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Article ; Online: Bacterial manganese sensing and homeostasis.

Waters, Lauren S

2020 Volume 55, Page(s) 96–102

Abstract: Manganese (Mn) plays a complex role in the survival of pathogenic and symbiotic bacteria in eukaryotic hosts and is also important for free-living bacteria to thrive in stressful environments. This review summarizes new aspects of regulatory strategies ... ...

Abstract	Manganese (Mn) plays a complex role in the survival of pathogenic and symbiotic bacteria in eukaryotic hosts and is also important for free-living bacteria to thrive in stressful environments. This review summarizes new aspects of regulatory strategies to control intracellular Mn levels and gives an overview of several newly identified families of bacterial Mn transporters. Recent illustrative examples of advances in quantification of intracellular Mn pools and characterization of the effects of Mn perturbations are highlighted. These discoveries help define mechanisms of Mn selectivity and toxicity and could enable new strategies to combat pathogenic bacteria and promote growth of desirable bacteria.
MeSH term(s)	Amino Acid Sequence ; Bacteria/chemistry ; Bacteria/metabolism ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Cell Membrane Permeability ; Gene Expression Regulation, Bacterial ; Homeostasis/physiology ; Manganese/chemistry ; Manganese/metabolism ; Membrane Transport Proteins/genetics ; Membrane Transport Proteins/metabolism ; Mutation ; Reactive Oxygen Species/metabolism ; Riboswitch ; Substrate Specificity ; Superoxide Dismutase/metabolism ; Transcription Factors/metabolism
Chemical Substances	Bacterial Proteins ; Membrane Transport Proteins ; Reactive Oxygen Species ; Riboswitch ; Transcription Factors ; Manganese (42Z2K6ZL8P) ; Superoxide Dismutase (EC 1.15.1.1)
Language	English
Publishing date	2020-02-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1439176-4
ISSN	1879-0402 ; 1367-5931
ISSN (online)	1879-0402
ISSN	1367-5931
DOI	10.1016/j.cbpa.2020.01.003
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Article: Regulation of Bacterial Manganese Homeostasis and Usage During Stress Responses and Pathogenesis.

Martin, Julia E / Waters, Lauren S

Frontiers in molecular biosciences

2022 Volume 9, Page(s) 945724

Abstract: Manganese (Mn) plays a multifaceted role in the survival of pathogenic and symbiotic bacteria in eukaryotic hosts, and it is also important for free-living bacteria to grow in stressful environments. Previous research has uncovered components of the ... ...

Abstract	Manganese (Mn) plays a multifaceted role in the survival of pathogenic and symbiotic bacteria in eukaryotic hosts, and it is also important for free-living bacteria to grow in stressful environments. Previous research has uncovered components of the bacterial Mn homeostasis systems that control intracellular Mn levels, many of which are important for virulence. Multiple studies have also identified proteins that use Mn once it is inside the cell, including Mn-specific enzymes and enzymes transiently loaded with Mn for protection during oxidative stress. Emerging evidence continues to reveal proteins involved in maintaining Mn homeostasis, as well as enzymes that can bind Mn. For some of these enzymes, Mn serves as an essential cofactor. For other enzymes, mismetallation with Mn can lead to inactivation or poor activity. Some enzymes may even potentially be regulated by differential metallation with Mn or zinc (Zn). This review focuses on new developments in regulatory mechanisms that affect Mn homeostasis and usage, additional players in Mn import that increase bacterial survival during pathogenesis, and the interplay between Mn and other metals during Mn-responsive physiological processes. Lastly, we highlight lessons learned from fundamental research that are now being applied to bacterial interactions within larger microbial communities or eukaryotic hosts.
Language	English
Publishing date	2022-07-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2022.945724
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Article ; Online: Evaluating the Acceptability and Feasibility of Collecting Passive Smartphone Data to Estimate Psychological Functioning in U.S. Service Members and Veterans: A Pilot Study.

Schultz, Lauren S / Murphy, Mikela A / Donegan, Macayla / Knights, Jonathan / Baker, Justin T / Thompson, Matthew F / Waters, Andrew J / Roy, Michael / Gray, Joshua C

Military medicine

2024

Abstract: Introduction: This study investigated the acceptability and feasibility of digital phenotyping in a military sample with a history of traumatic brain injury and co-occurring psychological and cognitive symptoms. The first aim was to evaluate the ... ...

