Relative amounts of antagonistic splicing factors, hnRNP A1 and ASF/SF2, change during neoplastic lung growth: implications for pre-mRNA processing

Pre-mRNA processing is an important mechanism for globally modifying cellular protein composition during tumorigenesis. To understand this process during lung cancer, expression of two key pre-mRNA alternative splicing factors was compared in a mouse model of early lung carcinogenesis and during regenerative growth following reversible lung injury. Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 and alternative splicing factor/splicing factor 2 (ASF/SF2) act antagonistically to modulate splice site selection. Both hnRNP A1 and ASF/SF2 contents rose in adenomas and during injury-induced hyperplasia compared to control lungs, as measured by immunoblotting. While both proteins increased similarly during compensatory hyperplasia, hnRNP A1 increased to a much greater extent than ASF/SF2 in tumors, resulting in a 6-fold increase of the hnRNP A1 to ASF/SF2 ratio. Immunohistochemical analysis showed that hnRNP A1 localized exclusively within tumor nuclei, while ASF/SF2 appeared in cytoplasm and/or nuclei, depending on the growth pattern of the tumor cells. We also demonstrated cancer-associated changes in the pre-mRNA alternative splicing of CD44, a membrane glycoprotein involved in cell-cell and cell-extracellular matrix interactions. hnRNP A1 and ASF/SF2 expression is thus differentially altered in neoplastic lung cells by mechanisms that do not strictly arise from increased cell division. These changes are influenced by tumor histology and may be associated with production of variant CD44 mRNA isoforms

Probabilistic and preferential sampling approaches offer integrated perspectives of Italian forest diversity

Aim: Assessing the performances of different sampling approaches for documenting community diversity may help to identify optimal sampling efforts and strategies, and to enhance conservation and monitoring planning. Here, we used two data sets based on probabilistic and preferential sampling schemes of Italian forest vegetation to analyze the multifaceted performances of the two approaches across three major forest types at a large scale. Location: Italy. Methods: We pooled 804 probabilistic and 16,259 preferential forest plots as samples of vascular plant diversity across the country. We balanced the two data sets in terms of sizes, plot size, geographical position, and vegetation types. For each of the two data sets, 1000 subsets of 201 random plots were compared by calculating the shared and exclusive indicator species, their overlap in the multivariate space, and the areas encompassed by spatially-constrained rarefaction curves. We then calculated an index of performance using the ratio between the additional and total information collected by each sampling approach. The performances were tested and evaluated across the three major forest types. Results: The probabilistic approach performed better in estimating species richness and diversity of species assemblages, but did not detect other components of the regional diversity, such as azonal forests. The preferential approach outperformed the probabilistic approach in detecting forest-specialist species and plant diversity hotspots. Conclusions: Using a novel workflow based on vegetation-plot exclusivities and commonalities, our study suggests probabilistic and preferential sampling approaches are to be used in combination for better conservation and monitor planning purposes to detect multiple aspects of plant community diversity. Our findings can assist the implementation of national conservation planning and large-scale monitoring of biodiversit

The Lantern Vol. 61, No. 2, Summer 1994

• She Was a Woman of Dignity • Retake, Scene 16 • Las Vegas Sweatshirt • Pitcher Hill • In Preparation for Wisdom (Teeth) • Moist Slacks • My Mother\u27s Purse • It Comes and Goes Everyday • The Simplicity of Marriage • The First Performance • Hunger • Pushkin\u27s Dream • Tuesday, October 19 • Poetry of Baseball • Some Things are More Important Than Others • Musician • Of What Befell Our Good Knight • Piranha • Oceans Apart • Brooklyn Cantos • Snowshower • Thankfully in Australia • Toothpaste and Tuna Fish • Living Space • Blue Monday • Afterglow • A Path to Consider • Endless Summer • Scaredy-Cathttps://digitalcommons.ursinus.edu/lantern/1144/thumbnail.jp

Mechanistic studies on ganciclovir cytotoxicity in cultured glioma cells that express the herpes simplex virus thymidine kinase gene.

