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1.
Microb Ecol ; 85(3): 781-795, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36826587

RESUMEN

Collectively, we have been reviewers for microbial ecology, genetics and genomics studies that include environmental DNA (eDNA), microbiome studies, and whole bacterial genome biology for Microbial Ecology and other journals for about three decades. Here, we wish to point out trends and point to areas of study that readers, especially those moving into the next generation of microbial ecology research, might learn and consider. In this communication, we are not saying the work currently being accomplished in microbial ecology and restoration biology is inadequate. What we are saying is that a significant milestone in microbial ecology has been reached, and approaches that may have been overlooked or were unable to be completed before should be reconsidered in moving forward into a new more ecological era where restoration of the ecological trajectory of systems has become critical. It is our hope that this introduction, along with the papers that make up this special issue, will address the sense of immediacy and focus needed to move into the next generation of microbial ecology study.


Asunto(s)
Ecología , Microbiota , Genómica , Genoma Bacteriano
2.
Am J Ind Med ; 66(1): 54-64, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36268908

RESUMEN

BACKGROUND: Metabolic syndrome (MetS) is especially prevalent among US truck drivers. However, there has been limited research exploring associations between MetS conditions with roadway crashes among truck drivers. The objective of this paper is to assess relationships between specific combinations of individual MetS components and crashes and near-misses. METHODS: Survey, biometric, and anthropometric data were collected from 817 truck drivers across 6 diverse US states. Survey data focused on demographics and roadway safety outcomes, and anthropometric/biometric data corresponded to five MetS conditions (waist circumference blood pressure, hemoglobin A1c, triglycerides, and high-density lipoprotein [HDL] cholesterol). Logistic regression was used to calculate odds ratios of lifetime crashes and near-miss 1-month period prevalence associated with: 1) specific MetS conditions regardless of presence or absence of other MetS conditions, and 2) specific MetS conditions and counts of other accompanying MetS conditions. RESULTS: Hypertension was the MetS characteristic most strongly associated with lifetime crash and 1-month near-miss outcomes, while high triglycerides, low HDL cholesterol, and large waist circumference were most commonly present among groups of conditions associated with crashes and near-misses. Overall, an increasing number of specific co-occurring MetS conditions were associated with higher reporting of roadway crashes. CONCLUSIONS: Specific combinations and higher prevalence of MetS conditions were associated with increased frequency of reported crashes. Moreover, when the co-occurrence of MetS conditions is aggregated, a dose-response relationship with crashes appears. These results suggest that policy changes and interventions addressing MetS may increase driver health and reduce crash risk.


Asunto(s)
Conducción de Automóvil , Síndrome Metabólico , Humanos , Vehículos a Motor , Accidentes de Tránsito , Síndrome Metabólico/epidemiología , Prevalencia
3.
Am J Community Psychol ; 71(3-4): 303-316, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36378746

RESUMEN

Focusing on non-Hispanic Black women (NHBW) in North Texas, this study employed participatory system dynamics modeling to explore three hypotheses: (1) stakeholders will conceptualize structural racism is a pervasive macrostructural force that exerts downstream impacts to shape and perpetuate maternal health disparities among NHBW; (2) stakeholders will identify key causal forces and leverage points that exist across levels of influence; and (3) stakeholders will identify complex interactions, in the form of circular causality, that are present among the key causal forces and leverage points that shape NHBW maternal health disparities. Nine participants engaged in a virtual system dynamics group model-building session that focused on eliciting key variables, behavior-over-time graphs (BOTGs), causal loop diagram (CLD), and targets for action. Participants identified 83 key variables. BOTGs included an average of 6.56 notations and time horizons that, on average, started in 1956. The CLD featured 11 reinforcing and seven balancing feedback loops. Eleven targets for action were identified. Structural racism was revealed as a pervasive macrostructural force that shaped maternal health outcomes among NHBW. Key causal forces and leverage points were identified across levels of influence. Finally, feedback loops within the CLD exhibited circular causality.


