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Article ; Online: Extracellular Matrix Regulation of Vascular Morphogenesis, Maturation, and Stabilization.

Davis, George E / Kemp, Scott S

Cold Spring Harbor perspectives in medicine

2023 Volume 13, Issue 4

Abstract: The extracellular matrix represents a critical regulator of tissue vascularization during embryonic development and postnatal life. In this perspective, we present key information and concepts that focus on how the extracellular matrix controls capillary ...

Abstract	The extracellular matrix represents a critical regulator of tissue vascularization during embryonic development and postnatal life. In this perspective, we present key information and concepts that focus on how the extracellular matrix controls capillary assembly, maturation, and stabilization, and, in addition, contributes to tissue stability and health. In particular, we present and discuss mechanistic details underlying (1) the role of the extracellular matrix in controlling different steps of vascular morphogenesis, (2) the ability of endothelial cells (ECs) and pericytes to coassemble into elongated and narrow capillary EC-lined tubes with associated pericytes and basement membrane matrices, and (3) the identification of specific growth factor combinations ("factors") and peptides as well as coordinated "factor" and extracellular matrix receptor signaling pathways that are required to form stabilized capillary networks.
MeSH term(s)	Humans ; Endothelial Cells/physiology ; Morphogenesis/physiology ; Extracellular Matrix/metabolism ; Signal Transduction/physiology ; Intercellular Signaling Peptides and Proteins ; Neovascularization, Physiologic/physiology ; Endothelium, Vascular ; Pericytes/metabolism
Chemical Substances	Intercellular Signaling Peptides and Proteins
Language	English
Publishing date	2023-04-03
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ISSN	2157-1422
ISSN (online)	2157-1422
DOI	10.1101/cshperspect.a041156
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Extracellular Matrix Remodeling in Vascular Disease: Defining Its Regulators and Pathological Influence.

Lin, Prisca K / Davis, George E

Arteriosclerosis, thrombosis, and vascular biology

2023 Volume 43, Issue 9, Page(s) 1599–1616

Abstract: Because of structural and cellular differences (ie, degrees of matrix abundance and cross-linking, mural cell density, and adventitia), large and medium-sized vessels, in comparison to capillaries, react in a unique manner to stimuli that induce vascular ...

Abstract	Because of structural and cellular differences (ie, degrees of matrix abundance and cross-linking, mural cell density, and adventitia), large and medium-sized vessels, in comparison to capillaries, react in a unique manner to stimuli that induce vascular disease. A stereotypical vascular injury response is ECM (extracellular matrix) remodeling that occurs particularly in larger vessels in response to injurious stimuli, such as elevated angiotensin II, hyperlipidemia, hyperglycemia, genetic deficiencies, inflammatory cell infiltration, or exposure to proinflammatory mediators. Even with substantial and prolonged vascular damage, large- and medium-sized arteries, persist, but become modified by (1) changes in vascular wall cellularity; (2) modifications in the differentiation status of endothelial cells, vascular smooth muscle cells, or adventitial stem cells (each can become activated); (3) infiltration of the vascular wall by various leukocyte types; (4) increased exposure to critical growth factors and proinflammatory mediators; and (5) marked changes in the vascular ECM, that remodels from a homeostatic, prodifferentiation ECM environment to matrices that instead promote tissue reparative responses. This latter ECM presents previously hidden matricryptic sites that bind integrins to signal vascular cells and infiltrating leukocytes (in coordination with other mediators) to proliferate, invade, secrete ECM-degrading proteinases, and deposit injury-induced matrices (predisposing to vessel wall fibrosis). In contrast, in response to similar stimuli, capillaries can undergo regression responses (rarefaction). In summary, we have described the molecular events controlling ECM remodeling in major vascular diseases as well as the differential responses of arteries versus capillaries to key mediators inducing vascular injury.
MeSH term(s)	Humans ; Endothelial Cells ; Vascular System Injuries/metabolism ; Extracellular Matrix/metabolism ; Adventitia ; Vascular Diseases/metabolism ; Vascular Remodeling
Language	English
Publishing date	2023-07-06
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.123.318237
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Article: Triggering multiple sclerosis at conception and early gestation: The variation in ultraviolet radiation is as important as its intensity.

Davis, George E / Davis, Matthew J / Lowell, Walter E

Heliyon

2023 Volume 9, Issue 6, Page(s) e16954

Abstract: ... is important at the MOC if UVR exceeds a threshold (e.g., if the sunspot number equals or is greater ...

