 gene, which encodes a putative PMO referred to as MoAA16. MoAA16 has been found to be highly expressed in planta during the early stages of fungal infection. The gene was optimized for heterologous expression in Pichia pastoris, and its oxidative cleavage activity on cellulose was characterized by analyzing soluble oligosaccharide products using highperformance anion exchange chromatography (HPAEC-PAD). The reaction catalyzed by MoAA16 requires 2 electrons from an electron donor, such as ascorbic acid, and aerobic conditions. It primarily produces Glc1 to Glc4 oligosaccharides, as well as oxidized cellobionic and cellotrionic acids. MoAA16 has been observed to enhance cellulase hydrolysis on phosphoric acid swollen cellulose (PASC) substrate, resulting in the production of more monosaccharide products. Conclusions: Our findings reveal the successful heterologous expression of MoAA16 in P. pastoris and its cellulose-active PMO properties. These results highlight the potential of MoAA16 as a promising candidate for applications in biofuel production and chemical synthesis.How to cite: Nguyen HM, Le LQ, Sella L, et al. Heterologous expression and characterization of a MoAA16 polysaccharide monooxygenase from the rice blast fungus Magnaporthe oryzae. Electron J Biotechnol 2023. https://doi.org/10.1016/j.ejbt.2023.06.002.
Keywords	Cellulose ; Enzymatic activity ; Fungal infection ; Heterologous expression ; Magnaporthe oryzae ; Monosaccharide ; Biotechnology ; TP248.13-248.65 ; Biology (General) ; QH301-705.5
Subject code	540
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: A machine learning approach to identifying suicide risk among text-based crisis counseling encounters.

Broadbent, Meghan / Medina Grespan, Mattia / Axford, Katherine / Zhang, Xinyao / Srikumar, Vivek / Kious, Brent / Imel, Zac

Frontiers in psychiatry

2023 Volume 14, Page(s) 1110527

Abstract: Introduction: With the increasing utilization of text-based suicide crisis counseling, new means of identifying at risk clients must be explored. Natural language processing (NLP) holds promise for evaluating the content of crisis counseling; here we ... ...

Abstract	Introduction: With the increasing utilization of text-based suicide crisis counseling, new means of identifying at risk clients must be explored. Natural language processing (NLP) holds promise for evaluating the content of crisis counseling; here we use a data-driven approach to evaluate NLP methods in identifying client suicide risk. Methods: De-identified crisis counseling data from a regional text-based crisis encounter and mobile tipline application were used to evaluate two modeling approaches in classifying client suicide risk levels. A manual evaluation of model errors and system behavior was conducted. Results: The neural model outperformed a term frequency-inverse document frequency (tf-idf) model in the false-negative rate. While 75% of the neural model's false negative encounters had some discussion of suicidality, 62.5% saw a resolution of the client's initial concerns. Similarly, the neural model detected signals of suicidality in 60.6% of false-positive encounters. Discussion: The neural model demonstrated greater sensitivity in the detection of client suicide risk. A manual assessment of errors and model performance reflected these same findings, detecting higher levels of risk in many of the false-positive encounters and lower levels of risk in many of the false negatives. NLP-based models can detect the suicide risk of text-based crisis encounters from the encounter's content.
Language	English
Publishing date	2023-03-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564218-2
ISSN	1664-0640
ISSN	1664-0640
DOI	10.3389/fpsyt.2023.1110527
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Article ; Online: Causal Assessment of Income Inequality on Self-Rated Health and All-Cause Mortality: A Systematic Review and Meta-Analysis.

Shimonovich, Michal / Campbell, Mhairi / Thomson, Rachel M / Broadbent, Philip / Wells, Valerie / Kopasker, Daniel / McCARTNEY, Gerry / Thomson, Hilary / Pearce, Anna / Katikireddi, S Vittal

The Milbank quarterly

2024 Volume 102, Issue 1, Page(s) 141–182

Abstract: Policy Points Income is thought to impact a broad range of health outcomes. However, whether income inequality (how unequal the distribution of income is in a population) has an additional impact on health is extensively debated. Studies that use ... ...

