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Article ; Online: Mechanisms and functions of protein S-acylation.

S Mesquita, Francisco / Abrami, Laurence / Linder, Maurine E / Bamji, Shernaz X / Dickinson, Bryan C / van der Goot, F Gisou

Nature reviews. Molecular cell biology

2024

Abstract: Over the past two decades, protein S-acylation (often referred to as S-palmitoylation) has emerged ... as an important regulator of vital signalling pathways. S-Acylation is a reversible ... protein S-acylation and deacylation has demonstrated profound effects on various cellular processes ...

Abstract	Over the past two decades, protein S-acylation (often referred to as S-palmitoylation) has emerged as an important regulator of vital signalling pathways. S-Acylation is a reversible post-translational modification that involves the attachment of a fatty acid to a protein. Maintenance of the equilibrium between protein S-acylation and deacylation has demonstrated profound effects on various cellular processes, including innate immunity, inflammation, glucose metabolism and fat metabolism, as well as on brain and heart function. This Review provides an overview of current understanding of S-acylation and deacylation enzymes, their spatiotemporal regulation by sophisticated multilayered mechanisms, and their influence on protein function, cellular processes and physiological pathways. Furthermore, we examine how disruptions in protein S-acylation are associated with a broad spectrum of diseases from cancer to autoinflammatory disorders and neurological conditions.
Language	English
Publishing date	2024-02-14
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2031313-5
ISSN	1471-0080 ; 1471-0072
ISSN (online)	1471-0080
ISSN	1471-0072
DOI	10.1038/s41580-024-00700-8
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Article ; Online: Survey of resuscitation practices at emergency medical service agencies in the U.S.

Chan, Paul S / McNally, Bryan / Al-Araji, Rabab / Kennedy, Kevin / Kennedy, Marci / Del Rios, Marina / Sperling, Jessica / Sasson, Comilla / Breathett, Khadijah / Dukes, Kimberly C / Girotra, Saket

Resuscitation plus

2023 Volume 16, Page(s) 100483

Abstract: ... activities at EMS agencies. We describe herein a novel survey to EMS agencies in a U.S. registry for OHCA ... summary data on EMS agency characteristics in the U.S. Upon linkage to CARES patient-level data ...

Abstract	Background: Survival for out-of-hospital cardiac arrest (OHCA) varies across emergency medical service (EMS) agencies. Yet, little is known about resuscitation response and quality improvement activities at EMS agencies. We describe herein a novel survey to EMS agencies in a U.S. registry for OHCA. Methods: Using data from the Cardiac Arrest Registry to Enhance Survival (CARES), we identified 577 EMS agencies with ≥10 OHCA cases annually between 2015 and 2019 that remained active in CARES. We administered a survey to EMS directors regarding agency characteristics, cardiac arrest response, relationships with first responders and dispatchers, quality improvement activities and perceived barriers in the community. Results: Of eligible EMS agencies, 470 (81.5%) completed the survey. The high completion rate was likely due to frequent personalized emails and phone calls, liaising with CARES state coordinators to encourage survey response, and multiple periodic drawings of an automated external defibrillator during the survey period for participating EMS agencies. The survey examined rates of resuscitation training modalities; use of resuscitation equipment and devices in the field; frequency of simulation; non-EMS stakeholder response to OHCA (dispatchers, fire, police); quality improvement; and community factors affecting bystander response to OHCA. Conclusions: In this study design paper on the RED-CASO survey, we provide summary data on EMS agency characteristics in the U.S. Upon linkage to CARES patient-level data, this survey will provide critical insights into 'best practices' at EMS agencies with the highest OHCA survival rates as well as provide insights into current disparities in outcomes.
Language	English
Publishing date	2023-10-11
Publishing country	Netherlands
Document type	Journal Article
ISSN	2666-5204
ISSN (online)	2666-5204
DOI	10.1016/j.resplu.2023.100483
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Article ; Online: Establishing RTS,S/AS01 as a benchmark for comparison to next-generation malaria vaccines in a mouse model.

