Desmin: molecular interactions and putative functions of the muscle intermediate filament protein

Desmin is the intermediate filament (IF) protein occurring exclusively in muscle and endothelial cells. There are other IF proteins in muscle such as nestin, peripherin, and vimentin, besides the ubiquitous lamins, but they are not unique to muscle. Desmin was purified in 1977, the desmin gene was characterized in 1989, and knock-out animals were generated in 1996. Several isoforms have been described. Desmin IFs are present throughout smooth, cardiac and skeletal muscle cells, but can be more concentrated in some particular structures, such as dense bodies, around the nuclei, around the Z-line or in costameres. Desmin is up-regulated in muscle-derived cellular adaptations, including conductive fibers in the heart, electric organs, some myopathies, and experimental treatments with drugs that induce muscle degeneration, like phorbol esters. Many molecules have been reported to associate with desmin, such as other IF proteins (including members of the membrane dystroglycan complex), nebulin, the actin and tubulin binding protein plectin, the molecular motor dynein, the gene regulatory protein MyoD, DNA, the chaperone alphaB-crystallin, and proteases such as calpain and caspase. Desmin has an important medical role, since it is used as a marker of tumors' origin. More recently, several myopathies have been described, with accumulation of desmin deposits. Yet, after almost 30 years since its identification, the function of desmin is still unclear. Suggested functions include myofibrillogenesis, mechanical support for the muscle, mitochondrial localization, gene expression regulation, and intracellular signaling. This review focuses on the biochemical interactions of desmin, with a discussion of its putative functions.

Disintegrins: integrin selective ligands which activate integrin-coupled signaling and modulate leukocyte functions

Extracellular matrix proteins and cell adhesion receptors (integrins) play essential roles in the regulation of cell adhesion and migration. Interactions of integrins with the extracellular matrix proteins lead to phosphorylation of several intracellular proteins such as focal adhesion kinase, activating different signaling pathways responsible for the regulation of a variety of cell functions, including cytoskeleton mobilization. Once leukocytes are guided to sites of infection, inflammation, or antigen presentation, integrins can participate in the initiation, maintenance, or termination of the immune and inflammatory responses. The modulation of neutrophil activation through integrin-mediated pathways is important in the homeostatic control of the resolution of inflammatory states. In addition, during recirculation, T lymphocyte movement through distinct microenvironments is mediated by integrins, which are critical for cell cycle, differentiation and gene expression. Disintegrins are a family of low-molecular weight, cysteine-rich peptides first identified in snake venom, usually containing an RGD (Arg-Gly-Asp) motif, which confers the ability to selectively bind to integrins, inhibiting integrin-related functions in different cell systems. In this review we show that, depending on the cell type and the microenvironment, disintegrins are able to antagonize the effects of integrins or to act agonistically by activating integrin-mediated signaling. Disintegrins have proven useful as tools to improve the understanding of the molecular events regulated by integrin signaling in leukocytes and prototypes in order to design therapies able to interfere with integrin-mediated effects.

An empirical comparison of atypical bulimia nervosa and binge eating disorder

The International Classification of Diseases, 10th edition (ICD-10) defines atypical bulimia nervosa (ABN) as an eating disorder that encompasses several different syndromes, including the DSM-IV binge eating disorder (BED). We investigated whether patients with BED can be differentiated clinically from patients with ABN who do not meet criteria for BED. Fifty-three obese patients were examined using the Structured Clinical Interview for DSM-IV and the ICD-10 criteria for eating disorders. All volunteers completed the Binge Eating Scale (BES), the Beck Depression Inventory, and the Symptom Checklist-90 (SCL-90). Individuals fulfilling criteria for both ABN and BED (N = 18), ABN without BED (N = 16), and obese controls (N = 19) were compared and contrasted. Patients with ABN and BED and patients with ABN without BED displayed similar levels of binge eating severity according to the BES (31.05 ± 7.7 and 30.05 ± 5.5, respectively), which were significantly higher than those found in the obese controls (18.32 ± 8.7; P < 0.001 and P < 0.001, respectively). When compared to patients with ABN and BED, patients with ABN without BED showed increased lifetime rates of agoraphobia (P = 0.02) and increased scores in the somatization (1.97 ± 0.85 vs 1.02 ± 0.68; P = 0.001), obsessive-compulsive (2.10 ± 1.03 vs 1.22 ± 0.88; P = 0.01), anxiety (1.70 ± 0.82 vs 1.02 ± 0.72; P = 0.02), anger (1.41 ± 1.03 vs 0.59 ± 0.54; P = 0.005) and psychoticism (1.49 ± 0.93 vs 0.75 ± 0.55; P = 0.01) dimensions of the SCL-90. The BED construct may represent a subgroup of ABN with less comorbities and associated symptoms.