Abstract	Policy Points Income is thought to impact a broad range of health outcomes. However, whether income inequality (how unequal the distribution of income is in a population) has an additional impact on health is extensively debated. Studies that use multilevel data, which have recently increased in popularity, are necessary to separate the contextual effects of income inequality on health from the effects of individual income on health. Our systematic review found only small associations between income inequality and poor self-rated health and all-cause mortality. The available evidence does not suggest causality, although it remains methodologically flawed and limited, with very few studies using natural experimental approaches or examining income inequality at the national level. Context: Whether income inequality has a direct effect on health or is only associated because of the effect of individual income has long been debated. We aimed to understand the association between income inequality and self-rated health (SRH) and all-cause mortality (mortality) and assess if these relationships are likely to be causal. Methods: We searched Medline, ISI Web of Science, Embase, and EconLit (PROSPERO: CRD42021252791) for studies considering income inequality and SRH or mortality using multilevel data and adjusting for individual-level socioeconomic position. We calculated pooled odds ratios (ORs) for poor SRH and relative risk ratios (RRs) for mortality from random-effects meta-analyses. We critically appraised included studies using the Risk of Bias in Nonrandomized Studies - of Interventions tool. We assessed certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework and causality using Bradford Hill (BH) viewpoints. Findings: The primary meta-analyses included 2,916,576 participants in 38 cross-sectional studies assessing SRH and 10,727,470 participants in 14 cohort studies of mortality. Per 0.05-unit increase in the Gini coefficient, a measure of income inequality, the ORs and RRs (95% confidence intervals) for SRH and mortality were 1.06 (1.03-1.08) and 1.02 (1.00-1.04), respectively. A total of 63.2% of SRH and 50.0% of mortality studies were at serious risk of bias (RoB), resulting in very low and low certainty ratings, respectively. For SRH and mortality, we did not identify relevant evidence to assess the specificity or, for SRH only, the experiment BH viewpoints; evidence for strength of association and dose-response gradient was inconclusive because of the high RoB; we found evidence in support of temporality and plausibility. Conclusions: Increased income inequality is only marginally associated with SRH and mortality, but the current evidence base is too methodologically limited to support a causal relationship. To address the gaps we identified, future research should focus on income inequality measured at the national level and addressing confounding with natural experiment approaches.
MeSH term(s)	Humans ; Cross-Sectional Studies ; Health Status ; Income
Language	English
Publishing date	2024-01-31
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	632829-5
ISSN	1468-0009 ; 0887-378X
ISSN (online)	1468-0009
ISSN	0887-378X
DOI	10.1111/1468-0009.12689
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Article ; Online: Targeted implementation of cool roofs for equitable urban adaptation to extreme heat

Broadbent, Ashley M. / Declet-Barreto, Juan / Krayenhoff, E. Scott / Harlan, Sharon L. / Georgescu, Matei

Science of the Total Environment. 2022 Mar., v. 811 p.151326-

2022

Abstract: Cities are facing the twin pressures of greenhouse gas driven climatic warming and locally induced urban heating. These pressures are threatening populations that are sensitive to extreme heat due to sociodemographic factors including economic means. ... ...

Abstract	Cities are facing the twin pressures of greenhouse gas driven climatic warming and locally induced urban heating. These pressures are threatening populations that are sensitive to extreme heat due to sociodemographic factors including economic means. Heat-reducing infrastructure adaptation measures such as reflective “cool” materials can reduce urban temperatures. Here we examine the needs-based equity implications associated with heat-reducing cool roofing in Maricopa County, Arizona through application of high-resolution urban-atmospheric simulations. We simulate heatwave conditions and evaluate the air temperature reduction arising from uniform cool roof implementation (i.e., the entire urbanized county), and contrast results against simulated cooling impacts of needs-based targeted cool roof implementation in sociodemographically heat sensitive areas. We find that installing cool roofs uniformly, rather than in a targeted fashion, provides on average 0.66 °C reduction in the highest heat sensitivity area and 0.39 °C temperature reduction in the lowest heat sensitivity area due in part to a higher roof area density in the heat sensitive area. Targeting cool roof implementation yields 0.45 °C cooling in the most sensitive areas compared to 0.22 °C cooling in the least sensitive areas, meaning that needs-based targeted cool roofs in high sensitivity areas provide more relief than cool roofs targeted at low sensitivity areas, thus providing more cooling where it is most needed. Needs-based targeted implementation has the dual benefits of concurrently producing more than twice as much cooling and reducing heat exposure for the largest absolute number of individuals in the densely populated, highly heat sensitive areas. Targeting cool roof implementation to high heat sensitivity areas, however, does not achieve thermally equal temperatures in Maricopa County because the high sensitivity areas were substantially warmer than low sensitivity areas prior to implementation. This study illustrates the utility of a new “Targeted Urban Heat Adaptation” (TUHA) framework to assess needs-based equity implications of heat-reducing strategies and underscores its importance by examining the impacts of cooling interventions across sociodemographically heterogeneous urban environments.
Keywords	air temperature ; cooling ; environment ; greenhouse gases ; heat ; infrastructure ; thermosensitivity ; urbanization ; Arizona ; Cool roofs ; Heat sensitivity index ; Needs-based adaptation ; Urban heat ; WRF
Language	English
Dates of publication	2022-03
Publishing place	Elsevier B.V.
Document type	Article ; Online
ZDB-ID	121506-1
ISSN	1879-1026 ; 0048-9697
ISSN (online)	1879-1026
ISSN	0048-9697
DOI	10.1016/j.scitotenv.2021.151326
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Article ; Online: Climate change disrupts the seasonal coupling of plant and soil microbial nutrient cycling in an alpine ecosystem.