Locke, Emily / Flores-Garcia, Yevel / Mayer, Bryan T / MacGill, Randall S / Borate, Bhavesh / Salgado-Jimenez, Berenice / Gerber, Monica W / Mathis-Torres, Shamika / Shapiro, Sarah / King, C Richter / Zavala, Fidel

NPJ vaccines

2024 Volume 9, Issue 1, Page(s) 29

Abstract: ... vaccines targeting the circumsporozoite protein (CSP). To improve upon the malaria vaccine, RTS,S/AS01 ... against this benchmark. We focus on RTS,S/AS01-induced antibody responses and functional activity ... doses of RTS,S/AS01 were given intramuscularly at 3-week intervals, with challenge 2-weeks after ...

Abstract	New strategies are needed to reduce the incidence of malaria, and promising approaches include vaccines targeting the circumsporozoite protein (CSP). To improve upon the malaria vaccine, RTS,S/AS01, it is essential to standardize preclinical assays to measure the potency of next-generation vaccines against this benchmark. We focus on RTS,S/AS01-induced antibody responses and functional activity in conjunction with robust statistical analyses. Transgenic Plasmodium berghei sporozoites containing full-length P. falciparum CSP (tgPb-PfCSP) allow two assessments of efficacy: quantitative reduction in liver infection following intravenous challenge, and sterile protection from mosquito bite challenge. Two or three doses of RTS,S/AS01 were given intramuscularly at 3-week intervals, with challenge 2-weeks after the last vaccination. Minimal inter- and intra-assay variability indicates the reproducibility of the methods. Importantly, the range of this model is suitable for screening more potent vaccines. Levels of induced anti-CSP antibody 2A10 equivalency were also associated with activity: 105 μg/mL (95% CI: 68.8, 141) reduced liver infection by 50%, whereas 285 μg/mL (95% CI: 166, 404) is required for 50% sterile protection from mosquito bite challenge. Additionally, the liver burden model was able to differentiate between protected and non-protected human plasma samples from a controlled human malaria infection study, supporting these models' relevance and predictive capability. Comparison in animal models of CSP-based vaccine candidates to RTS,S/AS01 is now possible under well controlled conditions. Assessment of the quality of induced antibodies, likely a determinant of durability of protection in humans, should be possible using these methods.
Language	English
Publishing date	2024-02-10
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-024-00819-x
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Article ; Online: The Dragon’s Paralysing Spell

James S. Dobson / Richard J. Harris / Christina N. Zdenek / Tam Huynh / Wayne C. Hodgson / Frank Bosmans / Rudy Fourmy / Aude Violette / Bryan G. Fry

Toxins, Vol 13, Iss 549, p

Evidence of Sodium and Calcium Ion Channel Binding Neurotoxins in Helodermatid and Varanid Lizard Venoms

2021 Volume 549

Abstract: Bites from helodermatid lizards can cause pain, paresthesia, paralysis, and tachycardia, as well as other symptoms consistent with neurotoxicity. Furthermore, in vitro studies have shown that Heloderma horridum venom inhibits ion flux and blocks the ... ...

Abstract	Bites from helodermatid lizards can cause pain, paresthesia, paralysis, and tachycardia, as well as other symptoms consistent with neurotoxicity. Furthermore, in vitro studies have shown that Heloderma horridum venom inhibits ion flux and blocks the electrical stimulation of skeletal muscles. Helodermatids have long been considered the only venomous lizards, but a large body of robust evidence has demonstrated venom to be a basal trait of Anguimorpha. This clade includes varanid lizards, whose bites have been reported to cause anticoagulation, pain, and occasionally paralysis and tachycardia. Despite the evolutionary novelty of these lizard venoms, their neuromuscular targets have yet to be identified, even for the iconic helodermatid lizards. Therefore, to fill this knowledge gap, the venoms of three Heloderma species ( H. exasperatum , H. horridum and H. suspectum ) and two Varanus species ( V. salvadorii and V. varius ) were investigated using Gallus gallus chick biventer cervicis nerve–muscle preparations and biolayer interferometry assays for binding to mammalian ion channels. Incubation with Heloderma venoms caused the reduction in nerve-mediated muscle twitches post initial response of avian skeletal muscle tissue preparation assays suggesting voltage-gated sodium (Na V ) channel binding. Congruent with the flaccid paralysis inducing blockage of electrical stimulation in the skeletal muscle preparations, the biolayer interferometry tests with Heloderma suspectum venom revealed binding to the S3–S4 loop within voltage-sensing domain IV of the skeletal muscle channel subtype, Na V 1.4. Consistent with tachycardia reported in clinical cases, the venom also bound to voltage-sensing domain IV of the cardiac smooth muscle calcium channel, Ca V 1.2. While Varanus varius venom did not have discernable effects in the avian tissue preparation assay at the concentration tested, in the biointerferometry assay both V. varius and V. salvadorii bound to voltage-sensing domain IV of both Na V 1.4 and Ca V 1.2, similar to ...
Keywords	Heloderma ; Varanus ; venom ; Toxicofera ; neurotoxic ; sodium channel ; Medicine ; R
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Regulation of ERK2 activity by dynamic S-acylation.

