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  1. Article ; Online: The multiple links between actin and mitochondria.

    Fung, Tak Shun / Chakrabarti, Rajarshi / Higgs, Henry N

    Nature reviews. Molecular cell biology

    2023  Volume 24, Issue 9, Page(s) 651–667

    Abstract: ... at more than 1 h post-dysfunction, a second round of actin polymerization prepares mitochondria ...

    Abstract Actin plays many well-known roles in cells, and understanding any specific role is often confounded by the overlap of multiple actin-based structures in space and time. Here, we review our rapidly expanding understanding of actin in mitochondrial biology, where actin plays multiple distinct roles, exemplifying the versatility of actin and its functions in cell biology. One well-studied role of actin in mitochondrial biology is its role in mitochondrial fission, where actin polymerization from the endoplasmic reticulum through the formin INF2 has been shown to stimulate two distinct steps. However, roles for actin during other types of mitochondrial fission, dependent on the Arp2/3 complex, have also been described. In addition, actin performs functions independent of mitochondrial fission. During mitochondrial dysfunction, two distinct phases of Arp2/3 complex-mediated actin polymerization can be triggered. First, within 5 min of dysfunction, rapid actin assembly around mitochondria serves to suppress mitochondrial shape changes and to stimulate glycolysis. At a later time point, at more than 1 h post-dysfunction, a second round of actin polymerization prepares mitochondria for mitophagy. Finally, actin can both stimulate and inhibit mitochondrial motility depending on the context. These motility effects can either be through the polymerization of actin itself or through myosin-based processes, with myosin 19 being an important mitochondrially attached myosin. Overall, distinct actin structures assemble in response to diverse stimuli to affect specific changes to mitochondria.
    MeSH term(s) Actins/metabolism ; Mitochondria/metabolism ; Formins/metabolism ; Myosins/metabolism ; Endoplasmic Reticulum/metabolism
    Chemical Substances Actins ; Formins ; Myosins (EC 3.6.4.1)
    Language English
    Publishing date 2023-06-05
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2031313-5
    ISSN 1471-0080 ; 1471-0072
    ISSN (online) 1471-0080
    ISSN 1471-0072
    DOI 10.1038/s41580-023-00613-y
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  2. Article ; Online: Fatty acyl-coenzyme A activates mitochondrial division through oligomerization of MiD49 and MiD51.

    Liu, Ao / Kage, Frieda / Abdulkareem, Asan F / Aguirre-Huamani, Mac Pholo / Sapp, Gracie / Aydin, Halil / Higgs, Henry N

    Nature cell biology

    2024  

    Abstract: Mitochondrial fission occurs in many cellular processes, but the regulation of fission is poorly understood. We show that long-chain acyl-coenzyme A (LCACA) activates two related mitochondrial fission proteins, MiD49 and MiD51, by inducing their ... ...

    Abstract Mitochondrial fission occurs in many cellular processes, but the regulation of fission is poorly understood. We show that long-chain acyl-coenzyme A (LCACA) activates two related mitochondrial fission proteins, MiD49 and MiD51, by inducing their oligomerization, which activates their ability to stimulate the DRP1 GTPase. The 1:1 stoichiometry of LCACA:MiD in the oligomer suggests interaction in the previously identified nucleotide-binding pocket, and a point mutation in this pocket reduces LCACA binding and LCACA-induced oligomerization for MiD51. In cells, this LCACA binding mutant does not assemble into puncta on mitochondria or rescue MiD49/51 knockdown effects on mitochondrial length and DRP1 recruitment. Furthermore, cellular treatment with BSA-bound oleic acid, which causes increased LCACA, promotes mitochondrial fission in an MiD49/51-dependent manner. These results suggest that LCACA is an endogenous ligand for MiDs, inducing mitochondrial fission and providing a potential mechanism for fatty-acid-induced mitochondrial division. Finally, MiD49 or MiD51 oligomers synergize with Mff, but not with actin filaments, in DRP1 activation, suggesting distinct pathways for DRP1 activation.
    Language English
    Publishing date 2024-04-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 1474722-4
    ISSN 1476-4679 ; 1465-7392
    ISSN (online) 1476-4679
    ISSN 1465-7392
    DOI 10.1038/s41556-024-01400-3
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  3. Article ; Online: Preventing unrecognised oesophageal intubation: a consensus guideline from the Project for Universal Management of Airways and international airway societies.