Abstract	Introduction: This study investigated the acceptability and feasibility of digital phenotyping in a military sample with a history of traumatic brain injury and co-occurring psychological and cognitive symptoms. The first aim was to evaluate the acceptability of digital phenotyping by (1a) quantifying the proportion of participants willing to download the app and rates of dropout and app discontinuation and (1b) reviewing the stated reasons for both refusing and discontinuing use of the app. The second aim was to investigate technical feasibility by (2a) characterizing the amount and frequency of transferred data and (2b) documenting technical challenges. Exploratory aim 3 sought to leverage data on phone and keyboard interactions to predict if a participant (a) is depressed and (b) has depression that improves over the course of the study. Materials and methods: A passive digital phenotyping app (Mindstrong Discovery) functioned in the background of the participants' smartphones and passively collected phone usage and typing kinematics data. Results: Fifteen out of 16 participants (93.8%) consented to install the app on their personal smartphone devices. Four participants (26.7%) discontinued the use of the app partway through the study, primarily because of keyboard usability and technical issues. Fourteen out of 15 participants (93.3%) had at least one data transfer, and the median number of days with data was 40 out of a possible 57 days. The exploratory machine learning models predicting depression status and improvement in depression performed better than chance. Conclusions: The findings of this pilot study suggest that digital phenotyping is acceptable and feasible in a military sample and provides support for future larger investigations of this technology.
Language	English
Publishing date	2024-04-15
Publishing country	England
Document type	Journal Article
ZDB-ID	391061-1
ISSN	1930-613X ; 0026-4075
ISSN (online)	1930-613X
ISSN	0026-4075
DOI	10.1093/milmed/usae144
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Article ; Online: No stone left unturned: a case of malignant mimicry.

Gearing, Peter F / Apte, Sameer S / Cohen, Lauren / Mohan, Helen / Heriot, Alexander G / Kong, Joseph C / Waters, Peadar S

ANZ journal of surgery

2021 Volume 92, Issue 5, Page(s) 1268–1270

Language	English
Publishing date	2021-10-13
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2050749-5
ISSN	1445-2197 ; 1445-1433 ; 0004-8682
ISSN (online)	1445-2197
ISSN	1445-1433 ; 0004-8682
DOI	10.1111/ans.17279
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Article ; Online: The small protein MntS evolved from a signal peptide and acquired a novel function regulating manganese homeostasis in Escherichia coli.

Wright, Zachary / Seymour, Mackenzie / Paszczak, Kalista / Truttmann, Taylor / Senn, Katherine / Stilp, Samuel / Jansen, Nickolas / Gosz, Magdalyn / Goeden, Lindsay / Anantharaman, Vivek / Aravind, L / Waters, Lauren S

Molecular microbiology

2023 Volume 121, Issue 1, Page(s) 152–166

Abstract: Small proteins (<50 amino acids) are emerging as ubiquitous and important regulators in organisms ranging from bacteria to humans, where they commonly bind to and regulate larger proteins during stress responses. However, fundamental aspects of small ... ...