Asunto(s)
Familia , Salud Materna , Femenino , Humanos , Texas
4.
Am J Ind Med ; 64(3): 217-219, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33423278

RESUMEN

As COVID-19 vaccines become available, supply is expected to initially fall short of demand. In response, the Advisory Committee on Immunization Practices (ACIP) has issued guidance on which groups should be prioritized to receive vaccines. For the first phase of vaccine allocation, the ACIP recommended healthcare personnel and long-term care facility residents as recipients. This recommendation was based on risks endemic to these populations, as well as ethical principles related to benefits and harms, mitigating health inequalities, and promoting justice. Commercial truck drivers have played a vital and underappreciated role during the COVID-19 pandemic. Despite the indispensable role that commercial drivers play in distributing vaccines, they have not been recommended for vaccine allocation in the next phase (1b) by the ACIP. However, the rationale and ethical principles cited for the first vaccine phase suggest that these workers should be recommended for inclusion. By doing so, the acquisition and transmission of COVID-19 may be mitigated, which would benefit both these workers and the US public. Further, persistent vulnerabilities render commercial truck drivers susceptible to severe COVID-19 infection; therefore, vaccination during the next phase is imperative to curb the exacerbation of extant health inequities. Finally, because present-day COVID-19 vulnerabilities in these workers have been shaped by unjust policies over the past several decades, and because COVID-19 public health policies have excluded and potentially exacerbated the impacts of the pandemic for these workers, allocating vaccines to commercial truck drivers is a necessary step toward promoting justice.


Asunto(s)
Vacunas contra la COVID-19/provisión & distribución , COVID-19/prevención & control , Vehículos a Motor , Ocupaciones , Asignación de Recursos , COVID-19/transmisión , Asignación de Recursos para la Atención de Salud , Humanos , Pandemias , Estados Unidos , Poblaciones Vulnerables
5.
Am J Ind Med ; 63(8): 659-662, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32452556

RESUMEN

U.S. long-haul truck drivers traverse great distances and interact with numerous individuals, rendering them vulnerable to acquiring and transmitting coronavirus disease 2019 (COVID-19). Together, the unique co-occurrence of pronounced health disparities and known COVID-19 infection, morbidity, and mortality risks suggest the possibility of a novel COVID-19 based truck driver syndemic due to advanced driver age and endemic health issues. In turn, COVID-19 sequelae may perpetuate existing health disparities. The co-occurrence of afflictions may also result in compromised safety performance. To curb the likelihood of a COVID-19 based truck driver syndemic, several action stepsare needed. First, key COVID-19 metrics need to be established for this population. Second, relationships between long-haul trucker network attributes and COVID-19 spread need to bedelineated. Third, mutually reinforcing interactions between endemic health disparities and COVID-19 vulnerability need to be elucidated. Finally, grounded in the aforementioned steps, policies and interventions need to be identified and implemented.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/epidemiología , Disparidades en el Estado de Salud , Vehículos a Motor , Salud Laboral , Neumonía Viral/epidemiología , Sindémico , Factores de Edad , Conducción de Automóvil , COVID-19 , Humanos , Pandemias , Factores de Riesgo , SARS-CoV-2 , Estados Unidos/epidemiología
6.
Matern Child Health J ; 24(9): 1093-1098, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32696248

