From affect programs to dynamical discrete emotions

According to Discrete Emotion Theory, a number of emotions are distinguishable on the basis of neural, physiological, behavioral and expressive features. Critics of this view emphasize the variability and context-sensitivity of emotions. This paper discusses some of these criticisms, and argues that they do not undermine the claim that emotions are discrete. This paper also presents some works in dynamical affective science, and argues that to conceive of discrete emotions as self-organizing and softly assembled patterns of various processes accounts more naturally than traditional Discrete Emotion Theory for the variability and context-sensitivity of emotions

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

Molecular targeted therapies in head and neck cancer - An update of recent developements -

Targeted therapies have made their way into clinical practice during the past decade. They have caused a major impact on the survival of cancer patients in many areas of clinical oncology and hematology. Indeed, in some hematologic malignancies, such as chronic myelogenous leukemia or non-Hodgkin's lymphomas, biologicals and antibodies specifically designed to target tumour-specific proteins have revolutionized treatment standards. In solid tumours, new drugs targeting EGF- or VEGF- receptors are now approved and are entering clinical practise for treatment of colon, lung, kidney and other cancers, either alone or in combination with conventional treatment approaches

How well do questionnaires on symptoms in neck-shoulder disorders capture the experiences of those who suffer from neck-shoulder disorders? A content analysis of questionnaires and interviews

<p>Abstract</p> <p>Background</p> <p>Previous research has indicated neck-shoulder disorders to have a fluctuating course incorporating a variety of symptoms. These findings awoke our interest to make a comparison between symptoms experienced by people affected with the disorder and the content of questionnaires that assess pain and other symptoms in neck-shoulder disorders. Thus the aims of this study were: -to explore the symptoms experienced by people with non-specific neck-shoulder problems, as well as experiences of nuances and temporal variations (fluctuations) of symptoms; -to investigate which sources were used in the development of ten questionnaires for assessing pain and other symptoms in the neck-shoulder; -to analyse the item content of the questionnaires; -to analyse the correspondence between the item content of the questionnaires and the symptoms described by the informants.</p> <p>Methods</p> <p>Content analysis of interviews with 40 people with non-specific neck-shoulder pain, and 10 questionnaires used to assess pain and other symptoms in neck-shoulder disorders.</p> <p>Results</p> <p>The interviews revealed a variety of symptoms indicating a bodily, mental/cognitive, and emotional engagement, and more general and severe symptoms than are usually considered in neck-shoulder questionnaires. Taking all questionnaires together many of the symptoms were considered, but most questionnaires only included a few of them. The informants were able to distinguish fluctuation of symptoms, and a variety of different qualities which were not usually considered in the questionnaires. Only two questionnaires had made use of the opinions of affected people in the development.</p> <p>Conclusion</p> <p>Few of the questionnaires had made use of the experiences of affected people in the development. The correspondence between the symptoms expressed by those affected and the content of the questionnaires was low. A variety of symptoms were expressed by the interviewees, and the participants were also able to distinguish nuances and fluctuations of symptoms. The present study points to the importance of other aspects than just pain and physical functioning as clinical trial outcome measures related to neck-shoulder disorders. To develop a condition-specific questionnaire, it is important to decide on the specific symptoms for the condition. Using the experiences of those affected, in combination with relevant research and professional knowledge, can enhance the validity of the questionnaires.</p

Larval Development of Aedes aegypti and Aedes albopictus in Peri-Urban Brackish Water and Its Implications for Transmission of Arboviral Diseases

Aedes aegypti (Linnaeus) and Aedes albopictus Skuse mosquitoes transmit serious human arboviral diseases including yellow fever, dengue and chikungunya in many tropical and sub-tropical countries. Females of the two species have adapted to undergo preimaginal development in natural or artificial collections of freshwater near human habitations and feed on human blood. While there is an effective vaccine against yellow fever, the control of dengue and chikungunya is mainly dependent on reducing freshwater preimaginal development habitats of the two vectors. We show here that Ae. aegypti and Ae. albopictus lay eggs and their larvae survive to emerge as adults in brackish water (water with <0.5 ppt or parts per thousand, 0.5–30 ppt and >30 ppt salt are termed fresh, brackish and saline respectively). Brackish water with salinity of 2 to 15 ppt in discarded plastic and glass containers, abandoned fishing boats and unused wells in coastal peri-urban environment were found to contain Ae. aegypti and Ae. albopictus larvae. Relatively high incidence of dengue in Jaffna city, Sri Lanka was observed in the vicinity of brackish water habitats containing Ae. aegypti larvae. These observations raise the possibility that brackish water-adapted Ae. aegypti and Ae. albopictus may play a hitherto unrecognized role in transmitting dengue, chikungunya and yellow fever in coastal urban areas. National and international health authorities therefore need to take the findings into consideration and extend their vector control efforts, which are presently focused on urban freshwater habitats, to include brackish water larval development habitats

Mastermind Mutations Generate a Unique Constellation of Midline Cells within the Drosophila CNS

Background: The Notch pathway functions repeatedly during the development of the central nervous system in metazoan organisms to control cell fate and regulate cell proliferation and asymmetric cell divisions. Within the Drosophila midline cell lineage, which bisects the two symmetrical halves of the central nervous system, Notch is required for initial cell specification and subsequent differentiation of many midline lineages. Methodology/Principal Findings: Here, we provide the first description of the role of the Notch co-factor, mastermind, in the central nervous system midline of Drosophila. Overall, zygotic mastermind mutations cause an increase in midline cell number and decrease in midline cell diversity. Compared to mutations in other components of the Notch signaling pathway, such as Notch itself and Delta, zygotic mutations in mastermind cause the production of a unique constellation of midline cell types. The major difference is that midline glia form normally in zygotic mastermind mutants, but not in Notch and Delta mutants. Moreover, during late embryogenesis, extra anterior midline glia survive in zygotic mastermind mutants compared to wild type embryos. Conclusions/Significance: This is an example of a mutation in a signaling pathway cofactor producing a distinct centra

The Promise and Challenge of Therapeutic MicroRNA Silencing in Diabetes and Metabolic Diseases

MicroRNAs (miRNAs) are small, non-coding, RNA molecules that regulate gene expression. They have a long evolutionary history and are found in plants, viruses, and animals. Although initially discovered in 1993 in Caenorhabditis elegans, they were not appreciated as widespread and abundant gene regulators until the early 2000s. Studies in the last decade have found that miRNAs confer phenotypic robustness in the face of environmental perturbation, may serve as diagnostic and prognostic indicators of disease, underlie the pathobiology of a wide array of complex disorders, and represent compelling therapeutic targets. Pre-clinical studies in animal models have demonstrated that pharmacologic manipulation of miRNAs, mostly in the liver, can modulate metabolic phenotypes and even reverse the course of insulin resistance and diabetes. There is cautious optimism in the field about miRNA-based therapies for diabetes, several of which are already in various stages of clinical trials. This review will highlight both the promise and the most pressing challenges of therapeutic miRNA silencing in diabetes and related conditions