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The Global Journalist in the 21st Century
The Global Journalist in the 21st Century systematically assesses the demographics, education, socialization, professional attitudes and working conditions of journalists in various countries around the world. This book updates the original Global Journalist (1998) volume with new data, adding more than a dozen countries, and provides material on comparative research about journalists that will be useful to those interested in doing their own studies.
The editors put together this collection working under the assumption that journalists' backgrounds, working conditions and ideas are related to what is reported (and how it is covered) in the various news media round the world, in spite of societal and organizational constraints, and that this news coverage matters in terms of world public opinion and policies. Outstanding features include:
Coverage of 33 nations located around the globe, based on recent surveys conducted among representative samples of local journalists
Comprehensive analyses by well-known media scholars from each country
A section on comparative studies of journalists
An appendix with a collection of survey questions used in various nations to question journalists
As the most comprehensive and reliable source on journalists around the world, The Global Journalist will serve as the primary source for evaluating the state of journalism. As such, it promises to become a standard reference among journalism, media, and communication students and researchers around the world.
eBook
Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy
DeNardo and colleagues report that inhibiting focal adhesion kinase in pancreatic ductal adenocarcinoma (PDAC) in mice reduces fibrosis and improves the efficacy of tumor immunotherapy. These findings suggest an approach to overcome the immunosuppressive tumor microenvironment of PDAC.
Single-agent immunotherapy has achieved limited clinical benefit to date in patients with pancreatic ductal adenocarcinoma (PDAC). This may be a result of the presence of a uniquely immunosuppressive tumor microenvironment (TME). Critical obstacles to immunotherapy in PDAC tumors include a high number of tumor-associated immunosuppressive cells and a uniquely desmoplastic stroma that functions as a barrier to T cell infiltration. We identified hyperactivated focal adhesion kinase (FAK) activity in neoplastic PDAC cells as an important regulator of the fibrotic and immunosuppressive TME. We found that FAK activity was elevated in human PDAC tissues and correlated with high levels of fibrosis and poor CD8
+
cytotoxic T cell infiltration. Single-agent FAK inhibition using the selective FAK inhibitor VS-4718 substantially limited tumor progression, resulting in a doubling of survival in the
p48-Cre
;
LSL-Kras
G12D
;
Trp53
flox/+
(KPC) mouse model of human PDAC. This delay in tumor progression was associated with markedly reduced tumor fibrosis and decreased numbers of tumor-infiltrating immunosuppressive cells. We also found that FAK inhibition rendered the previously unresponsive KPC mouse model responsive to T cell immunotherapy and PD-1 antagonists. These data suggest that FAK inhibition increases immune surveillance by overcoming the fibrotic and immunosuppressive PDAC TME and renders tumors responsive to immunotherapy.
Journal Article
The extracellular matrix and focal adhesion kinase signaling regulate cancer stem cell function in pancreatic ductal adenocarcinoma
Cancer stem cells (CSCs) play an important role in the clonogenic growth and metastasis of pancreatic ductal adenocarcinoma (PDAC). A hallmark of PDAC is the desmoplastic reaction, but the impact of the tumor microenvironment (TME) on CSCs is unknown. In order to better understand the mechanisms, we examined the impact of extracellular matrix (ECM) proteins on PDAC CSCs. We quantified the effect of ECM proteins, β1-integrin, and focal adhesion kinase (FAK) on clonogenic PDAC growth and migration in vitro and tumor initiation, growth, and metastasis in vivo in nude mice using shRNA and overexpression constructs as well as small molecule FAK inhibitors. Type I collagen increased PDAC tumor initiating potential, self-renewal, and the frequency of CSCs through the activation of FAK. FAK overexpression increased tumor initiation, whereas a dominant negative FAK mutant or FAK kinase inhibitors reduced clonogenic PDAC growth in vitro and in vivo. Moreover, the FAK inhibitor VS-4718 extended the anti-tumor response to gemcitabine and nab-paclitaxel in patient-derived PDAC xenografts, and the loss of FAK expression limited metastatic dissemination of orthotopic xenografts. Type I collagen enhances PDAC CSCs, and both kinase-dependent and independent activities of FAK impact PDAC tumor initiation, self-renewal, and metastasis. The anti-tumor impact of FAK inhibitors in combination with standard chemotherapy support the clinical testing of this combination.