RESUMEN

The coronavirus 2019 (COVID-19) pandemic and related policies have led to an unequal distribution of morbidity and mortality in the U.S. For Black women and birthing people, endemic vulnerabilities and disparities may exacerbate deleterious COVID-19 impacts. Historical and ongoing macro-level policies and forces over time have induced disproportionately higher rates of maternal morbidity and mortality among Black women and birthing people, and contemporary macroeconomic and healthcare policies and factors continue to hold particular consequence. These factors induce detrimental psychological, health, and behavioral responses that contribute to maternal health disparities. The COVID-19 pandemic is likely to disproportionately impact Black women and birthing people, as policy responses have failed to account for the their unique socioeconomic and healthcare contexts. The resulting consequences may form a 'vicious cycle', with upstream impacts that exacerbate upstream macro-level policies and forces that can further perpetuate the clustering of maternal morbidity and mortality in this population. Understanding the impacts of COVID-19 among Black women and birthing people requires theoretical frameworks that can sufficiently conceptualize their multi-level, interacting, and dynamic nature. Thus, we advocate for the proliferation of syndemic perspectives to guide maternal disparities research and prevention during the COVID-19 pandemic. These perspectives can enable a holistic and nuanced understanding of the intersection of endemic and COVID-19-specific vulnerabilities and disparities experienced by Black women and birthing people. Syndemic-informed research can then lead to impactful multi-level prevention strategies that simultaneously tackle both endemic and COVID-19-specific factors and outcomes that lead to the clustering of vulnerabilities and disparities over time.


Asunto(s)
Población Negra/estadística & datos numéricos , Infecciones por Coronavirus/prevención & control , Coronavirus , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Disparidades en Atención de Salud/estadística & datos numéricos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Negro o Afroamericano/estadística & datos numéricos , Betacoronavirus , COVID-19 , Comorbilidad , Infecciones por Coronavirus/epidemiología , Femenino , Disparidades en el Estado de Salud , Disparidades en Atención de Salud/etnología , Humanos , Salud Materna , Mortalidad Materna , Morbilidad , Neumonía Viral/epidemiología , Vigilancia de la Población , Investigación , SARS-CoV-2 , Factores Socioeconómicos , Sindémico , Estados Unidos/epidemiología
8.
Microb Ecol ; 85(3): 779-780, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36971795

Asunto(s)
Ecología , Genómica
9.
Prev Sci ; 19(8): 1019-1029, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29959717

RESUMEN

Chronic discrimination and associated socioeconomic inequalities have shaped the health and well-being of Black Americans. As a consequence of the intersection of these factors with rural deprivation, rural Black Americans live and work in particularly pathogenic environments that generate disproportionate and interacting chronic comorbidities (syndemics) compared to their White and/or urban counterparts. Traditional prevention research has been unable to fully capture the underlying complexity of rural minority health and has generated mostly low-leverage interventions that have failed to reverse adverse metabolic outcomes among rural Black Americans. In contrast, novel research approaches-such as system dynamics modeling-that seek to understand holistic system structure and determine complex health outcomes over time provide a robust framework to develop a more accurate understanding of the key factors contributing to type 2 diabetes. This framework can then be used to establish more efficacious interventions to address disparities among minorities in rural areas. This paper advocates for a unified complex systems epistemology and methodology in advancing rural minority health disparities research. Toward this goal, we (1) provide an overview of rural Black American metabolic health research, (2) introduce a complex systems framework in rural minority health disparities research, and (3) demonstrate how community-based system dynamics modeling and simulation can help us plow new ground in rural minority health disparities research and action. We anticipate that this paper can serve as a catalyst for a long-overdue discourse on the relevance of complex systems approaches in minority health research, with practical benefits for numerous disproportionately burdened communities.


Asunto(s)
Causalidad , Diabetes Mellitus Tipo 2/epidemiología , Disparidades en Atención de Salud , Grupos Minoritarios , Población Rural , Sindémico , Negro o Afroamericano , Diabetes Mellitus Tipo 2/etnología , Humanos , Prejuicio , Estados Unidos/epidemiología , Población Urbana , Población Blanca
10.
Microb Ecol ; 73(1): 61-74, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27613296

