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1.
Plants (Basel) ; 13(4)2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38498467

ABSTRACT

Conservation actions for rare species are often based on estimates of population size and number, which are challenging to capture in natural systems. Instead, many definitions of populations rely on arbitrarily defined distances between occurrences, which is not necessarily biologically meaningful despite having utility from a conservation management perspective. Here, we introduce a case study using the narrowly endemic and highly geographically disjunct leafy prairie-clover (Dalea foliosa), for which we use nuclear microsatellite loci to assess the current delimitations of populations and management units across its entire known range. We model future potential suitable niche space for the species to assess how currently defined populations could fare under predicted changes in climate over the next 50 years. Our results indicate that genetic variation within the species is extremely limited, particularly so in the distal portions of its range (Illinois and Alabama). Within the core of its range (Tennessee), genetic structure is not consistent with populations as currently defined. Our models indicate that predicted suitable niche space may only marginally overlap with the geology associated with this species (limestone glades and dolomite prairies) by 2070. Additional studies are needed to evaluate the extent to which populations are ecologically adapted to local environments and what role this could play in future translocation efforts.

2.
J Community Health ; 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38466490

ABSTRACT

Children from diverse ethnic groups are at significantly increased risk for dental caries. In particular, American Indian (AI) children have the highest incidence of detal caries of any ethnic group. The COVID-19 pandemic dramatically restricted health care access, including preventive oral health care. Given this context, it is unclear whether or not preventive oral health care for AI children has resumed since lockdown. To address this question, we surveyed adult AI caregivers (N = 152) of children aged 0-5 years, assessing recent (12-month) and pre-COVID (for caregivers of children aged 3-5 years) preventive oral and medical health services. We also examined medical health care access and utilization among caregivers. Among children aged 3-5 years old, both pre-pandemic and past year medical care utilization were generally high (80 and 90%, respectively) as was any oral health care utilization (64 & 78%, respectively). Oral health check-ups were more common over the last year (62%) compared to pre-COVID (44%). Recent health care utilization among children 1-5 years old in this sample were generally comparable to national estimates, except for higher reported preventive medical care (99% vs. 87.6%, respectively) and higher preventive oral care (96% vs. 59.6%, respectively). More caregivers reported delaying or foregoing needed health care due to COVID (28-38%) versus due to cost (8-17%). In this survey of AI caregivers, recent child preventive health care utilization was high, and changes in utilization following the lockdown phases of the pandemic were comparable for oral and medical health care.

3.
Curr Pharm Teach Learn ; 16(4): 244-254, 2024 04.
Article in English | MEDLINE | ID: mdl-38423845

ABSTRACT

Problem description\The University of Nebraska College of Pharmacy is interested in conducting and learning from an inventory of Justice, Equity, Diversity, and Inclusion (JEDI) within the college. QUALITY IMPROVEMENT METHODS: An extensive literature review was undertaken to define the terms included in JEDI and to craft a listing of ideal inventory components. RESULTS OF CQI INQUIRY: The terms used in JEDI were defined and a list of 148 ideal inventory components was created. This list is further segmented by the JEDI components themselves and by five assessment factors including: representation, curriculum & education, policies & procedures, support & resources, and college climate. INTERPRETATION AND DISCUSSION: The attempt to create an ideal listing of JEDI inventory components resulted in an unusably large number of potential items. This occurred intentionally to allow the next steps in the longitudinal creation of a workable, quantifiable, and evaluative JEDI inventory process. Describing these preliminary efforts are important in the ultimate acceptance of the results of the JEDI inventory. CONCLUSION: Deliberate and extensive listing of initial aspirations for a JEDI inventory of a College of Pharmacy or any institution allows for sufficient input and breadth to help assure that no significant factor is overlooked as the process is refined.


