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Book: Cell cycle checkpoints

Li, Willis X.

methods and protocols

(Methods in molecular biology ; 782 ; Springer protocols)

2011

Author's details	Willis X. Li, ed
Series title	Methods in molecular biology ; 782 Springer protocols
Collection
Language	English
Size	X, 307 S. : Ill., graph. Darst.
Publisher	Humana Press
Publishing place	New York u.a.
Publishing country	United States
Document type	Book
HBZ-ID	HT016889449
ISBN	978-1-61779-272-4 ; 1-61779-272-1
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Computational simulation of JAK/STAT signaling in somatic versus germline stem cells.

Li, Willis X

Developmental dynamics : an official publication of the American Association of Anatomists

2023

Abstract: Background: The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway regulates a variety of cellular processes. A major activation event in this pathway involves the phosphorylation of a tyrosine of STAT, converting ...

Abstract	Background: The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway regulates a variety of cellular processes. A major activation event in this pathway involves the phosphorylation of a tyrosine of STAT, converting unphosphorylated STAT (uSTAT) to phosphorylated STAT (pSTAT), an active transcription factor. In a noncanonical role, uSTAT contributes to the maintenance of heterochromatin stability. As such, an increase in pSTAT concurrently reduces uSTAT, resulting in heterochromatin loss, as observed in Drosophila somatic tissues. Paradoxically, an opposing phenomenon occurs in Drosophila male germline stem cells (GSCs), where the JAK/STAT pathway remains persistently active due to a continuous supply of ligands. Here, computational simulations were employed to dissect JAK/STAT pathway activation under different cellular contexts, mimicking somatic and germline cells. In these simulations, ordinary differential equations were leveraged to replicate the chemical reactions governing JAK/STAT signaling under different conditions. Results: The outcomes indicate that transient ligand stimulation, typical in somatic tissues, led to a momentary reduction in uSTAT levels. Conversely, sustained ligand stimulation, a characteristic feature of the GSC niche, resulted in elevated uSTAT levels at equilibrium. Conclusion: The simulation suggests that the duration of ligand exposure could explain the observed opposite effects of JAK/STAT activation on heterochromatin in somatic versus GSCs.
Language	English
Publishing date	2023-12-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	1102541-4
ISSN	1097-0177 ; 1058-8388
ISSN (online)	1097-0177
ISSN	1058-8388
DOI	10.1002/dvdy.684
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Article ; Online: Worldwide inverse correlation between Bacille Calmette-Guérin (BCG) immunization and COVID-19 mortality.

Li, Willis X

Infection

2021 Volume 49, Issue 3, Page(s) 463–473

Abstract: Purpose: The coronavirus disease 2019 (COVID-19) pandemic has spread to all countries in the world, and different countries have been impacted differently. The study aims to understand what factors contribute to different COVID-19 impacts at the country ...

Abstract	Purpose: The coronavirus disease 2019 (COVID-19) pandemic has spread to all countries in the world, and different countries have been impacted differently. The study aims to understand what factors contribute to different COVID-19 impacts at the country level. Methods: Multivariate statistical analyses were used to evaluate COVID-19 deaths and cases relative to nine other demographic and socioeconomic factors in all countries and regions of the world using data as of August 1, 2020. The factors analyzed in the study include a country's total COVID-19 deaths and cases per million population, per capita gross domestic product (GDP), population density, virus tests per million population, median age, government response stringency index, hospital beds availability per thousand population, extreme poverty rate, Bacille Calmette-Guérin (BCG) vaccination rate, and diphtheria-tetanus-pertussis (DTP3) immunization rate. Results: The study reveals that COVID-19 deaths per million population in a country most significantly correlates, inversely, with the country's BCG vaccination rate (r = - 0.50, p = 5.3e-5), and also significantly correlates a country's per capita GDP (r = 0.39, p = 7.4e-3) and median age (r = 0.30, p = 0.042), while COVID-19 cases per million population significantly correlate with per capita GDP and tests per thousand population. To control for possible confounding effects of age, the correlation was assessed in countries propensity score matched for age. The inverse correlation between BCG vaccination rates and COVID-19 case (r = - 0.30, p = 0.02) and death (r = - 0.42, p = 0.0007) remained significant among the top 61 countries with the highest median age. Conclusion: This study contributes to a growing body of evidence supporting the notion that BCG vaccination may be protective against COVID-19 mortality.
MeSH term(s)	Age Factors ; BCG Vaccine/administration & dosage ; COVID-19/epidemiology ; COVID-19/mortality ; COVID-19/prevention & control ; Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage ; Global Health/statistics & numerical data ; Gross Domestic Product ; Humans ; Immunization/statistics & numerical data ; Multivariate Analysis ; SARS-CoV-2
Chemical Substances	BCG Vaccine ; Diphtheria-Tetanus-Pertussis Vaccine
Language	English
Publishing date	2021-01-25
Publishing country	Germany
Document type	Journal Article
ZDB-ID	185104-4
ISSN	1439-0973 ; 0300-8126 ; 0173-2129
ISSN (online)	1439-0973
ISSN	0300-8126 ; 0173-2129
DOI	10.1007/s15010-020-01566-6
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Article: Worldwide inverse correlation between Bacille Calmette-Guérin immunization and COVID-19 morbidity and mortality.