    Chrimes, N / Higgs, A / Hagberg, C A / Baker, P A / Cooper, R M / Greif, R / Kovacs, G / Law, J A / Marshall, S D / Myatra, S N / O'Sullivan, E P / Rosenblatt, W H / Ross, C H / Sakles, J C / Sorbello, M / Cook, T M

    Anaesthesia

    2022  Volume 77, Issue 12, Page(s) 1395–1415

    Abstract: Across multiple disciplines undertaking airway management globally, preventable episodes of unrecognised oesophageal intubation result in profound hypoxaemia, brain injury and death. These events occur in the hands of both inexperienced and experienced ... ...

    Abstract Across multiple disciplines undertaking airway management globally, preventable episodes of unrecognised oesophageal intubation result in profound hypoxaemia, brain injury and death. These events occur in the hands of both inexperienced and experienced practitioners. Current evidence shows that unrecognised oesophageal intubation occurs sufficiently frequently to be a major concern and to merit a co-ordinated approach to address it. Harm from unrecognised oesophageal intubation is avoidable through reducing the rate of oesophageal intubation, combined with prompt detection and immediate action when it occurs. The detection of 'sustained exhaled carbon dioxide' using waveform capnography is the mainstay for excluding oesophageal placement of an intended tracheal tube. Tube removal should be the default response when sustained exhaled carbon dioxide cannot be detected. If default tube removal is considered dangerous, urgent exclusion of oesophageal intubation using valid alternative techniques is indicated, in parallel with evaluation of other causes of inability to detect carbon dioxide. The tube should be removed if timely restoration of sustained exhaled carbon dioxide cannot be achieved. In addition to technical interventions, strategies are required to address cognitive biases and the deterioration of individual and team performance in stressful situations, to which all practitioners are vulnerable. These guidelines provide recommendations for preventing unrecognised oesophageal intubation that are relevant to all airway practitioners independent of geography, clinical location, discipline or patient type.
    MeSH term(s) Humans ; Intubation, Intratracheal/methods ; Carbon Dioxide ; Capnography ; Esophagus ; Airway Management
    Chemical Substances Carbon Dioxide (142M471B3J)
    Language English
    Publishing date 2022-08-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 80033-8
    ISSN 1365-2044 ; 0003-2409
    ISSN (online) 1365-2044
    ISSN 0003-2409
    DOI 10.1111/anae.15817
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  4. Article ; Online: Benchmarking Refined and Unrefined AlphaFold2 Structures for Hit Discovery.

    Zhang, Yuqi / Vass, Marton / Shi, Da / Abualrous, Esam / Chambers, Jennifer M / Chopra, Nikita / Higgs, Christopher / Kasavajhala, Koushik / Li, Hubert / Nandekar, Prajwal / Sato, Hideyuki / Miller, Edward B / Repasky, Matthew P / Jerome, Steven V

    Journal of chemical information and modeling

    2023  Volume 63, Issue 6, Page(s) 1656–1667

    Abstract: The recently developed AlphaFold2 (AF2) algorithm predicts proteins' 3D structures from amino acid sequences. The open AlphaFold protein structure database covers the complete human proteome. Using an industry-leading molecular docking method (Glide), we ...

    Abstract The recently developed AlphaFold2 (AF2) algorithm predicts proteins' 3D structures from amino acid sequences. The open AlphaFold protein structure database covers the complete human proteome. Using an industry-leading molecular docking method (Glide), we investigated the virtual screening performance of 37 common drug targets, each with an AF2 structure and known
    MeSH term(s) Humans ; Binding Sites ; Molecular Docking Simulation ; Protein Binding ; Benchmarking ; Furylfuramide ; Peptide Elongation Factor 1/metabolism ; Proteins/chemistry ; Ligands
    Chemical Substances Furylfuramide (054NR2135Y) ; Peptide Elongation Factor 1 ; Proteins ; Ligands
    Language English
    Publishing date 2023-03-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 190019-5
    ISSN 1549-960X ; 0095-2338
    ISSN (online) 1549-960X
    ISSN 0095-2338
    DOI 10.1021/acs.jcim.2c01219
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  5. Article ; Online: Comment on: Transforming ophthalmic education into virtual learning during COVID-19 pandemic: a global perspective.

