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Article ; Online: Insulin signalling regulates Pink1 mRNA localization via modulation of AMPK activity to support PINK1 function in neurons.

Hees, J Tabitha / Wanderoy, Simone / Lindner, Jana / Helms, Marlena / Murali Mahadevan, Hariharan / Harbauer, Angelika B

Nature metabolism

2024 Volume 6, Issue 3, Page(s) 514–530

Abstract: Mitochondrial quality control failure is frequently observed in neurodegenerative diseases. The detection of damaged mitochondria by stabilization of PTEN-induced kinase 1 (PINK1) requires transport of Pink1 messenger RNA (mRNA) by tethering it to the ... ...

Abstract	Mitochondrial quality control failure is frequently observed in neurodegenerative diseases. The detection of damaged mitochondria by stabilization of PTEN-induced kinase 1 (PINK1) requires transport of Pink1 messenger RNA (mRNA) by tethering it to the mitochondrial surface. Here, we report that inhibition of AMP-activated protein kinase (AMPK) by activation of the insulin signalling cascade prevents Pink1 mRNA binding to mitochondria. Mechanistically, AMPK phosphorylates the RNA anchor complex subunit SYNJ2BP within its PDZ domain, a phosphorylation site that is necessary for its interaction with the RNA-binding protein SYNJ2. Notably, loss of mitochondrial Pink1 mRNA association upon insulin addition is required for PINK1 protein activation and its function as a ubiquitin kinase in the mitophagy pathway, thus placing PINK1 function under metabolic control. Induction of insulin resistance in vitro by the key genetic Alzheimer risk factor apolipoprotein E4 retains Pink1 mRNA at the mitochondria and prevents proper PINK1 activity, especially in neurites. Our results thus identify a metabolic switch controlling Pink1 mRNA localization and PINK1 activity via insulin and AMPK signalling in neurons and propose a mechanistic connection between insulin resistance and mitochondrial dysfunction.
MeSH term(s)	Humans ; AMP-Activated Protein Kinases/metabolism ; Insulin/metabolism ; Insulin Resistance ; Neurons/metabolism ; Phosphorylation ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Ubiquitin-Protein Ligases/genetics ; Animals ; Mice ; Protein Kinases/genetics ; Protein Kinases/metabolism
Chemical Substances	AMP-Activated Protein Kinases (EC 2.7.11.31) ; Insulin ; RNA, Messenger ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; PTEN-induced putative kinase (EC 2.7.11.1) ; Protein Kinases (EC 2.7.-)
Language	English
Publishing date	2024-03-19
Publishing country	Germany
Document type	Journal Article
ISSN	2522-5812
ISSN (online)	2522-5812
DOI	10.1038/s42255-024-01007-w
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Article ; Online: Anesthesia Risk Alert Program: A Proactive Safety Initiative.

Lee, Brent / Marhalik-Helms, Julie / Penzi, Leo

Joint Commission journal on quality and patient safety

2023 Volume 49, Issue 9, Page(s) 441–449

Abstract: Background: Analyzing adverse events data collected over a three-year period on all anesthetic cases, North American Partners in Anesthesia (NAPA), a nationwide anesthesia practice, found a correlation between certain high-risk clinical factors and a ... ...