Abstract	Background and objectives: Medical science needs to further elucidate the role of ultraviolet radiation (UVR), geographic latitude, and the role of vitamin D in the autoimmune disease multiple sclerosis (MS). We separated several papers into categories out of the thousands published and used their conclusions to explore the relationship between UVR and MS. Relevance: MS is increasing in incidence, particularly in women where MS is two to three times that in men and particularly severe in African Americans. Methods: We collected UVR data at our observatory in Central Maine and calculated the average coefficient of variation (CV Results: The month of conception (MOC) is more important than the month of birth (MOB) in explaining how UVR triggers the variable genetic predisposition to MS. We hypothesize that the rapidly increasing CV Limitations: One observatory at about 44° latitude. Conclusions: While variation in UVR is important at the MOC if UVR exceeds a threshold (e.g., if the sunspot number equals or is greater than 90, usually at a solar cycle MAX, or at elevations above approximately 3,000 feet above sea level), the MS mitigating vitamin D-VDR mechanism is overwhelmed and the genotoxic effects of higher-intensity UVR promote MS in those with a genetic predisposition. What is new in this research: This paper offers a new concept in MS research.
Language	English
Publishing date	2023-06-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e16954
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Article: The effect of ultraviolet radiation on the incidence and severity of major mental illness using birth month, birth year, and sunspot data.

Davis, George E / Davis, Matthew J / Lowell, Walter E

Heliyon

2022 Volume 8, Issue 3, Page(s) e09197

Abstract: ... of change (e.g., derivatives) and their respective integrals gave domains of each mental illness relative ... to the GP. Normalizing the GP to unity was then related to the factor 1.28, e.g., 28% more entropy, deduced ...

Abstract	Background and objectives: The evaluation of the severity of patients afflicted with major mental illness (MMI) has been problematic because of confounding variables and genetic variability. There have been multiple studies that suggest several human diseases, especially schizophrenia, are predisposed to be born in certain months or seasons. This observation implied an epigenetic effect of sunlight, likely ultraviolet radiation (UVR), which is damaging to DNA, especially in an embryo. This paper outlines a method to evaluate the severity of schizophrenia (SZ), bipolar disorder (BPD), and schizoaffective disorder (SZ-AFF) using the month/year of birth of those affected compared to the month/year of birth of the general population (GP). Relevance: Our previous research found that more intense UVR (equal to or greater than 90 sunspot number (SSN)) had a negative effect on the average human lifespan. Also, human birth rates vary in frequency by month of birth reflecting variables like availability of food, sunlight, and other unknown epigenetic factors. We wanted to see if the patient month of birth varied from the average birth months of the general population and if UVR has an epigenetic effect promoting these diseases. Methods: We obtained the month and year of birth of 1,233 patients admitted over a 15-year period to Maine's largest state psychiatric hospital and counted the months of birth for each diagnosis of SZ, BPD, and SZ-AFF, and compared these results to the general population's birth months of 4,265,555 persons from U. S. Census Year 2006. The number of patients in each month was normalized to August and compared with the normalized birth months of the general population (GP). Plots of the normalized months were considered rates of change (e.g., derivatives) and their respective integrals gave domains of each mental illness relative to the GP. Normalizing the GP to unity was then related to the factor 1.28, e.g., 28% more entropy, deduced from the Sun's fractal dimension imprinted on biological organisms. Results: The percent of patients meeting our criterion for severity: SZ = 27%; BPD = 26%; SZ-AFF = 100%. Conclusions: High UVR intensity or a rapid increase in UVR in early gestation are likely epigenetic triggers of major mental illness. BPD is more epigenetically affected than SZ or SZ-AFF disorders. We found that 52% of 1,233 patients comprised the core function of a tertiary-care psychiatric hospital. Also, mental illness exacerbated when the median SSN doubled. This work also validates the Kraeplinian dichotomy. What is new in this research: This paper offers a new paradigm for evaluating the severity of MMI and supports significant epigenetic effects from UVR.
Language	English
Publishing date	2022-03-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2022.e09197
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Article ; Online: Triggering multiple sclerosis at conception and early gestation

George E. Davis / Matthew J. Davis / Walter E. Lowell

Heliyon, Vol 9, Iss 6, Pp e16954- (2023)

The variation in ultraviolet radiation is as important as its intensity

2023

Abstract: ... a threshold (e.g., if the sunspot number equals or is greater than 90, usually at a solar cycle MAX, or ...