    Tzoumas, Nikolaos / Boote, Toby / Higgs, Jennie / Ellis, Heather / Dhillon, Baljean / Cackett, Peter

    Eye (London, England)

    2020  Volume 35, Issue 9, Page(s) 2648–2650

    MeSH term(s) COVID-19 ; Curriculum ; Education, Distance ; Humans ; Pandemics ; SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-09-14
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 91001-6
    ISSN 1476-5454 ; 0950-222X
    ISSN (online) 1476-5454
    ISSN 0950-222X
    DOI 10.1038/s41433-020-01182-6
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  6. Article ; Online: Social Mobilization for Ebola Virus Clinical Trials During a Public Health Crisis in Liberia.

    Kagan, Jonathan / Wilson, Barthalomew / Touchette, Nancy / Cone, Katherine / Kiawu, Hassan / Cooper, Joseph Boye / Endee, Juli / Bility, Khalipha / Doepel, Laurie / O'Neill, Rhys / Doe-Anderson, Jestina / Faley, Patrick Seeco / Higgs, Elizabeth / Lysander, Julia

    Progress in community health partnerships : research, education, and action

    2023  Volume 15, Issue 3, Page(s) 337–347

    Abstract: Background: At the invitation of the Liberia Ministry of Health and Social Welfare (LMOHSW), the U.S. Department of Health and Human Services joined the LMOHSW in establishing the Partnership for Research on Ebola Virus in Liberia (PREVAIL) to develop ... ...

    Abstract Background: At the invitation of the Liberia Ministry of Health and Social Welfare (LMOHSW), the U.S. Department of Health and Human Services joined the LMOHSW in establishing the Partnership for Research on Ebola Virus in Liberia (PREVAIL) to develop treatment and prevention strategies for Ebola virus disease (EVD). Social mobilization was a vital element of PREVAIL in a country with limited history of clinical research.
    Objectives: To innovate a social mobilization program for clinical trials during the Liberian EVD outbreak.
    Methods: PREVAIL's social mobilization included 1) advocacy for support from leaders, 2) engagement with communities to build trust, and 3) collaboration with media for quality communications.Lessons Learned and Conclusions: Social mobilization can support clinical trials. Trusted leaders and peer to peer communication are essential for sharing reliable information and countering mistrust. Real time monitoring of media can inform timely, specific messaging. Expert evaluation resources are essential for evidence-based effectiveness assessments.
    Language English
    Publishing date 2023-11-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2275483-0
    ISSN 1557-055X ; 1557-0541
    ISSN (online) 1557-055X
    ISSN 1557-0541
    DOI 10.1353/cpr.2021.0036
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  7. Article: Ancient genomic linkage couples metabolism with erythroid development.

    Preston, Alexandra E / Frost, Joe N / Badat, Mohsin / Teh, Megan / Armitage, Andrew E / Norfo, Ruggiero / Wideman, Sarah K / Hanifi, Muhammad / White, Natasha / Roy, Noémi / Ghesquiere, Bart / Babbs, Christian / Kassouf, Mira / Davies, James / Hughes, Jim R / Beagrie, Rob / Higgs, Douglas R / Drakesmith, Hal

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Generation of mature cells from progenitors requires tight coupling of differentiation and metabolism. During erythropoiesis, erythroblasts are required to massively upregulate globin synthesis then clear extraneous material and enucleate to produce ... ...

    Abstract Generation of mature cells from progenitors requires tight coupling of differentiation and metabolism. During erythropoiesis, erythroblasts are required to massively upregulate globin synthesis then clear extraneous material and enucleate to produce erythrocytes
    Language English
    Publishing date 2023-09-25
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.25.558944
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  8. Article ; Online: The APPLE Tree programme: Active Prevention in People at risk of dementia through Lifestyle, bEhaviour change and Technology to build REsiliEnce-randomised controlled trial.