RESUMEN

With its network of lotic and lentic habitats that shift during changes in seasonal connection, the tropical and subtropical large-river systems represent possibly the most dynamic of all aquatic environments. Pelagic water samples were collected from Brazilian floodplain lakes (total n = 58) in four flood-pulsed systems (Amazon [n = 21], Araguaia [n = 14], Paraná [n = 15], and Pantanal [n = 8]) in 2011-2012 and sequenced via 454 for bacterial environmental DNA using 16S amplicons; additional abiotic field and laboratory measurements were collected for the assayed lakes. We report here a global comparison of the bacterioplankton makeup of freshwater systems, focusing on a comparison of Brazilian lakes with similar freshwater systems across the globe. The results indicate a surprising similarity at higher taxonomic levels of the bacterioplankton in Brazilian freshwater with global sites. However, substantial novel diversity at the family level was also observed for the Brazilian freshwater systems. Brazilian freshwater bacterioplankton richness was relatively average globally. Ordination results indicate that Brazilian bacterioplankton composition is unique from other areas of the globe. Using Brazil-only ordinations, floodplain system differentiation most strongly correlated with dissolved oxygen, pH, and phosphate. Our data on Brazilian freshwater systems in combination with analysis of a collection of freshwater environmental samples from across the globe offers the first regional picture of bacterioplankton diversity in these important freshwater systems.


Asunto(s)
Bacterias/clasificación , Lagos/microbiología , Plancton/clasificación , Ríos/microbiología , Bacterias/genética , Bacterias/crecimiento & desarrollo , Biodiversidad , Brasil , ADN Bacteriano/genética , Ecosistema , Inundaciones , Plancton/genética , Plancton/crecimiento & desarrollo , ARN Ribosómico 16S/genética
11.
Am J Ind Med ; 59(8): 665-75, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27400443

RESUMEN

BACKGROUND: Obesity rates in long-haul truck drivers have been shown to be significantly higher than the general population. We hypothesized that commercial drivers with the highest levels of general obesity and abdominal adiposity would have higher concentrations of high sensitivity C-reactive protein (CRP), a marker of inflammation. METHODS: Survey and anthropometric data were collected from 262 commercial drivers. Weight, circumference measures, and blood analysis for CRP (N = 115) were conducted and compared to National Health and Nutrition Examination Survey (NHANES) data. CRP values were non-normally distributed and logarithmically transformed for statistical analyses. RESULTS: BMI, waist circumference, sagittal abdominal diameter, and CRP were significantly higher than in the general population. Anthropometric indices that included height (BMI, waist-to-height ratio, and sagittal diameter-to-height ratio), were most predictive of CRP values. CONCLUSIONS: Abdominal obesity is prevalent in commercial vehicle drivers and is an important indicator of the presence of inflammation in this population. Am. J. Ind. Med. 59:665-675, 2016. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Conducción de Automóvil , Proteína C-Reactiva/análisis , Vehículos a Motor , Obesidad/sangre , Enfermedades Profesionales/sangre , Adulto , Antropometría , Biomarcadores/sangre , Índice de Masa Corporal , Estudios Transversales , Humanos , Inflamación/sangre , Masculino , Persona de Mediana Edad , North Carolina/epidemiología , Encuestas Nutricionales , Obesidad/epidemiología , Enfermedades Profesionales/epidemiología , Proyectos Piloto , Valor Predictivo de las Pruebas , Factores de Riesgo , Diámetro Abdominal Sagital , Circunferencia de la Cintura
12.
bioRxiv ; 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38464199

RESUMEN

Discovering new bacterial signaling pathways offers unique antibiotic strategies. Here, through an unbiased resistance screen of 3,884 gene knockout strains, we uncovered a previously unknown non-lytic bactericidal mechanism that sequentially couples three transporters and downstream transcription to lethally suppress respiration of the highly virulent P. aeruginosa strain PA14 - one of three species on the WHO's 'Priority 1: Critical' list. By targeting outer membrane YaiW, cationic lacritin peptide 'N-104' translocates into the periplasm where it ligates outer loops 4 and 2 of the inner membrane transporters FeoB and PotH, respectively, to suppress both ferrous iron and polyamine uptake. This broadly shuts down transcription of many biofilm-associated genes, including ferrous iron-dependent TauD and ExbB1. The mechanism is innate to the surface of the eye and is enhanced by synergistic coupling with thrombin peptide GKY20. This is the first example of an inhibitor of multiple bacterial transporters.