Abstract	Background and objectives: Medical science needs to further elucidate the role of ultraviolet radiation (UVR), geographic latitude, and the role of vitamin D in the autoimmune disease multiple sclerosis (MS). We separated several papers into categories out of the thousands published and used their conclusions to explore the relationship between UVR and MS. Relevance: MS is increasing in incidence, particularly in women where MS is two to three times that in men and particularly severe in African Americans. Methods: We collected UVR data at our observatory in Central Maine and calculated the average coefficient of variation (CVUVR) for each month for 15 years (2007–2021, inclusive). Results: The month of conception (MOC) is more important than the month of birth (MOB) in explaining how UVR triggers the variable genetic predisposition to MS. We hypothesize that the rapidly increasing CVUVR is important in preventing an increase in the activity of the vitamin D receptor (VDR) from August to December, which then requires a higher intensity of UVR later in life to suppress the immune system, therefore predisposing to more MS. Limitations: One observatory at about 44° latitude. Conclusions: While variation in UVR is important at the MOC if UVR exceeds a threshold (e.g., if the sunspot number equals or is greater than 90, usually at a solar cycle MAX, or at elevations above approximately 3,000 feet above sea level), the MS mitigating vitamin D-VDR mechanism is overwhelmed and the genotoxic effects of higher-intensity UVR promote MS in those with a genetic predisposition. What is new in this research: This paper offers a new concept in MS research.
Keywords	Multiple sclerosis ; Month-of-conception ; Month-of-birth ; Ultraviolet radiation ; Latitude ; Elevation ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Elucidating the Morphogenic and Signaling Roles of Defined Growth Factors Controlling Human Endothelial Cell Lumen Formation Versus Sprouting Behavior.

Lin, Prisca K / Koller, Gretchen M / Davis, George E

The American journal of pathology

2023 Volume 193, Issue 12, Page(s) 2203–2217

Abstract: Five growth factors [ie, insulin, fibroblast growth factor-2 (FGF-2), stem cell factor, IL-3, and stromal-derived factor 1α] in combination are necessary for human endothelial cells (ECs) to undergo tube morphogenesis, a process requiring both lumen ... ...

Abstract	Five growth factors [ie, insulin, fibroblast growth factor-2 (FGF-2), stem cell factor, IL-3, and stromal-derived factor 1α] in combination are necessary for human endothelial cells (ECs) to undergo tube morphogenesis, a process requiring both lumen formation and sprouting behavior. This study investigated why these factors are required by subdividing the factors into 4 separate groups: insulin-only, insulin and FGF-2, no FGF-2 (all factors but without FGF-2), and all factors. The study found that the insulin-only condition failed to support EC morphogenesis or survival, the insulin and FGF-2 condition supported primarily EC lumen formation, and the no FGF-2 condition supported EC sprouting behavior. By comparison, the all-factors condition more strongly stimulated both EC lumen formation and sprouting behavior, and signaling analysis revealed prolonged stimulation of multiple promorphogenic signals coupled with inhibition of proregressive signals. Pharmacologic inhibition of Jak kinases more selectively blocked EC sprouting behavior, whereas inhibition of Raf, phosphatidylinositol 3-kinase, and Akt kinases showed selective blockade of lumen formation. Inhibition of Src family kinases and Notch led to increased sprouting coupled to decreased lumen formation, whereas inhibition of Pak, Mek, and mammalian target of rapamycin kinases blocked both sprouting and lumen formation. These findings reveal novel downstream biological and signaling activities of defined factors that are required for the assembly of human EC-lined capillary tube networks.
MeSH term(s)	Humans ; Endothelial Cells/metabolism ; Fibroblast Growth Factor 2/pharmacology ; Fibroblast Growth Factor 2/metabolism ; Cells, Cultured ; Morphogenesis ; Insulins/metabolism
Chemical Substances	Fibroblast Growth Factor 2 (103107-01-3) ; Insulins
Language	English
Publishing date	2023-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.1016/j.ajpath.2023.08.009
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Article ; Online: Defining the Functional Influence of Endothelial Cell-Expressed Oncogenic Activating Mutations on Vascular Morphogenesis and Capillary Assembly.

Lin, Prisca K / Sun, Zheying / Davis, George E

The American journal of pathology

2023 Volume 194, Issue 4, Page(s) 574–598

Abstract: This study sought to define key molecules and signals controlling major steps in vascular morphogenesis, and how these signals regulate pericyte recruitment and pericyte-induced basement membrane deposition. The morphogenic impact of endothelial cell (EC) ...