    Poppe, M / Duffy, L / Marchant, N L / Barber, J A / Hunter, R / Bass, N / Minihane, A M / Walters, K / Higgs, P / Rapaport, P / Lang, I A / Morgan-Trimmer, S / Huntley, J / Walker, Z / Brodaty, H / Kales, H C / Ritchie, K / Burton, A / Wenborn, J /
    Betz, A / Cooper, C

    Trials

    2022  Volume 23, Issue 1, Page(s) 596

    Abstract: ... facilitators trained and supervised by a clinical psychologist deliver ten, 1-h group video call sessions over ...

    Abstract Background: Large-scale trials of multidomain interventions show that modifying lifestyle and psychological risk factors can slow cognitive decline. We aim to determine if a lower intensity, personally tailored secondary dementia prevention programme for older people with subjective or mild objective memory decline, informed by behaviour change theory, reduces cognitive decline over 2 years.
    Methods: A multi-site, single-blind randomised controlled trial recruiting 704 older adults at high dementia risk due to mild cognitive impairment (MCI) or subjective cognitive decline (SCD). Participants are randomised using 1:1 allocation ratio to the APPLE Tree intervention versus control arm (dementia prevention information), stratified by site. The intervention explores and implements strategies to promote healthy lifestyle, increase pleasurable activities and social connections and improve long-term condition self-management. Two facilitators trained and supervised by a clinical psychologist deliver ten, 1-h group video call sessions over 6 months (approximately every fortnight), video-call 'tea breaks' (less structured, facilitated social sessions) in intervening weeks and individual goal-setting phone calls every 2 weeks. From 6 to 12 months, participants meet monthly for 'tea breaks', with those not attending receiving monthly goal-setting phone calls. Participants receive a food delivery, pedometer and website access to cognitive training and information about lifestyle modification. Follow-ups for all outcome measures are at 12 and 24 months. The primary outcome is cognition (Neuropsychological Test Battery (NTB) score) at 24 months. Secondary outcomes are quality of life, cost per quality-adjusted life year (QALY) and wellbeing and lifestyle factors the intervention targets (diet, vascular risk, body weight, activity, sleep, anxiety, depression, social networks and loneliness, alcohol intake and smoking). Participants from purposively selected sites participate in qualitative process evaluation interviews, which will be analysed using thematic analytic methods.
    Discussion: If effective, the intervention design, involving remote delivery and non-clinical facilitators, would facilitate intervention roll-out to older people with memory concerns.
    Trial registration: ISRCTN17325135 . Registration date 27 November 2019.
    MeSH term(s) Aged ; Cost-Benefit Analysis ; Dementia ; Humans ; Life Style ; Malus ; Quality of Life ; Single-Blind Method ; Tea ; Technology
    Chemical Substances Tea
    Language English
    Publishing date 2022-07-26
    Publishing country England
    Document type Journal Article ; Randomized Controlled Trial
    ZDB-ID 2040523-6
    ISSN 1745-6215 ; 1468-6694 ; 1745-6215
    ISSN (online) 1745-6215
    ISSN 1468-6694 ; 1745-6215
    DOI 10.1186/s13063-022-06557-6
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  9. Article ; Online: How do I… facilitate a rapid response to a public health emergency requiring plasma collection with a public-private partnership?

    Miller, Maureen J / Skrzekut, Adam / Kracalik, Ian / Jones, Jefferson M / Lofy, Kathryn H / Konkle, Barbara A / Haley, N Rebecca / Duvenhage, Michael / Bonnett, Tyler / Holbrook, Michael / Higgs, Elizabeth / Basavaraju, Sridhar V / Paranjape, Suman

    Transfusion

    2021  Volume 61, Issue 10, Page(s) 2814–2824

    Abstract: In March 2020, there were no treatment options for COVID-19. Passive immune therapy including anti-SARS-CoV-2 hyperimmune globulin (hIVIG) was a logical candidate for COVID-19 therapeutic trials, given past success treating emerging pathogens with ... ...