Subject(s)
Pharmaceutical Services , Pharmacy , Humans , Curriculum
4.
Open Forum Infect Dis ; 11(2): ofad679, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38370292

ABSTRACT

Background: Severe coccidioidomycosis presenting with respiratory failure is an uncommon manifestation of disease. Current knowledge of this condition is limited to case reports and small case series. Methods: A retrospective multicenter review of patients with coccidioidomycosis-associated acute respiratory distress syndrome (CA-ARDS) was conducted. It assessed clinical and laboratory variables at the time of presentation, reviewed the treatment course, and compared this cohort with a national database of patients with noncoccidioidomycosis ARDS. Survivors and nonsurvivors of coccidioidomycosis were also compared to determine prognostic factors. Results: In this study, CA-ARDS (n = 54) was most common in males, those of Hispanic ethnicity, and those with concurrent diabetes mellitus. As compared with the PETAL network database (Prevention and Early Treatment of Acute Lung Injury; n = 1006), patients with coccidioidomycosis were younger, had fewer comorbid conditions, and were less acidemic. The 90-day mortality was 15.4% for patients with coccidioidomycosis, as opposed to 42.6% (P < .0001) for patients with noncoccidioidomycosis ARDS. Patients with coccidioidomycosis who died, as compared with those who survived, were older, had higher APACHE II scores (Acute Physiology and Chronic Health Evaluation), and did not receive corticosteroid therapy. Conclusions: CA-ARDS is an uncommon but morbid manifestation of infection. When compared with a national database, the overall mortality appears favorable vs other causes of ARDS. Patients with CA-ARDS had a low overall mortality but required prolonged antifungal therapy. The utility of corticosteroids in this condition remains unconfirmed.

5.
Front Microbiol ; 13: 958742, 2022.
Article in English | MEDLINE | ID: mdl-36425033

ABSTRACT

Microorganisms naturally present at environmental contaminated sites are capable of biodegrading, biotransforming, or removing contaminants in soil and groundwater through bioremediation processes. Cleanup strategies and goals for site remediation can be effectively achieved by bioremediation leveraging the capabilities of microorganisms to biotransform contaminants into lesser or non-toxic end products; however, reproducible success can be limited by inadequate design or performance monitoring. A group of biological analyses collectively termed molecular biological tools (MBTs) can be used to assess the contaminant-degrading capabilities and activities of microorganisms present in the environment and appropriately implement bioremediation approaches. While successful bioremediation has been demonstrated through previously described lab-scale studies and field-scale implementation for a variety of environmental contaminants, design and performance monitoring of bioremediation has often been limited to inferring biodegradation potential, occurrence, and pathways based on site geochemistry or lab-scale studies. Potential field-scale application of MBTs presents the opportunity to more precisely design and monitor site-specific bioremediation approaches. To promote standardization and successful implementation of bioremediation, a framework for field-scale application of MBTs within a multiple lines of evidence (MLOE) approach is presented. The framework consists of three stages: (i) "Assessment" to evaluate naturally occurring biogeochemical conditions and screen for potential applicability of bioremediation, (ii) "Design" to define a site-specific bioremediation approach and inform amendment selection, and (iii) "Performance Monitoring" to generate data to measure or infer bioremediation progress following implementation. This framework is introduced to synthesize the complexities of environmental microbiology and guide field-scale application of MBTs to assess bioremediation potential and inform site decision-making.

6.
Nat Commun ; 13(1): 4907, 2022 08 20.
Article in English | MEDLINE | ID: mdl-35987899

ABSTRACT

While inequalities in science are common, most efforts to understand them treat scientists as isolated individuals, ignoring the network effects of collaboration. Here, we develop models that untangle the network effects of productivity defined as paper counts, and prominence referring to high-impact publications, of individual scientists from their collaboration networks. We find that gendered differences in the productivity and prominence of mid-career researchers can be largely explained by differences in their coauthorship networks. Hence, collaboration networks act as a form of social capital, and we find evidence of their transferability from senior to junior collaborators, with benefits that decay as researchers age. Collaboration network effects can also explain a large proportion of the productivity and prominence advantages held by researchers at prestigious institutions. These results highlight a substantial role of social networks in driving inequalities in science, and suggest that collaboration networks represent an important form of unequally distributed social capital that shapes who makes what scientific discoveries.