Azizi, Saara-Anne / Qiu, Tian / Brookes, Noah E / Dickinson, Bryan C

Cell reports

2023 Volume 42, Issue 9, Page(s) 113135

Abstract: ... are subject to S-acylation, a reversible lipid modification of cysteine residues, at C271/C254 ... The levels of ERK1/2 S-acylation are modulated by epidermal growth factor (EGF) signaling, mirroring ... that ERK1/2 S-acylation is mediated by "writer" protein acyl transferases (PATs) and "eraser" acyl protein ...

Abstract	Extracellular signal-regulated kinases (ERK1/2) are key effector proteins of the mitogen-activated protein kinase pathway, choreographing essential processes of cellular physiology. Here, we discover that ERK1/2 are subject to S-acylation, a reversible lipid modification of cysteine residues, at C271/C254. The levels of ERK1/2 S-acylation are modulated by epidermal growth factor (EGF) signaling, mirroring its phosphorylation dynamics, and acylation-deficient ERK2 displays altered phosphorylation patterns. We show that ERK1/2 S-acylation is mediated by "writer" protein acyl transferases (PATs) and "eraser" acyl protein thioesterases (APTs) and that chemical inhibition of either lipid addition or removal alters ERK1/2's EGF-triggered transcriptional program. Finally, in a mouse model of metabolic syndrome, we find that ERK1/2 lipidation levels correlate with alterations in ERK1/2 lipidation writer/eraser expression, solidifying a link between ERK1/2 activity, ERK1/2 lipidation, and organismal health. This study describes how lipidation regulates ERK1/2 and offers insight into the role of dynamic S-acylation in cell signaling more broadly.
MeSH term(s)	Animals ; Mice ; Acylation ; Epidermal Growth Factor/pharmacology ; Extracellular Signal-Regulated MAP Kinases ; Lipids ; MAP Kinase Signaling System ; Phosphorylation
Chemical Substances	Epidermal Growth Factor (62229-50-9) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; Lipids ; Mapk1 protein, mouse (EC 2.7.11.24)
Language	English
Publishing date	2023-09-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.113135
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Article ; Online: Phylogeny and biogeography of the northern temperate genus Dracocephalum s.l. (Lamiaceae).

Chen, Ya-Ping / Turdimatovich, Turginov Orzimat / Nuraliev, Maxim S / Lazarević, Predrag / Drew, Bryan T / Xiang, Chun-Lei

Cladistics : the international journal of the Willi Hennig Society

2022 Volume 38, Issue 4, Page(s) 429–451

Abstract: ... the biogeographical history of the three genera (defined as Dracocephalum s.l.). Based on a sampling of 66 taxa ... comprising more than 80% from extant species of Dracocephalum s.l., morphological, phylogenetic (maximum ... within Dracocephalum s.l. Analyses of divergence times suggest that the genus experienced an early rapid radiation ...