    Abstract In March 2020, there were no treatment options for COVID-19. Passive immune therapy including anti-SARS-CoV-2 hyperimmune globulin (hIVIG) was a logical candidate for COVID-19 therapeutic trials, given past success treating emerging pathogens with endogenous neutralizing antibodies. We established a plasma collection protocol for persons recovered from COVID-19. To speed recruitment in the first U.S. hotspot, Seattle, Washington, federal and state public health agencies collaborated with Bloodworks Northwest to collect convalescent plasma (CP) for manufacturing hIVIG. During March-December 2020, we identified and recruited prospective CP donors via letters to persons recovered from COVID-19 with laboratory-confirmed SARS-CoV-2 infection. Prospective donors were pre-screened and administered a medical history survey. Anti-SARS-CoV-2 neutralizing antibody (NAb) titers were classified as qualifying (≥1:80) or non-qualifying (<1:80) for enrollment based on a live virus neutralization assay. Generalized estimating equations were used to identify characteristics of donors associated with qualifying versus nonqualifying NAb titers. Overall, 21,359 letters resulted in 3207 inquiries, 2159 prescreenings with laboratory-confirmed SARS-CoV-2 infection, and 573 donors (27% of all pre-screenings with confirmed infection) who provided a screening plasma donation. Of 573 donors screened, 254 (44%) provided plasma with qualifying NAb titers, resulting in 1284 units for hIVIG manufacture. In a multivariable model, after adjusting for other factors, time (60 days) from COVID-19 symptom onset to screening was associated with lower odds of qualifying NAb (adjusted odds ratio = 0.67, 95% CI: 0.48-0.94). The collaboration facilitated a rapid response to develop and provide hIVIG for clinical trials and CP for transfusion. Only 1 in 12 donor inquiries resulted in a qualifying plasma donation. Challenges included recruitment and the relatively low percentage of persons with high NAb titers and limited screening capacity. This resource-intensive collaboration may not be scalable but informs preparedness and response strategies for plasma collection in future epidemics. Operational readiness plans with templates for screening, consent, and data collection forms are recommended.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Blood Specimen Collection ; COVID-19/therapy ; Emergencies ; Female ; Humans ; Immunization, Passive ; Male ; Middle Aged ; Public Health ; Public-Private Sector Partnerships ; SARS-CoV-2 ; Young Adult
    Language English
    Publishing date 2021-09-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 208417-x
    ISSN 1537-2995 ; 0041-1132
    ISSN (online) 1537-2995
    ISSN 0041-1132
    DOI 10.1111/trf.16630
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    Zs.A 284: Show issues Location:
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  10. Article ; Online: Filling the intervention gap: service evaluation of an intensive nonsurgical weight management programme for severe and complex obesity.

    McCombie, L / Brosnahan, N / Ross, H / Bell-Higgs, A / Govan, L / Lean, M E J

    Journal of human nutrition and dietetics : the official journal of the British Dietetic Association

    2018  Volume 32, Issue 3, Page(s) 329–337

    Abstract: ... weight loss maintenance, all delivered by staff with 8 h of training, in-service mentoring, ongoing specialist ...

    Abstract Background: Weight management including formula total diet replacement (TDR) is emerging as an effective intervention for severe and complex obesity, particularly with respect to type 2 diabetes (T2DM). However, no prospective audit and service evaluation of such programmes have been reported.
    Methods: Following initial feasibility piloting, the Counterweight-Plus programme was commissioned across a variety of healthcare providers. The programme includes: Screening, TDR (formula low energy diet), food reintroduction and weight loss maintenance, all delivered by staff with 8 h of training, in-service mentoring, ongoing specialist support and access to medical consultant expertise. Anonymised data are returned centrally for clinical evaluation.
    Results: Up to December 2016, 288 patients commenced the programme. Mean (SD) baseline characteristics were: age 47.5 (12.7) years, weight 128.0 (32.0) kg, body mass index 45.7 (10.1) kg m
    Conclusions: This nonsurgical approach is effective for many individuals with severe and complex obesity, representing an option before considering surgery. The results are equally effective in terms of weight loss for people with T2DM.
    MeSH term(s) Adult ; Body Mass Index ; Caloric Restriction/methods ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/therapy ; Female ; Humans ; Male ; Medical Audit ; Mentoring/methods ; Middle Aged ; Obesity/complications ; Obesity/therapy ; Program Evaluation ; Scotland ; Treatment Outcome ; Weight Loss ; Weight Reduction Programs/methods
    Language English
    Publishing date 2018-11-22
    Publishing country England
    Document type Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645183-4
    ISSN 1365-277X ; 0952-3871 ; 1465-8178
    ISSN (online) 1365-277X
    ISSN 0952-3871 ; 1465-8178
    DOI 10.1111/jhn.12611
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