Transfer of the herpes simplex virus thymidine kinase (HSV-TK) gene to cancer cells followed by ganciclovir (GCV) treatment has resulted in dramatic tumor regressions in animals, prompting clinical trials of HSV-TK/GCV gene therapy. Cells expressing HSV-TK can phosphorylate GCV to GCV triphosphate (TP) which interferes with cellular DNA synthesis. Initial studies showed that GCV was substantially more cytotoxic (IC\sb{99} = 0.3-0.5 $\mu$M) than related analogs, thymine arabinoside (araT) and acyclovir (ACV) (IC\sb{99}'s $>$1,000 $\mu$M) in C6 rat and U251 human glioma cells that express HSV-TK (C6BSTK & U251tk). To understand the basis for the unique cytotoxicity of GCV, this dissertation compared the metabolism and DNA effects of GCV, ACV, and araT in U251tk and C6BSTK cells. The superior cytotoxicity of GCV was not due to better metabolism compared to araT since CCVTP levels were 18-fold lower than araTTP levels (67 vs. 1235 pmols/10\sp7 cells) at equitoxic conc., the half-life of GCVTP was shorter than araTTP (11 vs. 41 hr), and less GCV incorporated into DNA. Also, both drugs incorporated into DNA primarily at internal positions. Interestingly, GCV weakly inhibited DNA synthesis compared to araT, and consequently cells doubled after a 24 hr exposure to 1 $\mu$M GCV (IC\sb{99.9}), while 100 $\mu$M araT (IC\sb{90}) inhibited growth for 3 days. After completing one cycle of DNA replication, CCV treated cells accumulated in early S-phase and remained there until cell death, indicating that GCV incorporation in the DNA template was important for cytotoxicity. One reason for the success of HSV-TK/GCV therapy is that limited expression of HSV-TK in a tumor is sufficient to kill the entire population with GCV, most likely due to transfer of GCV nucleotides from HSV-TK positive cells to HSV-TK negative bystander cells. Using a technique to identify GCVTP in bystander cells, it was observed that GCVTP levels increased with GCV conc. and exposure to U251tk cells, corresponding to bystander killing. Impressively, in 1:1 mixtures, 24 hr GCV (1-10 $\mu$M) treatments resulted in similar levels of GCVTP (150-1800 pmol/10\sp7 cells) in HSV-TK positive and negative cells. In summary, these studies provide insight on the cytotoxic mechanism of GCV in 100% HSV-TK positive cells and in co-cultures of cells that lack and express HSV-TK. This information may contribute to the design of protocols which enhance GCVTP anti-tumor activity.Ph.D.BiochemistryBiological SciencesCellular biologyHealth and Environmental SciencesOncologyPharmacologyPure SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/130812/2/9811172.pd

Individual, relational, and contextual dynamics of emotions

This volume of Research on Emotions in Organizations contributes to the ongoing study of emotion-related forces that shape the functioning of the individual, interpersonal workplace relationships and the organizational system as a whole. The chapters in this book demonstrate the complex interplay between emotion, cognitive processes, brain functioning and contextual factors that contribute to a better understanding of organizational behavior at multiple levels of workplace life and in the context of a fast paced, uncertain and dynamically changing work environment. Taken together, this volume provides recent advances on the dynamics of emotions and points to future research venues consistent with the increasing interest in cross-country investigation and the role of neuroscience in organizational psychology. This volume is organized in three parts to provide a coverage of the latest developments in each of the following areas. Part 1focuses on the micro-level self-related dynamics of emotions. Part 2 deals with the relational-centered dynamics of emotions, while Part 3 proposes emotional dynamics related to macro contextual factors