Abstract	The northern temperate genus Dracocephalum consists of approximately 70 species mainly distributed in the steppe-desert biomes of Central and West Asia and the alpine region of the Qinghai-Tibetan Plateau (QTP). Previous work has shown that Dracocephalum is not monophyletic and might include Hyssopus and Lallemantia. This study attempts to clarify the phylogenetic relationships, diversification patterns, and the biogeographical history of the three genera (defined as Dracocephalum s.l.). Based on a sampling of 66 taxa comprising more than 80% from extant species of Dracocephalum s.l., morphological, phylogenetic (maximum parsimony, likelihood, and Bayesian inference based on nuclear ITS and ETS, plastid rpl32-trnL, trnL-trnF, ycf1, and ycf1-rps15, and two low-copy nuclear markers AT3G09060 and AT1G09680), molecular dating, diversification, and ancestral range estimation analyses were carried out. Our results demonstrate that both Hyssopus and Lallemantia are embedded within Dracocephalum and nine well-supported clades can be recognized within Dracocephalum s.l. Analyses of divergence times suggest that the genus experienced an early rapid radiation during the middle to late Miocene with major lineages diversifying within a relatively narrow timescale. Ancestral area reconstruction analyses indicate that Dracocephalum s.l. originated in Central and West Asia and southern Siberia, and dispersed from Central and West Asia into the QTP and adjacent areas twice independently during the Pliocene. The aridification of the Asian interior possibly promoted the rapid radiation of Dracocephalum within this region, and the uplift of the QTP appears to have triggered the dispersal and recent rapid diversification of the genus in the QTP and adjacent regions. Combining molecular phylogenetic and morphological evidence, a revised infrageneric classification of Dracocephalum s.l. is proposed, which recognizes nine sections within the genus.
MeSH term(s)	Bayes Theorem ; Ecosystem ; Lamiaceae/genetics ; Phylogeny ; Plastids
Language	English
Publishing date	2022-03-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1462608-1
ISSN	1096-0031 ; 0748-3007
ISSN (online)	1096-0031
ISSN	0748-3007
DOI	10.1111/cla.12502
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Article ; Online: Impact of the COVID-19 Pandemic on Indicators of Psychological Health and Suicidal Ideation Within an Active Duty U.S. Military Population.

Baker, Justin C / Bhola, Simran / Tabares, Jeffrey V / Beckman, Derek / Martin, Christiana / Khazem, Lauren R / Bryan, AnnaBelle O / Bryan, Craig J

Military medicine

2023 Volume 188, Issue Suppl 6, Page(s) 450–456

Abstract: ... A total of 2055 military personnel and military-adjacent employees stationed at a U.S. Air Force base ...

Abstract	Introduction: The COVID-19 pandemic has had a significant impact on the psychological health of individuals. The pandemic has contributed to increased anxiety, elevated rates of depression, and worsening suicidal ideation among civilians. Reported rates of burnout are also elevated as employees and employers adapted to ever-changing work environments, finding it increasingly difficult to maintain a work-life balance. The objective of this study is to determine how the COVID-19 pandemic impacted the psychological health and rates of suicidal ideation of active duty military personnel in the USA. Materials and methods: A total of 2055 military personnel and military-adjacent employees stationed at a U.S. Air Force base completed a self-report survey that was administered six times from January 2020 to December 2021. Validated scales assessed measures of psychological health and suicidal ideation. General Estimating Equations were used to examine how indicators of time and psychological health predicted suicidal ideation in a military population. Results: Life satisfaction, happiness, feeling life is worthwhile, depression severity, and suicidal ideation did not statistically change across the six time points. Worry (P < .01) and depression (P < .001) did decrease significantly, while burnout (P = .01) significantly increased across these time points. Feeling life is worthwhile significantly predicted reduced suicidal ideation (B = -.19; SE = 0.05), while depression (B = 0.11; SE = 0.03), depression severity (B = 0.24; SE = 0.05), worry (B = 0.06; SE = 0.02), and burnout (B = 0.15; SE = 0.07) predicted increased suicidal ideation. Conclusions: The rates of depression and worry decreased throughout the pandemic for those in the study while rates of suicidal ideation remained constant, demonstrating the potential resilience of military personnel and military-adjacent employees in response to the COVID-19 pandemic. However, burnout increased and significantly predicted elevated rates of suicidal ideation, highlighting the importance of focusing on reducing workplace stressors for military personnel.
MeSH term(s)	Humans ; Suicidal Ideation ; Military Personnel ; Pandemics ; COVID-19/epidemiology ; Emotions ; Depression/epidemiology ; Depression/psychology
Language	English
Publishing date	2023-11-10
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	391061-1
ISSN	1930-613X ; 0026-4075
ISSN (online)	1930-613X
ISSN	0026-4075
DOI	10.1093/milmed/usad200
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Article ; Online: The Chitranjan S. Ranawat Award: Manipulation Under Anesthesia to Treat Postoperative Stiffness After Total Knee Arthroplasty: A Multicenter Randomized Clinical Trial.