Abstract	Background: Analyzing adverse events data collected over a three-year period on all anesthetic cases, North American Partners in Anesthesia (NAPA), a nationwide anesthesia practice, found a correlation between certain high-risk clinical factors and a number of critical events. Seeking to reduce the incidence of critical adverse events associated with these high-risk factors, the quality team of the NAPA Anesthesia Patient Safety Institute (NAPSI) developed the Anesthesia Risk Alert (ARA) program, which guides clinicians in proactively applying targeted risk mitigation interventions in five specific clinical scenarios. NAPSI is NAPA's Patient Safety Organization (PSO). Methods: ARA promotes a proactive (Safety II) approach to patient safety. The protocol incorporates innovative collaboration techniques to improve clinical decision-making, along with recommendations by professional medical societies. ARA risk mitigation strategies also adapt decision tools from other industries, such as red team/blue team methodology. Following implementation training to approximately 6,000 NAPA clinicians, ongoing compliance is tracked for the program's two components: screening patients for the five high-risk clinical scenarios and performing the associated mitigation strategy when one or more risk factor is identified. Results: Since launching the ARA program in 2019, clinician compliance consistently exceeds 95%. Simultaneously, available data indicate that the incidence of selected adverse events has decreased. Conclusion: ARA, developed as a process improvement initiative to reduce patient harm in several vulnerable perioperative patient populations, demonstrates how proactive safety strategies can improve clinical outcomes and create better perioperative cultures. At various sites, NAPA anesthesia clinicians reported that ARA's collaboration strategies were transformative behaviors that extended beyond the operating room. Other health care providers may customize the lessons learned from ARA with a Safety II approach.
MeSH term(s)	Humans ; Anesthesia/adverse effects ; Patient Safety ; Anesthesiology ; Risk Factors ; Operating Rooms
Language	English
Publishing date	2023-06-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1189890-2
ISSN	1938-131X ; 1549-425X ; 1553-7250 ; 1070-3241 ; 1549-3741
ISSN (online)	1938-131X ; 1549-425X
ISSN	1553-7250 ; 1070-3241 ; 1549-3741
DOI	10.1016/j.jcjq.2023.06.005
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Article: A Case of Reverse McConnell's Sign Associated With Acute Respiratory Distress Syndrome and Septic Shock.

Curtis, Brett / Ha, Albert / Xie, Jeffrey / Hyzy, Robert / Helms, Adam S

Cureus

2024 Volume 16, Issue 1, Page(s) e52166

Abstract: We present a case of reverse McConnell's sign, a rare echocardiographic finding of right ventricular apical hypokinesis and basal hyperkinesis, in a patient with acute respiratory distress syndrome and septic shock. Although multiple etiologies were ... ...

Abstract	We present a case of reverse McConnell's sign, a rare echocardiographic finding of right ventricular apical hypokinesis and basal hyperkinesis, in a patient with acute respiratory distress syndrome and septic shock. Although multiple etiologies were hypothesized, providers attributed this cardiomyopathy to increased right heart afterload from hypoxic pulmonary vasoconstriction. Cardiac function normalized as the patient's respiratory failure and sepsis resolved. This study highlights the value of early echocardiography to help guide management in critical illness. In our case, this finding helped initiate diuresis and establish a baseline for monitoring cardiac function as this patient's critical illness resolved. Literature has most commonly associated reverse McConnell's sign with massive pulmonary embolism and, more rarely, takotsubo cardiomyopathy. Given the absence of PE, takotsubo, or other identifiable cause, this case suggests that reverse McConnell's sign may more generally indicate acutely increased right ventricular afterload rather than a specific diagnosis. When reverse McConnell's sign is detected, treatment should focus on reversible causes of elevated right heart pressure (e.g., volume overload, PE) and increased pulmonary resistance.
Language	English
Publishing date	2024-01-12
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.52166
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Article: Interprofessional Active Learning for Chronic Pain: Transforming Student Learning From Recall to Application.

Helms, Jeb / Frankart, Laura / Bradner, Melissa / Ebersole, Jonathan / Regan, Beck / Crouch, Taylor

Journal of medical education and curricular development

2023 Volume 10, Page(s) 23821205231221950

Abstract: Chronic pain (CP) affects over 50 million Americans daily and represents a unique challenge for healthcare professionals due to its complexity. Across all health professions, only a small percentage of the curriculum is devoted to treating patients with ... ...

Abstract	Chronic pain (CP) affects over 50 million Americans daily and represents a unique challenge for healthcare professionals due to its complexity. Across all health professions, only a small percentage of the curriculum is devoted to treating patients with CP. Unfortunately, much of the content is delivered passively via lecture without giving students an opportunity to practice the communication skills to effectively treat patients in the clinic. An interprofessional team of health educators identified 5 essential messages that students frequently struggle to convey to patients with CP. Those messages were based on interprofessional and profession-specific competencies to treat patients with CP from the International Association for the Study of Pain. The 5 messages highlighted the importance of (1) therapeutic alliance, (2) consistent interdisciplinary language, (3) patient prognosis, (4) evidence for pain medicine, surgery, and imaging, and (5) early referral to the interprofessional team. For each message, the team summarized relevant research supporting the importance of each individual message that could serve as a foundation for didactic content. The team then developed active learning educational activities that educators could use to have students practice the skills tied to each message. Each learning activity was designed to be delivered in an interprofessional manner.
Language	English
Publishing date	2023-12-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2798123-X
ISSN	2382-1205
ISSN	2382-1205
DOI	10.1177/23821205231221950
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Article ; Online: Retinoids in health and disease: A role for hepatic stellate cells in affecting retinoid levels.