13.
Artículo en Inglés | MEDLINE | ID: mdl-37297614

RESUMEN

Work characteristics and worker well-being are inextricably connected. In particular, the characteristics of work organization shape and perpetuate occupational stress, which contributes to worker mental health and well-being outcomes. Consequently, the importance of understanding and addressing connections between work organization, occupational stress, and mental health and well-being-the focus of this Special Issue-increasingly demand attention from those affected by these issues. Thus, focusing on these issues in the long-haul truck driver (LHTD) sector as an illustrative example, the purpose of this commentary is as follows: (1) to outline current research approaches and the extant knowledge base regarding the connections between work organization, occupational stress, and mental health; (2) to provide an overview of current intervention strategies and public policy solutions associated with the current knowledge base to protect and promote worker mental health and well-being; and (3) to propose a two-pronged agenda for advancing research and prevention for workers during the 21st century. It is anticipated that this commentary, and this Special Issue more broadly, will both echo numerous other calls for building knowledge and engaging in this area and motivate further research within complementary current and novel research frameworks.


Asunto(s)
Salud Laboral , Estrés Laboral , Humanos , Salud Mental , Estrés Laboral/prevención & control , Vehículos a Motor
14.
Am J Health Promot ; 37(6): 755-759, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36719742

RESUMEN

A multitude of upstream occupational exposures influence poor dietary patterns that contribute to cardiometabolic health disparities among long-haul truck drivers in the United States. Herein, we delineate the unique characteristics of the truck driving profession that shape dietary patterns. Next, we discuss current health promotion efforts and why they are unlikely to be sufficient for improving population-level dietary patterns. We then advocate for prioritizing health promotion efforts that target upstream factors that influence population dietary patterns and have the potential to holistically and sustainably support drivers' nutrition. Finally, we propose novel research directions to catalyze upstream-oriented health promotion efforts.


Asunto(s)
Conducción de Automóvil , Humanos , Estados Unidos , Vehículos a Motor , Ocupaciones , Promoción de la Salud
15.
RSC Chem Biol ; 4(6): 422-430, 2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37292058

RESUMEN

Diacylglycerol kinases (DGKs) are metabolic kinases involved in regulating cellular levels of diacylglycerol and phosphatidic lipid messengers. The development of selective inhibitors for individual DGKs would benefit from discovery of protein pockets available for inhibitor binding in cellular environments. Here we utilized a sulfonyl-triazole probe (TH211) bearing a DGK fragment ligand for covalent binding to tyrosine and lysine sites on DGKs in cells that map to predicted small molecule binding pockets in AlphaFold structures. We apply this chemoproteomics-AlphaFold approach to evaluate probe binding of DGK chimera proteins engineered to exchange regulatory C1 domains between DGK subtypes (DGKα and DGKζ). Specifically, we discovered loss of TH211 binding to a predicted pocket in the catalytic domain when C1 domains on DGKα were exchanged that correlated with impaired biochemical activity as measured by a DAG phosphorylation assay. Collectively, we provide a family-wide assessment of accessible sites for covalent targeting that combined with AlphaFold revealed predicted small molecule binding pockets for guiding future inhibitor development of the DGK superfamily.

