An ILK/STAT3 pathway controls glioblastoma stem cell plasticity.

Glioblastoma (GBM) is driven by malignant neural stem-like cells that display extensive heterogeneity and phenotypic plasticity, which drive tumor progression and therapeutic resistance. Here, we show that the extracellular matrix-cell adhesion protein integrin-linked kinase (ILK) stimulates phenotypic plasticity and mesenchymal-like, invasive behavior in a murine GBM stem cell model. ILK is required for the interconversion of GBM stem cells between malignancy-associated glial-like states, and its loss produces cells that are unresponsive to multiple cell state transition cues.

The intrinsic substrate specificity of the human tyrosine kinome.

Phosphorylation of proteins on tyrosine (Tyr) residues evolved in metazoan organisms as a mechanism of coordinating tissue growth. Multicellular eukaryotes typically have more than 50 distinct protein Tyr kinases that catalyse the phosphorylation of thousands of Tyr residues throughout the proteome. How a given Tyr kinase can phosphorylate a specific subset of proteins at unique Tyr sites is only partially understood.

Impacts of decision support systems on cognition and performance for intelligence-gathering path planning.

Decision Support Systems (DSS) are tools designed to help operators make effective choices in workplace environments where discernment and critical thinking are required for effective performance. Path planning in military operations and general logistics both require individuals to make complex and time-sensitive decisions. However, these decisions can be complex and involve the synthesis of numerous tradeoffs for various paths with dynamically changing conditions.

Implementation of a Clinical Vessel Wall MR Imaging Program at an Academic Medical Center.

Background And Purpose: The slow adoption of new advanced imaging techniques into clinical practice has been a long-standing challenge. Principles of implementation science and the reach, effectiveness, adoption, implementation, maintenance (RE-AIM) framework were used to build a clinical vessel wall imaging program at an academic medical center.

Materials And Methods: Six phases for implementing a clinical vessel wall MR imaging program were contextualized to the RE-AIM framework.

Primary Small Cell Carcinoma of the Breast: An Approach to Medical and Surgical Management.

Primary small cell carcinoma of the breast (PSCCB) is a rare and aggressive tumor. Due to the small number of PSCCB cases, there are no established treatment protocols. We report a case of a 55-year-old perimenopausal woman who presented with a palpable left breast mass.

Delayed Diagnosis of Duodenal Metastasis From Primary Lung Adenocarcinoma: A Case Report.

The incidence of lung cancer metastasizing to the duodenum is rare, and its clinical presentation is still not fully understood due to its low frequency. It can be asymptomatic or present symptomatically in various ways. Here, we present the case of a 63-year-old female with an unusual case of duodenal metastasis from pulmonary adenocarcinoma, presenting with a new-onset seizure complicated by a fracture from a post-ictal fall.

Evaluation of a decision support system using Bayesian network modeling in an applied Multi-INT surveillance environment.

Sensemaking and decision-making are fundamental components of applied Intelligence, Surveillance, and Reconnaissance (ISR). Analysts acquire information from multiple sources over a period of hours, days, or even over the scale of months or years, that must be interpreted and integrated to predict future adversarial events. Sensemaking is essential for developing an appropriate mental model that will lead to accurate predictions sooner.

Research-practice partnership: supporting rural cancer survivors in Montana.

The objective of this Research-Practice Partnership was to disseminate and implement strategies to assist Community Health Centers in improving the care of rural cancer survivors in Montana. Funded by the National Cancer Institute's Community Outreach and Engagement mechanism, this project utilized the MAP-IT (Mobilize, Assess, Plan, Implement, Track) program planning framework from Healthy People 2020. Partners included Montana's Department of Public Health and Human Services' Cancer Control Program, Montana Primary Care Association, One Health Community Health Center, and Huntsman Cancer Institute at the University of Utah.

Operationalizing the structural vulnerability profile within the medical examiner context.

The medicolegal death investigation process in the United States, historically focused on personal identification and determination of cause and manner of death, has evolved in recent decades to include space for advocacy centered around public health. Particularly, in the domain of forensic anthropology, practitioners have begun to incorporate a structural vulnerability perspective on human anatomical variation, with the goals of articulating the social determinants of ill health and early death and ultimately influencing public policy. This perspective has explanatory power far beyond the anthropological sphere.

Mena regulates nesprin-2 to control actin-nuclear lamina associations, trans-nuclear membrane signalling and gene expression.

Interactions between cells and the extracellular matrix, mediated by integrin adhesion complexes, play key roles in fundamental cellular processes, including the sensing and transduction of mechanical cues. Here, we investigate systems-level changes in the integrin adhesome in patient-derived cutaneous squamous cell carcinoma cells and identify the actin regulatory protein Mena as a key node in the adhesion complex network. Mena is connected within a subnetwork of actin-binding proteins to the LINC complex component nesprin-2, with which it interacts and co-localises at the nuclear envelope.

Kindlin-1 regulates IL-6 secretion and modulates the immune environment in breast cancer models.

The adhesion protein Kindlin-1 is over-expressed in breast cancer where it is associated with metastasis-free survival; however, the mechanisms involved are poorly understood. Here, we report that Kindlin-1 promotes anti-tumor immune evasion in mouse models of breast cancer. Deletion of Kindlin-1 in Met-1 mammary tumor cells led to tumor regression following injection into immunocompetent hosts.

Pathogenicity of Type I Interferons in .