Subject(s)
Research Personnel , Social Networking , Humans
7.
Front Microbiol ; 13: 1005871, 2022.
Article in English | MEDLINE | ID: mdl-36845972

ABSTRACT

Leveraging the capabilities of microorganisms to reduce (degrade or transform) concentrations of pollutants in soil and groundwater can be a cost-effective, natural remedial approach to manage contaminated sites. Traditional design and implementation of bioremediation strategies consist of lab-scale biodegradation studies or collection of field-scale geochemical data to infer associated biological processes. While both lab-scale biodegradation studies and field-scale geochemical data are useful for remedial decision-making, additional insights can be gained through the application of Molecular Biological Tools (MBTs) to directly measure contaminant-degrading microorganisms and associated bioremediation processes. Field-scale application of a standardized framework pairing MBTs with traditional contaminant and geochemical analyses was successfully performed at two contaminated sites. At a site with trichloroethene (TCE) impacted groundwater, framework application informed design of an enhanced bioremediation approach. Baseline abundances of 16S rRNA genes for a genus of obligate organohalide-respiring bacteria (i.e., Dehalococcoides) were measured at low abundances (101-102 cells/mL) within the TCE source and plume areas. In combination with geochemical analyses, these data suggested that intrinsic biodegradation (i.e., reductive dechlorination) may be occurring, but activities were limited by electron donor availability. The framework was utilized to support development of a full-scale enhanced bioremediation design (i.e., electron donor addition) and to monitor remedial performance. Additionally, the framework was applied at a second site with residual petroleum hydrocarbon (PHC) impacted soils and groundwater. MBTs, specifically qPCR and 16S gene amplicon rRNA sequencing, were used to characterize intrinsic bioremediation mechanisms. Functional genes associated with anaerobic biodegradation of diesel components (e.g., naphthyl-2-methyl-succinate synthase, naphthalene carboxylase, alkylsuccinate synthase, and benzoyl coenzyme A reductase) were measured to be 2-3 orders of magnitude greater than unimpacted, background samples. Intrinsic bioremediation mechanisms were determined to be sufficient to achieve groundwater remediation objectives. Nonetheless, the framework was further utilized to assess that an enhanced bioremediation could be a successful remedial alternative or complement to source area treatment. While bioremediation of chlorinated solvents, PHCs, and other contaminants has been demonstrated to successfully reduce environmental risk and reach site goals, the application of field-scale MBT data in combination with contaminant and geochemical data analyses to design, implement, and monitor a site-specific bioremediation approach can result in more consistent remedy effectiveness.

9.
PLoS One ; 16(11): e0257335, 2021.
Article in English | MEDLINE | ID: mdl-34797826

ABSTRACT

Political elites both respond to public opinion and influence it. Elite policy messages can shape individual policy attitudes, but the extent to which they do is difficult to measure in a dynamic information environment. Furthermore, policy messages are not absorbed in isolation, but spread through the social networks in which individuals are embedded, and their effects must be evaluated in light of how they spread across social environments. Using a sample of 358 participants across thirty student organizations at a large Midwestern research university, we experimentally investigate how real social groups consume and share elite information when evaluating a relatively unfamiliar policy area. We find a significant, direct effect of elite policy messages on individuals' policy attitudes. However, we find no evidence that policy attitudes are impacted indirectly by elite messages filtered through individuals' social networks. Results illustrate the power of elite influence over public opinion.


Subject(s)
Public Opinion , Government , Humans , Investments , Longitudinal Studies , Private Sector , Students
10.
J Med Internet Res ; 23(11): e25287, 2021 11 23.
Article in English | MEDLINE | ID: mdl-34817389

ABSTRACT

BACKGROUND: Communicating official public health information about infectious diseases is complicated by the fact that individuals receive much of their information from their social contacts, either via interpersonal interaction or social media, which can be prone to bias and misconception. OBJECTIVE: This study aims to evaluate the effect of public health campaigns and the effect of socially communicated health information on learning about diseases simultaneously. Although extant literature addresses the effect of one source of information (official or social) or the other, it has not addressed the simultaneous interaction of official information (OI) and social information (SI) in an experimental setting. METHODS: We used a series of experiments that exposed participants to both OI and structured SI about the symptoms and spread of hepatitis C over a series of 10 rounds of computer-based interactions. Participants were randomly assigned to receive a high, low, or control intensity of OI and to receive accurate or inaccurate SI about the disease. RESULTS: A total of 195 participants consented to participate in the study. Of these respondents, 186 had complete responses across all ten experimental rounds, which corresponds to a 4.6% (9/195) nonresponse rate. The OI high intensity treatment increases learning over the control condition for all symptom and contagion questions when individuals have lower levels of baseline knowledge (all P values ≤.04). The accurate SI condition increased learning across experimental rounds over the inaccurate condition (all P values ≤.01). We find limited evidence of an interaction between official and SI about infectious diseases. CONCLUSIONS: This project demonstrates that exposure to official public health information increases individuals' knowledge of the spread and symptoms of a disease. Socially shared information also facilitates the learning of accurate and inaccurate information, though to a lesser extent than exposure to OI. Although the effect of OI persists, preliminary results suggest that it can be degraded by persistent contradictory SI over time.