16.
Nat Commun ; 14(1): 6282, 2023 10 07.
Artículo en Inglés | MEDLINE | ID: mdl-37805600

RESUMEN

Proteomic methods for RNA interactome capture (RIC) rely principally on crosslinking native or labeled cellular RNA to enrich and investigate RNA-binding protein (RBP) composition and function in cells. The ability to measure RBP activity at individual binding sites by RIC, however, has been more challenging due to the heterogenous nature of peptide adducts derived from the RNA-protein crosslinked site. Here, we present an orthogonal strategy that utilizes clickable electrophilic purines to directly quantify protein-RNA interactions on proteins through photoaffinity competition with 4-thiouridine (4SU)-labeled RNA in cells. Our photo-activatable-competition and chemoproteomic enrichment (PACCE) method facilitated detection of >5500 cysteine sites across ~3000 proteins displaying RNA-sensitive alterations in probe binding. Importantly, PACCE enabled functional profiling of canonical RNA-binding domains as well as discovery of moonlighting RNA binding activity in the human proteome. Collectively, we present a chemoproteomic platform for global quantification of protein-RNA binding activity in living cells.


Asunto(s)
Proteómica , ARN , Humanos , ARN/metabolismo , Proteínas de Unión al ARN/metabolismo , Sitios de Unión , Péptidos/metabolismo
17.
Soc Sci Med ; 305: 115048, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35617763

RESUMEN

Firearm violence is a major health problem in the United States that clusters asymmetrically across geographic and demographic lines, and the persistence and unequal distribution of firearm violence suggests that novel causal explanations and theoretical frameworks may be warranted to guide preventive strategies. Thus, this study explores the following three hypotheses that are grounded in complex systems theory: 1) trends in firearm homicides risks have shifted heterogeneously in Harris County across endemic degree of risk; 2) firearm homicides clusters have remained resilient in Harris County across the study time period; and 3), the associations between known contextual correlates of firearm homicides and the distribution of firearm homicides risks in Harris County have manifested as nonlinear. Using a retrospective study design (n = 4,397) from January 1, 2009-June 31, 2021, medicolegal death investigation data from the Harris County Institute of Forensic Sciences and estimates of community characteristics from the American Community Survey were analyzed using Joinpoint trend analysis, kernel density geospatial analysis, and proportion tests. Trend analyses revealed that firearm homicides risks shifted heterogeneously across endemic degree of risk, with geographical areas with lower initial firearm homicides risks experiencing more profound upward shifts across the time period of the study. Geospatial analyses identified the resiliency of firearm homicides clusters across the study period, particularly in central, southern, and south-western districts of the city. Finally, the relationships between known contextual correlates and the distribution of firearm homicides risks in Harris County appeared to be nonlinear, particularly regarding ethnicity. This study provides data-driven results that suggest the plausibility of complex systems theory in advancing the understanding of causality in firearm homicides. Further, these findings support the urgent need for complex systems-informed preventive efforts that account for spatiotemporal heterogeneity, key interactions that generate nonlinearity, and latent feedback loops that underlie resiliency in firearm homicides.


Asunto(s)
Armas de Fuego , Suicidio , Heridas por Arma de Fuego , Homicidio , Humanos , Estudios Retrospectivos , Texas/epidemiología , Estados Unidos , Violencia , Heridas por Arma de Fuego/epidemiología
18.
J Rural Health ; 38(4): 754-763, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35504852

RESUMEN

PURPOSE: Few studies have simultaneously assessed age and gender trends in homicide and suicide across the rural-urban continuum. Herein, we examine geographic and demographic trends in suicide and homicide death rates by: (1) determining overall macro and disaggregated trends; (2) examining differences in trends based on rural-urban county classification; and (3) identifying differences in stratified trends among age and gender classifications. METHODS: A retrospective study design used suicide and homicide data (n = 199,456) from years 2005to 2017 across 16 US states. Suicide and homicide deaths were grouped by age, gender, and rural-urban classification for descriptive analyses, and trends were analyzed using Joinpoint trend analysis software. FINDINGS: Violence resulted in 142,470 suicide and 56,986 homicide deaths between 2005 and 2017. Among both males and females, overall macro trends of suicide and homicide rates generally increased with greater rurality, and trends in rural rates differed from those in nonrural areas. Joinpoint trend analysis revealed significant increases in male suicide rates in large metropolitan (1.66%), micropolitan (1.78%), and rural areas (1.77%); female suicide rates in large metropolitan (2.17%), small metropolitan (3.25%), and micropolitan areas (3.26%); male homicide rates in large metropolitan areas (10.19%); and female homicide rates in rural areas (8.29%). Finally, when stratified by age, several significant trends were found, including increases in suicide rates among females aged 64 and older in rural areas (11.71%). CONCLUSIONS: Heterogeneous trends were found in suicide and homicide rates within specific rural-urban, age, and gender subgroups. Prevention efforts should proactively target those subgroups identified herein as most at-risk of violence.