Tuberculosis (TB) is a leading cause of mortality due to infectious disease and rates have increased during the emergence of COVID-19, but many of the factors determining disease severity and progression remain unclear. Type I Interferons (IFNs) have diverse effector functions that regulate innate and adaptive immunity during infection with microorganisms. There is well-documented literature on type I IFNs providing host defense against viruses; however, in this review, we explore the growing body of work that indicates high levels of type I IFNs can have detrimental effects to a host fighting TB infection.

Glioblastoma and the search for non-hypothesis driven combination therapeutics in academia.

Glioblastoma (GBM) remains a cancer of high unmet clinical need. Current standard of care for GBM, consisting of maximal surgical resection, followed by ionisation radiation (IR) plus concomitant and adjuvant temozolomide (TMZ), provides less than 15-month survival benefit. Efforts by conventional drug discovery to improve overall survival have failed to overcome challenges presented by inherent tumor heterogeneity, therapeutic resistance attributed to GBM stem cells, and tumor niches supporting self-renewal.

: Implications of Ageing on Infection and Maintaining Protection in the Elderly.

Several reports have suggested that ageing negatively affects the human body resulting in the alteration of various parameters important for sufficient immune health. Although, the breakdown of innate and adaptive immunity has been hypothesized to increase an individual's susceptibility to infections including (), little research has been done to bridge this gap and understand the pathophysiology underlying how ageing increases the pathogenesis of infection. Our objective was to study research from a plethora of resources to better understand the pathogenesis of ageing and its link to the human immune system.

Evaluation of Simulated Recognition Aids for Human Sensemaking in Applied Surveillance Scenarios.

Objective: We determined whether the human capability for sensemaking, or for identifying essential elements of information (EEIs), could be enhanced by a simulated recognition aid that directed attention to people and vehicles in scenes or by a simulated recognition aid that directed attention to EEIs.

Background: For intelligence analysts, sensemaking is challenging because it frequently involves making inferences about uncertain data. One way to enhance sensemaking may involve collaboration from a machine recognition aid such as Project Maven, an established algorithm that directs analysts' attention to people and vehicles in scenes.

Role of guard cell- or mesophyll cell-localized phytochromes in stomatal responses to blue, red, and far-red light.

Guard cell- or mesophyll cell-localized phytochromes do not have a predominant direct light sensory role in red- or blue-light-mediated stomatal opening or far-red-light-mediated stomatal closure of Arabidopsis. The role of phytochromes in blue- and red-light-mediated stomatal opening, and far-red-light- mediated decrease in opening, is still under debate. It is not clear whether reduced stomatal opening in a phytochrome B (phyB) mutant line, is due to phytochrome acting as a direct photosensor or an indirect growth effect.

Erythrocyte aggregation in sudden flow arrest is linked to hyperthermia, hypoxemia, and band 3 availability.

Background: Erythrocyte aggregation is a phenomenon that is commonly found in several pathological disease states: stroke, myocardial infarction, thermal burn injury, and COVID-19. Erythrocyte aggregation is characterized by rouleaux, closely packed stacks of cells, forming three-dimensional structures. Healthy blood flow monodisperses the red blood cells (RBCs) throughout the vasculature; however, in select pathological conditions, involving hyperthermia and hypoxemia, rouleaux formation remains and results in occlusion of microvessels with decreased perfusion.

Characterisation of a nucleo-adhesome.

In addition to central functions in cell adhesion signalling, integrin-associated proteins have wider roles at sites distal to adhesion receptors. In experimentally defined adhesomes, we noticed that there is clear enrichment of proteins that localise to the nucleus, and conversely, we now report that nuclear proteomes contain a class of adhesome components that localise to the nucleus. We here define a nucleo-adhesome, providing experimental evidence for a remarkable scale of nuclear localisation of adhesion proteins, establishing a framework for interrogating nuclear adhesion protein functions.

An in situ inferior vena cava ligation-stenosis model to study thrombin generation rates with flow.

Background: Blood flow-induced shear stress affects platelet participation in coagulation and thrombin generation. We aimed to develop an in vivo model to characterize thrombin generation rates under flow.

Methods: An in situ inferior vena cava (IVC) ligation-stenosis model was established using C57BL/6 mice.

A fluorogenic probe for granzyme B enables in-biopsy evaluation and screening of response to anticancer immunotherapies.

Immunotherapy promotes the attack of cancer cells by the immune system; however, it is difficult to detect early responses before changes in tumor size occur. Here, we report the rational design of a fluorogenic peptide able to detect picomolar concentrations of active granzyme B as a biomarker of immune-mediated anticancer action. Through a series of chemical iterations and molecular dynamics simulations, we synthesize a library of FRET peptides and identify probe H5 with an optimal fit into granzyme B.

The induction of pyrenoid synthesis by hyperoxia and its implications for the natural diversity of photosynthetic responses in .

In algae, it is well established that the pyrenoid, a component of the carbon-concentrating mechanism (CCM), is essential for efficient photosynthesis at low CO. However, the signal that triggers the formation of the pyrenoid has remained elusive. Here, we show that, in , the pyrenoid is strongly induced by hyperoxia, even at high CO or bicarbonate levels.

Pathway profiling of a novel SRC inhibitor, AZD0424, in combination with MEK inhibitors for cancer treatment.

A more comprehensive understanding of how cells respond to drug intervention, the likely immediate signalling responses and how resistance may develop within different microenvironments will help inform treatment regimes. The nonreceptor tyrosine kinase SRC regulates many cellular signalling processes, and pharmacological inhibition has long been a target of cancer drug discovery projects. Here, we describe the in vitro and in vivo characterisation of the small-molecule SRC inhibitor AZD0424.