Subject(s)
Communicable Diseases , Social Media , Humans , Learning , Public Health
11.
Curr Oncol ; 28(5): 3705-3716, 2021 09 24.
Article in English | MEDLINE | ID: mdl-34590604

ABSTRACT

Despite a global and nationwide decrease, Native Americans continue to experience high rates of cancer morbidity and mortality. Vaccination is one approach to decrease cancer incidence such as the case of cervical cancer. However, the availability of vaccines does not guarantee uptake, as evident in the Coronavirus 2019 pandemic. Therefore, as we consider current and future cancer vaccines, there are certain considerations to be mindful of to increase uptake among Native Americans such as the incidence of disease, social determinants of health, vaccine hesitancy, and historical exclusion in clinical trials. This paper primarily focuses on human papillomavirus (HPV) and potential vaccines for Native Americans. However, we also aim to inform researchers on factors that influence Native American choices surrounding vaccination and interventions including cancer therapies. We begin by providing an overview of the historical distrust and trauma Native Americans experience, both past and present. In addition, we offer guidance and considerations when engaging with sovereign Tribal Nations in vaccine development and clinical trials in order to increase trust and encourage vaccine uptake.


Subject(s)
Cancer Vaccines , Papillomavirus Infections , Papillomavirus Vaccines , Uterine Cervical Neoplasms , Female , Humans , Papillomavirus Infections/prevention & control , Uterine Cervical Neoplasms/prevention & control , American Indian or Alaska Native
12.
Adv Exp Med Biol ; 1319: 105-135, 2021.
Article in English | MEDLINE | ID: mdl-34424514

ABSTRACT

Naked mole-rats (Heterocephalus glaber) are small African rodents that have many unique behavioral and physiological adaptations well-suited for testing hypotheses about mammalian neural plasticity. In this chapter, we focus on three features of naked mole-rat biology and how they impact neural plasticity in this species: (1) their fossorial lifestyle, (2) their extreme longevity with a lack of demonstrable senescence, and (3) their unusual social structure. Critically, each of these features requires some degree of biological flexibility. First, their fossorial habitat situates them in an environment with characteristics to which the central nervous system is particularly sensitive (e.g., oxygen content, photoperiod, spatial complexity). Second, their long lifespan requires adaptations to combat senescence and declines in neural functioning. Finally, their extreme reproductive skew and sustained ability for release from reproductive suppression indicates remarkable neural sensitivity to the sociosexual environment that is distinct from chronological age. These three features of naked mole-rat life are not mutually exclusive, but they do each offer unique considerations for the possibilities, constraints, and mechanisms associated with adult neural plasticity.


Subject(s)
Longevity , Mole Rats , Animals , Brain , Neuronal Plasticity , Social Behavior
13.
IEEE Open J Eng Med Biol ; 2: 163-169, 2021.
Article in English | MEDLINE | ID: mdl-33987557

ABSTRACT

There are many benefits of the RADxSM Tech initiative worth exploring beyond that of the current acceleration of diagnostic tests being developed and deployed to the nation. One of those benefits has been the impact on work readiness for recent biomedical engineering (BME) graduates who have been hired by RADx Tech as Assistant Project Facilitators (APFs) and to the students and faculty members on applicant teams. This paper includes a literature review of the current status of BME professional skills development in traditional academic and clinical settings. The organizational structure of RADx Tech teams is described, including how recent BME graduates are integral to the process. Opportunities are discussed on how the RADx Tech structural model can be leveraged to improve professional skills education. It is concluded that the RADx Tech organizational structure and process including APFs may be replicable. Further research is planned to explore its impact.