Emotions and identity

The theme we have chosen for this volume, “Emotions and Identity,” addresses the role of emotions in defining who people are, and understand themselves to be, within organizations. Although definitions vary, organizational identity can be considered as a construct that “defines who one is in relation to [their work] role or position within a network of relationships” (Shaffer, Joplin, Bell, Lau, & Oguz, 2000, p. 442). Given that emotions influence perceptions and behaviors (and subsequently the very interactions that define the importance of identity), the chapters in this volume demonstrate the importance of emotion in forming and sustaining both individual and collective identities at work. Identities, like emotions, are constantly evolving and shifting in relation to the complex interplay between individuals and their environments. Internally, entities negotiate their identities in relation to the dual influence of emotions and cognition. Socially, entities renegotiate their identities in relation to others and shared understandings of social roles and norms. On a broader level, institutions also affect identity by prescribing sets of preferred behavior and internalizing the organization’s behavior through factors such as organizational culture. Ashkanasy (2003) notes further that emotions play an important role within all levels of organizations and can shape, interact with, and be affected by, the identities that emerge throughout organizations. Scholars have long understood attitudes to be evaluative cognitions about elements in an individual’s environment (Breckler, 1984). As such, attitudes are our assessment of the value (on some evaluative dimension) of the current state of those elements (of their degree of goodness, for example). Attitudes are how we feel about objects or people outside of ourselves. Frijda (1986) notes that emotion is in fact what happens when individuals evaluate themselves when they assess their own goodness or rightness. Thus, emotions of happiness or sadness or anger or calm or embarrassment and so on arise when we evaluate ourselves against our expectations. Arguably, the most important expectation we hold is that of our self-identity (Tyler, Kramer, & John, 2014); thus the importance to and centrality of identity in understanding the dynamics of emotions in organizations. Recognizing the multi-level implications of both emotions and identities, the authors of the chapters in this volume address emotions and identity on individual, group, occupational, and social role levels. Specifically, they investigate micro-level topics such as how individuals respond to injustice to identify as a collective, in addition to how broader occupational and gender identities influence emotions. In doing so, we organize this volume into four sections: Section 1: Identity, Anger, Diversity; Section 2: Public Sector Settings; Section 3: Gender, Emotions and Identity; and Section 4: Emotions and Identification with Work

Hepatic Transcriptome Analysis Identifies Divergent Pathogen-Specific Targeting-Strategies to Modulate the Innate Immune System in Response to Intramammary Infection.

Mastitis is one of the major risks for public health and animal welfare in the dairy industry. Two of the most important pathogens to cause mastitis in dairy cattle are Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). While S. aureus generally induces a chronic and subclinical mastitis, E. coli is an important etiological pathogen resulting in an acute and clinical mastitis. The liver plays a central role in both, the metabolic and inflammatory physiology of the dairy cow, which is particularly challenged in the early lactation due to high metabolic and immunological demands. In the current study, we challenged the mammary glands of Holstein cows with S. aureus or E. coli, respectively, mimicking an early lactation infection. We compared the animals' liver transcriptomes with those of untreated controls to investigate the hepatic response of the individuals. Both, S. aureus and E. coli elicited systemic effects on the host after intramammary challenge and seemed to use pathogen-specific targeting strategies to bypass the innate immune system. The most striking result of our study is that we demonstrate for the first time that S. aureus intramammary challenge causes an immune response beyond the original local site of the mastitis. We found that in the peripheral liver tissue defined biological pathways are switched on in a coordinated manner to balance the immune response in the entire organism. TGFB1 signaling plays a crucial role in this context. Important pathways involving actin and integrin, key components of the cytoskeleton, were downregulated in the liver of S. aureus infected cows. In the hepatic transcriptome of E. coli infected cows, important components of the complement system were significantly lower expressed compared to the control cows. Notably, while S. aureus inhibits the cell signaling by Rho GTPases in the liver, E. coli switches the complement system off. Also, metabolic hepatic pathways (e.g., lipid metabolism) are affected after mammary gland challenge, demonstrating that the liver restricts metabolic tasks in favor of the predominant immune response after infection. Our results provide new insights for the infection-induced modifications of the dairy cow's hepatic transcriptome following mastitis