Abstract	Small proteins (<50 amino acids) are emerging as ubiquitous and important regulators in organisms ranging from bacteria to humans, where they commonly bind to and regulate larger proteins during stress responses. However, fundamental aspects of small proteins, such as their molecular mechanism of action, downregulation after they are no longer needed, and their evolutionary provenance, are poorly understood. Here, we show that the MntS small protein involved in manganese (Mn) homeostasis binds and inhibits the MntP Mn transporter. Mn is crucial for bacterial survival in stressful environments but is toxic in excess. Thus, Mn transport is tightly controlled at multiple levels to maintain optimal Mn levels. The small protein MntS adds a new level of regulation for Mn transporters, beyond the known transcriptional and post-transcriptional control. We also found that MntS binds to itself in the presence of Mn, providing a possible mechanism of downregulating MntS activity to terminate its inhibition of MntP Mn export. MntS is homologous to the signal peptide of SitA, the periplasmic metal-binding subunit of a Mn importer. Remarkably, the homologous signal peptide regions can substitute for MntS, demonstrating a functional relationship between MntS and these signal peptides. Conserved gene neighborhoods support that MntS evolved from the signal peptide of an ancestral SitA protein, acquiring a life of its own with a distinct function in Mn homeostasis.
MeSH term(s)	Humans ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Manganese/metabolism ; Protein Sorting Signals ; Homeostasis ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Membrane Transport Proteins/metabolism ; Bacterial Proteins/metabolism
Chemical Substances	Manganese (42Z2K6ZL8P) ; Protein Sorting Signals ; Escherichia coli Proteins ; Membrane Transport Proteins ; Bacterial Proteins ; MntP protein, E coli
Language	English
Publishing date	2023-12-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	619315-8
ISSN	1365-2958 ; 0950-382X
ISSN (online)	1365-2958
ISSN	0950-382X
DOI	10.1111/mmi.15206
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Article: The small protein MntS evolved from a signal peptide and acquired a novel function regulating manganese homeostasis in

bioRxiv : the preprint server for biology

2023

Abstract: Small proteins (< 50 amino acids) are emerging as ubiquitous and important regulators in organisms ranging from bacteria to humans, where they commonly bind to and regulate larger proteins during stress responses. However, fundamental aspects of small ... ...

Abstract	Small proteins (< 50 amino acids) are emerging as ubiquitous and important regulators in organisms ranging from bacteria to humans, where they commonly bind to and regulate larger proteins during stress responses. However, fundamental aspects of small proteins, such as their molecular mechanism of action, downregulation after they are no longer needed, and their evolutionary provenance are poorly understood. Here we show that the MntS small protein involved in manganese (Mn) homeostasis binds and inhibits the MntP Mn transporter. Mn is crucial for bacterial survival in stressful environments, but is toxic in excess. Thus, Mn transport is tightly controlled at multiple levels to maintain optimal Mn levels. The small protein MntS adds a new level of regulation for Mn transporters, beyond the known transcriptional and post-transcriptional control. We also found that MntS binds to itself in the presence of Mn, providing a possible mechanism of downregulating MntS activity to terminate its inhibition of MntP Mn export. MntS is homologous to the signal peptide of SitA, the periplasmic metal-binding subunit of a Mn importer. Remarkably, the homologous signal peptide regions can substitute for MntS, demonstrating a functional relationship between MntS and these signal peptides. Conserved gene-neighborhoods support that MntS evolved from an ancestral SitA, acquiring a life of its own with a distinct function in Mn homeostasis. Significance: This study demonstrates that the MntS small protein binds and inhibits the MntP Mn exporter, adding another layer to the complex regulation of Mn homeostasis. MntS also interacts with itself in cells with Mn, which could prevent it from regulating MntP. We propose that MntS and other small proteins might sense environmental signals and shut off their own regulation via binding to ligands (e.g., metals) or other proteins. We also provide evidence that MntS evolved from the signal peptide region of the Mn importer, SitA. Homologous SitA signal peptides can recapitulate MntS activities, showing that they have a second function beyond protein secretion. Overall, we establish that small proteins can emerge and develop novel functionalities from gene remnants.
Language	English
Publishing date	2023-06-03
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.06.02.543501
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Article ; Online: Introduction to Disability and Antiableist Health Care: A Pilot, Student-Led Module for Preclinical Medical Students.

Smeltz, Lydia / Carpenter, Sandra / Benedetto, Lauren / Newcomb, Nora / Rubenstein, Dana / King, Tonya / Lunsford, Christopher / Shaw, Tanya / DeWaters, Ami L

American journal of physical medicine & rehabilitation

2024 Volume 103, Issue 5, Page(s) e54–e57

Abstract: Abstract: Physical medicine and rehabilitation physicians often care for disabled patients, who comprise America's largest marginalized population. Despite medical students' and physicians' discomfort with caring for disabled patients and the ... ...