14.
Sci Rep ; 10(1): 21876, 2020 12 14.
Article in English | MEDLINE | ID: mdl-33318501

ABSTRACT

Networked systems emerge and subsequently evolve. Although several models describe the process of network evolution, researchers know far less about the initial process of network emergence. Here, we report temporal survey results of a real-world social network starting from its point of inception. We find that individuals' ties undergo an initial cycle of rapid expansion and contraction. This process helps to explain the eventual interactions and working structure in the network (in this case, scientific collaboration). We propose a stylized concept and model of "churn" to describe the process of network emergence and stabilization. Our empirical and simulation results suggest that these network emergence dynamics may be instrumental for explaining network details, as well as behavioral outcomes at later time periods.


Subject(s)
Computer Simulation , Social Behavior , Social Networking , Humans
15.
Sci Adv ; 6(28): eabc2717, 2020 07.
Article in English | MEDLINE | ID: mdl-32923600

ABSTRACT

Cues sent by political elites are known to influence public attitudes and behavior. Polarization in elite rhetoric may hinder effective responses to public health crises, when accurate information and rapid behavioral change can save lives. We examine polarization in cues sent to the public by current members of the U.S. House and Senate during the onset of the COVID-19 pandemic, measuring polarization as the ability to correctly classify the partisanship of tweets' authors based solely on the text and the dates they were sent. We find that Democrats discussed the crisis more frequently-emphasizing threats to public health and American workers-while Republicans placed greater emphasis on China and businesses. Polarization in elite discussion of the COVID-19 pandemic peaked in mid-February-weeks after the first confirmed case in the United States-and continued into March. These divergent cues correspond with a partisan divide in the public's early reaction to the crisis.


Subject(s)
Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Betacoronavirus/isolation & purification , Betacoronavirus/physiology , COVID-19 , Consensus , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Humans , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Politics , Public Health , Public Opinion , SARS-CoV-2 , United States/epidemiology
16.
Horm Behav ; 121: 104720, 2020 05.
Article in English | MEDLINE | ID: mdl-32081743

ABSTRACT

In many social species, hierarchical status within the group is associated with differences in basal adrenocortical activity. We examined this relationship in naked mole-rats (Heterocephalus glaber), eusocial rodents with arguably the most extreme social hierarchies of all mammals. This species lives in colonies where breeding is restricted to one socially dominant 'queen' and her male consorts, and all other individuals are reproductively suppressed 'subordinates'. The relationship between cortisol and social status in naked mole-rats has not fully been elucidated, as prior results on this topic have been contradictory. We used non-invasive feces sampling to measure baseline cortisol levels in eight laboratory colonies of naked mole-rats, to either replicate or reject rank differences. First, we successfully validated an assay to measure fecal cortisol metabolites (FCMs). Removal from the colony for the validation experiment, either alone or with an opposite sex conspecific, induced prolonged elevation of FCM levels on a scale of days to weeks. This increase in cortisol did not prevent the removed animals from sexually maturing. In colony-housed animals, we found no relationship between rank in the social hierarchy and FCM levels. Further, queens, breeding males, and reproductively suppressed subordinates all had equivalent FCM levels. We conclude that this species shows little evidence of the 'stress of dominance' or 'stress of subordination' and that reproductive suppression in naked mole-rats is not driven by elevated cortisol levels.


Subject(s)
Feces/chemistry , Hierarchy, Social , Hydrocortisone/analysis , Mole Rats/physiology , Social Isolation/psychology , Animals , Female , Hydrocortisone/metabolism , Male , Reproduction/physiology , Social Behavior , Social Environment , Stress, Psychological/etiology , Stress, Psychological/metabolism , Up-Regulation
17.
Expert Opin Pharmacother ; 21(2): 213-231, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31955671