Asunto(s)
Homicidio , Suicidio , Femenino , Humanos , Masculino , Estudios Retrospectivos , Población Rural , Estados Unidos/epidemiología , Población Urbana
19.
Comput Urban Sci ; 2(1): 21, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-37096207

RESUMEN

A restless and dynamic intellectual landscape has taken hold in the field of spatial social network studies, given the increasingly attention towards fine-scale human dynamics in this urbanizing and mobile world. The measuring parameters of such dramatic growth of the literature include scientific outputs, domain categories, major journals, countries, institutions, and frequently used keywords. The research in the field has been characterized by fast development of relevant scholarly articles and growing collaboration among and across institutions. The Journal of Economic Geography, Annals of the Association of American Geographers, and Urban Studies ranked first, second, and third, respectively, according to average citations. The United States, United Kingdom, and China were the countries that yielded the most published studies in the field. The number of international collaborative studies published in non-native English-speaking countries (such as France, Italy, and the Netherlands) were higher than native English-speaking countries. Wuhan University, the University of Oxford, and Harvard University were the universities that published the most in the field. "Twitter", "big data", "networks", "spatial analysis", and "social capital" have been the major keywords over the past 20 years. At the same time, the keywords such as "social media", "Twitter", "big data", "geography", "China", "human mobility", "machine learning", "GIS", "location-based social networks", "clustering", "data mining", and "location-based services" have attracted increasing attention in that same time frame, indicating the future research trends.

20.
Biochem Pharmacol ; 197: 114908, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34999054

RESUMEN

The diacylglycerol kinase (DGK) family of lipid enzymes catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). Both DAG and PA are lipid signaling molecules that are of notable importance in regulating cell processes such as proliferation, apoptosis, and migration. There are ten mammalian DGK enzymes that appear to have distinct biological functions. DGKα has emerged as a promising therapeutic target in numerous cancers including glioblastoma (GBM) and melanoma as treatment with small molecule DGKα inhibitors results in reduced tumor sizes and prolonged survival. Importantly, DGKα has also been identified as an immune checkpoint due to its promotion of T cell anergy, and its inhibition has been shown to improve T cell activation. There are few small molecule DGKα inhibitors currently available, and the application of existing compounds to clinical settings is hindered by species-dependent variability in potency, as well as concerns regarding isotype specificity particularly amongst other type I DGKs. In order to resolve these issues, we have screened a library of compounds structurally analogous to the DGKα inhibitor, ritanserin, in an effort to identify more potent and specific alternatives. We identified two compounds that more potently and selectively inhibit DGKα, one of which (JNJ-3790339) demonstrates similar cytotoxicity in GBM and melanoma cells as ritanserin. Consistent with its inhibitor profile towards DGKα, JNJ-3790339 also demonstrated improved activation of T cells compared with ritanserin. Together our data support efforts to identify DGK isoform-selective inhibitors as a mechanism to produce pharmacologically relevant cancer therapies.


Asunto(s)
Diacilglicerol Quinasa/antagonistas & inhibidores , Diacilglicerol Quinasa/metabolismo , Ritanserina/análogos & derivados , Ritanserina/farmacología , Antagonistas de la Serotonina/farmacología , Relación Dosis-Respuesta a Droga , Células HEK293 , Humanos , Isoenzimas/antagonistas & inhibidores , Isoenzimas/metabolismo , Células Jurkat
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