Li, Willis X

Research square

2020

Abstract: The COVID-19 pandemic has spread to all countries in the world after more than six months since it was first reported in late 2019, and different countries have been impacted differently. Correlation analysis between COVID-19 death numbers and different ... ...

Abstract	The COVID-19 pandemic has spread to all countries in the world after more than six months since it was first reported in late 2019, and different countries have been impacted differently. Correlation analysis between COVID-19 death numbers and different demographic and socioeconomic factors for all world countries (n=210) as of June 1, 2020, reveals that COVID-19 deaths per million population in a country significantly correlates with the country's median age (r=0.48, p=4.8e-4) and per capita gross domestic product (GDP) (r=0.55, p=4.14e-5), and inversely correlates with the country's Bacille Calmette-Guérin (BCG) vaccination rate (r=-0.63, p=9.9e-7). COVID-19 death is found not significantly associated, however, with a country's policy stringency index, population density, extreme poverty rate, hospital beds availability per thousand people, and diphtheria-tetanus-pertussis (DTP3) immunization. Old age is likely a confounding factor for the correlation between COVID-19 and per capita GDP (r=0.66, p=2.3e-7). To control for possible confounding effects of age, countries with similar median age were grouped and analyzed. The inverse correlation between BCG vaccination rates and COVID-19 case (r=-0.338, p=0.0082) and death (r=-0.411, p=0.0011) remained significant among the top 61 countries with highest median age. The current study suggests that BCG might be protective against SARS-CoV-2 infection.
Keywords	covid19
Language	English
Publishing date	2020-07-16
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-42927/v1
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Article ; Online: Expression and prognostic role of STAT5a across cancer types.

Maninang, Christine / Li, Jinghong / Li, Willis X

Bioscience reports

2023 Volume 43, Issue 8

Abstract: Studies examining the role of signal transducer and activator of transcription 5 (STAT5) in various cancers have produced controversial results. To address this controversy, we examined the prognostic role of STAT5a in cancer patients across multiple ... ...

Abstract	Studies examining the role of signal transducer and activator of transcription 5 (STAT5) in various cancers have produced controversial results. To address this controversy, we examined the prognostic role of STAT5a in cancer patients across multiple cancers. Transcription levels of STAT5a between tumors and normal tissues, obtained from public databases, were analyzed for statistical differences using Cox regression analysis with the outcome as overall survival and covariate of interest as high STAT5a expression. Meta-analysis was then conducted to summarize the hazard ratio estimate from the Cox regression analyses. We found that STAT5a was significantly under-expressed in breast, lung, and ovarian cancers, while STAT5a was significantly overexpressed in lymphoid neoplasm diffuse large B-cell lymphoma, glioblastoma, and glioma. High STAT5a expression was significantly associated with favorable survival in bladder cancer (lnHR = -0.8689 [-1.4087, -0.3292], P-value = 0.0016), breast cancer (lnHR = -0.7805 [-1.1394, -0.4215], P-value < 0.0001) and lung cancer (lnHR = -0.3255 [-0.6427, -0.0083], P-value = 0.0443). After adjusting for clinicopathological factors, high STAT5a expression remained significantly associated with favorable survival in breast cancer (lnHR = -0.6091 [-1.0810, -0.1372], P-value = 0.0114). These results suggest that higher STAT5a expression is associated with favorable overall survival in breast cancer, and therefore might have protective effects, and that STAT5a expression could be a potential prognostic biomarker, especially in breast cancer. However, the prognostic role of STAT5a is dependent on cancer type.
MeSH term(s)	Humans ; Female ; STAT5 Transcription Factor/genetics ; STAT5 Transcription Factor/metabolism ; Prognosis ; Breast Neoplasms/metabolism ; Lung Neoplasms ; Proportional Hazards Models
Chemical Substances	STAT5 Transcription Factor
Language	English
Publishing date	2023-06-26
Publishing country	England
Document type	Meta-Analysis ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	764946-0
ISSN	1573-4935 ; 0144-8463
ISSN (online)	1573-4935
ISSN	0144-8463
DOI	10.1042/BSR20230612
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Article ; Online: Simulation of STAT and HP1 interaction by molecular docking.