Haaker, Maya W / Vaandrager, Arie B / Helms, J Bernd

Biochimica et biophysica acta. Molecular and cell biology of lipids

2020 Volume 1865, Issue 6, Page(s) 158674

Abstract: Vitamin A (retinol) is important for normal growth, vision and reproduction. It has a role in the immune response and the development of metabolic syndrome. Most of the retinol present in the body is stored as retinyl esters within lipid droplets in ... ...

Abstract	Vitamin A (retinol) is important for normal growth, vision and reproduction. It has a role in the immune response and the development of metabolic syndrome. Most of the retinol present in the body is stored as retinyl esters within lipid droplets in hepatic stellate cells (HSCs). In case of liver damage, HSCs release large amounts of stored retinol, which is partially converted to retinoic acid (RA). This surge of RA can mediate the immune response and enhance the regeneration of the liver. If the damage persists activated HSCs change into myofibroblast-like cells producing extracellular matrix, which increases the chance of tumorigenesis to occur. RA has been shown to decrease proliferation and metastasis of hepatocellular carcinoma. The levels of RA and RA signaling are influenced by the possibility to esterify retinol towards retinyl esters. This suggests a complex regulation between different retinoids, with an important regulatory role for HSCs.
MeSH term(s)	Carcinogenesis/pathology ; Carcinoma, Hepatocellular/pathology ; Esters/metabolism ; Extracellular Matrix/metabolism ; Hepatic Stellate Cells/cytology ; Hepatic Stellate Cells/metabolism ; Humans ; Lipid Droplets/metabolism ; Liver/cytology ; Liver/metabolism ; Liver/pathology ; Liver Neoplasms/pathology ; Liver Regeneration ; Signal Transduction/physiology ; Vitamin A/metabolism
Chemical Substances	Esters ; Vitamin A (11103-57-4)
Language	English
Publishing date	2020-02-24
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	60-7
ISSN	1879-2618 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2618 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbalip.2020.158674
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Article ; Online: Belowground insect herbivory induces systemic volatile emissions that strengthen neighbouring plant resistance aboveground.

Thompson, Morgan N / Arriaga, Jayda / Bradford, B Jack / Kurian, Rachel / Strozier, Gage / Helms, Anjel M

Plant, cell & environment

2023 Volume 47, Issue 2, Page(s) 714–725

Abstract: Plants transmit ecologically relevant messages to neighbouring plants through chemical cues. For instance, insect herbivory triggers the production of herbivore-induced plant volatiles (HIPVs), which can enhance neighbouring plant defences. HIPVs are ... ...

Abstract	Plants transmit ecologically relevant messages to neighbouring plants through chemical cues. For instance, insect herbivory triggers the production of herbivore-induced plant volatiles (HIPVs), which can enhance neighbouring plant defences. HIPVs are emitted from directly damaged plant tissues and from systemic, nondamaged tissues. Although volatile-mediated interplant interactions have been observed both above- and belowground, it remains unknown whether belowground herbivory induces systemic HIPVs aboveground that influence neighbouring plants. To explore how belowground herbivory affects interplant interactions aboveground, we characterised systemic HIPVs from squash induced by belowground striped cucumber beetle (Acalymma vittatum) larval herbivory. We exposed squash 'receiver plants' to systemic HIPVs or volatiles from nondamaged plants. We then measured herbivore resistance by challenging 'receiver plants' with aboveground-feeding herbivores: adult beetles (A. vittatum) or squash bugs (Anasa tristis). We discovered belowground-damaged plants emitted more (E)-β-ocimene, a key volatile from the systemic HIPV blend, than nondamaged controls, and that exposure to systemic HIPVs enhanced neighbouring plant resistance to aboveground squash bugs, but not adult beetles. Further investigations into the mechanism of interplant interaction revealed β-ocimene alone can elicit plant resistance against squash bugs. Overall, our findings reveal a novel form of volatile-mediated interactions between plants spanning across aboveground-belowground plant systems.
MeSH term(s)	Animals ; Herbivory ; Insecta ; Acyclic Monoterpenes ; Larva ; Coleoptera ; Plants ; Volatile Organic Compounds
Chemical Substances	beta-ocimene (13877-91-3) ; Acyclic Monoterpenes ; Volatile Organic Compounds
Language	English
Publishing date	2023-11-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	391893-2
ISSN	1365-3040 ; 0140-7791
ISSN (online)	1365-3040
ISSN	0140-7791
DOI	10.1111/pce.14762
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Article ; Online: Effects of masticatory loading on bone remodeling around teeth versus implants: Insights from a preclinical model.