Abdel, Matthew P / Salmons, Harold I / Larson, Dirk R / Austin, Matthew S / Barnes, C Lowry / Bolognesi, Michael P / Della Valle, Craig J / Dennis, Douglas A / Garvin, Kevin L / Geller, Jeffrey A / Incavo, Stephen J / Lombardi, Adolph V / Peters, Christopher L / Schwarzkopf, Ran / Sculco, Peter K / Springer, Bryan D / Pagnano, Mark W / Berry, Daniel J

The Journal of arthroplasty

2024

Abstract: Background: Manipulation under anesthesia (MUA) occurs in 4% of patients after total knee arthroplasty (TKA). Anti-inflammatory medications may target arthrofibrosis pathogenesis, but the data are limited. This multicenter randomized clinical trial ... ...

Abstract	Background: Manipulation under anesthesia (MUA) occurs in 4% of patients after total knee arthroplasty (TKA). Anti-inflammatory medications may target arthrofibrosis pathogenesis, but the data are limited. This multicenter randomized clinical trial investigated the effect of adjuvant anti-inflammatory medications with MUA and physical therapy on range of motion (ROM) and outcomes. Methods: There were 124 patients (124 TKAs) who developed stiffness after primary TKA for osteoarthritis enrolled across 15 institutions. All received MUA when ROM was < 90° at 4 to 12 weeks postoperatively. Randomization proceeded via a permuted block design. Controls received MUA and physical therapy, while the treatment group also received one dose of pre-MUA intravenous dexamethasone (8 mg) and 14 days of oral celecoxib (200 mg). The ROM and clinical outcomes were assessed at 6 weeks and 1 year. This trial was registered with ClinicalTrials.gov. Results: The ROM significantly improved a mean of 46° from a pre-MUA ROM of 72 to 118° immediately after MUA (P < .001). The ROM was similar between the treatment and control groups at 6 weeks following MUA (101 versus 99°, respectively; P = .35) and at one year following MUA (108 versus 108°, respectively; P = .98). Clinical outcomes were similar at both end points. Conclusions: In this multicenter randomized clinical trial, the addition of intravenous dexamethasone and a short course of oral celecoxib after MUA did not improve ROM or outcomes. However, MUA provided a mean ROM improvement of 46° immediately, 28° at 6 weeks, and 37° at 1 year. Further investigation in regards to dosing, duration, and route of administration of anti-inflammatory medications remains warranted. Level of evidence: Level 1, RCT.
Language	English
Publishing date	2024-02-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	632770-9
ISSN	1532-8406 ; 0883-5403
ISSN (online)	1532-8406
ISSN	0883-5403
DOI	10.1016/j.arth.2024.02.034
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Article ; Online: A review of evidence on gender equality, women’s empowerment, and food systems

Njuki, Jemimah / Eissler, Sarah / Malapit, Hazel J. / Meinzen-Dick, Ruth Suseela / Bryan, Elizabeth / Quisumbing, Agnes R. / Malapit, Hazel / Meinzen-Dick, Ruth / Quisumbing, Agnes

In Science and Innovations for Food Systems Transformation, eds. Joachim von Braun, Kaosar Afsana, Louise O. Fresco, Mohamed Hag Ali Hassan. Pp. 165-189

2023

Abstract: Achieving gender equality and women’s empowerment in food systems can result in greater ... for all. This chapter uses a scoping review to assess the current evidence on pathways between gender equality, women’s ... on women’s differing access to resources, shaped and reinforced by contextual social gender norms, and ...