Journal Article
Screening for AMPA receptor auxiliary subunit specific modulators
AMPA receptors (AMPAR) are ligand gated ion channels critical for synaptic transmission and plasticity. Their dysfunction is implicated in a variety of psychiatric and neurological diseases ranging from major depressive disorder to amyotrophic lateral sclerosis. Attempting to potentiate or depress AMPAR activity is an inherently difficult balancing act between effective treatments and debilitating side effects. A newly explored strategy to target subsets of AMPARs in the central nervous system is to identify compounds that affect specific AMPAR-auxiliary subunit complexes. This exploits diverse spatio-temporal expression patterns of known AMPAR auxiliary subunits, providing means for designing brain region-selective compounds. Here we report a high-throughput screening-based pipeline that can identify compounds that are selective for GluA2-CNIH3 and GluA2-stargazin complexes. These compounds will help us build upon the growing library of AMPAR-auxiliary subunit specific inhibitors, which have thus far all been targeted to TARP γ-8. We used a cell-based assay combined with a voltage-sensitive dye (VSD) to identify changes in glutamate-gated cation flow across the membranes of HEK cells co-expressing GluA2 and an auxiliary subunit. We then used a calcium flux assay to further validate hits picked from the VSD assay. VU0612951 and VU0627849 are candidate compounds from the initial screen that were identified as negative and positive allosteric modulators (NAM and PAM), respectively. They both have lower IC50/EC50s on complexes containing stargazin and CNIH3 than GSG1L or the AMPAR alone. We have also identified a candidate compound, VU0539491, that has NAM activity in GluA2(R)-CNIH3 and GluA2(Q) complexes and PAM activity in GluA2(Q)-GSG1L complexes.
Journal Article
Capture at the ER-mitochondrial contacts licenses IP3 receptors to stimulate local Ca2+ transfer and oxidative metabolism
Endoplasmic reticulum-mitochondria contacts (ERMCs) are restructured in response to changes in cell state. While this restructuring has been implicated as a cause or consequence of pathology in numerous systems, the underlying molecular dynamics are poorly understood. Here, we show means to visualize the capture of motile IP
3
receptors (IP3Rs) at ERMCs and document the immediate consequences for calcium signaling and metabolism. IP3Rs are of particular interest because their presence provides a scaffold for ERMCs that mediate local calcium signaling, and their function outside of ERMCs depends on their motility. Unexpectedly, in a cell model with little ERMC Ca
2+
coupling, IP3Rs captured at mitochondria promptly mediate Ca
2+
transfer, stimulating mitochondrial oxidative metabolism. The Ca
2+
transfer does not require linkage with a pore-forming protein in the outer mitochondrial membrane. Thus, motile IP3Rs can traffic in and out of ERMCs, and, when ‘parked’, mediate calcium signal propagation to the mitochondria, creating a dynamic arrangement that supports local communication.
The formation and dissolution of ER-Mitochondria contacts is unclear. Here, authors show that the IP3 receptor traffics in and out of the contacts and, when trapped, improves calcium signaling to stimulate energy metabolism.
Journal Article
The evolution of agenda-setting research and theory from 1972 to 2025: from newspapers and TV to social media and artificial intelligence
The third major study of agenda setting was done during the 1976 presidential election year, after Max and I had left Chapel Hill, and included nine waves of interviews with the same voters in Lebanon, New Hampshire; Evanston, Illinois; and Indianapolis, Indiana (Weaver et al., 1981). Donald Shaw was not involved in this study, which expanded agenda-setting research to focus on candidate images as well as issues. The next major book was a 1991 reader on agenda setting edited by David Protess of Northwestern University and Max, who had moved from Syracuse to Texas by that time (Protess & McCombs, 1991). In 1993, two other political scientists, Frank Baumgartner and Bryan Jones, published a book titled Agendas and Instability in American Politics that examined many issues over extended periods of time to reveal the dynamics of agenda setting between politicians, interest groups, and the news media (Baumgartner & Jones, 1993).