Xu, Kangxin / Li, Jinghong / Li, Willis X

Cellular signalling

2023 Volume 112, Page(s) 110925

Abstract: Heterochromatin Protein 1 (HP1) is a major component of heterochromatin. Multiple proteins have been shown to interact with HP1 with the HP1-binding motif PxVxL/I, thereby affecting heterochromatin stability. The HP1-interacting proteins include the ... ...

Abstract	Heterochromatin Protein 1 (HP1) is a major component of heterochromatin. Multiple proteins have been shown to interact with HP1 with the HP1-binding motif PxVxL/I, thereby affecting heterochromatin stability. The HP1-interacting proteins include the signal transducer and activator of transcription (STAT) protein, which can be regulated by phosphorylation on a tyrosine around amino acid 700 in the carboxyl terminus. Previous research has shown that unphosphorylated STAT (uSTAT) binds to HP1 via a PxVxI HP1-binding motif and maintains the stability of heterochromatin, while phosphorylated STAT (pSTAT) dissociates from HP1, resulting in heterochromatin disruption. To understand the theoretical basis of the biochemical observations, we employed computational modeling to investigate STAT-HP1 binding configurations and the effect of STAT phosphorylation on their interaction. Using STAT3 and HP1α protein structures for molecular docking and thermodynamic calculations, our computations predict that uSTAT homodimers have a higher affinity for HP1 and a lower affinity for DNA than pSTAT homodimers, and that phosphorylation induces a conformational change in STAT, shifting its binding preference from HP1 to DNA. The results of our modeling studies support the idea that phosphorylation drives STAT from HP1-binding to DNA-binding, suggesting a potential role for uSTAT in both maintaining and initiating heterochromatin formation.
MeSH term(s)	Chromobox Protein Homolog 5 ; Heterochromatin ; Molecular Docking Simulation ; Chromosomal Proteins, Non-Histone/metabolism ; DNA
Chemical Substances	Chromobox Protein Homolog 5 (107283-02-3) ; Heterochromatin ; Chromosomal Proteins, Non-Histone ; DNA (9007-49-2)
Language	English
Publishing date	2023-10-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1002702-6
ISSN	1873-3913 ; 0898-6568
ISSN (online)	1873-3913
ISSN	0898-6568
DOI	10.1016/j.cellsig.2023.110925
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Article ; Online: Canonical and non-canonical functions of STAT in germline stem cell maintenance.

Xing, Yalan / Larson, Kimberly / Li, Jinghong / Li, Willis X

Developmental dynamics : an official publication of the American Association of Anatomists

2023 Volume 252, Issue 6, Page(s) 728–741

Abstract: Background: Maintenance of the Drosophila male germline stem cells (GSCs) requires activation of the Janus kinase/signal transducer and activators of transcription (JAK/STAT) pathway by niche signals. The precise role of JAK/STAT signaling in GSC ... ...

Abstract	Background: Maintenance of the Drosophila male germline stem cells (GSCs) requires activation of the Janus kinase/signal transducer and activators of transcription (JAK/STAT) pathway by niche signals. The precise role of JAK/STAT signaling in GSC maintenance, however, remains incompletely understood. Results: Here, we show that, GSC maintenance requires both canonical and non-canonical JAK/STAT signaling, in which unphosphorylated STAT (uSTAT) maintains heterochromatin stability by binding to heterochromatin protein 1 (HP1). We found that GSC-specific overexpressing STAT, or even the transcriptionally inactive mutant STAT, increases GSC number and partially rescues the GSC-loss mutant phenotype due to reduced JAK activity. Furthermore, we found that both HP1 and STAT are transcriptional targets of the canonical JAK/STAT pathway in GSCs, and that GSCs exhibit higher heterochromatin content. Conclusions: These results suggest that persistent JAK/STAT activation by niche signals leads to the accumulation of HP1 and uSTAT in GSCs, which promote heterochromatin formation important for maintaining GSC identity. Thus, the maintenance of Drosophila GSCs requires both canonical and non-canonical STAT functions within GSCs for heterochromatin regulation.
MeSH term(s)	Animals ; Janus Kinases/genetics ; Janus Kinases/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Heterochromatin/genetics ; Heterochromatin/metabolism ; STAT Transcription Factors/genetics ; STAT Transcription Factors/metabolism ; Signal Transduction/physiology ; Drosophila/genetics ; Germ Cells/metabolism ; Chromobox Protein Homolog 5 ; Stem Cells ; Drosophila melanogaster/genetics ; Stem Cell Niche/physiology
Chemical Substances	Janus Kinases (EC 2.7.10.2) ; Drosophila Proteins ; Heterochromatin ; STAT Transcription Factors ; Chromobox Protein Homolog 5 (107283-02-3)
Language	English
Publishing date	2023-03-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1102541-4
ISSN	1097-0177 ; 1058-8388
ISSN (online)	1097-0177
ISSN	1058-8388
DOI	10.1002/dvdy.576
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Article: Worldwide inverse correlation between Bacille Calmette-Guérin immunization and COVID-19 morbidity and mortality

Li, Willis X.