Broadbent, Arthur A D / Newbold, Lindsay K / Pritchard, William J / Michas, Antonios / Goodall, Tim / Cordero, Irene / Giunta, Andrew / Snell, Helen S K / Pepper, Violette V L H / Grant, Helen K / Soto, David X / Kaufmann, Ruediger / Schloter, Michael / Griffiths, Robert I / Bahn, Michael / Bardgett, Richard D

Global change biology

2024 Volume 30, Issue 3, Page(s) e17245

Abstract: The seasonal coupling of plant and soil microbial nutrient demands is crucial for efficient ecosystem nutrient cycling and plant production, especially in strongly seasonal alpine ecosystems. Yet, how these seasonal nutrient cycling processes are ... ...

Abstract	The seasonal coupling of plant and soil microbial nutrient demands is crucial for efficient ecosystem nutrient cycling and plant production, especially in strongly seasonal alpine ecosystems. Yet, how these seasonal nutrient cycling processes are modified by climate change and what the consequences are for nutrient loss and retention in alpine ecosystems remain unclear. Here, we explored how two pervasive climate change factors, reduced snow cover and shrub expansion, interactively modify the seasonal coupling of plant and soil microbial nitrogen (N) cycling in alpine grasslands, which are warming at double the rate of the global average. We found that the combination of reduced snow cover and shrub expansion disrupted the seasonal coupling of plant and soil N-cycling, with pronounced effects in spring (shortly after snow melt) and autumn (at the onset of plant senescence). In combination, both climate change factors decreased plant organic N-uptake by 70% and 82%, soil microbial biomass N by 19% and 38% and increased soil denitrifier abundances by 253% and 136% in spring and autumn, respectively. Shrub expansion also individually modified the seasonality of soil microbial community composition and stoichiometry towards more N-limited conditions and slower nutrient cycling in spring and autumn. In winter, snow removal markedly reduced the fungal:bacterial biomass ratio, soil N pools and shifted bacterial community composition. Taken together, our findings suggest that interactions between climate change factors can disrupt the temporal coupling of plant and soil microbial N-cycling processes in alpine grasslands. This could diminish the capacity of these globally widespread alpine ecosystems to retain N and support plant productivity under future climate change.
MeSH term(s)	Ecosystem ; Soil ; Climate Change ; Seasons ; Soil Microbiology ; Nutrients
Chemical Substances	Soil
Language	English
Publishing date	2024-03-21
Publishing country	England
Document type	Journal Article
ZDB-ID	1281439-8
ISSN	1365-2486 ; 1354-1013
ISSN (online)	1365-2486
ISSN	1354-1013
DOI	10.1111/gcb.17245
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Article ; Online: Silvicultural experiment assessment using lidar data collected from an unmanned aerial vehicle

Cosenza, Diogo N. / Vogel, Jason / Broadbent, Eben N. / Silva, Carlos A.

Forest Ecology and Management. 2022 Oct., v. 522 p.120489-

2022

Abstract: ... biomass (Mg ha⁻¹), stem volume (m³ ha⁻¹), dominant height (m), and leaf area index (LAI, m² m⁻²). We used ...