Journal Article
IP3 receptor isoforms differently regulate ER-mitochondrial contacts and local calcium transfer
Contact sites of endoplasmic reticulum (ER) and mitochondria locally convey calcium signals between the IP
3
receptors (IP3R) and the mitochondrial calcium uniporter, and are central to cell survival. It remains unclear whether IP3Rs also have a structural role in contact formation and whether the different IP3R isoforms have redundant functions. Using an IP3R-deficient cell model rescued with each of the three IP3R isoforms and an array of super-resolution and ultrastructural approaches we demonstrate that IP3Rs are required for maintaining ER-mitochondrial contacts. This role is independent of calcium fluxes. We also show that, while each isoform can support contacts, type 2 IP3R is the most effective in delivering calcium to the mitochondria. Thus, these studies reveal a non-canonical, structural role for the IP3Rs and direct attention towards the type 2 IP3R that was previously neglected in the context of ER-mitochondrial calcium signaling.
Membrane contact sites between the ER and mitochondria are known to convey calcium signals between these two organelles via IP3 receptors, but the molecular mechanisms are currently unclear. Here, the authors show that IP3 receptors play a structural tethering role in maintaining ER-mitochondrial contacts.
Journal Article
Single-Cell Transcriptional Analysis Reveals Novel Neuronal Phenotypes and Interaction Networks Involved in the Central Circadian Clock
Single-cell heterogeneity confounds efforts to understand how a population of cells organizes into cellular networks that underlie tissue-level function. This complexity is prominent in the mammalian suprachiasmatic nucleus (SCN). Here, individual neurons exhibit a remarkable amount of asynchronous behavior and transcriptional heterogeneity. However, SCN neurons are able to generate precisely coordinated synaptic and molecular outputs that synchronize the body to a common circadian cycle by organizing into cellular networks. To understand this emergent cellular network property, it is important to reconcile single-neuron heterogeneity with network organization. In light of recent studies suggesting that transcriptionally heterogeneous cells organize into distinct cellular phenotypes, we characterized the transcriptional, spatial, and functional organization of 352 SCN neurons from mice experiencing phase-shifts in their circadian cycle. Using the community structure detection method and multivariate analytical techniques, we identified previously undescribed neuronal phenotypes that are likely to participate in regulatory networks with known SCN cell types. Based on the newly discovered neuronal phenotypes, we developed a data-driven neuronal network structure in which multiple cell types interact through known synaptic and paracrine signaling mechanisms. These results provide a basis from which to interpret the functional variability of SCN neurons and describe methodologies toward understanding how a population of heterogeneous single cells organizes into cellular networks that underlie tissue-level function.
Journal Article
Mitochondrial 'kiss-and-run': interplay between mitochondrial motility and fusion-fission dynamics
Visualizing mitochondrial fusion in real time, we identified two classes of fusion events in mammalian cells. In addition to complete fusion, we observed transient fusion events, wherein two mitochondria came into close apposition, exchanged soluble inter‐membrane space and matrix proteins, and re‐separated, preserving the original morphology. Transient fusion exhibited rapid kinetics of the sequential and separable mergers of the outer and inner membranes, but allowed only partial exchange of integral membrane proteins. When the inner membrane fusion protein Opa1 level was lowered or was greatly elevated, transient fusions could occur, whereas complete fusions disappeared. Furthermore, transient fusions began from oblique or lateral interactions of mitochondria associated with separate microtubules, whereas complete fusions resulted from longitudinal merging of organelles travelling along a single microtubule. In contrast to complete fusion, transient fusions both required and promoted mitochondrial motility. Transient fusions were also necessary and sufficient to support mitochondrial metabolism. Thus, Opa1 expression and cytoskeletal anchorage govern a novel form of fusion that has a distinct function in mitochondrial maintenance.
Journal Article