Abstract	Abstract: Physical medicine and rehabilitation physicians often care for disabled patients, who comprise America's largest marginalized population. Despite medical students' and physicians' discomfort with caring for disabled patients and the pervasiveness of ableism in health care, medical education lacks disability-focused education. Kern's approach to curriculum development and disability community input were used to design a three-part, elective curriculum for first-year medical students. Part one introduced disability models and language. Part two described how to perform a comprehensive history and physical examination for a disabled patient using ADEPT-CARE. Part three provided an overview of disability history and the disability rights movement. The curriculum's goal was to improve students' attitudes regarding disability health and self-perceived knowledge and confidence in caring for patients with disabilities. The curriculum was evaluated through presurvey and postsurvey. Students favorably reviewed the curriculum. One hundred percent of students ( n = 21) agreed or strongly agreed that the curriculum improved their knowledge of disability health, increased their perceived confidence in caring for patients with disabilities, and enhanced their medical education. There were no statistically significant differences in students' attitudes toward patients with disabilities after curriculum completion. Our asynchronous module provides one potential curriculum for increasing preclinical medical students' self-perceived knowledge of disability health.
MeSH term(s)	Humans ; Students, Medical ; Disabled Persons ; Attitude ; Education, Medical ; Delivery of Health Care ; Curriculum
Language	English
Publishing date	2024-01-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	219390-5
ISSN	1537-7385 ; 0002-9491 ; 0894-9115
ISSN (online)	1537-7385
ISSN	0002-9491 ; 0894-9115
DOI	10.1097/PHM.0000000000002399
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Article ; Online: Side Effects and Complications Associated with Treating Plutonium Intakes: A Retrospective Review of the Medical Records of LANL Employees Treated for Plutonium Intakes, with Supplementary Interviews.

Glover, Lauren / Bertelli, Luiz / Dumit, Sara / Poudel, Deepesh / Smith, Lauren / Waters, Tom / Klumpp, John

Health physics

2022 Volume 123, Issue 5, Page(s) 348–359

Abstract: Abstract: Anecdotal evidence indicates there may be unpublished physical and psychological events associated with the medical treatment of plutonium intakes. A thorough review was conducted of the medical and bioassay records of current and previous Los ...

Abstract	Abstract: Anecdotal evidence indicates there may be unpublished physical and psychological events associated with the medical treatment of plutonium intakes. A thorough review was conducted of the medical and bioassay records of current and previous Los Alamos National Laboratory (LANL) employees who had experienced plutonium intakes via wound or inhalation. After finding relatively incomplete information in the medical records, the research team interviewed current LANL employees who had undergone chelation therapy and/or surgical excision. Although the dataset is not large enough to reach statistically significant conclusions, it was observed that adverse events associated with treatment appear to be more frequent and more severe than previously reported.
MeSH term(s)	Biological Assay ; Chelation Therapy ; Humans ; Medical Records ; Plutonium/adverse effects ; Plutonium/analysis ; Retrospective Studies
Chemical Substances	Plutonium (53023GN24M)
Language	English
Publishing date	2022-08-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2406-5
ISSN	1538-5159 ; 0017-9078
ISSN (online)	1538-5159
ISSN	0017-9078
DOI	10.1097/HP.0000000000001603
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Article ; Online: Major vascular reconstruction in colorectal adenocarcinoma and retroperitoneal sarcoma: A retrospective study of safety and margins in a tertiary referral centre.

Apte, Sameer S / Cohen, Lauren Cl / Larach, Jose T / Mohan, Helen M / Snow, Hayden A / Wagner, Timothy / McCormick, Jacob J / Warrier, Satish K / Gyorki, David E / Waters, Peadar S / Heriot, Alexander G

Surgical oncology

2022 Volume 45, Page(s) 101871

Abstract: Background: The role of en bloc vascular resection and reconstruction (EVRR) is controversial in colorectal adenocarcinoma (CRC), but well-established in retroperitoneal sarcoma (RPS). Sparse data exists regarding these complex procedures.: Methods: ... ...