Abstract	This study sought to define key molecules and signals controlling major steps in vascular morphogenesis, and how these signals regulate pericyte recruitment and pericyte-induced basement membrane deposition. The morphogenic impact of endothelial cell (EC) expression of activating mutants of Kirsten rat sarcoma virus (kRas), mitogen-activated protein kinase 1 (Mek1), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), Akt serine/threonine kinase 1 (Akt1), Ras homolog enriched in brain (Rheb) Janus kinase 2 (Jak2), or signal transducer and activator of transcription 3 (Stat3) expression versus controls was evaluated, along with EC signaling events, pharmacologic inhibitor assays, and siRNA suppression experiments. Primary stimulators of EC lumen formation included kRas, Akt1, and Mek1, whereas PIK3CA and Akt1 stimulated a specialized type of cystic lumen formation. In contrast, the key drivers of EC sprouting behavior were Jak2, Stat3, Mek1, PIK3CA, and mammalian target of rapamycin (mTor). These conclusions are further supported by pharmacologic inhibitor and siRNA suppression experiments. EC expression of active Akt1, kRas, and PIK3CA led to markedly dysregulated lumen formation coupled to strongly inhibited pericyte recruitment and basement membrane deposition. For example, activated Akt1 expression in ECs excessively stimulated lumen formation, decreased EC sprouting behavior, and showed minimal pericyte recruitment with reduced mRNA expression of platelet-derived growth factor-BB, platelet-derived growth factor-DD, and endothelin-1, critical EC-derived factors known to stimulate pericyte invasion. The study identified key signals controlling fundamental steps in capillary morphogenesis and maturation and provided mechanistic details on why EC activating mutations induced a capillary deficiency state with abnormal lumens, impaired pericyte recruitment, and basement deposition: predisposing stimuli for the development of vascular malformations.
MeSH term(s)	Proto-Oncogene Proteins p21(ras)/genetics ; Endothelial Cells/metabolism ; Morphogenesis/genetics ; Platelet-Derived Growth Factor/metabolism ; Mutation ; RNA, Small Interfering/metabolism ; Class I Phosphatidylinositol 3-Kinases/metabolism
Chemical Substances	Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; Platelet-Derived Growth Factor ; RNA, Small Interfering ; Class I Phosphatidylinositol 3-Kinases (EC 2.7.1.137)
Language	English
Publishing date	2023-10-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.1016/j.ajpath.2023.08.017
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Article ; Online: Predictors of seasonal influenza and COVID-19 vaccination coverage among adults in Tennessee during the COVID-19 pandemic.

Cunningham-Erves, J / George, W / Sanderson, M / Stewart, E / Jin, S W / Davis, J / Brandt, H M

Frontiers in public health

2024 Volume 12, Page(s) 1321173

Abstract: Background: The COVID-19 pandemic has convoluted hesitancy toward vaccines, including the seasonal influenza (flu) vaccine. Because of COVID-19, the flu season has become more complicated; therefore, it is important to understand all the factors ... ...

Abstract	Background: The COVID-19 pandemic has convoluted hesitancy toward vaccines, including the seasonal influenza (flu) vaccine. Because of COVID-19, the flu season has become more complicated; therefore, it is important to understand all the factors influencing the uptake of these vaccines to inform intervention targets. This article assesses factors related to the uptake of influenza and COVID-19 vaccines among adults in Tennessee. Methods: A cross-sectional, secondary data analysis of 1,400 adults was conducted in Tennessee. The adult sample came from two data sources: Data source 1 completed a baseline survey from January to March 2022, and data source 2 was completed from May to August 2022. Data on vaccine attitudes, facilitators and barriers, and communication needs were collected via random digit dial by Scientific Telephone Samples (STS). Two multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) to predict sociodemographic and overall vaccine-related factors associated with receipt or non-receipt (referent) of COVID-19 and influenza vaccines. Results: Approximately 78% of the adult sample had received the COVID-19 vaccination. A significant positive association for COVID-19 vaccine uptake was seen among those who were older (aged 50-65) (aOR = 1.9; 95% CI: 1.2-3.2), Black (aOR = 2.0; 95% CI:1.3-2.8), and had a college education and higher (aOR = 2.3; 95% CI: 1.5-3.6). However, there was a significant negative association for persons reporting they were extremely religious (aOR = 0.5; 95% CI:0.3-0.9). Over 56% of the adult sample had received the influenza vaccination this season. Those who had a higher annual household income ($80,000+) (aOR = 1.9; 95% CI: 1.3-2.6) and had health insurance (aOR = 2.6; 95% CI: 1.4-4.8) had a significant positive association with influenza vaccine receipt. However, those who were employed part-time or were unemployed had a significant negative association for influenza vaccine receipt (aOR = 0.7; 95% CI: 0.5-0.9). Both COVID-19 and influenza vaccine receipt had strongly significant positive trends with increasing belief in effectiveness and trust ( Conclusion: Strategies to increase COVID-19 and influenza vaccination should be age-specific, focus on increasing geographical and financial access, and offer tailored messages to address concerns about these vaccines.
MeSH term(s)	Adult ; Humans ; Influenza Vaccines ; Influenza, Human/epidemiology ; Influenza, Human/prevention & control ; COVID-19 Vaccines ; Seasons ; Tennessee/epidemiology ; Cross-Sectional Studies ; Pandemics ; Vaccination Coverage ; COVID-19/epidemiology ; COVID-19/prevention & control ; Health Knowledge, Attitudes, Practice ; Vaccination
Chemical Substances	Influenza Vaccines ; COVID-19 Vaccines
Language	English
Publishing date	2024-03-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2024.1321173
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Article ; Online: The effect of ultraviolet radiation on the incidence and severity of major mental illness using birth month, birth year, and sunspot data