Tian, Ye / Sadowsky, Steven J / Brunski, John B / Yuan, Xue / Helms, Jill A

Clinical oral implants research

2022 Volume 33, Issue 3, Page(s) 342–352

Abstract: Objectives: Teeth connect to bone via a periodontal ligament, whereas implants connect to bone directly. Consequently, masticatory loads are distributed differently to periodontal versus peri-implant bone. Our objective was to determine how masticatory ... ...

Abstract	Objectives: Teeth connect to bone via a periodontal ligament, whereas implants connect to bone directly. Consequently, masticatory loads are distributed differently to periodontal versus peri-implant bone. Our objective was to determine how masticatory loading of an implant versus a tooth affected peri-implant versus periodontal bone remodeling. Our hypothesis was that strains produced by functional loading of an implant would be elevated compared with the strains around teeth, and that this would stimulate a greater degree of bone turnover around implants versus in periodontal bone. Materials and methods: Sixty skeletally mature mice were divided into two groups. In the implant group, maxillary first molars (mxM1) were extracted, and after socket healing, titanium alloy implants were positioned subocclusally. After osseointegration, implants were exposed, resin crowns were placed, and masticatory loading was initiated. In the control group, the dentition was left intact. Responses of peri-implant and periodontal bone were measured using micro-CT, histology, bone remodeling assays, and quantitative histomorphometry while bone strains were estimated using finite element (FE) analyses. Conclusions: When a submerged osseointegrated implant is exposed to masticatory forces, peri-implant strains are elevated, and peri-implant bone undergoes significant remodeling that culminates in new bone accrual. The accumulation of new bone functions to reduce both peri-implant strains and bone remodeling activities, equivalent to those observed around the intact dentition.
MeSH term(s)	Animals ; Bone Remodeling ; Crowns ; Dental Implants ; Finite Element Analysis ; Mice ; Osseointegration/physiology
Chemical Substances	Dental Implants
Language	English
Publishing date	2022-02-04
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	1067626-0
ISSN	1600-0501 ; 0905-7161
ISSN (online)	1600-0501
ISSN	0905-7161
DOI	10.1111/clr.13894
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Article ; Online: Tomato-Flavored Beverage and Onion-Flavored Chip Dip Made from Cottage Cheese Whey.

Demott, B J / Helms, A B / Sanders, O G

Journal of food protection

2019 Volume 40, Issue 8, Page(s) 540–542

Abstract: Whey from cottage cheese made by the short-set culture method was used to make tomato-flavored drink by addition of 6% dried tomato-spice flavoring material, and was found by 10 panelists to have a pleasing taste. Heat treatment of cottage cheese whey at ...

Abstract	Whey from cottage cheese made by the short-set culture method was used to make tomato-flavored drink by addition of 6% dried tomato-spice flavoring material, and was found by 10 panelists to have a pleasing taste. Heat treatment of cottage cheese whey at 93 to 99 C resulted in a precipitate containing over 9% total solids. This precipitate was further concentrated by centrifugation or filtration through a cotton cloth. The precipitates were blended with xanthan gum and onion-flavoring to produce a chip dip.
Language	English
Publishing date	2019-01-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	243284-5
ISSN	1944-9097 ; 0362-028X
ISSN (online)	1944-9097
ISSN	0362-028X
DOI	10.4315/0362-028X-40.8.540
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Article ; Online: Characterization of different oligomeric forms of CRISP2 in the perinuclear theca versus the fibrous tail structures of boar spermatozoa†.

Zhang, M / Bromfield, E G / Veenendaal, T / Klumperman, J / Helms, J B / Gadella, B M

Biology of reproduction

2021 Volume 105, Issue 5, Page(s) 1160–1170

Abstract: Mammalian sperm carry a variety of highly condensed insoluble protein structures such as the perinuclear theca, the fibrous sheath and the outer dense fibers, which are essential to sperm function. We studied the role of cysteine rich secretory protein 2 ...