Abstract	Collecting field data in silvicultural experiments can be challenging and time-consuming. Alternatively, unmanned aerial vehicles using laser scanners (UAV-lidar) can be used for cost-effective data collection in forest stands. This work aims to assess the capability of UAV-lidar to estimate biophysical forest attributes in silvicultural experiments. The showcase experiment refers to the IMPAC II (Intensive Management Practices Assessment Center II), a long-term project of 24 plots aiming to assess the effects of fertilization and weed control on forest growth and nutrient cycling in past and ongoing silvicultural treatments in a second rotation of loblolly pine (Pinus taeda L.) plantation at age 12 years. Treatment performances were assessed based on four biometric attributes related to forest productivity: Growing stock biomass (Mg ha⁻¹), stem volume (m³ ha⁻¹), dominant height (m), and leaf area index (LAI, m² m⁻²). We used the area-based approach (ABA) and multiple linear models to characterize these forest attributes in the different silvicultural treatments and use their predictions to run the experiment analysis. Two groups of ALS-derived metrics were tested in the modeling, traditional metrics and a novel group of metrics based on plant area density (PAD) distribution. Models using PAD-based metrics increased the correlation between observed and predicted values (R²) from 0.27–0.40 to 0.50–0.85 when compared to the same models using traditional metrics, while the relative root mean square errors (RMSE%) of the predictions were reduced from 6–18% to 4–12%. Experiment analysis using UAV-lidar data and PAD-based model predictors led to the same results as those using field observations: i) fertilization was the most effective treatment for enhancing stand attributes, especially in terms of biomass, stem volume, and LAI; ii) weed control alone provided marginal improvements in the stands; iii) actively retreating stands in both first and second rotation led to increased growth when compared to the carryover effects. UAV-lidar using PAD-based metrics was effective in characterizing enhanced silvicultural treatments and might benefit studies involving understory assessment.
Keywords	Pinus taeda ; administrative management ; biomass ; biometry ; cost effectiveness ; data collection ; forest growth ; forests ; leaf area index ; lidar ; understory ; unmanned aerial vehicles ; weed control ; Airborne laser scanning ; Forestry ; Remote sensing ; Drones ; Loblolly pine
Language	English
Dates of publication	2022-10
Publishing place	Elsevier B.V.
Document type	Article ; Online
ZDB-ID	751138-3
ISSN	0378-1127
ISSN	0378-1127
DOI	10.1016/j.foreco.2022.120489
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Article ; Online: Does the Beta-Lactam Matter? Nafcillin versus Cefazolin for Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections.

Burrelli, Corey C / Broadbent, Eleanor K / Margulis, Alice / Snyder, Graham M / Gold, Howard S / McCoy, Christopher / Mahoney, Monica V / Hirsch, Elizabeth B

Chemotherapy

2019 Volume 63, Issue 6, Page(s) 345–351

Abstract: Background: Antistaphylococcal penicillins have historically been regarded as the drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI). However, recent outcomes data compared to cefazolin treatment are ... ...

Abstract	Background: Antistaphylococcal penicillins have historically been regarded as the drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI). However, recent outcomes data compared to cefazolin treatment are conflicting. Objective: This study compared treatment failure and adverse effects associated with nafcillin and cefazolin for MSSA BSI. Methods: Adult inpatients with MSSA BSI between January 1, 2009 and August 31, 2015 were included in this retrospective cohort study if they received ≥72 h of nafcillin or cefazolin as directed therapy after no more than 72 h of any empiric therapy. The primary composite endpoint was treatment failure defined by clinician documentation, 30-day recurrence of infection, all-cause 30-day in-hospital mortality, or loss to follow-up. Secondary outcomes included antibiotic-related acute kidney injury (AKI), acute interstitial nephritis (AIN), hepatotoxicity, and rash. Results: Among 157 patients, 116 (73.9%) received nafcillin and 41 (26.1%) received cefazolin. The baseline characteristics were similar except cefazolin-treated patients had higher APACHE II scores and more frequent renal dysfunction. No difference in the composite treatment failure outcome (28.4 vs. 31.7%; p = 0.69) was detected between the nafcillin and cefazolin groups, respectively. In a sensitivity analysis excluding patients without known follow-up, there was no significant difference of treatment failure. AKI, AIN, hepatotoxicity, and rash were all numerically more frequent among nafcillin-treated patients. Conclusions: Among nafcillin- or cefazolin-treated patients with MSSA BSI, there was no significant difference in treatment failure. Observing more frequent presumptive adverse effects associated with nafcillin receipt, future prospective studies evaluating cefazolin appear warranted.
MeSH term(s)	Acute Kidney Injury/etiology ; Adult ; Aged ; Anti-Bacterial Agents/adverse effects ; Anti-Bacterial Agents/therapeutic use ; Bacteremia/drug therapy ; Bacteremia/microbiology ; Bacteremia/pathology ; Cefazolin/adverse effects ; Cefazolin/therapeutic use ; Creatinine/blood ; Female ; Humans ; Male ; Middle Aged ; Nafcillin/adverse effects ; Nafcillin/therapeutic use ; Retrospective Studies ; Severity of Illness Index ; Staphylococcus aureus/enzymology ; Staphylococcus aureus/isolation & purification ; Tertiary Care Centers ; Treatment Outcome ; beta-Lactamases/metabolism
Chemical Substances	Anti-Bacterial Agents ; Nafcillin (4CNZ27M7RV) ; Creatinine (AYI8EX34EU) ; beta-Lactamases (EC 3.5.2.6) ; Cefazolin (IHS69L0Y4T)
Language	English
Publishing date	2019-04-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	6708-8
ISSN	1421-9794 ; 0009-3157
ISSN (online)	1421-9794
ISSN	0009-3157
DOI	10.1159/000499033
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Article ; Online: Gallid herpesvirus