How to increase brand quality perception with audiovisual content? : Exploring the role of emotions in B2C and B2B contexts

This study discusses how audiovisual content can influence brand quality perceptions. The purpose of this study is to explore how audiovisual content creation can increase brand quality perceptions. This research problem is addressed with three sub questions, which aim at clarifying the role of emotions between content marketing and brand quality perception, explaining how different functions of audiovisual content can increase brand quality perception, and by identifying and comparing the key differences in content creation in business-to-consumer and business-to-businesscontexts. The theoretical background of the study is in brand personality, consumer emotions, consumerbrand relationships, content marketing and B2B branding literature. The empirical research part includes a single-case study. The case company was a Swiss startup that wished to build a highquality brand for both B2C and B2B segments. The empirical data was collected in September 2014. Eight interviews were conducted; seven with target segment representatives and one with an existing customer of the case company. The empirical findings were analyzed with thematic analysis and finally a 5-stage framework was created based on the findings of the research, offering a guideline for high-quality content creation. This study finds that emotions play an important role in brand quality perceptions. Psychological processes, emotion, cognition and conation, influence the engagement process of the target segment which ultimately can lead to activation and electronic word-of-mouth. Brand quality perception is the result of the overall emotion of the brand. The overall emotion derives from brand personality, brand concept, product attributes and utilitarian benefits of the brand. The entertaining and educational functions of the audiovisual content can target and evoke these emotional processes, and result in increased quality perceptions. In the B2B context, emotions are found to play a relatively smaller role in the quality perception processes. However, the significance of emotions cannot be ignored, since they can emphasize the value for the buying organization, and build on the trust and loyalty among the potential customers. The final framework presents five stages of content creation that ultimately improve brand quality perceptions. These stages help marketers to design and implement their content and evoke positive emotions in their target segment as part of a quality-based marketing strategy. Further research is warranted to quantitatively test the generalizability of the framework. Further research is also suggested to make the framework adaptable to different stages of the brand life cycle.

Managing Customer Co-creation: Empirical Evidence from Finnish High-tech SMEs

The purpose of this thesis is to find out how customer co-creation activities are managed in Finnish high-tech SMEs by understanding managers’ views on relevant issues. According to theory, issues such as firm size, customer knowledge implementation, lead customers, the fuzzy front-end of product/service development as well as the reluctance to engage in customer co-creation are some of the field’s focal issues. The views of 145 Finnish SME managers on these issues were gathered as empirical evidence through an online questionnaire and analyzed with SPSS statistics software. The results show, firstly, that Finnish SME managers are aware of the issues associated with customer co-creation and are able to actively manage them. Additionally, managers performed well in regards to collaborating with lead customers and implemented customer knowledge evenly in various stages of their new product and service development processes. Intellectual property rights emerged as an obstacle deterring managers from engaging in co-creation. The results suggest that in practice managers would do well by looking for more opportunities to implement customer knowledge in the early and late stages of new product and service development, as well as by actively searching for lead customers.

Nitric oxide synthesis and biological functions of nitric oxide released from ruthenium compounds

During three decades, an enormous number of studies have demonstrated the critical role of nitric oxide (NO) as a second messenger engaged in the activation of many systems including vascular smooth muscle relaxation. The underlying cellular mechanisms involved in vasodilatation are essentially due to soluble guanylyl-cyclase (sGC) modulation in the cytoplasm of vascular smooth cells. sGC activation culminates in cyclic GMP (cGMP) production, which in turn leads to protein kinase G (PKG) activation. NO binds to the sGC heme moiety, thereby activating this enzyme. Activation of the NO-sGC-cGMP-PKG pathway entails Ca2+ signaling reduction and vasodilatation. Endothelium dysfunction leads to decreased production or bioavailability of endogenous NO that could contribute to vascular diseases. Nitrosyl ruthenium complexes have been studied as a new class of NO donors with potential therapeutic use in order to supply the NO deficiency. In this context, this article shall provide a brief review of the effects exerted by the NO that is enzymatically produced via endothelial NO-synthase (eNOS) activation and by the NO released from NO donor compounds in the vascular smooth muscle cells on both conduit and resistance arteries, as well as veins. In addition, the involvement of the nitrite molecule as an endogenous NO reservoir engaged in vasodilatation will be described.