Abstract	Mammalian sperm carry a variety of highly condensed insoluble protein structures such as the perinuclear theca, the fibrous sheath and the outer dense fibers, which are essential to sperm function. We studied the role of cysteine rich secretory protein 2 (CRISP2); a known inducer of non-pathological protein amyloids, in pig sperm with a variety of techniques. CRISP2, which is synthesized during spermatogenesis, was localized by confocal immunofluorescent imaging in the tail and in the post-acrosomal region of the sperm head. High-resolution localization by immunogold labeling electron microscopy of ultrathin cryosections revealed that CRISP2 was present in the perinuclear theca and neck region of the sperm head, as well as in the outer dense fibers and the fibrous sheath of the sperm tail. Interestingly, we found that under native, non-reducing conditions CRISP2 formed oligomers both in the tail and the head but with different molecular weights and different biochemical properties. The tail oligomers were insensitive to reducing conditions but nearly complete dissociated into monomers under 8 M urea treatment, while the head 250 kDa CRISP2 positive oligomer completely dissociated into CRISP2 monomers under reducing conditions. The head specific dissociation of CRISP2 oligomer is likely a result of the reduction of various sulfhydryl groups in the cysteine rich domain of this protein. The sperm head CRISP2 shared typical solubilization characteristics with other perinuclear theca proteins as was shown with sequential detergent and salt treatments. Thus, CRISP2 is likely to participate in the formation of functional protein complexes in both the sperm tail and sperm head, but with differing oligomeric organization and biochemical properties. Future studies will be devoted to the understand the role of CRISP2 in sperm protein complexes formation and how this contributes to the fertilization processes.
MeSH term(s)	Animals ; Cell Adhesion Molecules/genetics ; Cell Adhesion Molecules/metabolism ; Cytoskeleton/metabolism ; Male ; Sperm Tail/metabolism ; Spermatogenesis ; Spermatozoa/metabolism ; Sus scrofa/physiology
Chemical Substances	Cell Adhesion Molecules
Language	English
Publishing date	2021-07-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1118-6
ISSN	1529-7268 ; 0006-3363
ISSN (online)	1529-7268
ISSN	0006-3363
DOI	10.1093/biolre/ioab145
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Article ; Online: Linking the Mechanics of Chewing to Biology of the Junctional Epithelium.

Yuan, X / Liu, B / Cuevas, P / Brunski, J / Aellos, F / Petersen, J / Koehne, T / Bröer, S / Grüber, R / LeBlanc, A / Zhang, X / Xu, Q / Helms, J A

Journal of dental research

2023 Volume 102, Issue 11, Page(s) 1252–1260

Abstract: The capacity of a tissue to continuously alter its phenotype lies at the heart of how an animal is able to quickly adapt to changes in environmental stimuli. Within tissues, differentiated cells are rigid and play a limited role in adapting to new ... ...

Abstract	The capacity of a tissue to continuously alter its phenotype lies at the heart of how an animal is able to quickly adapt to changes in environmental stimuli. Within tissues, differentiated cells are rigid and play a limited role in adapting to new environments; however, differentiated cells are replenished by stem cells that are defined by their phenotypic plasticity. Here we demonstrate that a Wnt-responsive stem cell niche in the junctional epithelium is responsible for the capability of this tissue to quickly adapt to changes in the physical consistency of a diet. Mechanical input from chewing is required to both establish and maintain this niche. Since the junctional epithelium directly attaches to the tooth surface via hemidesmosomes, a soft diet requires minimal mastication, and consequently, lower distortional strains are produced in the tissue. This reduced strain state is accompanied by reduced mitotic activity in both stem cells and their progeny, leading to tissue atrophy. The atrophied junctional epithelium exhibits suboptimal barrier functions, allowing the ingression of bacteria into the underlying connective tissues, which in turn trigger inflammation and mild alveolar bone loss. These data link the mechanics of chewing to the biology of tooth-supporting tissues, revealing how a stem cell niche is responsible for the remarkable adaptability of the junctional epithelium to different diets.
MeSH term(s)	Animals ; Epithelial Attachment ; Gingiva ; Mastication ; Connective Tissue ; Biology ; Epithelium
Language	English
Publishing date	2023-08-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80207-4
ISSN	1544-0591 ; 0022-0345
ISSN (online)	1544-0591
ISSN	0022-0345
DOI	10.1177/00220345231185288
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