ABSTRACT

Introduction: Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is a disease phenotype that shares T helper lymphocyte cell Th1/neutrophilic/non-Type-2 Inflammation pathways thought to be key in COPD and Th2/eosinophilic/Type-2 inflammatory pathways of asthma. The pharmacology of treating ACOS is challenging in severe circumstances.Areas covered: This review evaluates the stepwise treatment of ACOS using pharmacological treatments used in both COPD and asthma. The most common medications involve the same inhalers used to treat COPD and asthma patients. Advanced stepwise therapies for ACOS patients are based on patient characteristics and biomarkers. Very few clinical trials exist that focus specifically on ACOS patients.Expert opinion: After inhalers, advanced therapies including phosphodiesterase inhibitors, macrolides, N-acetylcysteine and statin therapy for those ACOS patients with a COPD appearance and exacerbations are available. In atopic ACOS patients with exacerbations, advanced asthma therapies (leukotriene receptor antagonists and synthesis blocking agents.) are used. ACOS patients with elevated blood eosinophil/IgE levels are considered for immunotherapy or therapeutic monoclonal antibodies blocking specific Th2/Type-2 interleukins or IgE. Symptom control, stabilization/improvement in pulmonary function and reduced exacerbations are the metrics of success. More pharmacological trials of ACOS patients are needed to better understand which patients benefit from specific treatments.Abbreviations: 5-LOi: 5-lipoxygenase inhibitor; ACOS: asthma - COPD overlap syndrome; B2AR: Beta2 adrenergic receptors; cAMP: cyclic adenosine monophosphate; cGMP: cyclic guanosine monophosphate; CI: confidence interval; COPD: chronic obstructive pulmonary disease; CRS : chronic rhinosinusitis; cys-LT: cysteinyl leukotrienes; DPI: dry powder inhaler; EMA: European Medicines Agency; FDA: US Food and Drug Administration; FDC: fixed-dose combination; FeNO: exhaled nitric oxide; FEV1: forced expiratory volume in one second; FVC: forced vital capacity; GM-CSF: granulocyte-macrophage colony-stimulating factor; ICS : inhaled corticosteroids; IL: interleukin; ILC2: Type 2 innate lymphoid cells; IP3: Inositol triphosphate; IRR: incidence rate ratio; KOLD: Korean Obstructive Lung Disease; LABA: long-acting B2 adrenergic receptor agonist; LAMA: long-acting muscarinic receptor antagonist; LRA: leukotriene receptor antagonist; LT: leukotrienes; MDI: metered-dose inhalers; MN: M-subtype muscarinic receptors; MRA: muscarinic receptor antagonist; NAC: N-acetylcysteine; NEB: nebulization; OR: odds ratio; PDE: phosphodiesterase; PEFR: peak expiratory flow rate; PGD2: prostaglandin D2; PRN: as needed; RR: risk ratio; SABA: short-acting B2 adrenergic receptor agonist; SAMA: short-acting muscarinic receptor antagonist; SDMI: spring-driven mist inhaler; Th1: T helper cell 1 lymphocyte; Th2: T helper cell 2 lymphocytes; TNF-α: tumor necrosis factor alpha; US : United States.


Subject(s)
Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome/drug therapy , Bronchodilator Agents/therapeutic use , Administration, Inhalation , Adrenal Cortex Hormones/therapeutic use , Adrenergic beta-2 Receptor Agonists/therapeutic use , Forced Expiratory Volume , Humans , Muscarinic Antagonists/therapeutic use , Nebulizers and Vaporizers , Vital Capacity
18.
Cancer Res ; 79(18): 4703-4714, 2019 09 15.
Article in English | MEDLINE | ID: mdl-31337652

ABSTRACT

Human prostate cancer confined to the gland is indolent (low-risk), but tumors outside the capsule are aggressive (high-risk). Extracapsular extension requires invasion within and through a smooth muscle-structured environment. Because integrins respond to biomechanical cues, we used a gene editing approach to determine if a specific region of laminin-binding α6ß1 integrin was required for smooth muscle invasion both in vitro and in vivo. Human tissue specimens showed prostate cancer invasion through smooth muscle and tumor coexpression of α6 integrin and E-cadherin in a cell-cell location and α6 integrin in a cell-extracellular matrix (ECM) distribution. Prostate cancer cells expressing α6 integrin (DU145 α6WT) produced a 3D invasive network on laminin-containing Matrigel and invaded into smooth muscle both in vitro and in vivo. In contrast, cells without α6 integrin (DU145 α6KO) and cells expressing an integrin mutant (DU145 α6AA) did not produce invasive networks, could not invade muscle both in vitro and in vivo, and surprisingly formed 3D cohesive clusters. Using electric cell-substrate impedance testing, cohesive clusters had up to a 30-fold increase in normalized resistance at 400 Hz (cell-cell impedance) as compared with the DU145 α6WT cells. In contrast, measurements at 40,000 Hz (cell-ECM coverage) showed that DU145 α6AA cells were two-fold decreased in normalized resistance and were defective in restoring resistance after a 1 µmol/L S1P challenge as compared with the DU145 α6WT cells. The results suggest that gene editing of a specific α6 integrin extracellular region, not required for normal tissue function, can generate a new biophysical cancer phenotype unable to invade the muscle, presenting a new therapeutic strategy for metastasis prevention in prostate cancer. SIGNIFICANCE: This study shows an innovative strategy to block prostate cancer metastasis and invasion in the muscle through gene editing of a specific α6 integrin extracellular region.