Abstract	Achieving gender equality and women’s empowerment in food systems can result in greater food security and better nutrition, as well as more just, resilient and sustainable food systems for all. This chapter uses a scoping review to assess the current evidence on pathways between gender equality, women’s empowerment and food systems. The chapter uses an adaptation of the food system framework to organize the evidence and identify where evidence is strong, and where gaps remain. Results show strong evidence on women’s differing access to resources, shaped and reinforced by contextual social gender norms, and on links between women’s empowerment and maternal education and important outcomes, such as nutrition and dietary diversity. However, evidence is limited on issues such as gender considerations in food systems for women in urban areas and in aquaculture value chains, best practices and effective pathways for engaging men in the process of women’s empowerment in food systems, and how to address issues related to migration, crises and indigenous food systems. While there are gender-informed evaluation studies examining the effectiveness of gender- and nutrition-sensitive agricultural programs, evidence indicating the long-term sustainability of such impacts remains limited. The chapter recommends key areas for investment: improving women’s leadership and decision-making in food systems, promoting equal and positive gender norms, improving access to resources, and building cross-contextual research evidence on gender and food systems. PR 2 Promoting Healthy Diets and Nutrition for all; 3 Building Inclusive and Efficient Markets, Trade Systems, and Food Industry; IFPRI4; Poverty, Gender, and Inclusion (PGI); Food and Nutrition Policy; Natural Resources and Resilience (NRR); Transformation Strategies
Keywords	WORLD ; gender ; women's empowerment ; gender equality ; food systems ; food security ; nutrition ; dietary diversity ; urban areas ; women ; men ; migration ; crises ; agricultural programs ; investments ; maternal education ; aquaculture value chains ; indigenous food systems
Subject code	360
Language	English
Publisher	Springer
Publishing country	us
Document type	Article ; Online
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Article ; Online: A method for comparing multiple imputation techniques: A case study on the U.S. national COVID cohort collaborative.

Journal of biomedical informatics

2023 Volume 139, Page(s) 104295

Abstract: Healthcare datasets obtained from Electronic Health Records have proven to be extremely useful for assessing associations between patients' predictors and outcomes of interest. However, these datasets often suffer from missing values in a high proportion ...

Abstract	Healthcare datasets obtained from Electronic Health Records have proven to be extremely useful for assessing associations between patients' predictors and outcomes of interest. However, these datasets often suffer from missing values in a high proportion of cases, whose removal may introduce severe bias. Several multiple imputation algorithms have been proposed to attempt to recover the missing information under an assumed missingness mechanism. Each algorithm presents strengths and weaknesses, and there is currently no consensus on which multiple imputation algorithm works best in a given scenario. Furthermore, the selection of each algorithm's parameters and data-related modeling choices are also both crucial and challenging. In this paper we propose a novel framework to numerically evaluate strategies for handling missing data in the context of statistical analysis, with a particular focus on multiple imputation techniques. We demonstrate the feasibility of our approach on a large cohort of type-2 diabetes patients provided by the National COVID Cohort Collaborative (N3C) Enclave, where we explored the influence of various patient characteristics on outcomes related to COVID-19. Our analysis included classic multiple imputation techniques as well as simple complete-case Inverse Probability Weighted models. Extensive experiments show that our approach can effectively highlight the most promising and performant missing-data handling strategy for our case study. Moreover, our methodology allowed a better understanding of the behavior of the different models and of how it changed as we modified their parameters. Our method is general and can be applied to different research fields and on datasets containing heterogeneous types.
MeSH term(s)	Humans ; COVID-19 ; Algorithms ; Research Design ; Bias ; Probability
Language	English
Publishing date	2023-01-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2057141-0
ISSN	1532-0480 ; 1532-0464
ISSN (online)	1532-0480
ISSN	1532-0464
DOI	10.1016/j.jbi.2023.104295
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