Abstract	Background: The role of en bloc vascular resection and reconstruction (EVRR) is controversial in colorectal adenocarcinoma (CRC), but well-established in retroperitoneal sarcoma (RPS). Sparse data exists regarding these complex procedures. Methods: Patients undergoing curative intent EVRR for advanced CRC and RPS between 2014 and 2021 at a tertiary centre were included. Morbidity, margins, recurrence, and survival were evaluated. Results: 24 patients underwent EVRR with 48 reconstructions (11 CRC and 13 RPS). For CRC, 100% of patients underwent Iliac system reconstructions. For RPS, inferior vena cava reconstructions were the most common (69.2%). There were 2 arterial and 1 venous graft thromboses. Primary graft patency was 89.4% arterial and 93.1% venous, while secondary patency was 100% arterial and 96.5% venous at last follow up. 1 venous and 1 arterial graft required reoperation for bleeding. There were no compromised limbs. Major complications occurred in 6 patients (25.0%) with no observed difference between CRC and RPS (OR 0.43 95%CI[0.60,3.19], P = 0.41). R1 margins occurred 1 CRC (90.9%) and 3 RPS (76.9%), with no R2 resections. All vascular resection margins were clear. There were 6 CRC (50%) and 4 RPS (33.3%) recurrences. Median recurrence time was 20.9 months for CRC and 'not yet reached' for RPS. Median follow-up was 19.4 months for CRC and 21.4 months for RPS. Conclusion: EVRR for locally advanced CRC or RPS is safe and achieves favorable R0 resection rates. CRC patients with major vascular invasion can still be considered for curative intent surgery. Larger cohorts with longer follow up are needed to assess oncologic outcomes.
MeSH term(s)	Humans ; Retrospective Studies ; Margins of Excision ; Tertiary Care Centers ; Treatment Outcome ; Retroperitoneal Neoplasms/pathology ; Sarcoma/pathology ; Soft Tissue Neoplasms ; Colorectal Neoplasms/surgery ; Colorectal Neoplasms/pathology ; Adenocarcinoma/surgery ; Neoplasm Recurrence, Local/surgery
Language	English
Publishing date	2022-10-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1107810-8
ISSN	1879-3320 ; 0960-7404
ISSN (online)	1879-3320
ISSN	0960-7404
DOI	10.1016/j.suronc.2022.101871
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Article ; Online: A Countercultural Heritage: Rediscovering the Relationship-Centered and Social Justice Roots of Family Medicine-A Perspective from the Keystone IV Conference.

Waters, Richard C / Stoltenberg, Mark / Hughes, Lauren S

Journal of the American Board of Family Medicine : JABFM

2016 Volume 29 Suppl 1, Page(s) S45–8

Abstract: The 2015 G. Gayle Stephens Keystone conference convened a cohort of primary care professionals to discuss what promises personal physicians will make to their patients going forward. New physicians were prompted to rediscover the foundational values of ... ...

Abstract	The 2015 G. Gayle Stephens Keystone conference convened a cohort of primary care professionals to discuss what promises personal physicians will make to their patients going forward. New physicians were prompted to rediscover the foundational values of and historic context for family medicine. At the heart of this rediscovery was learning of the writings and teachings of Dr. G. Gayle Stephens, a founder of family medicine who emphasized the essentiality of relationship-centered care and social justice to the new specialty. Dr. Stephens viewed family medicine as being in a countercultural relationship to mainstream medicine, as family medicine fought for justice and equity in an inequitable and fragmented health care system. Here we argue that by reaffirming and renewing this countercultural heritage the new generation of family physicians will have better clarity in approaching the many challenges in health care today. Particularly for trainees and new physicians, the historic lens offered by Dr. Stephens's writing and other foundational documents allows us to better see ourselves in a trajectory of ongoing health care reform.
MeSH term(s)	Delivery of Health Care/legislation & jurisprudence ; Delivery of Health Care/organization & administration ; Family Practice/methods ; Family Practice/trends ; Health Care Reform ; Healthcare Disparities ; Humans ; Insurance, Health ; Physician-Patient Relations ; Physicians, Family/psychology ; Primary Health Care/methods ; Primary Health Care/trends ; Social Justice ; United States
Language	English
Publishing date	2016-07-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2239939-2
ISSN	1558-7118 ; 1557-2625
ISSN (online)	1558-7118
ISSN	1557-2625
DOI	10.3122/jabfm.2016.S1.160002
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