Subject(s)
Cell Communication , Gene Editing , Integrin alpha6/genetics , Muscle Neoplasms/pathology , Prostatic Neoplasms/pathology , Animals , Apoptosis , Cell Adhesion , Cell Movement , Cell Proliferation , Extracellular Matrix/genetics , Extracellular Matrix/metabolism , Extracellular Matrix/pathology , Female , Humans , Integrin alpha6/chemistry , Integrin alpha6/metabolism , Male , Mice , Mice, Inbred NOD , Mice, SCID , Muscle Neoplasms/genetics , Muscle Neoplasms/metabolism , Neoplasm Invasiveness , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
19.
Neuroimage ; 197: 24-36, 2019 08 15.
Article in English | MEDLINE | ID: mdl-30928689

ABSTRACT

A recurrent theme of both cognitive and network neuroscience is that the brain has a consistent subnetwork structure that maps onto functional specialization for different cognitive tasks, such as vision, motor skills, and attention. Understanding how regions in these subnetworks relate is thus crucial to understanding the emergence of cognitive processes. However, the organizing principles that guide how regions within subnetworks communicate, and whether there is a common set of principles across subnetworks, remains unclear. This is partly due to available tools not being suited to precisely quantify the role that different organizational principles play in the organization of a subnetwork. Here, we apply a joint modeling technique - the correlation generalized exponential random graph model (cGERGM) - to more completely quantify subnetwork structure. The cGERGM models a correlation network, such as those given in functional connectivity, as a function of activation motifs - consistent patterns of coactivation (i.e., connectivity) between collections of nodes that describe how the regions within a network are organized (e.g., clustering) - and anatomical properties - relationships between the regions that are dictated by anatomy (e.g., Euclidean distance). By jointly modeling all features simultaneously, the cGERGM models the unique variance accounted for by each feature, as well as a point estimate and standard error for each, allowing for significance tests against a random graph and between graphs. Across eight functional subnetworks, we find remarkably consistent organizational properties guiding subnetwork architecture, suggesting a fundamental organizational basis for subnetwork communication. Specifically, all subnetworks displayed greater clustering than would be expected by chance, but lower preferential attachment (i.e., hub use). These findings suggest that human functional subnetworks follow a segregated highway structure, in which tightly clustered subcommunities develop their own channels of communication rather than relying on hubs.


Subject(s)
Brain/anatomy & histology , Brain/physiology , Cognition/physiology , Connectome/methods , Adult , Data Interpretation, Statistical , Female , Humans , Magnetic Resonance Imaging , Male , Models, Neurological , Neural Pathways/anatomy & histology , Neural Pathways/physiology , Young Adult
20.
PLoS One ; 14(4): e0214453, 2019.
Article in English | MEDLINE | ID: mdl-30995266

ABSTRACT

Models of contagion dynamics, originally developed for infectious diseases, have proven relevant to the study of information, news, and political opinions in online social systems. Modelling diffusion processes and predicting viral information cascades are important problems in network science. Yet, many studies of information cascades neglect the variation in infectivity across different pieces of information. Here, we employ early-time observations of online cascades to estimate the infectivity of distinct pieces of information. Using simulations and data from real-world Twitter retweets, we demonstrate that these estimated infectivities can be used to improve predictions about the virality of an information cascade. Developing our simulations to mimic the real-world data, we consider the effect of the limited effective time for transmission of a cascade and demonstrate that a simple model of slow but non-negligible decay of the infectivity captures the essential properties of retweet distributions. These results demonstrate the interplay between the intrinsic infectivity of a tweet and the complex network environment within which it diffuses, strongly influencing the likelihood of becoming a viral cascade.


Subject(s)
Information Dissemination/methods , Probability , Social Media , Algorithms , Communication , Computer Simulation , Humans , Reproducibility of Results
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