Sadigh, Yashar / Powers, Claire / Spiro, Simon / Pedrera, Miriam / Broadbent, Andrew / Nair, Venugopal

NPJ vaccines

2018 Volume 3, Page(s) 21

Abstract: Live herpesvirus-vectored vaccines are widely used in veterinary medicine to protect against many infectious diseases. In poultry, three strains of herpesvirus vaccines are used against Marek's disease (MD). However, of these, only the herpesvirus of ... ...

Abstract	Live herpesvirus-vectored vaccines are widely used in veterinary medicine to protect against many infectious diseases. In poultry, three strains of herpesvirus vaccines are used against Marek's disease (MD). However, of these, only the herpesvirus of turkeys (HVT) has been successfully developed and used as a recombinant vaccine vector to induce protection against other avian viral diseases such as infectious bursal disease (IBD), Newcastle disease (ND) or avian influenza (AI). Although effective when administered individually, recombinant HVT vectors have limitations when combined in multivalent vaccines. Thus there is a need for developing additional viral vectors that could be combined with HVT in inducing protection against multiple avian diseases in multivalent vaccines.
Language	English
Publishing date	2018-05-28
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-018-0056-6
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Article ; Online: TANGO1 inhibitors reduce collagen secretion and limit tissue scarring.

Raote, Ishier / Rosendahl, Ann-Helen / Häkkinen, Hanna-Maria / Vibe, Carina / Küçükaylak, Ismail / Sawant, Mugdha / Keufgens, Lena / Frommelt, Pia / Halwas, Kai / Broadbent, Katrina / Cunquero, Marina / Castro, Gustavo / Villemeur, Marie / Nüchel, Julian / Bornikoel, Anna / Dam, Binita / Zirmire, Ravindra K / Kiran, Ravi / Carolis, Carlo /

Andilla, Jordi / Loza-Alvarez, Pablo / Ruprecht, Verena / Jamora, Colin / Campelo, Felix / Krüger, Marcus / Hammerschmidt, Matthias / Eckes, Beate / Neundorf, Ines / Krieg, Thomas / Malhotra, Vivek

Nature communications

2024 Volume 15, Issue 1, Page(s) 3302

Abstract: Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring and fibrosis and compromise tissue function. Despite the widespread occurrence of fibrotic diseases and scarring, effective therapies are lacking. A promising ... ...

Abstract	Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring and fibrosis and compromise tissue function. Despite the widespread occurrence of fibrotic diseases and scarring, effective therapies are lacking. A promising approach would be to limit the amount of collagen released from hyperactive fibroblasts. We have designed membrane permeant peptide inhibitors that specifically target the primary interface between TANGO1 and cTAGE5, an interaction that is required for collagen export from endoplasmic reticulum exit sites (ERES). Application of the peptide inhibitors leads to reduced TANGO1 and cTAGE5 protein levels and a corresponding inhibition in the secretion of several ECM components, including collagens. Peptide inhibitor treatment in zebrafish results in altered tissue architecture and reduced granulation tissue formation during cutaneous wound healing. The inhibitors reduce secretion of several ECM proteins, including collagens, fibrillin and fibronectin in human dermal fibroblasts and in cells obtained from patients with a generalized fibrotic disease (scleroderma). Taken together, targeted interference of the TANGO1-cTAGE5 binding interface could enable therapeutic modulation of ERES function in ECM hypersecretion, during wound healing and fibrotic processes.
MeSH term(s)	Humans ; Animals ; Fibroblasts/metabolism ; Fibroblasts/drug effects ; Collagen/metabolism ; Wound Healing/drug effects ; Cicatrix/metabolism ; Cicatrix/pathology ; Cicatrix/drug therapy ; Zebrafish ; Skin/metabolism ; Skin/pathology ; Skin/drug effects ; Fibrosis ; Peptides/pharmacology ; Peptides/metabolism ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum/drug effects ; Scleroderma, Systemic/metabolism ; Scleroderma, Systemic/drug therapy ; Scleroderma, Systemic/pathology ; Extracellular Matrix/metabolism ; Extracellular Matrix/drug effects
Chemical Substances	Collagen (9007-34-5) ; Peptides
Language	English
Publishing date	2024-04-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-47004-1
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