Silencing HIF-1α reduces the adhesion and secretion functions of acute leukemia hBMSCs

Hypoxia inducible factor-1α (HIF-1α) is an important transcription factor, which plays a critical role in the formation of solid tumor and its microenviroment. The objective of the present study was to evaluate the expression and function of HIF-1α in human leukemia bone marrow stromal cells (BMSCs) and to identify the downstream targets of HIF-1α. HIF-1α expression was detected at both the RNA and protein levels using real-time PCR and immunohistochemistry, respectively. Vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α) were detected in stromal cells by enzyme-linked immunosorbent assay. HIF-1α was blocked by constructing the lentiviral RNAi vector system and infecting the BMSCs. The Jurkat cell/BMSC co-cultured system was constructed by putting the two cells into the same suitable cultured media and conditions. Cell adhesion and secretion functions of stromal cells were evaluated after transfection with the lentiviral RNAi vector of HIF-1α. Increased HIF-1α mRNA and protein was detected in the nucleus of the acute myeloblastic and acute lymphoblastic leukemia compared with normal BMSCs. The lentiviral RANi vector for HIF-1α was successfully constructed and was applied to block the expression of HIF-1α. When HIF-1α of BMSCs was blocked, the expression of VEGF and SDF-1 secreted by stromal cells were decreased. When HIF-1α was blocked, the co-cultured Jurkat cell’s adhesion and migration functions were also decreased. Taken together, these results suggest that HIF-1α acts as an important transcription factor and can significantly affect the secretion and adhesion functions of leukemia BMSCs.

Acute effect of alcohol intake on sine-wave Cartesian and polar contrast sensitivity functions

The aim of this study was to assess contrast sensitivity for angular frequency stimuli as well as for sine-wave gratings in adults under the effect of acute ingestion of alcohol. We measured the contrast sensitivity function (CSF) for gratings of 0.25, 1.25, 2.5, 4, 10, and 20 cycles per degree of visual angle (cpd) as well as for angular frequency stimuli of 1, 2, 4, 24, 48, and 96 cycles/360°. Twenty adults free of ocular diseases, with normal or corrected-to-normal visual acuity, and no history of alcoholism were enrolled in two experimental groups: 1) no alcohol intake (control group) and 2) alcohol ingestion (experimental group). The average concentration of alcohol in the experimental group was set to about 0.08%. We used a paradigm involving a forced-choice method. Maximum sensitivity to contrast for sine-wave gratings in the two groups occurred at 4 cpd sine-wave gratings and at 24 and 48 cycles/360° for angular frequency stimuli. Significant changes in contrast sensitivity were observed after alcohol intake compared with the control condition at spatial frequency of 4 cpd and 1, 24, and 48 cycles/360° for angular frequency stimuli. Alcohol intake seems to affect the processing of sine-wave gratings at maximum sensitivity and at the low and high frequency ends for angular frequency stimuli, both under photopic luminance conditions.

Innovation Process and Organizational Adoption of Disruptive Innovation: Empirical Evidence from Finnish Bio-Economy Companies.

The thesis aims to build a coherent view and understanding of the innovation process and organizational technology adoption in Finnish bio-economy companies with a focus on innovations of a disruptive nature. Disruptive innovations are exceptional hence in order to create generalizations and a unified view of the subject the perspective is also on less radical innovations. Other interests of the thesis are how ideas are discovered and generated and how the nature of the innovation and size of the company affect the technology adoption and innovation process. The data was collected by interviewing six small and six large Finnish bio-economy companies. The results suggest companies regardless of size consider innovation as a core asset in the competitive markets. Organizations want to be considered innovators and early adopters yet these qualities are limited by certain, mainly resource-based factors. In addition the industry, scalability and Finland’s geographical location when seeking funding provide certain challenges. The innovation process may be considered relatively similar whether the idea or technology stems from an internal or external source suggesting the technology adoption process can in fact be linked to the innovation process theories. Thus the thesis introduces a new theoretical model which based on the results of the study and the theories of technology adoption and innovation process aims on characterizing how ideas and technology from both external and internal sources generate into innovations. The innovation process is in large bio-economy companies most often similar to or a modified version of the stage-gate model, while small companies generally have less structured processes. Nevertheless the more disruptive the innovation, the less it fits in the structured processes. This implies disruptive innovation cannot be put in a certain mould but it is rather processed case-by-case.

Empirical studies on software quality construction: Exploring human factors and organizational influences

Software quality has become an important research subject, not only in the Information and Communication Technology spheres, but also in other industries at large where software is applied. Software quality is not a happenstance; it is defined, planned and created into the software product throughout the Software Development Life Cycle. The research objective of this study is to investigate the roles of human and organizational factors that influence software quality construction. The study employs the Straussian grounded theory. The empirical data has been collected from 13 software companies, and the data includes 40 interviews. The results of the study suggest that tools, infrastructure and other resources have a positive impact on software quality, but human factors involved in the software development processes will determine the quality of the products developed. On the other hand, methods of development were found to bring little effect on software quality. The research suggests that software quality is an information-intensive process whereby organizational structures, mode of operation, and information flow within the company variably affect software quality. The results also suggest that software development managers influence the productivity of developers and the quality of the software products. Several challenges of software testing that affect software quality are also brought to light. The findings of this research are expected to benefit the academic community and software practitioners by providing an insight into the issues pertaining to software quality construction undertakings.