George E. Davis, Jr. / Matthew J. Davis / Walter E. Lowell

Heliyon, Vol 8, Iss 3, Pp e09197- (2022)

2022

Abstract: ... of the general population (GP). Plots of the normalized months were considered rates of change (e.g., derivatives) and ... then related to the factor 1.28, e.g., 28% more entropy, deduced from the Sun's fractal dimension imprinted ...

Abstract	Background and objectives: The evaluation of the severity of patients afflicted with major mental illness (MMI) has been problematic because of confounding variables and genetic variability. There have been multiple studies that suggest several human diseases, especially schizophrenia, are predisposed to be born in certain months or seasons. This observation implied an epigenetic effect of sunlight, likely ultraviolet radiation (UVR), which is damaging to DNA, especially in an embryo. This paper outlines a method to evaluate the severity of schizophrenia (SZ), bipolar disorder (BPD), and schizoaffective disorder (SZ-AFF) using the month/year of birth of those affected compared to the month/year of birth of the general population (GP). Relevance: Our previous research found that more intense UVR (equal to or greater than 90 sunspot number (SSN)) had a negative effect on the average human lifespan. Also, human birth rates vary in frequency by month of birth reflecting variables like availability of food, sunlight, and other unknown epigenetic factors. We wanted to see if the patient month of birth varied from the average birth months of the general population and if UVR has an epigenetic effect promoting these diseases. Methods: We obtained the month and year of birth of 1,233 patients admitted over a 15-year period to Maine's largest state psychiatric hospital and counted the months of birth for each diagnosis of SZ, BPD, and SZ-AFF, and compared these results to the general population's birth months of 4,265,555 persons from U. S. Census Year 2006. The number of patients in each month was normalized to August and compared with the normalized birth months of the general population (GP). Plots of the normalized months were considered rates of change (e.g., derivatives) and their respective integrals gave domains of each mental illness relative to the GP. Normalizing the GP to unity was then related to the factor 1.28, e.g., 28% more entropy, deduced from the Sun's fractal dimension imprinted on biological ...
Keywords	Month of birth ; Solar cycles ; Epigenome ; Schizophrenia ; Bipolar disorder ; Schizoaffective disorder ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: The Caribbean and Mesoamerica Biogeochemical Isotope Overview (CAMBIO).

Ebert, Claire E / Hixon, Sean W / Buckley, Gina M / George, Richard J / Pacheco-Fores, Sofía I / Palomo, Juan Manuel / Sharpe, Ashley E / Solís-Torres, Óscar R / Davis, J Britt / Fernandes, Ricardo / Kennett, Douglas J

Scientific data

2024 Volume 11, Issue 1, Page(s) 349

Abstract: The Caribbean & Mesoamerica Biogeochemical Isotope Overview (CAMBIO) is an archaeological data community designed to integrate published biogeochemical data from the Caribbean, Mesoamerica, and southern Central America to address questions about dynamic ... ...

Abstract	The Caribbean & Mesoamerica Biogeochemical Isotope Overview (CAMBIO) is an archaeological data community designed to integrate published biogeochemical data from the Caribbean, Mesoamerica, and southern Central America to address questions about dynamic interactions among humans, animals, and the environment in the region over the past 10,000 years. Here we present the CAMBIO human dataset, which consists of more than 16,000 isotopic measurements from human skeletal tissue samples (δ
MeSH term(s)	Animals ; Humans ; Archaeology ; Caribbean Region ; Central America ; Isotopes ; Lead
Chemical Substances	Isotopes ; Lead (2P299V784P)
Language	English
Publishing date	2024-04-08
Publishing country	England
Document type	Dataset ; Journal Article
ZDB-ID	2775191-0
ISSN	2052-4463 ; 2052-4463
ISSN (online)	2052-4463
ISSN	2052-4463
DOI	10.1038/s41597-024-03167-6
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