Research square

Abstract: The COVID-19 pandemic has spread to all countries in the world after more than six months since it was first reported in late 2019, and different countries have been impacted differently Correlation analysis between COVID-19 death numbers and different ... ...

Abstract	The COVID-19 pandemic has spread to all countries in the world after more than six months since it was first reported in late 2019, and different countries have been impacted differently Correlation analysis between COVID-19 death numbers and different demographic and socioeconomic factors for all world countries (n=210) as of June 1, 2020, reveals that COVID-19 deaths per million population in a country significantly correlates with the country's median age (r=0 48, p=4 8e-4) and per capita gross domestic product (GDP) (r=0 55, p=4 14e-5), and inversely correlates with the country's Bacille Calmette-Guérin (BCG) vaccination rate (r=-0 63, p=9 9e-7) COVID-19 death is found not significantly associated, however, with a country's policy stringency index, population density, extreme poverty rate, hospital beds availability per thousand people, and diphtheria-tetanus-pertussis (DTP3) immunization Old age is likely a confounding factor for the correlation between COVID-19 and per capita GDP (r=0 66, p=2 3e-7) To control for possible confounding effects of age, countries with similar median age were grouped and analyzed The inverse correlation between BCG vaccination rates and COVID-19 case (r=-0 338, p=0 0082) and death (r=-0 411, p=0 0011) remained significant among the top 61 countries with highest median age The current study suggests that BCG might be protective against SARS-CoV-2 infection
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #670886
Database	COVID19

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Article ; Online: Worldwide inverse correlation between Bacille Calmette-Guérin immunization and COVID-19 mortality

Li, Willis X

2020

Abstract: Abstract The coronavirus disease 2019 (COVID-19) pandemic has spread to all countries in the world after more than half a year since it was first reported in late 2019, and different countries have been impacted differently. Multivariate statistical ... ...

Abstract	Abstract The coronavirus disease 2019 (COVID-19) pandemic has spread to all countries in the world after more than half a year since it was first reported in late 2019, and different countries have been impacted differently. Multivariate statistical analyses were used to evaluate COVID-19 deaths and cases relative to nine other demographic and socioeconomic factors in all countries and regions of the world using data as of August 1, 2020. The factors analyzed in the study include a country’s total COVID-19 deaths and cases per million population, per capita gross domestic product (GDP), population density, virus tests per million population, median age, government response stringency index, hospital beds availability per thousand population, extreme poverty rate, Bacille Calmette-Guérin (BCG) vaccination rate, and diphtheria-tetanus-pertussis (DTP3) immunization rate. The study reveals that COVID-19 deaths per million population in a country most significantly correlates, inversely, with the country’s BCG vaccination rate, and also significantly correlates a country’s per capita GDP and median age, while COVID-19 cases per million population significantly correlate with per capita GDP and tests per thousand population. This study contributes to a growing body of evidence supporting the notion that BCG vaccination may be protective against COVID-19 mortality.
Keywords	covid19
Publishing date	2020-09-30
Publisher	eScholarship, University of California
Publishing country	us
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Worldwide inverse correlation between Bacille Calmette-Guérin immunization and COVID-19 morbidity and mortality.

Li, Willis X

2020

Abstract	The COVID-19 pandemic has spread to all countries in the world after more than six months since it was first reported in late 2019, and different countries have been impacted differently. Correlation analysis between COVID-19 death numbers and different demographic and socioeconomic factors for all world countries (n=210) as of June 1, 2020, reveals that COVID-19 deaths per million population in a country significantly correlates with the country's median age (r=0.48, p=4.8e-4) and per capita gross domestic product (GDP) (r=0.55, p=4.14e-5), and inversely correlates with the country's Bacille Calmette-Guérin (BCG) vaccination rate (r=-0.63, p=9.9e-7). COVID-19 death is found not significantly associated, however, with a country's policy stringency index, population density, extreme poverty rate, hospital beds availability per thousand people, and diphtheria-tetanus-pertussis (DTP3) immunization. Old age is likely a confounding factor for the correlation between COVID-19 and per capita GDP (r=0.66, p=2.3e-7). To control for possible confounding effects of age, countries with similar median age were grouped and analyzed. The inverse correlation between BCG vaccination rates and COVID-19 case (r=-0.338, p=0.0082) and death (r=-0.411, p=0.0011) remained significant among the top 61 countries with highest median age. The current study suggests that BCG might be protective against SARS-CoV-2 infection.
Keywords	covid19
Publishing date	2020-07-16
Publisher	eScholarship, University of California
Publishing country	us
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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